The Science of Paediatrics_ MRCPCH Mastercourse

629 CHAPTER THIRTY-TWO recent years, youth unemployment has also risen and was 14% in 2015, almost three times the overall rate. The health of these adolescents and young adults who are not in employment, education or training is of increasing concern. Table 32.1 Infant and childhood mortality rates by age and sex, UK, 2012 Age (years) Male Female Overall Number of deaths Infant deaths per 1000 live births 4.4 3.5 4.0 3219 Deaths per 100,000 population in age group 1–4 18 15 16 523 5–9 9 8 9 325 10–14 11 8 10 340 15–19 33 15 24 959 Source: Office for National Statistics. (From: Why children die: death in infants, children, and young people in the UK Part A. © Royal College of Paediatrics and Child Health and National Children’s Bureau 2014.) Table 32.2 HEADSSS acronym for psychosocial history in adolescents H Home life Relationships, social support, household chores E Education School, exams, work experience, career, university, financial issues A Activities Exercise, sport, other leisure activities Social relationships, friends, peers, who can they rely on? D Driving Aged 16 if has high-rate mobility component of the Disability Living Allowance (DLA) Drugs Drug use, cigarettes, alcohol. How much? How often? Diet Weight, caffeine (diet drinks), binges/ vomits S Sex Concerns, periods, contraception (and in relation to medication) Sleep How much? Hard to get to sleep? Wake often? Suicide/affect Early waking? Depression, self-harm, body image (From: Tom Lissauer, Graham Clayden. Illustrated Textbook of Paediatrics, 4th edn. Edinburgh: Mosby Elsevier, 2012.) Question 32.1 Death in childhood Which of the following age groups has the highest mortality from all causes in the UK? Select ONE answer only. A. 1–4-year-olds B. 5–9-year-olds C. 10–14-year-olds D. 15–19-year-olds E. No significant difference Mortality in adolescence Adolescence is often considered a healthy stage of life, but there are deaths among 10–24 year olds which are often preventable. The main causes of death in this age group are external, namely traffic accidents, violencerelated or self-harm, followed by neoplasms, diseases of the nervous system (e.g. muscular dystrophy) and congenital and chromosomal abnormalities. Although overall trends have been decreasing since 2003, death in the 15–19 and 20–24-yearold age groups is more common than in younger children if infants are excluded. In particular disease groups, the reduction in mortality seen in other age groups has not occurred. For example, adolescentonset cancer mortality is unchanged compared to the improved rates in child and adult-onset disease. Rejection-related death following cardiac transplant is highest in the adolescent and young adult age groups. The explanation for these differences is not yet known, but intrinsic factors, such as the impact of aspects of adolescent development including puberty and brain development, as well as extrinsic factors, such as health service provision, are likely to be contributing factors. Resilience The other core principle underpinning adolescent medicine is that of resilience. Resilience refers to the ability to rebound from adversity and be flexible and adaptable, with resilient individuals even managing to thrive against what appears to be overwhelming odds. When taking a history from a young person, it is important to consider resilience as well as risk. What talents, resources and skills does this individual young person possess which will protect his health and emotional well-being? The HEADSSS psychosocial screening tool is useful in this regard (Table 32.2). Answer 32.1 D. 15–19-year-olds. See Table 32.1 for infant and childhood mortality rates.

32 630Adolescent medicine in children, especially those that are active in sports. It may happen in 4–5% of children by the age of six, and up to 6% of adults. Spondylolysis is three times more common in boys than girls. Growth spurts and involvement in contact sports may explain this observed sex difference. Spondylolysis may cause pain in a particular spot in the low back and spasm of the muscles along the spine. Often it will cause pain into the buttocks or thighs. Initially, plain spine X-rays may not show a fracture and MRI scanning of the spine may be required to confirm the diagnosis. It is likely to heal with a change in activity, rest, and avoiding hyperextension and rotation. Bracing may be helpful if symptoms do not improve. If symptoms do not improve, spondylolisthesis, the forward displacement of one vertebra on another, may be responsible. Likewise, premature fusion of epiphyses, which may also occur as a consequence of inflammatory arthritis leading to asymmetrical growth, should be considered during examination of affected young people. Distribution of drugs can be affected by the changes in body size and composition characteristic of puberty. The increase in lean body mass during adolescence is usually greater in boys than girls, resulting in girls having relatively more body fat than boys in late puberty; this has implications for the volume of distribution of some drugs. Pubertal assessment (including the identification of abnormal pubertal timing) is important in all clinical interactions with young people, particularly with respect to the impact of puberty on psychosocial development. The use of pubertal self-assessment tools are useful in the clinical consultation and provide a means of facilitating discussions in this area with individual young people. Other aspects of adolescent physical growth include bone mass development, with 40% of adult bone mass being accrued during this period. This is coupled with a reduction in observed vitamin D levels, which can result in suboptimal bone mineralization, an increased fracture risk and more commonly bone pain. The proportion of children with vitamin D insufficiency increases with age. In the UK, 11–16% of adolescents (aged 11–18 years) have vitamin D deficiency compared to less than 7% of children aged between 1.5 and 10 years of age. This has led to some countries, like the USA, to recommend routine vitamin D supplementation for all adolescents. Psychological development Development of a perception of one’s own body, such as how it looks, feels and moves (body image), is Specifics of adolescent development Physical development The physical hallmark of development in adolescence is puberty. This has been discussed in detail in Chapter 12, Growth and puberty. In girls, the growth spurt occurs before the onset of menses, whereas in boys, the growth spurt occurs later. In certain conditions, this has significant consequences. The peak onset of eating disorders in males tends to occur before or during the growth spurt, whereas, in females, onset is typically after the growth spurt. Risk of growth stunting following eating disorders is therefore higher in males. Rapid growth seems to increase the risk of some symptoms. Adolescent back pain is more common in those with increased truncal length. Back pain occurs commonly in adolescents, affecting up to 50% of children by age 18–20 years. Whilst an underlying cause is not identified in most children, it is important to consider spondylolysis and spondylolisthesis, particularly in active and rapidly growing adolescents. Spondylolysis is a fracture of the pars interarticularis or pedicle. This is most likely to affect the lower lumbar vertebrae and be caused by an injury or repetitive activity. The activities that most likely cause spondylolysis include extension (bending backwards) and rotation. Spondylolysis can also cause back pain Question 32.2 Adolescent medicine Which of the following statements are true (T) and which are false (F)? A. Back pain is a common, usually benign symptom in late adolescence (17–19 years). B. During adolescence, most boys have an increase in percentage body fat. C. The risk of limb length abnormality in children with juvenile idiopathic arthritis (JIA) is greatest during puberty. D. The risk of permanent reduction in adult height is greater in girls with an eating disorder than in boys. E. Vitamin D levels are usually higher in adolescence than in younger, school-aged children. Answer 32.2 A. True; B. False; C. True; D. False; E. False. See below for discussion.

631 CHAPTER THIRTY-TWO Social development The key social developmental milestones during adolescence are detailed in Box 32.2. Assessment of social development should be routine during all adolescent consultations in view of the implications for the rest of development (i.e. physical, cognitive and psychological). The role of peers and close friends is important during adolescence, particularly with regard to sources of support and influence on adherence and health promoting and health risk behaviours. Vocational development is another key series of adolescent milestones to consider and not simply one of assessment of educational achievement. Vocational readiness also encompasses prior work experience, communication skills (including those of disclosure), expectations of the young person, family, psychological state (such as self-esteem), knowledge and resources. Impact of a health condition on such development is integral to adolescent health practice. Social development may be difficult for parents and carers, who may struggle when a young person starts to question previously concretely held views, especially around healthcare. Young people may also find an increased confidence and interest in peer opinions, which may differ from that of their parents! It should be remembered that abstract thought and identity associated with the rapid changes in the physical body that come with puberty. Body image is shaped by perception, emotions, and physical sensations and can vary in response to mood, physical experience and environment. There are intrinsic influences of body image (self-esteem and self-evaluation) as well as extrinsic influences (evaluation by others, cultural messages and societal standards). Addressing body image, particularly in the peri-pubertal phase, is important. The other key features of psychological development in adolescence were first described in 1929 by Piaget and later by Erikson in 1950. Piaget identified that during adolescence there is a shift in cognitive style from the concrete processes of childhood to more abstract ways of thinking, allowing problemsolving using hypotheses and propositions. Erikson then identified search and acquisition of identity as being characteristic of development in adolescence. Both abstract thought and independent identity are important skills to acquire for successful function as an adult. These are important concepts for doctors working with young people, as a better understanding of the cognitive level of individual young people will inform the consultation and help to understand the impact of current interventions and exposures upon future health outcomes. For example, the use of immediate motivators are preferable with concrete thinkers whereas future motivators are fine to use with abstract thinkers. The different perceptions of young people undergoing similar problems is important to consider in consultation and is exemplified in the case history below. Finally, one must recognize that there may be delay in the development of abstract thought in adolescents with chronic conditions or regression to concrete thought during times of stress. Box 32.2 Social developmental milestones during adolescence Early adolescence • Realization of differences from parents • Beginning of strong peer identification • Early exploratory behaviours Mid adolescence • Emotional separation from parents • Strong peer group identification • Exploratory/risk behaviours • Early notions of vocational future Late adolescence • Development of social autonomy • Development of intimate relationships • Development of vocational capability Case history Adherence to drugs A 13-year-old boy with juvenile idiopathic arthritis has come to see you in clinic. His mother tells you that he has not been taking his methotrexate as regularly as you had prescribed. The boy says that he is feeling fine at the moment. Question: What do you think a young person who has developed concrete thinking skills will believe about the need for methotrexate, prescribed as a long-acting, disease-modifying antirheumatic medication? Answer: The doctors told me that if I miss my methotrexate then my arthritis will get worse, but I have forgotten it a couple of times and haven’t got worse so I don’t think I need it any more. Question: What do you think a young person who has developed abstract thinking skills will believe about the need for methotrexate? Answer: I missed my methotrexate because I was busy and forgot to take it. However, I realize it is a long-acting sort of drug and I still need to take it in order to stop the arthritis coming back and doing long-term damage to my joints, so I’ve put an alarm on my phone which will hopefully remind me to take it in future.

32 632Adolescent medicine third decade. The time lag between growth in the central areas of the brain and the prefrontal cortex effectively leads to a period of developmental mismatch between activity and control (Fig. 32.1) – a period of time associated with greatest risk and of key importance in health behaviours in young people. These processes appear to start earlier in females and finish later in males. Although it is attractive to link these events with the physical events observed in puberty, studies have yet to capture such an association effectively. The amount of brain development which occurs in adolescence has significance for exposure to drugs and alcohol during this period. Pubertal timing in itself has implications for aspects of both social and psychological development (Table 32.3) and it is therefore important to acknowledge that chronological age is not always a good correlate of adolescent developmental status. Engaging young people Communication Communication with young people needs to reflect the cognitive, emotional, social and behavioural changes in development throughout adolescence, mentioned already in this chapter. Young people value adults who are approachable, open, trustworthy, honest, who listen, explain things in ways they understand, take the time to learn how development might come into conflict during decisionmaking in a young person’s health behaviour – for example, a young person with diabetes might understand that withholding their insulin and eating a highsugar snack will make their blood sugar rise and make them feel unwell; but also might feel conflicted with the possibility of appearing different whilst out for a meal with their peers. Fig. 32.1 Brain development and the adolescent mismatch. (From Casey BJ, et al. The adolescent brain. Ann N Y Acad Sci 2008;1124:111–26, with permission.) Limbic regions - emotion and reward Functional development Prefrontal cortex - abstract thought, planning, inhibition and forward planning Adolescence Age Table 32.3 Pubertal timing and adolescent development Early puberty Late puberty ↑ risk of substance use ↑ risk of early sexual behaviour Self-esteem – ↓ girls, ↑ in boys ↑ risk of depression and other psychological problems in girls ↑ frequency of disturbed body image in girls ↑ engagement in exploratory & delinquent behaviour ↓ self-esteem in boys ↑ risk of osteopenia in girls ↑ frequency of disturbed body image in boys Question 32.3 Adolescent brain development Regarding the development of the adolescent brain, which of the following statements is most correct? Select ONE answer only. A. Behavioural and MRI studies have shown that there is no development of executive functions. B. Changes in the frontal and parietal regions are particularly pronounced. C. Grey-matter development is linear. D. There is a marked decrease in the proportional content of the central dopaminergic regions of the brain. E. There is no remodelling as neural plasticity ceases by the age of 10. Integrating psychological and physical development through neuroscience Recent advances in the field of magnetic resonance brain imaging have allowed a better understanding of brain development during adolescence. Whilst most brain size has been acquired by late childhood, rates of neuronal pruning are at their greatest level since the neonatal period. Adolescent brain development initially sees a significant increase in the proportional content of the central, dopaminergic regions of the brain – areas associated with sensation-seeking and important for learning new skills. At a later stage of adolescent development, there is more pronounced development of the prefrontal cortex, which is responsible for executive function, and can be thought of conceptually as the domain of abstract thought and forward planning. This process continues well into the Answer 32.3 B. Changes in the frontal and parietal regions are particularly pronounced. MRI studies confirm non-linear grey-matter development in the frontal and parietal regions of the adolescent brain.

633 CHAPTER THIRTY-TWO Better wording such as ‘Which school do you go to?’ or ‘Which subjects do you enjoy?’ open up discussion and are more developmentally appropriate. A proactive, anticipatory approach to adolescents is advocated by using tools such as HEADSSS and supported by evidence that suggests young people are more likely to have positive perceptions of the health professional and are more likely to take an active role in treatment when there has been discussion of a sensitive health topic. Opportunistic use of the HEADSSS tool has been shown to result in the identification of issues requiring intervention in almost a third of adolescents. they prefer to communicate and are not patronising. Paediatricians need to adopt all of these skills for effective consultation whilst being aware of the dynamic shifts in parental roles, which occur during adolescence. The right of children and young people to participate in matters affecting them, including healthcare, is laid out in both Article 12 of the United Nations Convention on the Rights of the Child (UNCRC) and Working together to safeguard children, encouraging professionals to hear ‘the voice’ of children and young people. The Department of Health’s You’re welcome document focuses on including, involving and supporting the participation of young people in healthcare, promoting the idea that hearing and responding to the voice of young people is central to the delivery of good healthcare. Two fundamental aspects of adolescent healthcare are, firstly, the opportunity for young people to be seen independently of their parents/caregivers and, secondly, that they understand their rights with respect to confidentiality. Data would suggest that such practices are not yet universal. Autonomy during clinic visits has also been reported to be a major determinant of transition readiness for young people with long-term conditions. A core component of the consultation is the assessment of the young person’s understanding of what confidentiality means and the conditions when confidentiality has to be broken. Research suggests that such confidential care is of particular importance to young people, who will forgo healthcare if confidentiality is not assured (in particular, those who are not getting on with their parents, who exhibit health risk behaviours and/or have mental health issues). Motivational interviewing techniques (the idea that motivation to change is elicited from the young person, and not imposed from outside forces) are ideal for use with adolescents, as they address resistance or ambivalence as well as emphasizing selfresponsibility in changing or modifying one’s behavior. For example, asking the young person questions such as ‘How might you like things to be different?’ or ‘How does ______ interfere with things that you would like to do?’ encourages them to suggest behavioural changes themselves and thus set realistic goals. Adolescents are reported to be worse at reading facial expressions and body language than either children or adults. The young person may think that the health professional is angry when they are simply concentrating on a physical exam, or thinking about which drug dose to use. The wording of questions should bear in mind the stage of adolescence. Questions such as ‘How are you doing at school?’ during early adolescence are guaranteed to get a single word response such as ‘OK’ or ‘fine’. Question 32.4 Consent and the UK law Which of the following statements concerning current UK law are true (T) and which are false (F)? A. A social worker, nurse or teacher who has consensual sex with a 17-year-old is committing a sexual offence. B. Consensual sex between two 14-year-olds is lawful where both parties are ‘Fraser competent’. C. Sex between a 12-year-old girl and a 14-yearold boy would not be classified as ‘rape’ if she fully consented and was deemed to be ‘Fraser competent’. D. The age of consent is 16 years for heterosexual activity and 18 years for homosexual activity. E. The duty of confidentiality owed to an 18-yearold girl seeking contraception is absolute. Answer 32.4 A. True; B. False; C. False; D. False; E. False. The Sexual Offences Act provides a tier of protection for ‘older’ children (16–17-year-olds) from adults in a ‘position of trust’ where the adult has a professional relationship with the young person – consent of the young person is NOT relevant. Although prosecution for consensual sex between individuals under 16 is uncommon it is unlawful. Penetrative sex with an individual under 13 years is classified as rape. The age of consent for heterosexual or homosexual sex in the UK is 16 years. There are many possible reasons for breaking confidentiality and it is not an absolute duty. See www.gmc-uk.org/guidance/ethical_ guidance/confidentiality.asp for further details.

32 634Adolescent medicine There is growing evidence that the brains of people with chronic pain are different at a functional, structural and molecular level. These changes are reversible, but it is not known whether these changes represent cause or effect. The pain neuro-matrix is the combination of cortical mechanisms which produce pain when activated. This matrix encompasses both nociceptive and nonnociceptive (cognitive, beliefs and attitudes) mechanisms, all of which need to be considered when assessing an adolescent with chronic pain. Once activated, there is increasing conviction of the central nervous system that body tissue is in danger and under threat. Whilst the threat remains, so will the pain. Hence, any pain management programme needs to both identify and reduce the threat. The mainstay of pain management in adolescents is a multidisciplinary approach. These frequently include several of the following components: education, goal-setting, a graded activity programme with pacing, anxiety management and relaxation, sleep hygiene, coping strategies, desensitization, relapse prevention and school reintegration. Cognitive behaviour therapeutic techniques are particularly useful with modification of negative and unhelpful thinking and relapse prevention. Outcomes have been reported to be much better than in adults, with the majority experiencing complete recovery. Exploratory and risk behaviours Exploratory behaviours are part of normal adolescent social development and only when they become unsafe or risky do they become health risk behaviours. Smoking, drug and alcohol use, dangerous driving, violence, shoplifting and unprotected sexual activity all occur in young people at increasingly younger ages. Most adolescents emerge from this transitional stage well, but genetics and childhood experience all affect behaviour. In addition, we are starting to understand how these factors act in the context of a brain that is changing, with its own impact on behaviour. As cognitive control over high-risk behaviours and the ability to moderate behaviour in social situations is still maturing, they are more likely to engage in risky behaviours. Evidence suggests that health risk behaviours started in adolescence tend to persist into adult life. Substance use The main substances used by adolescents in the UK today are alcohol, tobacco, and cannabis. Alcohol is currently the substance of greatest concern in the UK. Consent and the UK law All people aged 16 and over are presumed in UK law to have the capacity to consent to medical treatment unless there is evidence to the contrary. Children under 16 may also be legally competent if they have sufficient understanding. Encouraging adolescents in decision-making may aid the ‘non-competent’ adolescent in the development of competency over time, by presenting them with information appropriate to their age and level of education. By exploring adolescents’ wishes and feelings about their health issues and discussing management options with them whilst they still have the support of their parents, healthcare professionals can empower young people to make their own decisions and prepare them for adulthood. Chapter 35, Ethics, discusses issues of consent and competency in greater detail. Chronic pain syndromes Pain is a common presentation during adolescence, with a prevalence of up to 25% of young people presenting with pain. When this pain becomes chronic (longer than 3 months), young people may experience adverse effects on their psychosocial or vocational development. This in turn leads to significant cost to UK society. Furthermore, chronic pain in childhood and early adolescence has been linked with chronic pain in early adulthood. Effective pain management during adolescence is therefore of prime importance. The mean onset of chronic pain syndromes is early adolescence, with greater female predominance. Frequency of pain is reported to increase with age and the commonest sites of pain in the absence of an underlying condition are headache, abdomen, limbs and back. Pain is also increasingly recognized as a significant morbidity in association with other longterm conditions including cystic fibrosis, cerebral palsy and juvenile idiopathic arthritis. In young people with cerebral palsy, pain is a major determinant of health-related quality of life. Fatigue and sleep disturbance are frequent associated symptoms of chronic pain and asking about them is integral to the assessment of affected young people. Chronic pain may also result in school absence, impaired leisure and peer activities, as well as psychological problems. The purpose of pain is to act as a motivational driver for protection. Pain is closely associated with fear and stress responses as part of a protective mechanism. Even when the threat is not real, the brain may misinterpret signals (e.g. stress) as a ‘threat’, leading to a pain response.

