Paediatrics

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10 Paediatrics

Paediatrics is the branch of medicine dealing with the development, diseases and disorders of children. Infancy and childhood is a period of rapid growth and development. The various organs, body systems and enzymes that handle drugs develop at different rates; hence, drug dosage, formulation, response to drugs and adverse reactions vary throughout childhood. Compared with adult medicine, drug use in children is not extensively researched and the range of licensed drugs in appropriate dosage forms is limited.

For many purposes it has been common to subdivide childhood into the following periods:

For the purpose of drug dosing, children over 12 years of age are often classified as adults. This is inappropriate because many 12 year olds have not been through puberty and have not reached adult height and weight. The International Committee on Harmonization (2001) has suggested that childhood be divided into the following age ranges for the purposes of clinical trials and licensing of medicines:

These age ranges are intended to reflect biological changes: the newborn (birth to 4 weeks) covers the climacteric changes after birth, 4 weeks to 2 years the early growth spurt, 2–11 years the gradual growth phase and 12–18 years puberty and the adolescent growth spurt to final adult height. Manufacturers of medicines and regulatory authorities are working towards standardising the age groups quoted in each product’s Summary of Product Characteristics.

Demography

The 2001 census revealed that dependent children still make up a substantial number of people, at 11.7 million, but figures published by the Office for National Statistics in 2009 indicate that over the last 25 years the percentage of the population aged 16 years and under has decreased from 21% to 19%. This trend is predicted to continue and by 2033 the percentage of the population under 16 years old is predicted to be 18%. The UK census in 2011 will be the next opportunity to confirm this trend.

Children make substantial use of hospital-based services. It has been estimated that of the 14 million attendances at hospital emergency departments reported each year in England, 2.9 million were for children. At the same time there were 4.5 million outpatient attendances and 700,000 in-patient admissions. The 10 most common admission diagnoses in a specialist children’s hospital over an 18-month period are shown in Table 10.1.

Table 10.1 Top 10 diagnoses on admission to a specialist children’s hospital

Ranking Diagnosis
1 Respiratory tract infections
2 Chronic diseases of tonsils and adenoids
3 Asthma
4 Abdominal and pelvic pain
5 Viral infection (unspecified site)
6 Non-suppurative otitis media
7 Inguinal hernia
8 Unspecified head injury
9 Gastroenteritis/colitis
10 Undescended testicle

Congenital anomalies

Congenital anomalies remain an important cause of infant and child mortality in England and Wales, and account for an increasing proportion of infant deaths. The National Congenital Anomaly System (NCAS), established in 1964 in the wake of the thalidomide tragedy, has monitored congenital anomalies nationally in England and Wales. Registers such as NCAS are important in planning service delivery and alerting specialists to conditions where research is required. However, it relies on voluntary notifications and collaborates with local registers to improve the quality and quantity of data (see Useful Paediatric Websites at end of chapter).

Data for 2008 are available but there is ongoing discussion about the future direction of the recording service, given the wide variability in reporting between areas with and without regional congenital anomaly registers. In 2007, a new classification of congenital anomalies was introduced to include tighter rules for deciding which congenital anomalies should be included in the Office for National Statistics report making year on year comparisons more difficult.

In 2008, there were 175 central nervous system (CNS) anomalies, for example, hydrocephalus, 282 cleft lip/palate, 932 heart and circulatory, 258 hypospadias and 225 Down’s syndrome reported to NCAS.

Neural tube defects (spina bifida) are one example of devastating congenital malformations that have been influenced by public health intervention programmes. The results of a long-term study (MRC Vitamin Study Research Group, 1991) showed that folate supplementation prevented 72% of neural tube defects when given to women at high risk of having a child with a neural tube defect. Hence, folate supplementation is now part of the routine advice given in antenatal clinics.

Infections

Despite a dramatic decline in the incidence of childhood infectious diseases during the twentieth century, they remain an important cause of ill health in childhood. Major advances in the prevention of infections have been achieved through the national childhood vaccination programme.

The importance of maintaining high vaccine uptake has been demonstrated by the resurgence of vaccine-preventable diseases where children have not been vaccinated. Adverse publicity surrounding the MMR (measles, mumps and rubella) vaccine, involving a possible association with Crohn’s disease and autism, resulted in a loss of public confidence in the vaccine and a decrease in MMR coverage. This occurred in spite of rigorous scientific investigation and evidence refuting the claims. The annual coverage for MMR for 2-year olds declined from 92% in 1992 to 87% in 2000 and data for 2004 show that it dropped to 81.5%. Although this decline is far less than that seen for pertussis in the 1970s, if MMR coverage remains at this level or declines further, resurgences of MMR in primary schoolchildren will become more common. NHS information centre data revealed 85% of children in England had received the MMR vaccine in 2007/8. However, to achieve herd immunity, 95% of children need to be immunised; unless this figure is improved a measles epidemic still remains a possibility.