635 CHAPTER THIRTY-TWO A fifth of young people aged 16–24 are exceeding the recommended limit of 21 units of alcohol per week for men, and 14 units for women. The proportion of school-aged children drinking has decreased slightly in recent years. However, the mean weekly consumption by school children has increased. About 40% of young people report binge drinking. The UK has one of the highest rates of admission to the emergency department or hospital due to alcohol use in 15–16-year-olds in Europe. Current trends suggest that the number of adolescent smokers is decreasing in the UK. There are, however, more female smokers than male. One hypothesis is that this discrepancy is related to the greater use of tobacco for weight control in females. Smoking in young people remains a significant concern due to long-term consequences, such as addiction, carcinogenic effects and the reduction of the oxygen-carrying capacity of the blood by carbon monoxide, but also short-term effects, such as respiratory illness and decreased physical fitness. Smokers are more likely to use alcohol, smoke cannabis and use other illegal drugs, in addition to participating in risky behaviours. Two thirds of new smokers start before the age of 18. The impact of electronic cigarettes in this age group is as yet unknown. Since 2001, there has been a downward trend in the school-aged population who report using illegal substances at any point in the last year. In 2011, 26% of 13–15-year-old males and 21% of females reported some experimentation. The substance most commonly used is cannabis. Use of class A drugs, volatile substances (glue sniffing, etc.) and other drugs is much rarer. There has been concern about a growth in the availability of synthetic or new drugs that have not yet been made illegal and are available on the internet (‘legal highs‘). The most popular are synthetic cannabinoids, and speed or ecstasy-type substitutes. There has also been an increase in the popularity of energy drinks amongst young people. The main psychoactive ingredient tends to be caffeine, but they also contain varying quantities of other potentially harmful substances. Robust research on prevalence and use is not yet available for the UK. When screening for smoking practices, it is important to clarify exactly what young people smoke, i.e. tobacco alone or with cannabis. Young people who co-use cannabis and tobacco are reported to have greater dependency, more psychosocial problems and poorer cessation outcomes. Case history Substance misuse Joseph, a 14-year-old boy is admitted to the emergency department with a history of being hyperactive, restless and ‘not himself’. His pupils are dilated. He admits to smoking cannabis and taking ‘a pill’ at a party, but is not sure what it was. What advice would you give him about the consequences of cannabis use? The use of cannabis in adolescence has been linked to a range of developmental and social problems. Research suggests that persistent use is associated with significant neuropsychological disturbance, including cognitive and memory problems and declining IQ. Significantly, studies indicate that cessation of marijuana use does not fully restore neuropsychological functioning among adolescent users. In addition to memory, attention and learning, cannabis use is linked with poor school performance, increased risk-taking behaviour and an increased risk of mental health issues. What are the physiological effects of recreational drugs? These are summarized in Table 32.4. What are the different types of approach to health promotion that could be adopted? Health promotion is important, as unhealthy adolescent behaviours can become long-term risk factors for chronic health conditions in adulthood. Health promotion can be approached to target: • Individuals – Health professionals can use consultations for opportunistic health promotion and use techniques such as motivational interviewing and brief intervention to encourage change. • Training – Programs that involve adolescents in activities enhancing competence and capacity and help them avoid negative choices and outcomes. • Families/schools and communities – Health promotion in the environment most familiar to the young person, aiming to decrease risk factors and increase protective factors within peer groups of adolescents. • Society as a whole – Global health promotion using social media/television and advertising can be very effective.

32 636Adolescent medicine Table 32.4 Physiological effects of recreational drugs during adolescence Recreational drug Clinical effects Extreme use Central nervous system stimulants Cocaine (incl crack) MDMA (Ecstasy) Alkyl nitrites Amphetamines Dilated pupils Tachycardia, hypertension Increased energy Euphoria Feelings of enhanced sociability, sexuality and confidence Paranoid psychosis Depression Seizures Extreme anxiety states Myocardial infarction/cerebrovascular accidents Hallucinations Central nervous system depressants Gases Glues and aerosols Alcohol Barbiturates Benzodiazepines Slurred speech Relaxation/decreased inhibition Impaired memory/ thinking Decreased motor skills Respiratory depression Seizures Liver disease Heart disease Hallucinogens Cannabis LSD Magic mushrooms Ketamine Hallucinations Dizziness, nausea and vomiting Feelings of enhanced mental capacity Psychosis Poor judgement leading to serious injury/death Anxiety/depression Analgesics Heroin Morphine Codeine Pinpoint pupils Analgesia Intoxication followed by euphoria Constipation Drowsiness Respiratory depression Blood-borne infections (from sharing needles) Myocardial infarction/cerebrovascular accidents Question 32.5 Sexually transmissible diseases Following (A–J) is a list of diagnoses: A. Bacterial vaginosis B. Chlamydia trachomatis C. Genital warts D. Herpes simplex E. HIV F. Neisseria gonorrhoeae G. Non-gonococcal urethritis H. Scabies I. Syphilis J. Trichomonas vaginalis Choose the most likely diagnosis for each of the following. Select ONE answer only for each question. 1. A 16-year-old student presents for the ‘emergency contraceptive pill’ after an unprotected sexual episode the previous night. She has had five sexual partners in the past 6 months and does not use condoms or any other contraceptives. Her periods have been regular, but she has recently noted some spotting between periods. Last menstrual period was 4 weeks ago. The genital exam reveals normal vulva and vagina. Her cervix appears inflamed, bleeds easily, with a purulent discharge coming from the cervical os. The bimanual exam is normal without cervical motion pain, uterine or adnexal tenderness. NAAT test is positive. 2. A 16-year-old male presents to the STD clinic with a sore on his penis for one week. He had an unprotected sexual episode 3 weeks earlier without a condom. Physical exam shows no oral, perianal, or extra-genital lesions. Genital exam shows a red, indurated, clean-based, and nontender lesion on the ventral side of the penis near the frenulum. He has two enlarged tender right inguinal nodes and no urethral discharge. 3. A 15-year-old girl presents with a widespread pruritic rash present for one week. She lives in a children’s home and has been sexually active for 6 months, only using condoms ‘occasionally’. Physical exam shows a widespread erythematous papular rash pronounced on her buttocks, abdomen, hands, elbows and axilla.

637 CHAPTER THIRTY-TWO Answer 32.5 1. B. Chlamydia trachomatis. With a positive NAAT test, this history could describe both Neisseria gonorrhoea and Chlamydia trachomatis. In the 16–25-year-old age group, chlamydia is the commonest bacterial sexually transmitted infection and hence the most likely diagnosis. 2. I. Syphilis. The genital examination describes a chancre, a painless ulceration most commonly formed during the primary stage of syphilis. 3. H. Scabies. Scabies is extremely contagious and usually spreads through skin-to-skin contact with someone who is already infected. It spreads most easily in crowded conditions and those with a lot of close contact – among families, in nurseries, children’s homes and boarding schools. Sexual health in adolescence In addition to puberty, adolescents also develop an understanding of their gender identity and sexual orientation. Gender identity refers to whether they consider themselves masculine, feminine or both (transgendered), whilst sexual orientation refers to patterns of attraction to others and includes physical, emotional, sexual, and romantic attraction. The average age for first heterosexual intercourse in the UK is 16 years and whilst two thirds of 16–19-yearolds have a sexual partner, one in ten of those do not use contraception. Risk-taking sexual behaviour may result in sexually transmitted infections (STIs) and/or unplanned pregnancy. Taking a sexual history is therefore an important part of health screening and an opportunity for health promotion. When taking a sexual history, it is important to be non-judgmental and supportive, use gender-neutral language and avoid assumptions about the patient’s sexual orientation, sexual behaviours, or number of partners. Paediatricians must be aware of the significant psychological, social and medical issues faced by adolescents who are gay, lesbian or bisexual, all of which can have an impact on self-esteem and identity formation. Starting discussions around pubertal development can be a useful strategy to introduce these potentially sensitive topics as well as building on what they are learning at school in sex and relationship education. The latter is particularly useful in addressing parental concerns. Sexual health is an important consideration for all young people, including young people with long-term health conditions. Such young people often have Box 32.3 Implications of long-term conditions (including therapy) to sexual and future reproductive health Physical aspects • Oral (e.g. kissing with peanut allergy!) • Musculoskeletal and/or neurological abnormalities, e.g. limited hand function re condom use, masturbation • Fatigue Reproductive • Heredity issues • Fertility issues Drug-related • Contraception on teratogenic drugs • Egg/sperm storage on cytotoxic therapy • Drug side effects on e.g. function, desire, menstrual cycle Infection risk on immunosuppression Psychological • Sexual identity • Disclosure • Body image • Self-confidence/esteem/efficacy Cultural Opportunity additional issues due to the implications of their condition and/or its therapy for their sexual and reproductive health (Box 32.3). Sexually transmitted infections in the UK Case history 16-year-old Rose presents with a history of vaginal discharge and pain during sexual intercourse. She and her boyfriend are not using condoms ‘as she is on the pill’. She did do one of those STI ‘selftest kits’ at school 6 months previously but doesn’t know what it was testing for. What are the common STIs of adolescence? Chlamydia is the commonest STI diagnosis amongst adolescents in the UK, with those under 25 years accounting for 64% of all new chlamydia cases. It is often asymptomatic but may present with unusual discharge, post-coital/inter-menstrual bleeding, lower abdominal pain, sterile pyuria or dysuria. Long-term complications include pelvic inflammatory disease, ectopic pregnancy and

32 638Adolescent medicine sexual intercourse, although lowest levels of use remain within the 16–19-year-old age group. In addition, use of contraception may be irregular or incorrect. Awareness of resources is also variable, with only 47% of 15-year-olds knowing where the local service for contraceptive advice is. Transitional care Due to the advances in paediatrics, an increasing number of children are surviving into adolescence and adulthood. Transitional care is a key element of adolescent healthcare irrespective of the presence or absence of chronic illness or disability. All young people will hopefully make the transition from childhood to adulthood and, in doing so, move from the family home to live independently, from school to further education, training or work. This process is mirrored in healthcare with the transition of young people from paediatric to adult services. Many young people make these transitions successfully but some experience great difficulty. Transition has been defined as ‘a multi-faceted, active process that attends to the medical, psychosocial and educational/vocational needs of adolescents as they move from child- to adult-centred care’. Transfer is but a single event within a much longer process of transition, although these two terms are often erroneously used interchangeably. Research supports current guidance that transitional care should start in early adolescence with transfer generally occurring in late adolescence in a planned and coordinated manner. Conditions for successful transition include planning, patient education, skills training and a willingness to address the concerns of both the young person and their parents. Dedicated transition clinics help create an appropriate environment for this process to be facilitated in a patient-centred and coordinated fashion. As transitional care is multidimensional, it can involve primary care, education, social care and vocational services as well as the paediatric and adult secondary care services. Effective communication, continuity, appropriate staff competencies and consistency within and between these various systems are vital to ensure successful transitional care for young people with long-term conditions. Youth-friendly health services There is increasing interest, both nationally and internationally, as to what determines a youth-friendly health service (Box 32.4). Developmentally appropriate healthcare for age is every child and adolescent’s right and is thought likely to improve their health infertility. Treatment is with a single dose of azithromycin or a longer course of doxycycline. Gonorrhoea is the second most common STI diagnosis in adolescence in the UK. It too can be asymptomatic or can present with urethral discharge, dysuria or inter-menstrual bleeding. Complications are similar to those of chlamydia. Treatment is with a single dose of a cephalosporin. Genital warts are caused by the human papillomavirus (HPV), typically by two strains of the virus, type 6 and 11. Other strains of HPV can cause cervical cancer. The HPV vaccine routinely offered to 12–13-year-old girls as part of the childhood vaccination programme protects against genital warts in addition to cervical cancer. Warts are found on the penis, anus and vagina and often resolve spontaneously but can be treated with creams and/or cryotherapy. Genital herpes is caused by the herpes simplex virus (HSV), resulting in painful blisters on the genitals and surrounding area. There is no cure for genital herpes but symptoms can be controlled using antiviral medicines. Although not usually thought of as an STI, Candida can be passed on to sexual partners during intercourse. Symptoms typically include itching, soreness, redness and an odourless ‘cottage cheese’-like discharge. Candida often occurs during treatment with steroid therapy. What can you tell Rose about the National Chlamydia Screening Programme? In 2003, the National Chlamydia Screening Programme was established in England to control chlamydia through early detection and treatment of asymptomatic infection, thereby also reducing onward transmission and the consequences of untreated infection. The programme has resulted in a decrease in the prevalence of chlamydia among sexually active under-25-year-olds. It offers free and confidential self-test kits for under-25-yearolds, eliminating the need for an examination. In addition, the ‘3Cs & HIV’ programme has been set up in England to support primary care physicians and sexual health centres to: • Provide the ‘3Cs’, offering of a chlamydia screen, signposting or provision of contraceptive advice and free condoms, during routine consultations with 15–24-year-olds • Deliver HIV testing in young people over 16 years. Contraception The UK Government’s new sexual health strategy aims to increase knowledge and awareness of all methods of contraception for all ages. Research suggests that the majority of young people do use contraception during

639 CHAPTER THIRTY-TWO Box 32.4 Core indicators of youth-friendly healthcare • Accessibility of healthcare • Staff attitude • Communication • Medical competency • Guideline-driven care • Age-appropriate environments • Youth involvement in healthcare • Health outcomes outcomes. It will also improve the experience of young people, enhance their well-being and strengthen their self-determination. It is hypothesized that youth-friendly services will increase engagement, thereby reducing healthcare costs and healthcare utilization in the long term. This is particularly pertinent to those young people who tend to be under-represented in research, such as those from minority ethnic communities, looked-after young people, care leavers, asylum seekers and teenage parents. Several important features of developmentally appropriate healthcare for adolescents have already been discussed, including routine psychosocial screening, opportunity to be seen independently of parents and confidential service provision. The UK You’re welcome quality criteria for youthfriendly health services reflect this and have been validated with respect to young people’s satisfaction. Every clinical encounter with a young person represents a potential opportunity to raise awareness of their developing strengths and the role they can play in their own health and well-being. Paediatricians can motivate and assist adolescents in taking on responsibility for their own health, actively promote their strengths and in so doing convey belief in young people. Further reading Cashman K. Vitamin D in childhood and adolescents. Postgrad Med J 2007;83:230–5. Department of Health (UK). Chief Medical Officer’s annual report 2012. Our children deserve better: prevention pays. London: Department of Health; 2013. Hagell A, Coleman J, Brooks F. Key data on adolescence 2013. London: Association for Young People’s Health; 2013. Payne D, Martin C, Viner R, Skinner R. Adolescent medicine in paediatric practice. Arch Dis Child 2005;90:1133–7. Sawyer SM, Afifi RA, Bearinger LH, et al. Adolescence: a foundation for future health. Lancet 2012;379(9826):1630– 40. Steinbeck K, Kohn M. A clinical handbook in adolescent medicine. A guide for health professionals who work with adolescents and young adults. Singapore: World Scientific Publishing Co. Pte. Ltd; 2013. Viner RM, Ozer EM, Denny S, et al. Adolescence and the social determinants of health. Lancet 2012;379(9826): 1641–52.

This page intentionally left blank

LEARNING OBJECTIVES By the end of this chapter the reader should: • Know about the major causes of child mortality globally • Know about the most common illnesses in low resource countries: pneumonia, gastroenteritis, malaria, HIV infection, tuberculosis, measles • Know about intervention programmes to improve health: immunization, paediatric life support courses, integrated management of childhood illness (IMCI) • Know about the identification, pathophysiology, clinical features and management of malnutrition • Know about the major causes of neonatal morbidity and death • Be aware of neglected issues in global child health: adolescent health, mental health, neglected tropical diseases • Be aware of vulnerable children: child labour, street children, armed conflict 641 CHAPTER THIRTY-THREE Epidemiology and child survival just five countries: India, Nigeria, Democratic Republic of Congo, Pakistan, and China. What are the major causes of child mortality worldwide? Data capture and ascertainment of causes of death are fraught with difficulty in countries without proper systems in place for birth and death registration. Of the 12 million deaths in 1990 only 2.7% were medically certified. Many countries use techniques such as verbal autopsy, which involves questioning family members regarding the child’s symptoms immediately prior to death in order to retrospectively assign a diagnosis. Data suggest that the major causes of under-5 mortality are pneumonia (13%), preterm birth complications (15%), complications during birth (11%), diarrhoea (9%) and malaria (7%) (Fig. 33.1). Malnutrition is a major underlying cause of death and undernutrition is thought to contribute to 45% of under-5 deaths. There are important inter-country and interregional differences that need to be considered before planning specific public health interventions. For example, malaria is a more significant threat in Africa, where it is responsible for 15% of deaths in children Dan Magnus, Anu Goenka, Bhanu Williams Global child health C H A P T E R 33 Case history Chances of survival A baby girl, Aminatta, is born to subsistence farmers in rural Senegal. What is Aminatta’s chance of surviving to her 5th birthday? Senegal’s under-5 mortality rate in 2013 was 55 per 1000 live births, compared to UK figures of 5 per 1000 live births and Sierra Leone’s 161 per 1000 live births. Millennium Development Goal (MDG) 4 aimed to reduce the under-5 mortality rate by two thirds between 1990 and 2015. In 2013 there were 6.3 million child deaths worldwide, compared to 12 million in 1990. The global under-5 mortality rate (defined as deaths in children under the age of 5 years per 1000 live births) has fallen from 90/1000 in 1990 to 48/1000 in 2012. In sub-Saharan Africa, 1 in 11 children die before their 5th birthday. In which countries do most child deaths occur? Large population size combined with high mortality rates mean almost half (49%) of child deaths occur in

33 642Global child health more likely to experience worse clinical outcomes for most illnesses compared with children from more wealthy backgrounds. This is partly because children living in poverty are more likely to be underweight and micronutrient deficient, have less resistance to disease, are less likely to be able to reach a health facility and less likely to receive adequate care. As well as poverty, mortality is higher in rural rather than urban areas and to a mother with little or no education. In addition, preventive public health measures such as vaccination, vitamin A supplementation and insecticide-treated net distribution tend to have the worst coverage amongst the poorest populations with the greatest need. Child health can be measured using a variety of numerical indicators. The most common, showing the rates for sub-Saharan Africa, are displayed in Table 33.1. Most child deaths are preventable through the scaling up of evidence-based child health interventions, adapted according to country-specific local disease epidemiology, with an emphasis on targeting the most vulnerable children. Educating girls is likely to have a positive impact on reducing child mortality under 5, compared with south-east Asia, where it contributes just 1% to under-5 mortality. Though neonatal causes still account for a substantial proportion of under-5 deaths in most low-resource settings, their contribution varies, e.g. 52% of under-5 deaths in south-east Asia, compared with 30% in Africa. In the post-neonatal period in South and Central America, it is injuries that are the single largest threat to under-5 survival, causing 16% of mortality. What indicators can be used to measure child health and inequalities of child health? There are marked inter- and intra-country inequalities in child health. In 2012 the under-5 mortality rate was 147/1000 live births in Somalia, 56/1000 in India and 5/1000 in the United Kingdom. Marked inequalities in health also occur within countries. The poorer the child, the more likely they are to be exposed to risk factors for ill health. Unclean water and poor sanitation lead to diarrhoeal disease, while inadequate housing, air pollution and overcrowding promote the spread of respiratory pathogens. Poorer children are Fig. 33.1 Major causes of child deaths in 2012. (From Committing to Child Survival: A Promise Renewed (UNICEF, 2013) with permission.) Prematurity 15% Intra-partum related complications, including birth asphyxia 11% Neonatal sepsis 10% (tetanus 1%) Congenital anomalies 4% Other 4% Pneumonia 13% Diarrhoea 9% Malaria 7% HIV/AIDS 2% Measles 2% Injuries 5% Congenital anomalies 7% Other 11% Neonatal 44% < 5 years (excluding neonatal) 56%

643 CHAPTER THIRTY-THREE International child health programmes The role of international organizations in delivering programmes for improving global child health Individual governments fund and facilitate important global health programmes, often through government organizations, e.g. USAID (United States Agency for International Development) and DFID (UK Department for International Development). However, it is intergovernmental organizations such as the United Nations or the International Labour Organization that often exert the greatest influence through cross-country collaborations and large, well-funded global partnerships. It is under the auspices of the United Nations that the World Health Organization, the World Bank and UNICEF are able to function and to deliver some of the most influential child health initiatives. The field-level implementation of such child health improvement initiatives is often achieved in collaboration with non-governmental organizations (NGOs), who rely on public and donor funding, e.g. Oxfam, and the Malaria Consortium. NGOs may operate internationally (e.g. Médecins Sans Frontières), nationally or regionally. Effective co-ordination between NGOs as well as government programmes are critical factors in determining the success of child health improvement initiatives. Governmental, intergovernmental and NGO partnerships only form part of the global picture on efforts to improve child health. Public–private partnerships also play an important role in financing and rolling out global health initiatives; GAVI (Global Alliance for Vaccines and Immunization) is a good example of this. Private foundations, such as the Bill and Melinda Gates Foundation, also provide significant investment and funding into global health programmes and research. Major threats to child survival and studies have demonstrated a strong correlation between maternal education and child mortality. However, it has been argued that maternal education may be a proxy measure of socio-economic status; once paternal education and access to piped water and sanitation is taken into consideration, the impact of maternal education has been shown to be less marked, although still significant. Why have child deaths fallen? As well as rising wealth in many countries, the reduction in child deaths may be attributed to the implementation of child survival initiatives. Despite impressive reductions in child mortality in some countries, such as Rwanda and Bangladesh, the slowest improvements have been in West and Central Africa and it is unlikely that the MDG4 target will be met globally. The greatest gains in reducing postneonatal under-5 mortality have occurred with the scaling up and improved coverage of preventative interventions, such as vaccinations and insecticidetreated nets for prevention of malaria. In stark contrast to the progress achieved in reducing post-neonatal under-5 mortality, efforts to reduce neonatal mortality have been hampered by a lack of a continuum between maternal and child care, which is discussed further below. Table 33.1 Child health indicators Indicator Definition UK rate Sub-Saharan Africa rate Under-5 mortality rate Under 5 years of age: deaths per 1000 live births 5 98 Infant mortality rate Under 1 year of age: deaths per 1000 live births 4 64 Neonatal mortality rate Deaths before 28 days of age per 1000 live births 3 32 Perinatal mortality rate Stillbirths and early neonatal deaths (deaths before 1 week of age) per 1000 live and stillbirths 7.6 Unknown Stillbirth rate Stillbirths (WHO definition – infants born with no signs of life ≥ 28 weeks’ gestation; in UK ≥ 24 weeks’ gestation) per 1000 live and stillbirths 4.9 Unknown Case history Acute febrile illness Tomoka is a 2-year-old girl living in rural Malawi who has a short history of fever, cough, coryza, rash and diarrhoea. She is taken to a primary healthcare clinic by her aunt. Her mother died

33 644Global child health deaths from malaria occur in children under 5 and pregnant women. There has been some progress in reducing morbidity and mortality attributable to severe malaria, which is usually caused by Plasmodium falciparum. Plasmodium vivax and ovale cause less severe disease but have a liver hypnozoite stage that requires specific treatment to effect eradication. While Plasmodium malariae is seldom associated with severe disease, it can be associated with nephrotic syndrome. The WHO 2013 malaria report stated there were 627,000 deaths from malaria in 2010, 77% of which were in children under 5. The Roll Back Malaria Partnership has been coordinating international efforts since 1998 to scale up preventative diagnostic and therapeutic interventions with the overarching vision of freeing the world of the burden of malaria. Central to prevention of malaria is the use of long-lasting insecticide-treated bed nets (ITNs), which reduce the vector population of Anopheles mosquitoes. Currently, approximately 40% of children in sub-Saharan Africa sleep under an ITN. Households can be further protected from mosquitoes by indoor residual spraying (IRS) with insecticides. Various candidate malaria vaccines are in development, which, even if partially efficacious, could substantially reduce mortality and morbidity. The clinical presentation of malaria involves non-specific symptoms such as fever and headache. Clinical assessment alone carries the risks of both over-treatment and under-treatment. It is therefore essential to confirm the diagnosis before initiating treatment. The diagnosis of malaria in low-resource settings has been facilitated by the use of rapid diagnostic tests (RDTs), which are cost effective, require minimal training and can be used by community health workers. The management of acute severe malaria depends not only on prompt access to appropriate antimalarial drugs, but also effective treatment of hypoglycaemia, anaemia and convulsions. The superiority of artemisinin-based antimalarial treatment over quinine was demonstrated in two large multicentre trials involving more than 6500 children: the SEAQUAMAT study in south-east Asia and the AQUAMAT study in sub-Saharan Africa. The latter trial, a multicentre randomized controlled trial of children with severe malaria, showed significantly reduced mortality (relative risk reduction 22.5%, 95% Confidence Interval (CI) 8.1–36.9; odds ratio for death 0.75, 95% CI 0.63–0.9) and reduced coma and seizures with artemisinin compared with quinine. Since the publication of these landmark studies, the WHO recommends artemisinin combination treatment (ACT) as first line in severe malaria. Artemisinin is combined with partner drugs to delay the development of drug resistance. Nonetheless, artemisinin resistance has emerged in south-east Asia. Pneumonia and diarrhoea Tomoka’s clinical presentation encompasses diarrhoeal disease and possibly pneumonia. They account for the majority of child deaths outside the neonatal period and the global burden is highest in Africa and south-east Asia. Pneumonia and diarrhoea are often considered together as they share common risk factors and programmatic solutions, including tackling poverty, undernutrition, poor hygiene, suboptimal breastfeeding, zinc deficiency as well as improving access to vitamin A and vaccination. The World Health Organization (WHO) has streamlined its case definitions to stratify the clinical severity of pneumonia and diarrhoeal disease. Pneumonia is now simply classified as ‘pneumonia’ and ‘severe pneumonia’ and diarrhoea is divided into syndromes (acute, persistent, bloody, etc.) with assessment of level of dehydration (none, some and severe). These classifications rely on objective clinical symptoms and signs that can be easily elicited by community health workers and staff working in primary care, facilitating the early referral of appropriate cases to secondary care. Oral rehydration solution (ORS) remains the cornerstone of management of diarrhea, coupled with continued feeding. Effective management of pneumonia relies largely on access to antibiotics. The treatment of hypoxaemia with oxygen has also been shown to reduce pneumonia deaths. Approximately one third of severe episodes of diarrhoea and pneumonia are preventable by vaccination. Despite increased vaccination coverage, the majority of pneumonia deaths are attributable to vaccinepreventable organisms such as Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Roll-out of pneumococcal conjugate vaccine (PCV) lags behind Hib vaccine, despite the benefits of PCV even extending to children with viral pneumonia. Rotavirus vaccine continues to be introduced into the immunization schedules of many countries and effective coverage reduces mortality attributable to diarrhoea. Malaria Tomoka’s clinical presentation does not immediately suggest malaria but it is important to assess all febrile children who live in endemic areas for malaria. Most recently after an illness characterized by chronic cough and wasting. Tomoka’s health card has been lost, which contained details of her past medical history, vaccination status and growth charts. What are the major threats to her survival? Which intervention programmes would be of greatest benefit for Tomoka’s health? These are listed below.

645 CHAPTER THIRTY-THREE HIV infection is very unlikely if the child has two negative PCRs (one after 3 months) or two negative antibody tests if <12 months or one negative antibody test after 18 months. Tomoka needs to be assessed for the clinical features and complications of HIV infection. HIV infects CD4+ T cells, macrophages and neuronal cells, amongst others. Primary HIV infection is a mostly mild, mononucleosis-like illness, which resolves spontaneously, with the virus entering a phase of clinical latency. As infection progresses, the CD4+ cell count drops, determining the further clinical course of manifestation of opportunistic infections and malignancies. HIV can cause a chronic encephalopathy with developmental delay and faltering growth. The advance to acquired immune deficiency syndrome Exclusive formula feeding reduces the risk of HIV infection, although risk of death from gastroenteritis and other causes may be increased. Delivery by caesarean section reduces the risk but may not be indicated if the mother’s viral load is suppressed. Giving all women antiretroviral therapy irrespective of CD4 T-cell count or clinical staging is now WHO recommended policy. Tomoka’s mother died recently after a wasting illness. In a setting with high rates of HIV transmission, suspicion should be raised that Tomoka may have been vertically infected with HIV. Approximately 2 million children globally are currently living with HIV, most of whom acquired the infection perinatally. The rate of new paediatric infections has significantly declined, primarily due to the success of prevention of mother-to-child transmission (PMTCT) interventions. Maternal-to-child transmission of HIV without any of the preventative interventions listed in Box 33.1 can be between 30% and 40%; with intervention, this can be reduced to <1%. Tomoka’s HIV status should be ascertained as soon as possible. As Tomoka is 2 years old, a positive antibody test would indicate she is HIV-infected. HIV antibody is placentally transferred, and therefore a positive antibody test before the age of 18 months may indicate maternal HIV infection only. HIV proviral polymerase chain reaction (PCR) is the diagnostic test of choice in infants. At birth, HIV PCR has a low sensitivity (due to low viral load) and does not rule out infection. By 3 months, sensitivity is almost 100%. Box 33.1 Prevention of mother-to-child transmission (PMTCT) interventions • Primary HIV prevention in women of childbearing age through education, selfdetermination and condom use. • Universal lifelong antiretroviral therapy for all pregnant women, aiming to suppress viral load before delivery (WHO plan B+). • Treatment of coexistent sexually transmitted infections in the mother. • Caesarian section, although vaginal delivery can be considered if viral load suppressed and mother well. Avoid prolonged rupture of membranes. • A minimum of 6 weeks of postnatal antiretroviral prophylaxis for the newborn. • Exclusive breastfeeding for the first 6 months of life in low-resource settings, where the use of artificial (formula) feeding is associated with greater risks of mortality from gastroenteritis and pneumonia. Thereafter, introduction of complementary foods at 6 months of age with concomitant continuation of breastfeeding until 12 months. • Breast milk pasteurization or ‘flash heating’ has been associated with reduced transmission. • Mixed breast and artificial feeding is the least desirable option, due to the increased mortality associated primarily with gastroenteritis and pneumonia, as well as increased HIV transmission (artificial feeding is associated with increased mucosal inflammation, which can act as a ‘portal of entry’ for the HIV virion in infants co-fed with breast milk). • Support for mothers who choose exclusive artificial feeding, providing this is acceptable, feasible, affordable, sustainable and safe (AFASS criteria) Question 33.1 HIV transmission Which of the following has been shown to reduce the risk of mother-to-child HIV transmission in lowresource settings? The answer to each may be true (T) or false (F). A. Breast and artificial feeding rather than exclusive breastfeeding B. Co-existent sexually transmitted diseases in the mother C. Delivery by caesarean section D. Exclusive formula feeding E. Giving all women antiretroviral therapy irrespective of CD4 T-cell count or clinical staging HIV Answer 33.1 A. False; B. False; C. True; D. True; E. True.

33 646Global child health developing primary progressive disease, which can involve dissemination to any organ in the body. The number of new case notifications of TB in children is rising, despite the overall global fall in TB incidence and prevalence since 2000. In 2012, there were an estimated 530,000 new cases of childhood TB and 74,000 deaths. This increase may represent improved surveillance methods in children rather than a true increase in disease incidence. Despite this, the overall case burden of childhood TB is still likely to be underestimated; case detection of TB in children is difficult due to its non-specific clinical presentation, paucibacillary nature and absence of available diagnostic tests which are both sensitive and specific. The diagnosis is usually made from a composite of clinical features, radiology, tuberculin skin testing (TST), microscopy and culture of respiratory specimens along with newer PCR methods such as the Xpert MTB/RIF assay, an automated assay to identify Mycobacterium tuberculosis (MTB) DNA and resistance to rifampicin (RIF). The TST relies on the development of a delayed-type hypersensitivity reaction to tuberculin purified protein derivative, which is a combination of proteins from M. tuberculosis, some of which are also present in BCG vaccine. Therefore, children who have received BCG may have a false positive TST, and a different cut-off is used in the UK to allow for this. Interferon-gamma release assays (IGRAs) were developed to circumvent this problem and measure T-cell interferon-gamma production to proteins that are unique to M. tuberculosis and not present in BCG (ESAT-6, CFP-10 and TB7.7). Sensitivity and specificity is less than in adults. Neither the TST nor IGRAs can be reliably used to distinguish between latent and active disease, as they indicate infection by the organism. However, one or both can be used during contact tracing to identify which individuals have been infected. The microbiological confirmation of TB requires culture or PCR. Liquid culture is the most sensitive method of bacteriological confirmation. Almost half of low- and middle-income countries have adopted the WHO guidance recommending the use of Xpert MTB/RIF assay, which is more sensitive than microscopy and can be performed within 100 minutes. The management of childhood TB is hampered by the lack of paediatric drug preparations, in particular fixed dose combinations. This is especially true for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB), where there is an urgent need for child-friendly preparations. There are few signs that this will be met in the near future. Treatment of latent TB is effective at preventing development to active TB disease. Primary chemoprophylaxis is the practice of giving preventative therapy, usually isoniazid, to immunocompetent children who have been exposed to an individual with (AIDS)-defining diseases in children is highly variable; however, untreated infants and children have a high risk of progression to severe infections and death. In contrast, some vertically infected children may be asymptomatic into their teenage years. The CD4+ cell count and the HIV viral load are therefore the most important laboratory parameters to monitor in HIVinfected children. A randomized controlled trial (CHER trial) involved 377 HIV-positive infants assigned to receive early antiretroviral therapy (ART) at diagnosis in early infancy, or delayed ART until such time that immunological (CD4+ count) and clinical (WHO Clinical Stage) criteria were met. The study demonstrated a 75% reduction in mortality and disease progression with early antiretroviral therapy (ART) at diagnosis compared with delayed treatment. WHO guidelines now recommend the commencement of lifelong ART for all HIV-infected children and adolescents irrespective of CD4 count. Some countries have not yet incorporated this guidance owing to the cost. However, even prior to this revised WHO guidance, a significant number of HIV-infected children in low-resource settings found themselves within the ‘treatment gap’: in 2011, only 23% of eligible HIV-infected children were receiving ART compared with 51% of adults. The integration of HIV into the host genome (CD4+ lymphocytes) and subsequent virion replication is reliant on the error-prone reverse transcriptase enzyme. This process provides many opportunities for the virus to develop resistant mutants to ART. To minimize this, highly active antiretroviral therapy (HAART), a combination of a minimum of 3 drugs, is used. First-line antiretroviral therapy involves 2 nucleoside reverse transcriptase inhibitors (usually abacavir and lamivudine) and either a non-nucleoside reverse transcriptase inhibitor (usually efavirenz in children over 3 years of age) or a protease inhibitor (usually lopinavir/ ritonavir). Recent data from the ARROW study has shown it is possible to keep children well and virally suppressed in low-resource settings without regular laboratory testing for efficacy (CD4+ cell counts) and toxicity (haematology and biochemistry). The results of this study suggest that ART roll-out and adherence support services should take priority in low-resource settings where there is no comprehensive HIV care programme. Tuberculosis Tomoka’s mother had a chronic cough, which may indicate that Tomoka has been infected with tuberculosis (TB). Initial pulmonary tuberculosis is characterized by the primary complex (Ghon focus with local adenitis), which usually resolves with calcification or scarring. Children under 5 years are at high risk of