An important gastro-intestinal infection that appears to be increasing is infection with verotoxin-producing Escherichia coli (VTEC). This is important because it is the main cause of haemolytic uraemic syndrome, a severe condition which can lead to acute renal failure in children. VTEC is an example of an emerging infection. Before the 1980s it was unknown and during the 1990s reports of infection with VTEC in children in the UK tripled from 172 in 1991 to 531 in 1999. In 2009 the rates of VTEC 0157 decreased as age increased, with significantly higher rates in the 0–4 year age group (8 per 100,000) than in 5–9 year olds (4 per 100,000) and a further decrease (2 per 100,000) in the 10–19 year age group. It is a public health priority to improve VTEC 0157 surveillance and improve diagnostic testing.

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children in the UK, in whom it causes bronchiolitis, tracheobronchitis and pneumonia. It is responsible for seasonal outbreaks of respiratory tract infection most commonly between October and April. The main burden of disease is borne by children under 2 years and there are around 7000–10000 confirmed laboratory reports of RSV in children in England and Wales each year. During the winter months, RSV is the single greatest cause of admission to hospital in children.

Drugs, smoking and alcohol

The harm that drugs, smoking and drinking can do to the health of children and young people is recognised and a number of targets have been set in an attempt to reduce prevalence. Recent figures on smoking, alcohol and drug use among young people have been provided by the NHS Information Centre in their 2008 report.

In 2008, 6% of schoolchildren smoked regularly (at least once a week). Girls are more likely to smoke than boys and the prevalence increases with age. Around 14% of 15-year olds smoke regularly compared to 0.5% of 11-year olds. However, the prevalence of smoking amongst children has halved since its peak in the mid-1990s (13% in 1996), suggesting a decline in prevalence to below government targets. In 2007, the minimum age for buying tobacco was increased from 16 years old to 18 years old.

More than half of pupils (52%) aged 11–15 years have drunk alcohol in their lifetime. In 2008, a national survey identified that the mean amount of alcohol consumed by pupils who had drunk in the last week was 14.6 units. Boys drink more than girls and older pupils drink more than younger pupils. In one large survey, 17% of pupils aged 11–15 years old admitted to being drunk in the last 4 weeks.

The prevalence of drug use has declined since 2001. In 2008, 22% of pupils said that they had ever used drugs with 33% reporting that they had ever been offered drugs. Pupils were most likely to have taken cannabis (9%). Five percent of pupils had sniffed glue or other volatile substances in the last year and 2.9% had sniffed poppers. Overall, 3.6% of pupils had taken class A drugs in the last year.

Nutrition and exercise

Health during childhood can impact upon well-being in later life. Good nutrition and physical exercise are vital both for growth and development and for preventing health complications in later life. In addition, dietary patterns in childhood and adolescence have an influence on dietary preferences and eating patterns in adulthood.

In 2000, an international definition of overweight and obesity in childhood and adolescence was proposed to help calculate internationally comparable prevalence rates of overweight and obesity in children and adolescents. The definition interprets overweight and obesity in terms of reference points for body mass index (BMI, in kg/m2) by age and sex, and is linked to the widely used adult overweight cut-off point of 25 and adult obesity cut-off point of 30.

In 2004, it was estimated that 14% of boys and 17% of girls aged 2–15 years of age were obese. Probable reasons for a rise in overweight and obesity in children are changes in diets and an inactive lifestyle. There is evidence that obesity at an early age tends to continue to adulthood.

Being overweight is linked to the development of type 2 diabetes, high blood pressure, heart disease, stroke, certain cancers and other types of illnesses. Therefore, healthy eating is not only important in relation to weight but also contributes to reducing the risk of heart disease, stroke and some cancers in later life. It is recommended that a well-balanced diet providing all the nutrients required should include at least five portions of fruit and vegetables a day. It is now practice in many areas for infant children (aged 4–7 years) each day to be provided with a piece of free fruit during school break time.

The normal child

Growth and development are important indicators of a child’s general well-being and paediatric practitioners should be aware of the normal development milestones in childhood. In the UK, development surveillance and screening of babies and children is well established through child health clinics.

Weight is one of the most widely used and obvious indicators of growth, and progress is assessed by recording weights on a percentile chart (Fig. 10.1). A weight curve for a child which deviates from the usual pattern requires further investigation. Separate recording charts are used for boys and girls and since percentile charts are usually based on observations of the white British population, adjustments may be necessary for some ethnic groups. The World Health Organization (WHO) has challenged the widely used growth charts, based on growth rates of infants fed on formula milk. In 2006, it published new growth standards based on a study of more than 8000 breast-fed babies from six countries around the world. The optimum size is now that of a breast-fed baby. Recently, new growth charts have been introduced for children from birth to 4 years of age. These combine the UK and WHO data. Copies can be accessed at http://www.rcpch.ac.uk/Research/UK-WHO-Growth-Charts.