647 CHAPTER THIRTY-THREE Measles Tomoka has presented with clinical features that would also be compatible with a diagnosis of measles. Deaths from measles are disproportionately high in low-resource settings, where vaccination coverage is suboptimal and levels of malnutrition are high. Severe complications are more common in children with impaired cellular immunity (such as malnourished children) and include pneumonia, laryngotracheobronchitis, and keratoconjunctivitis. Treatment with vitamin A reduces morbidity and mortality in children through promoting epithelial integrity. Systemic antibiotics may also be indicated, allied with eye/mouth care. The control of measles relies on herd immunity through vaccination, and outbreaks may occur when more than 10% of the population are susceptible. Eradication is possible, as measles does not cause latent transmissible infection, and humans are the only reservoir of infection. Despite dramatic progress in reducing mortality, the World Health Assembly target of reducing measles mortality by 90% between 2000 and 2010 was not met. Recent large outbreaks in Africa were likely due to poor vaccination coverage in certain high-burden countries (Nigeria, Ethiopia, Democratic Republic of Congo) as well as inadequate funding for supplemental immunization activities, such as mass vaccination campaigns. Which intervention programmes would be of greatest benefit for Tomoka’s health? Expanded programme of immunization (EPI) Vaccination could have prevented several of the important infectious pathogens potentially responsible for Tomoka’s clinical presentation. Approximately sputum smear-positive TB for more than 8 hours to prevent development of progressive TB disease, even if there is no initial evidence of TB infection. HIVinfected children are at significantly increased risk of developing TB, although ART markedly reduces this risk. Some authorities recommend offering TB chemoprophylaxis to all children with HIV infection when initially diagnosed, and after each TB exposure. Aside from chemoprophylaxis, the prevention of childhood TB relies mainly on effective case detection and treatment of TB in the adult population. By coordinating global organizations, the STOP-TB Partnership aims to eliminate TB as a public health problem by 2050. In 2013, the WHO published the first targeted roadmap outlining the steps to ‘end childhood TB deaths’, emphasizing the need for increased investment in the development of effective, novel, child-friendly diagnostics and therapeutics. Question 33.2 Tuberculosis A 3-year-old girl is referred because her grandfather has recently been diagnosed with smear-positive pulmonary tuberculosis. She lives with her older brother, parents and grandfather. She has been asymptomatic and has a normal examination. Which of the following would not be useful in determining her management? Select ONE answer only. A. Chest X-ray B. Interferon-gamma release assay (Quantiferon or T-spot) C. Mycobacterial M, C & S of her grandfather’s sputum D. Mycobacterial M, C & S of her nasopharyngeal aspirate E. Tuberculin skin test (Mantoux) D. Mycobacterial M, C & S of her nasopharyngeal aspirate. Contact tracing is a vital part of tuberculosis control programmes. Household contacts of a smear-positive pulmonary TB case are at highest risk of acquiring infection. Once infection has occurred, the majority of individuals are able to contain it within the lungs, with a small number developing progressive primary disease. This is more likely in children under 5 years of age, and in those who are immunocompromised. Children are also more likely than adults to develop extrapulmonary TB. In older children and adults, the infection becomes latent and disease can occur later by re-activation. This is most likely in the first two years following initial infection or during any periods of immunocompromise including old age (immunosenescence). The purpose of contact tracing is to identify active cases of TB, as well as those who are latently infected. Active cases can be identified on clinical assessment and chest X-ray. Microbiological confirmation can be achieved using induced sputum or gastric aspirates, and sometimes bronchoscopy, but not via nasopharyngeal aspirate. A positive microbiological sample is required to confirm drug susceptibility. Obtaining positive isolates from the source case are therefore useful, and therefore knowing culture and sensitivity of the grandfather’s sputum is important. Answer 33.2

33 648Global child health EPI schedule, including balancing the limitations of the national health budget against the relative contribution of endemic diseases to morbidity and mortality. Polio is likely to be the next vaccine-preventable infection to be eradicated. The Global Polio Eradication Initiative aims to eradicate polio by 2018, by concentrating efforts on two countries accounting for 99% of cases: Afghanistan and Pakistan. As part of these efforts, GAVI will also assist with the replacement of live oral polio vaccine with injectable inactivated polio vaccine in 124 countries, to eliminate vaccine-derived cases of polio. There is a need for more evidence to define optimal vaccination schedules. It has been shown in observational studies that neonatal BCG vaccination is associated with significant reductions in all causes of child mortality. The putative mechanism of this phenomenon is heightened host immune surveillance following the stimulatory effect of BCG on the immune system. There is further evidence to suggest that DTP reduces some of the survival advantage conferred by the neonatal BCG vaccination. The analyses underlying such associations are controversial but highlight the need for more high quality randomized studies comparing vaccination schedules. 2–3 million deaths per year are prevented by immunization. In 1974, the success of the smallpox eradication programme prompted the World Health Assembly to establish the Expanded Programme of Immunization (EPI). The goal of EPI is to provide universal access to relevant vaccines for all at risk. In 2012, more than 80% of infants had been vaccinated against diphtheria, tuberculosis, pertussis, polio, measles and tetanus. However, vaccination coverage within countries and between countries is inequitable. In 2010, vaccine-preventable diseases were responsible for the deaths of an estimated 1.5 million children, and approximately 19.3 million children did not receive three doses of the diphtheria–tetanus–polio (DTP) vaccine, with more than one third of these children living in Africa. In 2013, the Global Alliance for Vaccines and Immunization (GAVI), Decade of Vaccines Collaboration and WHO formulated the Global Vaccine Access Plan (GVAP); this aims to achieve universal access to all immunizations by 2020. Vaccination schedules vary between countries. Figure 33.2 demonstrates how vaccination schedules vary across two low-income countries (Chad and Malawi), a middle-income country (India) and a high-income country (United Kingdom). Complex factors govern each individual country’s choice of Fig. 33.2 Comparison of country-specific EPI vaccination schedules for Chad, Malawi, India, and the United Kingdom, 2015. (Adapted from WHO data, 2013 – http://apps.who.int/immunization_monitoring/globalsummary/schedules) 10 weeks -3 months 14 weeks -4 months Birth 6–9 months 1 year 2 years 3 years 12–13 years 13–18 years 6 weeks -2 months DTwPHibHep OPV DTwPHibHep OPV BCG OPV Measles YF DTwPHibHep OPV Chad DTwPHibHep OPV Rotavirus PCV DTwPHibHep OPV PCV BCG Measles DTwPHibHep OPV Rotavirus PCV Malawi DTwPHibHep OPV DTwPHibHep OPV BCG OPV Measles OPV JapEnc* DTwP OPV JapEnc* TT DTwP OPV TT DTwPHibHep OPV India DTaPHiblPV MenC Rotavirus Hep B* DTaPHiblPV PCV MenB Hep B* BCG* Hep B* DtaPIPV MMR Influenza MMR PCV MenB HibMenC HPV TdIPV MenACWY DTaPHiblPV PCV Rotavirus MenB Hep B* United Kingdom BCG = Bacille Calmette-Guerin vaccine, OPV = Oral Polio vaccine, Hep B = Hepatitis B vaccine, DTwPHibHep = Diphtheria/Tetanus/whole cell Pertussis/Haemophilus influenzae b/Hepatitis B vaccine, PCV = Pneumococcal conjugate vaccine, DTaPHiblPV = Diphtheria/Tetanus toxoid/Acellular pertussis/Haemophilus influenzae b/Inactivated polio vaccine, MenB = 4 component meningococcal B vaccine, MenC = Meningococcal C conjugate vaccine, YF = Yellow Fever vaccine, JapEnc = Japanese Encephalitis vaccine, MMR = measles, mumps and rubella vaccine, HibMenC = Haemophilus influenza b/Meningococcal C booster, DTwP = Diphtheria/Tetanus toxoid/Whole cell pertussis booster, DtaPIPV = Diphtheria/Tetanus toxoid/Acellular pertussis/ Inactivated polio booster, HPV = Human Papillomavirus vaccine, TdIPV = Tetanus/Diphtheria toxoid/Inactivated polio booster, TT = tetanus toxoid booster, MenACWY = Meningococcal ACWY conjugate vaccine *Given to high-risk groups Legend

649 CHAPTER THIRTY-THREE How can effective interventions be integrated at a consultation at the clinic? Integrated management of childhood illness (IMCI) Tomoka’s presentation may potentially involve a number of different pathologies with overlapping clinical features: pneumonia, diarrhoea, TB, measles, HIV and malaria. Figure 33.3 summarizes the range of evidence-based interventions that tackle these major threats to child survival. Tomoka also has several wider health issues that need to be addressed in the consultation, such as nutritional assessment, vitamin A status, deworming and immunization status. The programmatic response to the complex health needs of children such as Tomoka was previously characterized by fragmented, multiple vertical programmes with little overall integration. To address this, the Integrated Management of Childhood Illness (IMCI) approach was developed by the WHO and UNICEF during the early 1990s. IMCI is a comprehensive system to assess the sick child for common conditions in the primary healthcare setting, while addressing wider health issues such as the assessment of nutritional status and provision of feeding advice. Healthcare workers are also reminded to consider other systematic nutritional interventions, such as regular vitamin A administration and deworming. In addition, IMCI prompts healthcare workers to assess HIV, TB and immunization status during every patient contact. Many individual countries have adapted IMCI protocols to include relevant clinical conditions according to their individual local epidemiology. For example, dengue Question 33.3 Vaccination Which of the following vaccinepreventable diseases cannot be eradicated from the community by achieving sufficient herd immunity? Select ONE answer only. A. Measles B. Pertussis C. Polio D. Tetanus E. Tuberculosis Answer 33.3 D. Tetanus. Tetanus is found widely in the environment and does not have a human-only reservoir. Case history Fluid resuscitation as supportive therapy Tomoka, age 10 months, is referred urgently to her local district hospital in Uganda. On arrival, she is noted to be febrile, with a capillary refill time of 3 seconds, a raised respiratory rate of 60 breaths/ min and heart rate of 150 beats per minute. Should Tomoka receive intravenous fluid bolus resuscitation? The key evidence to address this scenario comes from the FEAST trial, which randomized 3000 children over the age of 3 months with fever Recognition and treatment of sick children, e.g. ETAT (Emergency Triage, Assessment and Treatment) courses Tomoka is acutely unwell and her survival at a busy rural health clinic may depend upon effective triage and, if necessary, prompt resuscitation and treatment. Child mortality is highest within 24 hours of acute illness. The WHO Emergency Triage, Assessment and Treatment (ETAT) training course using scenario-based teaching is a system of paediatric life support adapted to the commonest causes of hospital admission in southern Africa. The implementation of ETAT at a busy emergency department in a Malawian tertiary hospital led to a 50% reduction in inpatient mortality. In Kenya, Uganda and Rwanda, the course has been expanded (ETAT+ – Emergency Triage Assessment and Treatment plus Admission), to include initial hospital treatment. and impaired circulation to receive intravenous fluid bolus, or no bolus. Interim analyses demonstrated the unexpected finding of increased mortality at 48 hours in the fluid bolus group (relative risk 1.45; 95% confidence interval: 1.13–1.86) and thus the study was halted early. In light of the findings of the FEAST trial, Tomoka should not receive a fluid bolus, and this is endorsed by the ETAT+ guidelines. However, the study’s definition of shock has been debated – for an acute infectious illness with severely impaired circulation (all of: cold periphery, capillary refill time >3 seconds, weak peripheral pulse and AVPU score <A), then 20 mL/kg over 1–2 hours is recommended. Furthermore, fluid bolus resuscitation is still recommended for shocked children with diarrhoea, burns or trauma.

33 650Global child health Undernutrition is also associated with impaired and suboptimal cognitive development. The current global burden of morbidity and mortality associated with malnutrition lies predominantly with undernutrition in low-resource settings, and overnutrition in wealthy countries and in the rapidly increasing middle class in middle-income countries. In 2012, there were an estimated 51 million children with wasting and a further 162 million with stunting; 80% of these were living in either south Asia or sub-Saharan Africa. The aetiology of undernutrition is usually multifactorial. Poverty is the most important underlying predisposing factor, exacerbated by lack of food security created by civil conflict, drought and natural disasters. Protective factors that reduce the probability of a child becoming undernourished include longer duration of breastfeeding, higher maternal age at first birth and up-to-date immunization status. The period from conception to the child’s second birthday, or ‘first 1000 days’, has been targeted for nutritional interventions. The most effective preventative interventions include breastfeeding promotion and supplementary feeding programmes, including micronutrient supplements, e.g. vitamin A. Helminth infections (such as hookworm) have been associated with malnutrition and impaired school performance, and periodic systematic fever is highlighted as an important cause of fever or shock in the Indian adaptation of IMCI. Neonatal health also plays an important part in the Indian version, which has thus been dubbed IMNCI (Integrated Management of Neonatal and Childhood Illness). IMCI categorizes acute clinical conditions, such as diarrhea, into simple clinical ‘traffic light’-coloured classifications depending on severity, each with a corresponding management pathway. The other key elements of IMCI include healthcare worker training, systems development and engagement with the community and families. In Tanzania, IMCI has been shown to be cost effective while improving the quality of referral patterns. Given the efficacy of IMCI, there is an urgent need to improve its coverage as well as promoting local adaptation and integration with private sector services. Malnutrition Malnutrition is an underlying factor in approximately half of deaths in under-5-year-olds. Undernourished children are significantly more likely to die from common childhood conditions, e.g. diarrhoea, respiratory tract infections, malaria, measles, TB and HIV. Fig. 33.3 Prevention, community management and hospital management of the major threats to child survival. Emergency Triage, Assessment and Treatment (ETAT) ETAT+ Expanded Programme on Immunization (EPI) Integrated Management of Childhood Illness (IMCI) WHO Ten Steps to Recovery for inpatient management of severe complicated malnutrition Ambulatory management of uncomplicated malnutrition with ready-to-use therapeutic food (RTUF) Antibiotic therapy Detection of very severe pneumonia and hospital referral Antibiotic and oxygen therapy Prevention Community Management Hospital Management Oral Rehydration Therapy (ORS) and continued feeding Water, Sanitation and Hygiene (WASH) Breastfeeding Promotion Vaccination (Hib, PCV, measles, rotavirus, cholera) Vitamin A and Zinc supplementation Household Food Security School Feeding Programmes Deworming Access to near-patient Rapid Diagnostic Testing (RDT) for malaria Access to Artemisinin Combination Therapy (ACT) Insecticide Treated Bed Net Vector control, indoor residual spraying, etc. Effective childhood TB case detection and access to high-quality laboratory services Child-friendly TB treatment programmes Effective adult TB control programmes BCG vaccination Contact Tracing and Isoniazid Preventative Treatment Prevention of Mother-To-Child Transmission (PMTCT) Access to HIV serological (antibody) and virological (antigen) testing Child-friendly antiretroviral treatment programmes Pneumonia Diarrhoea Malnutrition Malaria Tuberculosis HIV

651 CHAPTER THIRTY-THREE Fig. 33.4 Malnutrition: the link between pathophysiology, clinical features and management. Macronutrient Deficiency (Protein–Energy Malnutrition) Micronutrient Deficiency Poverty Poor food security Poor feeding practices Disease Renal tubule dysfunction Na+/K+ pump malfunction Vitamin A deficiency Zinc deficiency Iron deficiency Vitamin D deficiency Decreased basal metabolic rate Deficient immune and inflammatory response Wasting of the myocardium Small intestinal bacterial overgrowth and villous atrophy Pathology Total body sodium excess Total body potassium depletion Xerophthalmia Reduced immunity Subclinical deficiency common Acrodermatitis enteropathica Anaemia Impaired cognitive development Rickets Hypothermia, hypoglycaemia Occult invasive infection Reduced cardiac output/ contractility Diarrhoea / feed intolerance Clinical features Supplementation and Increased dietary exposure Low sodium ORS Potassium supplementation Keep warm and give feed/glucose Management Antibiotics Rehydrate enterally (cautious use of IV fluids) Gentle introduction of feeds Question 33.4 Kwashiorkor Which of the following clinical features would suggest increased risk of death? Select ONE answer only. A. A ‘flaky-paint’ skin rash with hyperkeratosis (thickened skin) and desquamation B. Angular stomatitis C. Distended abdomen and enlarged liver D. Hair sparse and depigmented skin E. Oedema of the feet deworming is recommended alongside vitamin A administration in many countries. Undernutrition has profound physiological implications. Figure 33.4 summarizes the key pathological processes involved in macronutrient deficiency and common micronutrient deficiencies. The physiological changes or ‘reductive adaptation’ that occur in the severely undernourished state heavily influence management. The WHO has simplified the case definitions for malnutrition. The definition of severe acute malnutrition includes full-blown clinical conditions such as marasmus and kwashiorkor, as well as children who present with less obvious clinical signs but are below defined anthropometric thresholds. Weight-forage is a sensitive and specific index of acute malnutrition. It is usually expressed as standard deviations from the mean (or Z-score), or as percentage of the expected (or median) value. Severe malnutrition is defined as a weight-for-height more than 3 standard deviations below the median on the WHO growth chart. Height-for-age is a measure of stunting and an index of chronic malnutrition. The measurement, calculation and interpretation of such anthropometric measures necessitate proficient numeracy skills, and are prone to error. Therefore, the WHO advocates the use of a highly effective proxy measure of severe malnutrition in children aged 6 months to 5 years: measurement of the mid upper arm circumference (MUAC). This is relatively simple and quick to perform, and does not require specialized equipment beyond a tape measure (Fig. 33.5). The regular assessment of MUAC is recommended in all children between 6 months and 5 years of age; measurement below 115 mm correlates highly with severe acute malnutrition. Answer 33.4 E. Oedema of the feet. Some children with acute protein–energy malnutrition develop oedema and these children have kwashiorkor (rather than marasmus). Although all forms of malnutrition are life-threatening, the risk of death with kwashiorkor is higher than it is in children with marasmus.

33 652Global child health Fig. 33.6 Severe malnutrition represents the ‘tip of the iceberg’. Most children with moderate malnutrition remain ‘hidden’. “Visible” “Hidden” Mild malnutrition "growing but sub-optimal" Moderate malnutrition “not growing well” Uncomplicated severe acute malnutrition Complicated severe acute malnutrition Marasmus and Kwashiorkor Case history A low-birth-weight baby Adina is born in a health centre after an uncertain but probably less than 9-month gestation in rural Ethiopia. Her mother is 16 years old. Adina weighs 1.6 kg and has signs of mild respiratory distress. What are the main threats to her survival? They are described below. Fig. 33.5 MUAC measurement on a child at a primary health care clinic. It is colour-coded to facilitate recognition of malnutrition (red is <115 mm). Oedema is the key clinical feature which distinguishes kwashiorkor from marasmus. Though kwashiorkor and marasmus are easily recognizable clinically, severe malnutrition only represents the ‘tip of the iceberg’ (Fig. 33.6); moderate malnutrition is more prevalent and often goes unnoticed, and is associated with a greater number of associated deaths. The most effective method of detecting moderate malnutrition is systematic regular anthropometric assessment, a key feature of IMCI protocols. Regardless of the anthropometric severity of malnutrition, the presence of certain clinical risk factors ‘complicate’ malnutrition and have been shown to significantly increase the risk of mortality: lethargy, high fever, severe dehydration, palmar pallor or pneumonia. ‘Complicated’ malnutrition is an indication for admission to a hospital or specialized feeding centre. The WHO Ten Steps to Recovery addresses the priorities for the inpatient of complicated severe acute malnutrition – the ‘stabilization phase’ (hypoglycaemia, hypothermia, dehydration, early feeding, antibiotics, electrolyte and micronutrient supplementation) and the ‘rehabilitation phase’ (catch-up growth, sensory stimulation and preparation for discharge). There is growing evidence that ‘uncomplicated’ malnutrition should be treated in community-based supplemental feeding programmes. The emerging cornerstone of these programmes is the use of ready-to-use therapeutic foods (RUTF), which are sweet-tasting, energy-dense pastes that are enriched with micronutrients. Commercial RUTF preparations are inexpensive and relatively imperishable, and are an important nutritional intervention particularly for organizations working in difficult circumstances, such as conflict or natural disaster. School feeding programmes are also a sustainable nutritional intervention, using local produce to feed children during their school day, and can improve school attendance, concentration and performance as well as gender equity in access to education. Neonatal health

653 CHAPTER THIRTY-THREE How many neonates die? In 2012, there were 2.9 million neonatal deaths globally and the global neonatal mortality rate fell from 33 deaths per 1000 live births in 1990 to 21 deaths per 1000 live births in 2012. Deaths within the first 28 days of life comprised 44% of under-5 deaths globally in 2012. The vast majority of these deaths (99%) occur in low-income countries. Why are newborns dying? The decline in neonatal mortality has been strikingly slower than the decline in under-5 mortality. The highest risk of death is within the first 24 hours of life, with 75% of neonatal deaths occurring within the first week. The leading causes of neonatal death are preterm delivery (29%), severe infections such as sepsis and pneumonia (25%) and perinatal asphyxia (23%). Neonatal tetanus is a major cause of death in many areas. Intrauterine growth restriction is an important co-morbidity. There is a strong link between maternal and child health. A young, stunted mother, who is anaemic during pregnancy due to repeated malaria infections and has not accessed antenatal care, is at increased risk of obstructed labour, will have poor reserves to overcome postpartum haemorrhage, and is at increased risk of sepsis. Her baby will be at increased risk of intrauterine growth restriction and prematurity, perinatal asphyxia and developing neonatal tetanus. If the mother dies, the risk of her child dying rises substantially. Poverty and poor maternal education are major determinants of maternal and neonatal mortality, as well as for child mortality, as discussed above. The planning of effective interventions has been informed by the three delay model: delay in recognition of severe illness, delay in seeking and accessing care and delay in receiving care within the health facility. Neonatal mortality rates are lowest in countries with the highest rates of institutional delivery and skilled birth attendants. However, research has demonstrated that low-cost community educational tools are also effective at reducing mortality. A meta-analysis of trials of the effect of participatory women’s groups on maternal and newborn survival in Nepal, India, Bangladesh and Malawi involving almost 120,000 births showed that local non-medical female facilitators who have received a short training course reduced neonatal and maternal mortality by raising awareness of the common problems in pregnancy and finding locally feasible solutions. Neonatal deaths fell by 23% and maternal deaths by 37%. It has been estimated that up to 41,000 maternal deaths and 283,000 neonatal deaths could be averted annually in a cost-effective and sustainable manner if women’s groups were introduced to 74 high-mortality countries. Improving access to family planning and increased birth spacing also improves neonatal outcomes. Many neonatal deaths (between 41% and 72%) can be prevented with skilled birth attendants at delivery and good, basic care of the newborn infant. Collection of epidemiological data and its application to results of trials have allowed evidence-based interventions to be evaluated (Table 33.2). Neonatal intensive care is required for very few babies. In the UK, the neonatal mortality rate had fallen to below 15 per 1000 live births before neonatal intensive care was introduced. Only 14% of babies born in low-resource countries are low birth weight (<2.5 kg); however, they account for 60–80% of deaths. The major problems for babies born preterm and growth restricted (such as Adina in the case history above) are need for respiratory support, infection, thermoregulation, hypoglycaemia, hydration and feeding. The majority of deaths in moderately preterm babies are preventable by establishing breastfeeding, maintaining warmth and by prevention and early treatment of infections. Helping Babies Breathe is a training programme which aims to equip community workers and midwives with essential skills in basic neonatal resuscitation with airway opening manoeuvres and mask ventilation. A training course on early newborn care (WHO Essential Newborn Care) has also been developed, but training alone does not necessarily reduce mortality rate. The risk of infection can be minimized by diligent handwashing. Kangaroo mother care, where the baby is nursed on its mother’s chest 24 hours a day, improves thermoregulation and reduces cross-infection. Support to establish breastfeeding, or frequent nasogastric or cup feeds of expressed breast milk, will avoid dehydration and hypoglycaemia. If the condition of a premature baby such as Adina deteriorates, she would require intravenous antibiotics, oxygen therapy and possibly respiratory support. Basic respiratory support such as ‘bubble CPAP’ can be used for respiratory distress syndrome in low-resource settings. Oxygen therapy is often provided using oxygen concentrators. Oxygen cylinders should be available to provide oxygen therapy when power cuts occur, but are expensive. Exclusive breastfeeding reduces the risk of later deaths from infections. Neonatal tetanus has been estimated to cause 200,000 neonatal deaths per year, predominantly after the first week of life. Promotion of clean delivery practices, clean cord care and administration of 2 doses of tetanus toxoid vaccine to the mother prevents neonatal tetanus. The fall in neonatal mortality observed in India was achieved largely from a reduction in tetanus deaths. Clostridium tetani is an obligate anaerobic Gram-positive bacillus which is ubiquitous in the

33 654Global child health has received less attention than that of younger children, despite the importance of adolescence as the ‘foundation of adult health’. The leading causes of death in adolescence globally are injuries (both road traffic accidents and suicide) as well as maternal causes. How can adolescent health be improved globally? Interventions against non-communicable diseases should target adolescence, when long-term patterns of health behaviour are being established. This includes initiatives to maintain physical activity and good nutrition, to discourage alcohol and tobacco abuse, to improve mental and sexual health. Access to education and national wealth are the strongest determinants of adolescent health. Supportive families, schools and peers are needed to ensure good health outcomes. Programmes specifically targeting adolescents are required, taking into account relevant intercountry epidemiology. In HIV-endemic countries, programmes addressing HIV prevention in adolescents will be particularly important. environment and forms spores resistant to disinfectant and heat. Though it is not possible to eradicate the organism from the environment, the WHO have set a goal of worldwide elimination of the disease, defined as less than 1 case per 1000 live births in every district of every country. Once infected, the case fatality rate for neonatal tetanus is 100% for out-of-hospital cases, and approaches 60% even with full hospital care involving benzodiazepines, tetanus immune globulin and respiratory as well as feeding support. Perinatal asphyxia and other intrapartum-related conditions are not only a major cause of neonatal mortality but also of long-term neurodisability. Neglected issues in global child health Adolescent health What are the major threats to adolescent health? Historically, the health of adolescents (defined by the WHO as young people aged between 10 and 19 years) Table 33.2 Evidence-based interventions for saving newborn lives Intervention Grade of evidence Reduction (%) in all causes of neonatal mortality/major risk factor Antenatal Folic acid supplementation IV Incidence of neural tube defects (72%) Tetanus toxoid immunization V Perinatal mortality (33–58%) Neonatal tetanus (88–100%) Syphilis screening and treatment IV Prevalence dependent Intermittent presumptive treatment for malaria IV Neonatal mortality (32%) Pre-eclampsia/eclampsia prevention IV Prematurity (34%) Low birth weight (31%) Detection + treatment asymptomatic bacteriuria IV Prematurity/low birth weight (40%) Intrapartum Antibiotics for premature rupture of membranes IV Incidence of infections (32%) Corticosteroids for preterm labour IV Respiratory distress syndrome Neonatal mortality (40%) Detection and management of breech by caesarean section IV Perinatal/neonatal death (71%) Labour surveillance IV Early neonatal deaths (40%) Clean delivery practices IV Neonatal mortality (58–78%) Incidence of neonatal tetanus (55–99%) Postnatal Resuscitation of newborn baby IV Neonatal mortality (6–42%) Breastfeeding V Neonatal mortality (55–87%) Prevention and management of hypothermia IV Neonatal mortality (18–42%) Kangaroo care IV Incidence of infections (51%) Community-based pneumonia case management V Neonatal mortality (27%) (From Darmstadt GL, et al. Evidence-based cost-effective interventions: how many newborn babies can we save? Lancet: Neonatal survival 2005.)

655 CHAPTER THIRTY-THREE in these children. Studies have shown associations between helminth infection and undernutrition, anaemia, poor growth, school attendance and poor performance in cognition tests. In deworming programmes, drug therapy is given to all children attending school. There is some debate about the level of their effectiveness, but the World Bank and the WHO promote helminth control programmes in developing countries as a cost-effective intervention. The most commonly used drugs for the treatment of common helminths are albendazole or mebendazole, which can be administered as a single tablet to all children, regardless of size or age. Only in the most heavily infected communities is treatment required more than once a year. Trachoma Trachoma is the leading preventable cause of blindness globally. It is caused by repeated and persistent infection with Chlamydia trachomatis resulting in progressive keratoconjunctivitis and scarring (trichiasis). The major risk factor is poor facial hygiene across communities. Children are disproportionately affected, as transmission is facilitated by living in close proximity to an affected family member. The WHO has set 2020 as the target for global elimination, by means of the SAFE strategy: surgery for trichiasis, antibiotics for active trachoma, facial cleanliness and environmental improvement. There is good evidence for these interventions, e.g. mass annual antibiotic (azithromycin) distribution appears to be an effective and safe method of reducing the prevalence of trachoma. Vulnerable children Several problems facing vulnerable children in a global context – child labour, street children and armed conflict – will be considered. Advocacy for them and all children can be considered within the context of the United Nations Convention on the Rights of the Child. Child labour The International Labour Organization defines child labour as ‘work that deprives children of their childhood, their potential and their dignity, and that is harmful to physical and mental development.’ It refers to work that: • is mentally, physically, socially or morally dangerous and harmful to children • deprives children of opportunities to attend school • obliges children leave school prematurely • requires children to attempt to combine school attendance with excessively long and heavy work. Mental health What is the burden of mental health in childhood and adolescence globally? There are difficulties in obtaining reliable data on the burden of mental health disorders in low-resource settings. However, figures suggest that suicide is a leading cause of death in young people living in India and China. Among non-fatal illnesses, the largest disease burden in adolescence is due to mental health disorders, with 75% of all mental disorders first manifesting in this age group. Neglected tropical diseases The neglected tropical diseases (NTDs) (Box 33.2) are a group of infections prevalent in low-resource settings across Asia, Africa and the Americas. The WHO’s Department of Control of Neglected Tropical Diseases describes 17 NTDs. Of these, two are targeted for eradication (dracunculiasis, also called guinea-worm disease, by 2015, and yaws by 2020) and four for elimination (blinding trachoma, human African trypanosomiasis, leprosy and lymphatic filariasis) by 2020. The WHO describes several key strategy areas for trying to tackle NTDs, including: preventive chemotherapy; innovative and intensified disease management; vector control and pesticide management; safe drinking water, basic sanitation and hygiene services; and zoonotic disease management. Two examples of particularly prevalent neglected disease threats to children are described below. Helminthiasis Around 1 billion children live in areas that are stable for transmission of soil-transmitted helminths. Worm infections are most common in school-aged children and worms account for 20% of disability-adjusted life years (DALYs) lost due to communicable diseases Box 33.2 WHO neglected tropical diseases Buruli ulcer (Mycobacterium ulcerans infection) Chagas disease Lymphatic filariasis Onchocerciasis (river blindness) Rabies Schistosomiasis Soil-transmitted helminthiases Taeniasis/ cysticercosis Trachoma Yaws (endemic treponematoses) Dengue/severe dengue Dracunculiasis (guineaworm disease) Echinococcosis Food-borne trematodiases Human African trypanosomiasis (sleeping sickness) Leishmaniasis Leprosy

33 656Global child health those that encourage them to try to leave (‘pull factors’). They are poverty and family breakdown, but warfare, conflict and natural disasters are also responsible for increasing numbers. Street children are at particular risk of poor nutrition, accidents, violence and sexual abuse and have poor access to healthcare. They are amongst the most vulnerable of children. Armed conflict and children Globally, more than 1 billion children under the age of 18 live in countries or territories affected by armed conflict. Approximately 300 million are less than 5 years of age. In countries affected by armed conflict, children are the most vulnerable to the effects of war and violence. They may be affected as the witnesses and victims of conflict, they may be used as ‘human shields’ or may themselves be ‘recruited’ or forced into being participants in conflict as combatants or in military support roles. Conflict-affected countries and territories have shown less progress towards the Millennium Development Goals (MDGs) and invariably suffer poorer child health and education indicators. ‘Six grave violations’ – what are they? In an effort to try to better protect children in conflict and to aid the gathering of evidence to try to bring justice to the perpetrators of violence against children, the United Nations Security Council has identified six categories of violations – the so-called ‘six grave violations’: 1. Killing or maiming children 2. Recruitment or use of child soldiers 3. Attacks against schools or hospitals 4. Rape and other grave sexual violence 5. Abduction of children 6. Denial of humanitarian access The true measure of a nation’s standing is how well it attends to its children – their health and safety, their material security, their education and socialization, and their sense of being loved, valued, and included in families and societies into which they are born. UNICEF Innocenti Report Card 7 (2007) Looking to the future: Sustainable Development Goals The Millennium Development Goals (MDGs) ended in 2015. Although the MDG4 target of a two-thirds reduction in under-five mortality was not reached, a decline by more than half, from 90 to 43 deaths/1000 live births between 1990 and 2015 was achieved. It is estimated that in 2010 about 213 million children were involved in child labour. Approximately 115 million perform hazardous work; the number of children involved in hazardous work is declining. Most child labourers work in agriculture (60%), with only 20% of working children in paid employment and the majority as unpaid family members. Street children Case history George is an 8-year-old boy living on the streets of western Kenya. His mother died 2 years ago, so he lives with his father, who has an alcohol problem. George decided to run away to the streets of the nearby city from his rural home 12 months ago and has been living and working there since. During the day, he tries to scavenge for food and to earn money by doing odd jobs and by begging. At night he tries to find a quiet, safe place to sleep where he uses cardboard and old blankets to keep warm. He has recently started sniffing glue. What is meant by a ‘street child’? The term ‘street child’, used by the Commission on Human Rights in 1994, described ‘any girl or boy […] for whom the street (in the broadest sense of the word, including unoccupied dwellings, wasteland, etc.) has become his or her habitual abode and/or source of livelihood, and who is inadequately protected, supervised or directed by responsible adults.’ There is, however, continuing debate about the definition of ‘street children’ and also the stigma that often accompanies this label. Many now regard children to be either ‘of’ the street (those most vulnerable children who live and work on the streets) or ‘on’ the street (those children who go to the streets for work but have a home or family connections to return to). The number of street children globally is difficult to estimate with precision and depends on the definition used, but estimates vary from 30–170 million. A study conducted in eastern and southern Africa in 1999 in 65 towns and cities that interviewed over 3000 street children found that their ages ranged between 6 and 17 years, the majority being 9–14 years old; three quarters were boys. The majority worked on the streets during the day and returned home at night, but 8% worked and lived on the streets. What causes children to live on the streets? Groups working with street children describe elements that drive children to the streets (‘push factors’) and

657 CHAPTER THIRTY-THREE SDG3 sub-targets remains to be seen. The specific neonatal focus is because progress in reducing mortality has lagged behind that of older children. Further reading Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 2015;385(9966):430–40. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011;364:2483–95. UNICEF. United Nations convention on the rights of the child. <http://www.unicef.org.uk/Documents/Publication-pdfs/ UNCRC_PRESS200910web.pdf>; 1989 [accessed 06.09.15]. UNICEF. Committing to child survival: a promise renewed. Progress report 2014 <http://www.unicef.cz/odkazove_ zdroje_textove_materialy/detska_umrtnost/apr_2014_ web_15sept14.pdf>; 2014 [accessed 06.09.15]. World Health Organization. Pocket book of hospital care for children. 2nd ed. Geneva: WHO Press; 2013. The Millenium Development Goals have been replaced by 17 Sustainable Development Goals (SDGs) for 2016–2030, which have a broader agenda and include all countries, not just those of low and middle income. The SDGs include not only ending poverty and hunger, achieving inclusive and equitable education, and water and sanitation for all, but also achieving gender equality and combating climate change among others. Only one has health as its primary focus, namely SDG3, to ‘ensure healthy lives and promote well-being for all at all ages’. It includes the sub-target to end preventable deaths of newborns and children under 5 years of age by 2030, with all countries aiming to reduce neonatal mortality to at least 12 per 1000 live births and under-5 mortality to at least 25 per 1000 live births. The impressive reductions in child mortality seen with the MDGs were largely because of political pressure to meet specific targets; whether the same attention will be paid to achieving the more numerous

This page intentionally left blank

LEARNING OBJECTIVES By the end of this chapter the reader should: • Be aware of life-limiting conditions and their epidemiology • Know about the principles of symptom control – pain, nausea and vomiting, dyspnoea, constipation, skin conditions and emergencies • Be aware of the ethical issues in children with life-limiting conditions • Know about the practical issues around the death of a child • Be aware of bereavement and grief 659 CHAPTER THIRTY-FOUR Philosophy of palliative medicine A child’s illness profoundly impacts on child and family, particularly when the illness might lead to death. The science of medicine is increasingly able to intervene to cure even serious illness. However, a significant number of children cannot be cured. They have a ‘life-limiting condition’ (LLC), an illness which leads to premature death and/or a prolonged period of chronic illness. If cure is the only solution medicine can offer, doctors will never meet the needs of children living with LLC. Cure is a powerful way to improve the lives of ill children; fortunately, it is not the only way. widely used is the ACT/RCPCH system, which defines four categories of LLC based on the trajectory of the condition. Conditions in the different categories are: • Category I – those for which death and cure are both possible outcomes (e.g. cancer). • Category II – might be living a normal or nearnormal life in the present moment despite having a condition that will inevitably lead to premature death (e.g. Duchenne muscular dystrophy). • Category III – relentlessly progressive towards death without any such normal period. • Category IV – heterogeneous and unpredictable because the underlying condition is not progressive; premature death results from the cumulative effects of the condition, rather than from the condition itself (e.g. cerebral palsy). The exact proportions are not clear (see below), but some reports suggest that categories I and IV each account for roughly a third of all LLCs, with II and III together making up the remaining third. The multidimensional nature of palliative care means that it is informed by research in a wide range of disciplines, from anthropology – for example, Bluebond-Langner’s seminal work on how children see dying – to bioethics, moral philosophy and theology. Over the last fifteen years, it is perhaps in the fields of opioid pharmacology and epidemiology that the impact of scientific research is most obvious to paediatricians. Richard D W Hain With contributions by Megumi Baba, Joanne Griffiths, Susie Lapwood, YiFan Liang, Mike Miller Palliative medicine C H A P T E R 34 Key point Palliative care (Box 34.1) refers to the support healthcare can offer where cure is not possible. Palliative medicine refers to the contribution that doctors can make to that care. Unlike most medical specialties, palliative care is not defined by organ system, aetiology or age group, but by a philosophy of care. That complicates definitions. There have been many attempts to define which medical conditions are included in LLC. The most

34 660Palliative medicine Symptom control Pain Pain management: • Is an essential component of palliative care. • Requires assessment, communication, planning and a sound knowledge of pharmacology and physiology. • Is often under-recognized in children with disability. • Can dramatically improve quality of life for child and family if done well. According to the International Association for the Study of Pain, pain is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.’ It is: • Subjective (whatever the child says it is) • Influenced by past pain experiences and concerns about personal well-being or that of others • Influenced by context (different situations). One of the barriers to good symptom management has traditionally been the belief that morphine should be withheld from children wherever possible, and that codeine was safer because it was weaker. A series of studies of morphine in children has shown that there is no pharmacological basis for a reluctance to prescribe morphine in children. In contrast, recent clinical studies have shown that the metabolism of codeine is dangerously unpredictable. Studies have made it clear that conventional practice in respect of opioids in children perversely recommended an alternative to morphine that was both less effective and more dangerous. Epidemiology is beginning to shape palliative care. The ACT/RCPCH categories are descriptions of types of condition, rather than a list of diagnoses. They are not precise enough for epidemiological purposes. That has meant that, until recently, it was impossible to develop services for children with LLCs based on evidence. That has recently changed as a result of studies. One assigned an ICD10 code to around 400 of the commonest LLCs presenting to hospice and palliative care teams in the UK. Another used an analysis of prospective ‘hospital episode’ data. The result was that for the first time we now know that 32 in every 10,000 children in England are living with a LLC and that its prevalence has increased by almost a third in the last decade. Palliative care in children provides a good illustration of the need for clinical practice to be informed by science, even when cure is no longer possible. Pharmacology and epidemiology are fields of research whose findings have begun to transform the way we can care for children with LLCs. Box 34.2 Evidence of pain in a non-verbal child • Crying and change in vocalization • Quietening/becoming withdrawn • Frowning/grimacing on passive movement • Increasing seizure or spasm frequency • Change in feeding pattern • Hypersensitivity to stimuli • A change in posture or behaviour (e.g. head banging, rubbing a limb) • Increased flexion or extension Key point Total pain expresses the concept that pain always occurs in the context of emotional need, fears, past experiences and understanding of the pain as well as biological experience. Box 34.1 What is palliative care? Palliative care: • Is aimed at improving life quality, rather than duration. • Considers all aspects of life, including psychological, emotional and spiritual as well as physical. • Considers the needs of the family as well as the child. • Intervenes only when the benefit of intervention outweighs its burden. • Is multi-professional and multidisciplinary. Palliative care is not: • Withdrawal of care. • Synonymous with euthanasia. • What is left after medical treatment has failed. All children, including the extremely preterm, are able to feel pain. Pain in palliative care is usually neither wholly acute nor entirely chronic. It has elements of both, and may be complicated by the existential context of deterioration towards death. Assessment of pain Assessment of pain in children requires: • Detailed history (also from the child, if possible) • Observation of the child (Box 34.2), ideally in a variety of settings

661 CHAPTER THIRTY-FOUR • Examination Pharmacological approach: the pain ladder • Consideration of all possible contributing factors (including psychological, spiritual and social) • Discussion with parents, especially in the nonverbal child • Use of pain assessment tools appropriate for age and cognitive ability. The two most commonly-used types of pain scale are ‘faces’-type tools and scales based on observation of behaviour patterns associated with pain in nonverbal children, such as the Paediatric Pain Profile. Faces-type tools are based on a Likert scale and illustrate varying pain intensity using drawings of children’s faces. Unlike the Paediatric Pain Profile, most ‘faces’-type scales were validated for assessment of acute pain in cognitively normal children, rather than in children with LLCs. Management of pain Consider and treat specific reversible causes • Constipation • Gastro-oesophageal reflux • Orthopaedic, especially hip dislocation Consider non-pharmacological measures • Attention to reversible sources of fear and anxiety • Counterirritants (hot or cold packs, acupuncture or TENS), distraction techniques • Behavioural techniques (cognitive behavioural therapy, relaxation, visualization or art therapy) Fig. 34.1 WHO analgesia ladder showing use of analgesics according to severity of pain. Recently, the WHO ladder recommends only simple analgesics and opioids. Opioids are no longer divided into minor and major, as high dose of a weak opioid is pharmacologically equivalent to a low dose of a strong one. Simple analgesics are: paracetamol, NSAID, aspirin where appropriate. Opioids are: morphine, diamorphine, fentanyl, buprenorphine, methadone. Codeine is no longer recommended in most places owing to pharmacogenetic variation in its hepatic activation to morphine, which leads to inconsistent effectiveness. Tramadol is an opioid but has additional non-opioid analgesic properties that make it equivalent to morphine, but it is often poorly tolerated. OME = Oral Morphine Equivalent (measure of opioid potency) Step 1 Mild pain WHO analgesia ladder Step 2 Moderate pain Drugs Breakthrough dose Simple analgesics Opioids Opioids As indicated 0.1mg/kg OME 1-4hrly 1/10 to 1/6 of total daily background dose, given 1–4 hrly Background dose None Usually none Starting dose 1 mg/kg/ 24h OME, then increased as determined by breakthrough requirements Step 3 Severe pain Key point The WHO pain ladder (Fig. 34.1) is the basis for rational management of palliative pain. It expresses the concept that increases in the intensity of pain should be matched by changes both in the type of analgesic, and the manner in which they are prescribed. There are three steps on the WHO pain ladder. As pain intensity increases and the effect of prescribing on one step becomes inadequate, the prescriber should move to the next step. Each step is characterized by: • A specific class of analgesic • A specific approach to dosing (regular versus ‘as needed’) • The need to consider adjuvants (Box 34.3) appropriate to the nature of pain Key point An adjuvant is a medication or other intervention that is not an analgesic but, used alongside analgesics, its actions can reduce pain in certain specific situations.

34 662Palliative medicine For prescription of major opioids (Box 34.4), there are three phases, namely: initiation, titration and maintenance. The opioids can be given as immediate release (e.g. oramorph, buccal diamorphine), continuous release (e.g. MST, transcutaneous patch, syringe driver). There should always be both regular (background) and ‘as needed’ doses. This is a specialist skill and should be undertaken in discussion with the local or regional palliative care team. Nausea and vomiting • Nausea and vomiting are distressing symptoms that may cause more upset than pain. • Full control of nausea and vomiting is more difficult than that of pain – negotiating acceptable goals with the family may be necessary. • In children with cognitive impairment, feeds are a common cause – liaise with dietitians to manipulate volumes/rates/type of feed. • Constipation is another common cause. Key point Mediators of nausea and vomiting act through receptors in the gastrointestinal tract, liver and brain (chemoreceptor trigger zone and vomiting centre). Rational management of nausea and vomiting relies on knowledge of receptors. Box 34.4 Common fears and myths about morphine • ‘It is the ‘death drug’.’ Explanation with family to increase understanding about benefits and side-effects. • ‘It will stop my child breathing.’ Respiratory depression is extremely rare when opioids are used for pain. It is avoided by careful titration of dose. • ‘It has all kinds of side effects.’ There are adverse effects, but fear of them is often disproportionate to the reality: • Drowsiness: The child is likely to be drowsy for 3–5 days when first starting strong opioids or when doses are increased. • Nausea and vomiting: This can occur when first starting, is less common than in adults and wears off. • Constipation: Laxatives are necessary and can be titrated according to need. • Other side effects should be monitored but are rare (e.g. pruritus, urinary retention, nightmares) • ‘It is addictive.’ Explain to the family about issues relating to addiction and dependence. Physical dependence is not usually a primary concern in the palliative care setting, but opioids should always be weaned slowly if the pain resolves to avoid withdrawal. • ‘Once you start morphine, there’s nothing to turn to later when the pain becomes really bad.’ Tolerance probably occurs if opioids are used for long periods. The remedy is to increase the dose of opioids. Families may find it beneficial to understand the principle of tolerance rather than assuming that escalating doses of analgesia imply disease progression. • ‘People will break in and steal it.’ Discuss safe storage, particularly in the home setting. Box 34.3 Adjuvants to analgesics These depend on characteristics of pain: • Bone pain – NSAID, radiotherapy (if metastatic cause), bisphosphonates (especially in presence of osteopenia), steroids (if metastatic cause) • Nerve pain – Anticonvulsants, antidepressants, NMDA antagonists (ketamine, methadone), baclofen, steroids (if cause is pressure, e.g. from tumour oedema) • Muscle spasm – Baclofen, benzodiazepines, botulinum toxin • Cerebral irritation – Phenobarbital, benzodiazepines • Neurolytic and other interventions – Regional nerve blocks and spinal blocks Nausea and vomiting due to: • Gastrointestinal tract damage (chemotherapy, radiotherapy) is often mediated through 5-HT3 receptors and blocked by 5-HT3 antagonists (ondansetron, granisetron) • Liver swelling/damage or toxins (infection, metabolic, uraemia, drugs) are often mediated through dopamine receptors and blocked by dopamine blockers (domperidone, metoclopramide, haloperidol). Because metoclopramide blocks dopamine receptors in the CNS as well as peripherally, it is both more effective than domperidone and more likely to cause adverse neurological effects. • Vestibular problems (travel sickness, vertigo) and raised intracranial pressure is largely mediated through acetylcholine and histamine (H1) and is blocked by anticholinergics, anti-H1 (cyclizine acts at both receptors) medications. Additional factors to consider are: • Levomepromazine (phenothiazine) blocks most receptors and is good second-line treatment, or first-line if cause is multifactorial/not known

663 CHAPTER THIRTY-FOUR Dyspnoea The profound and multidimensional significance of difficulty breathing is illustrated by the dual meanings of words like ‘inspire’ and ‘expire’. In paediatric palliative care, respiratory arrest is the most common mode of death and altered pattern of breathing is one of the critical signs that death is approaching. Dyspnoea is a common and distressing symptom. • Functional delay – can use prokinetics (dopamine antagonists, erythromycin) • Efferent (motor) pathway is through vagus nerve (acetylcholine) so anticholinergics are often partially effective irrespective of cause • Steroids can be valuable by reducing: – Oedema (e.g. in raised intracranial pressure) – Tissue damage – Release of emetogenic mediators but adverse (Cushingoid, etc.) effects after prolonged administration of steroids can limit their usefulness. In bowel obstruction, consider: • Anticholinergic to relieve spasm (hyoscine butylbromide (buscopan)) • Analgesic to relieve pain (strong opioid parenterally) • Anti-secretory to reduce hypersecretion (octreotide) Gastro-oesophageal reflux (GOR) is common but does not always cause discomfort. The risk is increased by prone position, decreased activity, medication and liquid feeds (all more likely among debilitated patients). A presumptive diagnosis and treatment of GOR may be appropriate in pain and discomfort related to feeding without an obvious cause. In reflux, consider: • Antacid to relieve pain (ranitidine, proton blockers) • Prokinetic to improve gastric emptying (domperidone, metoclopramide) • Dopamine blocker to reduce reflux (domperidone, metoclopramide) Key point Dyspnoea is a subjective sensation of uncomfortable breathing. Like pain, dyspnoea is ‘what the child says it is’. It is not an objective phenomenon. Regarding dyspoea: • Different factors contribute to the symptom, including physical, psychosocial and existential/ spiritual factors. • Fear and anxiety play a significant part in its pathophysiology (they can be both cause and effect of dyspnea, causing a vicious cycle). • Breathing can be abnormal (e.g. tachypnoea) without being uncomfortable and vice versa. Causes of dyspnoea in children with life-limiting conditions (Fig. 34.2) can be: • Reversible (e.g. chest infection, fluid overload, pressure from metastatic tumour) • Inevitable (e.g. muscle weakness in Duchenne muscular dystrophy) • Irreversible but amenable to palliation (e.g. secretions pooling in the hypopharynx in the last hours/days of life, causing ‘death rattle’). Answer 34.1 1. J. Ondansetron. 5-HT3 antagonists, as chemotherapy induced. 2. D. Domperidone. Treatment for gastrooesophageal reflux. Metoclopramide generally contraindicated because of dystonia. 3. G. Metoclopramide. Liver and gastric outlet obstruction. Significant long-term adverse effects unlikely because of age and probable short prognosis. 1. Nausea and vomiting in an eight-year-old boy receiving cisplatin for cancer 2. Nausea and vomiting associated with feeding in a boy with severe quadriplegic cerebral palsy with dystonic movements. 3. Nausea and vomiting in a 14-year-old with advanced metastatic Ewing’s sarcoma that is causing compression of the stomach from liver infiltration. Question 34.1 Nausea and vomiting The following are used in the treatment of nausea and vomiting: A. Acupressure B. Cyclizine C. Dexamethasone D. Domperidone E. Haloperidol F. Methotrimeprazine (Nozinan®) G. Metoclopramide H. Nabilone I. Octreotide J. Ondansetron For each of the scenarios below, choose the most appropriate first-line intervention. Select ONE answer for each. Note: Each answer may be used more than once.

34 664Palliative medicine Fig. 34.2 Causes of dyspnea. CP, cerebral palsy; DMD, Duchenne muscular dystrophy; SMA, spinal muscular atrophy; SVC, superior vena caval. General Anxiety Respiratory tract infection Non-oncology Secretions- inability to swallow or cough due to muscle weakness/ poor coordination. e.g. CP Respiratory muscle weakness e.g. DMD, SMA Chest wall deformity Severe kyphoscoliosis Heart failure Large ascites Pleural effusion Oncology Airway obstruction by tumour SVC obstruction Lymphangitis carcinomatosis Respiratory muscle weakness and fatigue Cachexia anorexia syndrome Pneumonia Assessment None of the assessment tools to measure dyspnoea is widely used in paediatrics. Assessment should include: • Cause • Severity • Impact on life quality • Meaning to the child/family (e.g. intimation of approaching death) • Relieving and exacerbating factors Management Management of dyspnoea: • is multidimensional • is multidisciplinary • requires carefully considering burden versus benefit of any intervention (e.g. the distress of dyspnoea caused by pleural effusion must be set against the distress of thoracocentesis). General approaches will usually offer benefit irrespective of the cause. Non-pharmacological approaches Non-pharmacological approaches to dyspnoea include: • Explanation and reassurance through exploration of the situation with the child and family • Other psychological interventions to reduce and manage anxiety, such as relaxation therapy • Physiotherapy, positioning • Environmental control, e.g. position, room temperature and humidity, use of fan • Complementary therapy Pharmacological Pharmacological treatment of dyspnoea is as follows: • Opioids (25–50% of analgesic dose) reduces breathlessness without affecting oxygen saturation or pCO2. Families and professionals may need explanation about this. • Low-dose benzodiazepines, especially midazolam (ask advice from specialist paediatric palliative medicine team) Dyspnoea due to: • Muscle weakness (e.g. Duchenne muscular dystrophy, spinal muscular atrophy) – may be helped by non-invasive positive pressure ventilation if cause is respiratory muscle weakness • Anxiety – may respond to discussion and other non-pharmacological approaches or to benzodiazepines • Hypoxia – often responds to oxygen • Respiratory infection – may be ameliorated using antibiotics or physiotherapy • SVC (superior vena caval) obstruction (usually by tumour) – may be improved by steroids, radiotherapy or a stent • Bronchospasm – is improved by bronchodilators • Malignant pleural effusion – often improved by thoracocentesis (usually temporarily) and pleurodesis

665 CHAPTER THIRTY-FOUR starting opioids. Naloxone and methylnaltrexone antagonize constipating effect of opioids, but their effectiveness is variable and can jeopardize pain control. Skin symptoms • Kyphoscoliosis and chest wall deformity – may require orthopaedic intervention and physiotherapy • Excessive respiratory secretions – may respond to appropriate hydration, anticholinergics like hyoscine hydrobromide and glycopyrronium, physiotherapy, suctioning and positioning Question 34.2 Dyspoea Which of the following statements is true about treating dyspnoea in children receiving palliative care? Select ONE answer only. A. Anticholinergics should be prescribed alongside antibiotics for dyspnoea due to chest infection to reduce secretions. B. Dyspnoea responds to lower doses of opioids than pain does. C. Oxygen provides symptomatic relief irrespective of the oxygen saturation. D. The main function of opioids in dyspnoea is to reduce the respiratory rate. E. Thoracocentesis is not appropriate for drainage of pleural effusion. Constipation, anorexia, cachexia, hiccough Delayed emptying of the bowel resulting in a colon filling with faeces, especially if hard, is a significant cause of distress. Children with life-limiting conditions are likely to have multiple risk factors: • Reduced motility • Reduced fibre intake • Relative dehydration • Abnormal central neurological control • Medications that slow gut transit time. Opioid-induced constipation It is usually good practice to start a simulant laxative (e.g. docusate or Movicol®) at the same time as Key point Skin may be the primary condition causing life-limitation (Box 34.5) or the source of symptoms in life-limiting conditions. Skin symptoms can have marked psychological sequelae. Box 34.5 Epidermolysis bullosa • The most common of life-limiting skin conditions • Extreme skin and mucosa fragility resulting in complications • Blistered areas and wounds heal with scarring • Scarring leads to contractures, progressive and permanent disability • Problems include severe pain, blistering throughout the gut, renal failure, cardiomyopathy and squamous cell carcinoma Pruritus • A difficult symptom to control • Similar transmission to pain sensation; can also have a primary or neurogenic origin • Careful assessment may identify amenable causes, e.g. opioids, uraemia, cholestasis or topical sensitivity • Education about general skin care, nutrition and hydration is important • Wide-ranging therapies, e.g. topical medications, antihistamines, antiepileptics, ultraviolet phototherapy or acupuncture Wounds • Malignant wounds are relatively rare in paediatrics • Pressure ulcers are more common: – Occur when pressure compromises tissue blood flow – Most common at bony prominences – Prevention is through education, nutrition and vigilance • Wound management focuses on controlling distressing related symptoms • Symptoms include pain, exudate, odour, bleeding; antifungal agents may reduce odour Answer 34.2 B. Dyspnoea responds to lower doses of opioids than pain does. Oxygen is only useful in dyspnoea if hypoxia is the cause. The main function of opioids in dyspnoea is to reduce the sensation of breathlessness. Thoracocentesis should be considered, though it is often not appropriate to carry it out and pleural effusions may rapidly recur. Anticholinergics should not be prescribed alongside antibiotics as they may interfere with each other’s actions.

34 666Palliative medicine • Needs admission and management with fluids and bisphosphonates Acute intestinal obstruction See above for information on acute intestinal obstruction. Terminal seizures • Relatively common in the final few hours of life in children with many metabolic conditions • Often not possible to control entirely; need to reassure parents that although seizures are frightening to watch they are unlikely to be distressing to the person experiencing them • If necessary, use continuous subcutaneous infusions of phenobarbital, midazolam or both (but see below). If both are required, a second syringe driver is necessary as phenobarbital cannot be given in the same driver as midazolam. Where possible, management of palliative care emergencies in children with life-limiting conditions should always be undertaken in discussion with the local or regional palliative care team. Ethics at end of life The moral theories that underpin medical ethics fall into four categories that differ in where they put the moral focus: • Moral rules (deontological – e.g. ‘You should never hurt a child under any circumstances’) • Practical outcome of a moral decision (consequentialist – e.g. ‘It is right to hurt this child if it will benefit her enough, or benefit enough other children’) • Certain acts (e.g. ‘Hurting children is always wrong, irrespective of the benefit it might have’) • Nature of the decision-maker (virtue theories – e.g. ‘A good paediatrician would avoid hurting her patient unless it was unavoidable to help the child’) • Vital to manage emotional reactions, e.g. fear, anxiety, depression, anger and lowered self-esteem • Tissue viability nurses can often advise as to suitable dressings Emergencies Even in palliative care, situations arise that demand urgent intervention. In palliative care, an ‘emergency’ is a symptom or set of symptoms that is serious, and for which there is a specific therapeutic approach, but occurs so rarely that the approach is likely to be unfamiliar to most paediatricians. Cord compression • Context – usually malignant disease • Onset often insidious (increasing pain, urinary retention, incontinence of urine or faeces, numbness) • Needs urgent discussion with oncology team • High-dose dexamethasone as temporary measure while radiotherapy and/or surgery are considered • Likelihood of functional recovery small if symptoms have been present for more than 48 hours Acute haemorrhage • Context – usually malignant disease, often haematological (like acute myeloid leukaemia), or occasionally erosion of major blood vessel by solid tumour • Very rare in reality, but fear is common, especially if there has been haemoptysis or oozing gums • Consider procoagulants (tranexamic acid) • Consider localized radiotherapy • Ensure green towels are available at bedside (blood less obvious than on white sheets) • Ensure patient has access to appropriate doses of anxiolytic (midazolam) by rapidly available route Crescendo pain • Rapidly increasing pain, often complicating (or complicated by) anxiety • May need ‘rapid titration’ of intravenous opioids against pain • Requires inpatient admission and liaison with specialist paediatric or adult palliative care team Symptomatic hypercalcaemia • Rare in children but can complicate malignant disease • Signs are confusion, dehydration and worsening pain Key point Although there are different moral theories that underlie ethics, they tend to overlap in their most important conclusions. An understanding of theory is important because it allows a structured and reasoned approach to considering ethical quandaries in practice. This is considered further in Chapter 35, Ethics.

667 CHAPTER THIRTY-FOUR However, healthcare professionals often feel differently about withholding treatment rather than withdrawing it. It is important to acknowledge the difference in the way the two decisions are perceived, and impact on the healthcare team and the family, but it should not influence the ethical decision that is made unless that difference impacts on the child’s own interests. The period prior to death and practicalities around death There are four key things to consider as it becomes clear that the end of a child’s life is approaching: • Recognition that death is imminent • Place of care • Advanced care planning • Practical therapeutics Recognition that death is imminent That death has become imminent needs to be recognized, though predicting the exact time of death is rarely possible. It is best to avoid being too precise or using numbers (‘I think it will be about three months’), but it is unhelpful to refuse to speculate at all (‘We will just have to take it day by day’). However, one usually knows the time frame, and parents usually have a realistic idea from their own observations about what is happening, by gauging their child’s deterioration in the last month or week. By finding out what families think, it is often possible to find oneself reassuring them instead of having to give estimates. Seeking advice from nursing colleagues is also often helpful; they are especially skilled at recognizing changes in circulation and breathing pattern that indicate death may be close. Sometimes parallel planning is required. It is perfectly reasonable to suggest, for example, that the child may die in the next few days from a chest infection, but that if this does not happen, death might not be for some weeks. Place of care The three places where a child can be cared for in the last few days of life are home, hospice, or hospital ward. While most families in the UK express a preference that the child should die at home, an increasing number of children’s hospices offer end-of-life care in a ‘home from home’ environment that also offers appropriate medical support. Every effort should be made to accommodate the family’s preferences. If those preferences are unrealistic, this should be discussed well in advance. The most In the UK, moral theories form the basis for three practical systems of ethics that relate to children at the end of life: • The ‘four principles’ approach – not designed for children • The ‘children’s rights’ approach – legal rather than ethical • The RCPCH guidelines: Making decisions to limit treatment in life-limiting and life-threatening conditions in children: A framework for practice (2015) All rely on the concept of a child’s ‘best interests’ – that is, what course of action will, on balance, do the child most good and/or least harm. The concept of ‘best interests’ is complicated in children: • Interests are conceived more broadly than lifeprolongation, so physical benefits need to be weighed against emotional/spiritual ones • Life quality is subjective, but many children with LLCs are not able to express preferences • The interests of parents and children are not always separable. Even where they are separable in principle, they may not be in practice. Two ethical quandaries are particularly likely in palliative care: double effect and withdrawing and withholding life-sustaining treatment. Double effect Since all medical interventions have more than one possible result, and since it is logically possible for the doctor to intend only one of them, it is inevitable that any intervention will have consequences that are foreseen but not intended. Rarely, the effect of some of these may be to shorten a patient’s life. Whether a consequence is foreseen or intended can depend in part on how directly it flows from the action. The principle of double effect relies on a sound understanding of therapeutics and pharmacology; it does not simply permit all consequences of an action. Key point The distinction between intended and foreseen consequences is ethically significant. In palliative care, it relies on correct prescribing in strict accordance with current knowledge of symptom management. Withdrawing versus withholding life-sustaining treatment The decision to withdraw treatment is not the same as the decision to withhold it, but if the ‘best interests’ test is applied, the answer will always be the same.

34 668Palliative medicine Many of the commonest medications used in the last few hours of life are compatible with one another in the same syringe driver: • Opioids like morphine or diamorphine • Anxiolytics like midazolam • Antiemetics like levomepromazine The transdermal route provides an attractive alternative to subcutaneous infusion for some drugs, e.g. fentanyl, buprenorphine and hyoscine. The subcutaneous route can also be used for breakthrough medications, but the buccal route is usually preferable. It permits rapid absorption that avoids first-pass, is not dependent on safe swallow or predictable gastrointestinal absorption, and parents/carers can easily be shown how to administer drugs. Diamorphine and midazolam are commonly given by this route. The need for artificial nutrition and hydration should be carefully reviewed. Artificial nutrition in the last few hours usually confers little benefit and can complicate symptom management. The risk of continuing with full hydration is that some symptoms, particularly ‘death rattle’, can be made worse. The benefits of discontinuing fluids are, for some families, offset by their anxiety around the possibility of dehydration. This can be reduced if fluids are reduced to 50%–75% of maintenance, rather than being discontinued completely. If necessary, hydration can be given subcutaneously to avoid the need for hospital admission or repeated attempts at intravenous access. ‘Death rattle’ – upper airway secretions making an unpleasant sound – does not usually distress the patient, but often merits treatment for the sake of those caring for the child. Treatment is by anticholinergic therapy via a transcutaneous patch or subcutaneous syringe driver. appropriate forum for those discussions is in the context of advance care planning discussions, often centred around completing an ‘end-of-life care pathway’. Some families change their mind at the time of death itself. Advanced care planning Issues around advanced care planning are: • Discussions at the end of life itself mean a child’s clinical status is precisely known, but there is little time for sensitive discussion. • Exploration that takes place well in advance allows plenty of time, but as there is often little precise information about how it will happen, discussions are necessarily largely hypothetical. Neither discussion on its own is adequate. There must be both early discussions that are largely hypothetical, and urgent discussions at the end of life that are informed by the precise circumstances at the time. Advanced care planning should include consideration about emergency care, including preferences in respect of end-of-life interventions (particularly invasive ventilation). When there is no time for those discussions, the medical team will usually proceed with maximum intervention as a way of ‘buying time’, and perhaps keeping more options open while such discussions take place. Inevitably, this means that some children are subjected to highly unpleasant interventions from which they cannot benefit, simply because there has been no time for adequate discussion about them. Anticipated symptoms at the end of life and how they can be managed should also be considered. Advanced care planning documents are available and provide a structured approach to difficult discussions. They also provide a record of the conclusions reached, which can be disseminated to relevant professionals so that communication is optimized. This includes ambulance and police services, allowing them to respond appropriately and sensitively to a death that is expected. Practical therapeutics at the end of life At the end of life, assess which medications are essential. The enteral route is to be preferred where possible, but as end of life approaches, the enteral route is often no longer possible as the child cannot take medications orally and absorption may be erratic. Some oral medications (e.g. steroids) are also often no longer necessary when death is imminent. The subcutaneous continuous syringe drive is then the preferred route driver for background medications. Question 34.3 Emergency care plans Which of the following statements about emergency care plans are true (T) and which are false (F)? A. Once signed, they allow doctors to withhold intensive care without further discussion. B. They are legally binding on doctors. C. They are legally binding on patients. D. They have legal significance. E. They make inappropriate interventions less likely.

669 CHAPTER THIRTY-FOUR colleagues in psychology, particularly play therapists. • All children should have the opportunity to talk about their condition, but no child should be forced to talk about it if they do not wish to. Box 34.6 Reasons for collusion • To protect child or young person from painful news • Fear that he/she will ‘give up’ if he/she knows the truth • To avoid having to discuss a difficult topic with the child • To avoid parents having to face the truth themselves Many of the reasons, therefore, have the child’s own best interests at heart, but such silence is usually counterproductive. Key point All children and young people should be given the opportunity to talk about their condition and death, but no child or young person should be forced to talk about it if they choose not to. Collusion refers to the ‘conspiracy of silence’ that may exist between parents and doctors, in which the nature and/or severity of a child’s diagnosis are kept from him/her (Box 34.6). It should never be assumed that a child does not want to know what is going on. The challenge is how to find out whether the child or young person wants to talk about their illness and death, without talking about it. That can only be done by allowing an opportunity to choose to explore it or not. Factors to consider regarding collusion are: • Patient and empathic communication by all members of the team may help encourage the child to feel confident that topics are not ‘beyond discussion’. • For some children, the best way of actively encouraging exploration may be to involve Key points about avoiding collusion Once collusion has developed, it can be hard to undo. Where possible, it is preferable to avoid it happening in the first place: • Involve the young person from the start in all discussions about their illness • Share any new information with the patient and family simultaneously • Encourage the family themselves to discuss issues openly • Allow the patient to correct the parents’ misunderstandings where possible, in their presence. At the same time, it is important to: • Respect genuine coping strategies • Be sensitive to the rare circumstances when the consequences of even raising the issue would do more harm than good. Bereavement, grief and mourning Key point Bereavement, grief and mourning are not the same: • Bereavement describes the state of having lost someone or something dear. • Grief is the emotional and social reaction to bereavement. • Mourning is the external expression of grief. No parent expects to bury their child, yet in England and Wales alone, there are about 4000 deaths of infants and children annually, so that about 8000 parents each year face the death of their own child, and 5000 children face the loss of a sibling. The death of a child symbolizes the loss of a future, as well as of the individual in the present. Grief begins at communication of the diagnosis, for both the child and the family, in anticipation of losing: • The child him/herself, who would have been expected to grow and develop towards independence as a young adult • The child’s skills and independence. Answer 34.3 A. False. B. False. C. False. D. True. E. False. Whilst emergency care plans are often used and can be helpful documents they are not legally binding upon doctors or parents. Doctors still need to decide what interventions are in the child’s best interests at the time. They do however form part of the written medical record and therefore do have some legal standing. Courts will sometimes order that they are carried out. If used wisely they provide valuable background information about complex patients and can be helpful in difficult clinical situations. Collusion

34 670Palliative medicine • Children experience similar emotions and difficulties to adults, but without adult skills of verbalization. • Hence, grief may not be noticed or may present as behavioural or physical problems. Children may suffer anticipatory grief when they understand that death is inevitable, and then on the actual loss of a loved one. Factors influencing how a family grieves the death of a child Factors include: • How they coped with prior losses • Whether they have experienced the death of another child • How effective family support systems are • Whether members of the family have a spiritual understanding or religious faith Bereaved parents may be at risk of guilt, anger, depression, anxiety, and post-traumatic stress. Surviving siblings may have a variety of psychosocial difficulties, e.g. guilt, anxiety, depression, post-traumatic stress symptoms, sleep problems and social withdrawal. Families also undergo significant changes following the death of a child (e.g. increased parental and marital Grief may be experienced by: • The child him/herself with a life-limiting illness • A sibling or close friend • Parents or other family members. There are many theories regarding grief. The traditional theories tended to concentrate on ‘coming to terms’ and ‘letting go’, whereas current theories concentrate on developing a new relationship within the bereaved person’s life. Some models of grief are listed in Box 34.7. Children’s responses to death and bereavement In children: • Responses to death and bereavement are very variable and change with age, intellect, communication skills and emotional maturity, as well as the significance of the loss, the nature of the death, previous personal and family experiences of loss and trauma, their own resilience and the support they receive. Box 34.7 Models of grief Theoretical models of grief • Bowlby’s attachment theory: When an attachment is threatened or destroyed, the reaction is to cry and search for the lost person. • Parkes’ four phases of grief: Numbness, yearning, disorganization and despair, reorganization and recovery. • Worden’s four tasks of grieving: Accept the reality of the loss, experience the pain of grief, adjust to the environment without the deceased present, withdraw emotional energy and reinvest in another relationship. Practical models • Dual process model: Grief is seen as a dual process, comprising a loss-orientated response and a restoration-orientated one. The bereaved person oscillates between the two, and is able both to confront the loss and be distracted from it. • Continuing bonds: Emphasizes that resolution of grief involves a continuing bond, which the survivor maintains with the deceased. Through grief, the bond may be transformed from something painful into something that may give solace and inspiration. • Growing around grief: Emphasizes that the grief does not shrink, but life eventually grows around it. Box 34.8 Complicated grief Complicated grief has been defined as a deviation from the normal grief experience in time course, intensity or both. In a child, this may manifest as behavioural regression, excessive self-criticism, self-harm, taking on a parental role, truanting, silence and withdrawal or overt depression. Risk factors for adverse outcomes may include: • Features of the loss: e.g. sudden, violent, mutilating, random or prolonged death • Features of the bereaved person: e.g. multiple losses, previous psychological or behavioural problems, child less than 5 years old or adolescent • Features of the relationship: e.g. complicated, ambivalent or abusive relationships, unsupported or conflicted family, attachment issues, death of a parent, mental illness in surviving parent, death of father (for adolescent boys), death of mother (for young children). Bereaved children, and parents experiencing the death of a child, are at increased risk of adverse outcomes. Protective factors may include: • A ‘good death’, use of rituals, death in a hospice, resilient personality factors, consistent care from residual parent, religious faith

671 CHAPTER THIRTY-FOUR strain). Their grief may be complicated (Box 34.8). The death of a child causes a reorganization of the family. Helping Families may be helped by: • Support for all family members beginning at diagnosis, using opportunities to encourage communication, encouragement to make the most of the present, to create memories, and to plan and prepare for a good death. • Practical suggestions before and after the death which could include making a memory box, making a family record, making handprints, writing a child’s ‘will’ to give them choice over what happens to treasured possessions, permanency planning (helping children understand what will happen to them when a loved one dies), and supporting children in telling the story of the person’s end of life and afterwards. • Seeing the body and attending the funeral; may be helpful for a child to allow them to begin to say goodbye, to accept the finality of the death, to understand what has happened and to be less afraid. But this should be the child’s choice. • Being offered choices and control, including children. • Offering, in the case of a child’s death, to inform others and provide support to parents, siblings, grandparents, carers, close friends, school staff Question 34.4 Palliative care in children Which of the following statements regarding palliative care of children are true (T) and which are false (F)? A. Codeine is preferable to low-dose morphine for moderate pain B. Cord compression is typically sudden because it is likely to be caused by collapse of the vertebrae from osteopenia or metastatic disease. C. Intensive care should not be considered if a child is receiving palliative care. D. Seizures in the terminal phase should not be treated, as treatment may hasten the child’s death. E. When parents ask about prognosis, in order to retain their trust it is better to make an educated guess than to admit you are uncertain. Answer 34.4 A. False B. False C. False D. False E. False A. Codeine is a pro-drug of morphine and has an unpredictable metabolism due to variation in the enzymes that convert it into its active form. Morphine is therefore safer and more predictable. B. In children, cord compression usually has a slow onset and is caused by an expanding soft tissue mass. C. Intensive care should always be considered for a child when the benefit is likely to outweigh the risk of harm, irrespective of the nature of the child’s condition. D. Seizures are distressing for the child and family and should be treated. It may sometimes hasten the child’s death, but the primary aim is to provide symptomatic relief. E. This would be deceitful and therefore unprofessional, and a wrong guess is likely to undermine the relationship more than admitting uncertainty. However, vague answers or deflecting rather than addressing the question is also unhelpful. and all who shared in the child’s life for as long as they need it. For immediate family members, this can be several years. • Being informed about the resources locally and nationally to support grieving children and families. Conclusion In this chapter, we have shown that palliative medicine relies on a sound understanding of pathophysiology and therapeutics combined with a skilled and empathic approach to communication. Families faced with losing a child are living through some of the most difficult times people can experience. Doctors are able to accompany them as ‘knowledgeable companions’. Paradoxically, the key to being able to help is to acknowledge that medical treatment can sometimes fail to cure, and that for some children cure is impossible. However, the prospect of a cure is not the only thing medicine can offer such a family. There are many other ways for a doctor to help, and it is these which comprise palliative medicine, and which have been described in this chapter Further reading Association for Paediatric Palliative Medicine. APPM Master Formulary 2015 (3rd edition). <http://www.appm .org.uk/10.html>; 2015 [accessed 07.09.15].

34 672Palliative medicine Hunt A, Goldman A, Seers K, et al. Clinical validation of the paediatric pain profile. Dev Med Child Neurol 2004;46:9–18. Hunt AM, Joel S, Dick G, Goldman A. Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain. J Pediatr 1999;135(1):47–55. International Association for the Study of Pain. <www.iasppain.org>; [accessed 07.09.15]. Mashayekhi SO, Ghandforoush-Sattari M, Routledge PA, Hain RD. Pharmacokinetic and pharmacodynamic study of morphine and morphine 6-glucuronide after oral and intravenous administration of morphine in children with cancer. Biopharm Drug Dispos 2009;30(3):99–106. Wolfe J, Hinds P, Sourkes B. Textbook of interdisciplinary pediatric palliative care. Philadelphia: Elsevier, Saunders; 2010. Association for Paediatric Palliative Medicine. Combined curriculum in paediatric palliative medicine, 2nd ed. <http:// www.appm.org.uk/resources/PPM+Curriculum+2015.pdf>; 2015 [accessed 07.09.15]. Bluebond-Langner M. The private worlds of dying children. Princeton University Press; 1980. Czerny N, editor. Oxford textbook of palliative medicine. Oxford: Oxford University Press; 2012. Fraser LK, Miller M, Hain R, et al. Rising national prevalence of life-limiting conditions in children in England. Pediatrics 2012;129(4):e923–9. Goldman A, Hain R, Liben S. Oxford textbook of palliative care for children. 2nd ed. Oxford: Oxford University Press; 2012. Hain R, Devins M, Hastings R, Noyes J. Paediatric palliative care: development and pilot study of a ‘Directory’ of life-limiting conditions. BMC Palliat Care 2013;12(1):43. Hain R, Jassal SS, editors. Paediatric palliative medicine. Oxford: Oxford University Press; 2010. Hain R Symptom management in paediatric palliative care – online edition. <www.paed.pallcare.info>; 2015 [accessed 07.09.15].

LEARNING OBJECTIVE By the end of this chapter the reader should: • Understand ethical issues relating to clinical care and conducting trials and research with children. 673 CHAPTER THIRTY-FIVE Paediatrics and child health, perhaps more than any other speciality, has recently been the focus of difficult decision-making. Children born months too early or living from infancy on machines are now commonplace. Newspapers carry stories about carers refusing evidence-based radiotherapy for their children’s brain tumours in favour of alternative therapies or about the historic and contemporary abuse of children by celebrities and politicians. Major changes in our laws and practice have followed scandals in which parents discovered that their deceased children’s organs had been retained without their knowledge – allegedly as part of a research study – and that children had died in heart centres where operative mortality was significantly greater than elsewhere. What can ethics offer in all this? It is first useful to define the term. One of the simplest definitions is that ethics is the branch of philosophy that deals with matters of right and wrong, and therefore medical ethics is a branch of ethics that deals with matters of right or wrong in medicine. Ethics textbooks cannot escape some ancient Greeks and so two other definitions feature here: An attempt to find out our chief end or highest good. Aristotle How we ought to live. Socrates The Socratic concept is especially worthy of reflection as it could be suggested that paediatric ethics could at one level be about how paediatricians ought to practise (live). Healthcare professionals often ask whether a particular treatment or practice is ‘ethical.’ The answer being sought is whether the treatment or practice is morally acceptable – i.e. is it right? This is ultimately defined by society as a whole, through the values that are upheld as being important. For example, a society that regards equal distribution of resources as an important value will strive to develop a healthcare system that allows equal access to healthcare. Within such a society, any action that prevents access to healthcare on the grounds of wealth, gender, race, sexuality, etc., would be deemed unethical. In a different society, where healthcare is only provided on monetary payment, inequality in healthcare access may not be judged to be unethical. In order to answer the question of whether an action is ethical or not, one needs to have an understanding of: • What terms such as right and wrong, good and bad, mean. Most people, as moral agents, will have their own intuitive sense of what these terms mean, but they are usually influenced by the society within which people exist. • Moral theories to determine what is right or wrong, good or bad. There are several moral theories, such as consequentialism, deontology, virtue ethics and feminist ethics. These different moral theories provide guiding principles by which an action can be judged. • Practical application of moral theories to determine whether an action is ethical, i.e. right or wrong, good or bad. Ethical principles can provide an appropriate framework in order to achieve this. Joe Brierley Ethics C H A P T E R 35

35 674Ethics effective in reducing long-term morbidity and mortality and utilitarians would prioritize the latter over the former. However, if intensive care provided the only chance of survival for a critically ill child, would any parent favour the utilitarian argument? Furthermore, it is unclear how the utilitarian argument can be limited – closing hospitals in the UK or decreasing national spending on nuclear weapons and redistributing the savings to the lowest income countries in the world might arguably yield greater happiness for a greater number. Deontology Unlike the outcome-based approach of consequentialism, deontology provides a rule-based approach. Morality is based on the intentions of actions, not the consequences. Actions are therefore: • Obligatory – must be carried out, e.g. resuscitation of a patient in the event of an unexpected cardiac arrest • Permissible – neither obligatory or forbidden, e.g. the treatment of ‘colic’ with gripe water • Supererogatory – morally praiseworthy if performed, e.g. donating a kidney to a relative • Forbidden – not permissible under any circumstances, e.g. actively killing a patient. Immanuel Kant, the major proponent of deontology, formulated what is known as the categorical imperative – according to Kant, it is an absolute duty to act morally. If any action is immoral, then we ought not to perform it. The two formulations of the categorical imperative that are important in medical ethics are: • The formula of the universal law – to act only if the principle of the action can be applied universally to all. For example, lying to a patient to provide false reassurance about their prognosis cannot be applied universally – if all doctors lied to their patients about prognosis, patients would not trust their doctors and therefore would not be reassured by what they said. • The formula of the end in itself – when any action involves a person, to never treat the person only as a means to an end, but always at the same time as an end. For example, administering a placebo to a child to reassure their parent is not morally acceptable, unless the child was benefiting from the treatment at the same time. The doctrine of double effect is the converse of the above example. An action can be justified even if it causes serious harm, if the harm is a side effect of bringing about a good end. The use of high doses of opiates to alleviate the pain of a terminally ill patient This chapter provides a brief introduction to commonly used moral theories. It looks at the ‘four principles’ approach to medical ethics, using this approach to apply moral theory to medical situations. It explores some common clinical scenarios within paediatrics and child health which pose ethical dilemmas. They illustrate the use of moral theories and ethical principles to provide guidance regarding appropriate action. There is rarely an answer that is completely black or white – however, this approach demonstrates how actions can be ethically justified. In the final part of the chapter, the issues surrounding medical research involving children are considered. Moral theories There are several moral theories that can be used to make ethical arguments. Those most often used in medical ethics are consequentialism, deontology, virtue ethics and feminist ethics. Consequentialism Consequentialism judges acts to be right or wrong according to the results/consequences produced. An act leading to a positive outcome is morally more acceptable than one that produces a negative outcome. According to critics of consequentialism no act is, therefore, non-permissible. Consequentialists can argue back that if abhorrent acts are allowed and generalized there would be less overall benefit to people. A positive outcome depends on what value is being optimized, e.g. pleasure, happiness, wealth, etc. A hedonist will always act in such a way as to maximize pleasure over other values, such as, say, honesty. Often, in consequentialist arguments, a calculation needs to be made to determine the net benefit, taking into account the benefits and negative effects of any action. Utilitarianism, a form of consequentialism, aims to maximize the overall utility in the world that an action can bring about. The utilitarian ‘greatest happiness principle’ suggests that one should always act to provide the greatest happiness to the greatest number. Consequentialism is popular as it is practical. Logically, it is analogous to ‘evidence-based medicine’. It allows the application of judgement in the form of a calculation to justify any action – nothing is universally forbidden. Consequentialism, however, is not without drawbacks. Expensive therapies with low probabilities of success do not fare well against the utilitarian yardstick. For example, intensive care is resource hungry, with high levels of mortality (especially in adults) and morbidity. Public education programmes about chronic disease management, such as asthma and diabetes, in comparison may be more cost

675 CHAPTER THIRTY-FIVE without consent constitutes the tort of battery – unless they can be shown to lack capacity. Young people between 16 and 18 years are presumed to be able to consent, but cannot refuse medical treatment held to be in their best interest. Their parents can consent, though clinicians would be wise to seek help from the courts before treating if the situation is not an emergency, and even then rapid decisions to treat have recently been made (An NHS Foundation Hospital v P, 2014). It is possible that many involved in child health might consider the ethical aspects at variance from the stark legal situation, given attempts to introduce ‘assent taking’ from children un-/not yet able to consent in both research and clinical practice. Although the decision in the Gillick case was limited to provision of contraceptive advice, Lord Justice Scarman’s reasoning has become influential to the extent that children deemed Gillick-competent can now consent to treatment at any age, though in reality such maturity is generally only attained over the age of 13 years. He stated: As a matter of law, the parental right to determine whether or not the minor child below the age of 16 will have medical treatment terminates if and when the child achieves sufficient understanding and intelligence to understand fully what is proposed. Lord Justice Scarman Any paediatricians faced with ethical dilemmas involving young people must have a clear understanding of and the ability to test for both capacity and the child’s competence to consent to what is proposed. Certainly, one place where ethics and the law coalesce is in children of any age having a right to be involved in decision-making about their healthcare (Gillick v West Norfolk and Wisbech Area Health Authority, 1985). The four principles of medical ethics Perhaps the most influential concept in modern medical ethics, and not without its critics, is principlism. In the 1970s, Beauchamp and Childress formulated their four principles of biomedical ethics, which have become the dominant cornerstone of ethical consideration in healthcare practice. The principles are often used as a framework to deliberate on ethical questions about therapies. The four principles are: i. Respect for autonomy Autonomy is the ability to self-govern. In order to possess autonomy, an individual must be able to have could be deemed moral, even though it could lead to respiratory depression and death. Virtue ethics Unlike deontology and consequentialism, virtue ethics does not focus on acts per se, but on the character of the moral agent, i.e. the person morally responsible for the act. Having a given virtue predisposes a person to act in a certain way – for example, a generous person is likely to donate towards charity. Virtues are defined by the person’s actions, but also their attitudes and internal values. Therefore, actions are morally appropriate if they conform to a virtuous individual’s habits of valuing, assessing and acting according to the virtue in question. In other words, an action is honest if it is consistent with the actions of an honest individual. It is worth noting, however, that individuals are unlikely to be able to always act according to a given virtue. Negative desires may be a result of circumstances and context. The virtuous will attempt to fight the negative desires and perform the right act accordingly. Virtue ethics therefore accepts the complexity of practical situations, which duty- or consequence-based theories may not. Feminist ethics or ethics of care This approach is often contrasted with other classic approaches in its communitarian, contextual and caring approach. Some have argued they are perfect for child health dilemmas (Brierley and Larcher 2011) as they focus less on individualistic rights-based solutions, but rather view the child in its true context as part of a family with parents, brothers and sisters, of a community with family and friends and of a society of other co-dependent people. However, there is a need to ensure the child is not merely considered as the property of its parents. The influential Gillick case clearly established that ‘parental rights are derived from parental duty…and…exist only so long as they are needed for the protection of…the child.’ (Gillick v West Norfolk and Wisbech Area Health Authority, 1985). Indeed, for paediatricians, one also needs to clarify the law surrounding decision-making for children. (Further details can be found by reference to GMC and BMA guidance and healthcare law textbooks.) Parents or those with parental rights are privileged to make healthcare decisions (e.g. consent) for their children, as long as they are acting in that child’s best interests. If they are not, such as refusing radiotherapy for a treatable brain tumour, the courts will ensure treatment occurs. Over the age of 18 years, children become autonomous adults and can decide for themselves. Treatment

35 676Ethics The extremely preterm infant You are called as the neonatal registrar to talk to parents who have presented to the delivery suite. Juliet is a 38-year-old woman, who is 22+5 weeks pregnant with her third pregnancy. She has just had a leak of liquor, and her cervix is 4 cm dilated. She has two healthy children, 2 and 5 years old, with her husband George. You counsel the couple regarding the poor prognosis of babies born at 22 weeks. If Juliet delivers in the next few hours then the baby will not be considered viable. Even if he or she is born with a heartbeat, you will not resuscitate him/her. However, if the baby is born after 23 weeks, he/she will have a better chance of survival. They will still be at high risk of all the complications of extreme prematurity (sepsis, intraventricular haemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia). You quantify the risks according to national and local audit figures. You offer to resuscitate the baby if born after 23 weeks, provided that Juliet and George agree to this. Juliet and George feel that this is their last attempt at adding to their family. They have strong religious beliefs and are convinced that their baby will survive. They are unhappy with your decision not to resuscitate their baby if he/she is born in the next few hours. They want you to do everything to help their child survive. principle of beneficence. Beyond the requirement to provide positive benefit, beneficence also encompasses utility, whereby benefits and risks are balanced to provide an overall positive result. An act of beneficence may therefore involve a reduction in risk to a patient, e.g. vaccination or thrombo-prophylaxis for children or adults. iv. Justice The principle of justice involves the fair and consistent treatment of all people within a population. In medical ethics, the principle mainly refers to distributive justice, or the fair and equitable distribution of resources within a population. The fairness of distribution is based on specific principles, e.g. clinical need. The equity is based on treating equals equally, i.e. patients with the same degree of clinical need get the same degree of care irrespective of ability to pay, of religion, of racial group or indeed age. The four principles are not independent of each other. For example, surgery is not performed on a patient who does not consent, even if he is unlikely to survive without it, out of respect for his autonomy – despite this meaning arguably not acting in a beneficent way. The four principles approach does not set a hierarchy for the principles when they come into conflict with each other, which has often been the focus of criticism. However, the principles aim to provide a framework for ethical deliberation. The emphasis on each principle will depend on the context. For example, in a society where autonomy is held in highest regard, respect for autonomy may overrule considerations of beneficence. Conversely, in societies where medicine has a more paternalistic identity, beneficence may take precedence over autonomy. desires, be able to formulate options that can realize those desires and be able to select the most appropriate option. Autonomous actions should be intentional, fully understood and devoid of controlling influences. In order to exercise autonomy, a patient must be able to express the problem for which they wish to have treatment, understand the various treatment options and consent to the most appropriate option. Consequently, it would be unethical to treat a patient against their wishes, fail to present the available treatment options to them, or influence or disregard their consented option. For children, this might be the relative autonomy (if that can exist) of a Gillick-competent child, or the autonomy of parents to decide for their children – restricted by the need to act in the child’s best interests, however this might be determined. ii. Non-maleficence The principle of non-maleficence is embodied in the maxim primum non nocere, or above all, do no harm. Harm is defined as an abrogation of one’s interests. Within medicine, this would include causing pain, death, incapacity, etc. However, ‘causing’ death may not always be against a patient’s interests; if a patient’s condition is unbearable to the point that they wish to die, then continuation of life-sustaining treatment may be both maleficent and disrespectful of their autonomy. Therefore, non-maleficence could be interpreted as not acting against a patient’s interests, and is the same for adults and children. iii. Beneficence In addition to not acting against the patient’s interests, one of the ends of medicine is to act in the patient’s interests, by promoting their welfare. This is the Case history Text continued on page 683

677 CHAPTER THIRTY-FIVE Ethical dilemmas: • Who should decide whether the baby should be resuscitated or not? • What considerations should be taken into account? • Should the parents’ age, social background or religion have an impact on the decision? • What if the parents did not want the baby to be resuscitated, as they did not feel they could look after a baby with chronic health problems? These are complex ethical questions without a right or wrong answer. However, the law may provide boundaries to the relevant ethical arguments. Therefore, the answers may be different in different countries. In the UK, according to the Abortion Act 1967, a pregnancy can be terminated up to 24 weeks of gestation (or beyond to protect the physical or mental health of the woman, or if the child is likely to be born with severe disabilities). This can be the choice of the pregnant woman, and this is respected to protect her autonomy. The unborn fetus has no legal rights (rightly or wrongly – this is still a topic of debate). However, once the child is born, he/she becomes an individual person, subject to rights and interests like anybody else. As with most children up to a certain developmental age, a newborn baby is not autonomous: they do not have the ability to govern themselves, form their own opinions of how they should live, or execute actions according to those opinions. Others have to decide for them and look after them, which is the role and responsibility of parents, as enshrined in the Children Act 1989. The guiding principle for these decisions is the welfare of the child; in medical ethics terminology synonymous with the principles of beneficence and non-maleficence. Whilst most parents will act in the best interests of their child, this may not always be the case. Compromises are made to meet the interests of the family unit, e.g. rather than sending their son to a school with a better reputation 30 miles away, parents may decide to send him to his sister’s school, closer to home, so that they can travel together. Although this may not be in the individual child’s best interests, it does not form an argument for placing the child in foster care – staying in his own family is likely to be far more favourable. Similarly for medical choices, most parents will take decisions for their children in their best interests. The medical team may need to intervene if the parental decision puts the child at risk of significant harm (known as the ‘no harm principle’). Applying this to the case above, we need to determine what risk of harm the child is being placed in after birth. According to the EPICure 2 data from 2006, the survival to discharge from hospital of babies born at less than 23 weeks of gestation is very rare. At 23 weeks, the survival chances are close to 20%, at 24 weeks 40% and at 25 weeks over 60%. In cases where babies have been resuscitated at, or especially below, 22 weeks, even the institution of maximal intensive care has rarely helped. Intensive care therapy can be harmful – most procedures such as intubation, intravenous line insertion and heel pricks are distressing, even though babies may be provided with analgesia to minimize pain. This is largely justified if the chance of survival is reasonable – the baby has potential of a life ‘worth living’. However, as babies born at 22 weeks are unlikely to survive, one could consider that the burdens of intensive care outweigh the potential benefits. Such a life may be considered not worth living. One must also be mindful of justice – neonatal intensive care is not a limitless resource. If a baby with an extremely poor chance of survival takes the last available neonatal cot and denies one with a reasonably good chance of survival, both may end up suffering. In order to maximize benefits, we may need to limit who we can offer intensive care to. Many extremely premature babies will develop chronic health needs. They may remain dependent on their parents for longer. This has an impact on the parents, who may have to give up their jobs to look after their child, and siblings, who may miss out on opportunities as their parents have to devote resources to the less able child. Therefore, although we must try and protect the welfare of individual children whom we as healthcare professionals are looking after, we must be aware of the interdependence between the child and their family. Ultimately, this may affect the welfare of the child – a child with health needs will need dedicated care from their family, which may be compromised if the family did not want the child to be resuscitated at birth, for example. Based on the evidence (albeit that of EPICure 1995) and such ethical considerations, the Nuffield Council of Bioethics in 2006 formulated the guidelines in Box 35.1. The guidelines were formulated by a working group of healthcare professionals, ethicists, lawyers and parents. They are guidelines and not legally binding. It is possible that with time and improving medical care they will need revision. Nonetheless, they form a consensus opinion, and therefore will carry weight in a court of law. In the above case there are strong ethical arguments, based on current evidence, to not resuscitate the baby if born before 23 weeks. This should be discussed with the parents, explaining the reasoning behind the decision. This is best done by a paediatrician with experience in the area, respectfully and with empathy for the parents.

35 678Ethics The non-immunized child Henry, a 10-month-old child, is admitted to the paediatric ambulatory care ward following a generalized febrile seizure associated with a 3-day coryzal illness. The seizure stopped spontaneously after 2 minutes. This was his second seizure. You realize from the history taken at presentation that Henry has never been immunized. His mother, who is at his bedside, does not feel immunization is necessary. She believes that natural immunity alone is effective in preventing childhood infections, and vaccines carry an unnecessary risk of side effects. Her 4-year-old daughter had some of her early vaccines, but did not have her MMR or booster vaccines. She has never suffered any severe illnesses needing hospital, and is now fit and well. The family seem fairly well informed about health choices. Henry is well grown and there are no other causes for concern about his care. There has been no social services involvement in the family. You remain concerned that Henry has not been immunized. He has already had two febrile seizures. While you understand that being immunized may not have prevented them, you are concerned that it increases Henry’s predisposition to more serious illnesses. You express this to Henry’s mother, who thinks immunization itself can increase the risk of seizures. She also thinks that these are likely viral illnesses, for which there are no vaccines. It is difficult to argue with Henry’s mother. However, you are still concerned that Henry’s health is being affected by his mother’s choices. His father is not at the bedside, but has not expressed any wishes for Henry to be immunized. Ethical dilemma: • Should Henry’s mother’s opposition to immunization be pursued further, in the form of child protection proceedings? The question at hand could be framed in public health terms, namely should immunization be made compulsory? Currently in the UK, an immunization schedule is offered to parents, but is not compulsory. Parents are required to consent to vaccines being administered as proxy decision-makers for children. If they do not consent, the vaccines are not administered. Notably, when parents have disagreed on immunization and the dispute has ended up in court, the UK courts have ruled for the children to be vaccinated in their best interests. Most interactions between the public and healthcare involve an illness or medical problem. Immunization as part of a schedule is an intervention administered to a well person to prevent future illness. It does this in two ways: by preventing the disease being vaccinated against in that individual, and by generating herd immunity, so that the disease is not propagated within the population. What is the extent of these benefits to the individual? The vaccines offered protect against disease, but the protection is not absolute. Vaccine failure can occur due to failure of adequate immunity to develop. The vaccines protect against a limited number of serotypes; for example, the current pneumococcal vaccine protects against the 13 most common serotypes in the UK. The protection diminishes with age. For some diseases, such as polio, there is sufficient Case history Box 35.1 Guidelines for providing intensive care to extremely premature neonates in the UK according to the Nuffield Council of Bioethics At 25 weeks and above Intensive care should be initiated and the baby admitted to a neonatal intensive care unit, unless he or she is known to be affected by some severe abnormality incompatible with any significant period of survival. Between 24 weeks, 0 days and 24 weeks, 6 days Normal practice should be that a baby will be offered full invasive intensive care and support from birth and admitted to a neonatal intensive care unit, unless the parents and the clinicians are agreed that, in the light of the baby’s condition, it is not in his or her best interests to start intensive care. Between 23 weeks, 0 days and 23 weeks, 6 days It is very difficult to predict the future outcome for an individual baby. Precedence should be given to the wishes of the parents. However, where the condition of the baby indicates that he or she will not survive for long, clinicians should not be obliged to proceed with treatment wholly contrary to their clinical judgement, if they judge that treatment would be futile. Between 22 weeks, 0 days and 22 weeks, 6 days Standard practice should be not to resuscitate the baby. Resuscitation should only be attempted and intensive care offered if parents request resuscitation, and reiterate this request, after thorough discussion with an experienced paediatrician about the risks and long-term outcomes, and if the clinicians agree that it is in the baby’s best interests. Before 22 weeks Any intervention at this stage is experimental. Attempts to resuscitate should only take place within a clinical research study that has been assessed and approved by a research ethics committee and with informed parental consent.