Height (or length in children less than 2 years of age) is another important tool in developmental assessment. In a similar way to weight, height or length should follow a percentile line. If this is not the case or if growth stops completely, then further investigation is required. The normal rate of growth is taken to be 5 cm or more per year and any alteration in this growth velocity should be investigated.

For infants up to 2 years of age, head circumference is also a useful parameter to monitor. In addition to the above, assessments of hearing, vision, motor development and speech are undertaken at the child health clinics. A summary of age-related development is shown in Fig. 10.2.

Child health clinics play a vital role in the national childhood immunisation programme, which commences at 2 months of age. Immunisation is a major success story for preventive medicine, preventing diseases that have the potential to cause serious damage to a child’s health, or even death. An example of the impact that immunisation can have on the profile of infectious diseases is demonstrated by the meningitis C immunisation campaign, which began in November 1999. The UK was the first country to introduce the meningitis C conjugate (MenC) vaccine and uptake levels have been close to 90%. The programme was targeted at under-20 year olds and has been a huge success, with a 90% reduction in cases in that age group. Authorities were hoping to mirror the success of the meningitis C campaign with the introduction of the seven valent pneumococcal vaccine into the routine UK childhood immunisation schedule in April 2006. Post-licensing surveillance has shown a large reduction in both invasive and non-invasive disease incidence due to vaccine serotypes in vaccinated individuals. However, during the same period, the UK has seen an increase in invasive disease due to the non-vaccine serotypes, caused for a large part by the six serotypes not covered by the seven valent vaccine, but present in a new 13 valent vaccine. In April 2010, the 13 valent pneumoccocal vaccine replaced the seven valent vaccine in the standard immunisation schedule. Human papilloma virus vaccine has also recently been introduced to the immunisation programme in the UK for females aged 12–13 years of age, to reduce the risk of cervical cancer.

Advice on the current immunisation schedule can be found in the current edition of the British National Formulary for Children.

Drug disposition

Pharmacokinetic factors

An understanding of the variability in drug disposition is essential if children are to receive rational and appropriate drug therapy (Anderson and Holford, 2008, 2009). For convenience, the factors that affect drug disposition will be dealt with separately. However, when treating a patient all the factors have a dynamic relationship and none should be considered in isolation.

Absorption

Topical absorption

Advances in transdermal drug delivery systems have led to an increased use of this route of administration. For example, patch formulations of hyoscine hydrobromide have been found to be very useful to dry up secretions in children with excess drooling; likewise fentanyl patches can be useful in pain management. Percutaneous absorption, which is inversely related to the thickness of the stratum corneum and directly related to skin hydration, is generally much greater in the newborn and young infant than in the adult. This can lead to adverse drug reactions (ADRs). For example, the topical application of a preparation containing prilocaine and lidocaine (EMLA) should not be used in preterm infants because of concerns about significant absorption of prilocaine in this age group, which may lead to methaemoglobinaemia. The development of needle-free subcutaneous jet injection systems appears to bring many benefits as a method of drug administration. They have been shown to give comparable levels to standard subcutaneous injections and overcome the problems of needle phobia, with less pain on administration. This system has been used with growth hormone, insulin, sedation prior to procedures and vaccination in children.

Another route of topical absorption is ophthalmically. Significant amounts of drugs may be absorbed from ophthalmic preparations through ophthalmic or nasolacrimal duct absorption; for example, administration of phenylephrine eye drops can lead to hypertensive episodes in children.

Drug metabolism

At birth the majority of the enzyme systems responsible for drug metabolism are either absent or present in considerably reduced amounts compared with adult values, and evidence indicates that the various systems do not mature at the same time. This reduced capacity for metabolic degradation at birth is followed by a dramatic increase in the metabolic rate in the older infant and young child. In the 1–9 year age group in particular, metabolic clearance of drugs is shown to be greater than in adults, as exemplified by theophylline, phenytoin and carbamazepine. Thus, to achieve plasma concentrations similar to those observed in adults, children in this age group may require a higher dosage than adults on a milligram per kilogram basis (Table 10.3).

Table 10.3 Theophylline dosage in children older than 1 year

Age Dosage (mg/kg/day)
1–9 years 24
9–12 years 20
12–16 years 18
Adult 13

Metabolic pathways that play only a minor role in adults may play a more significant role in children and compensate for any deficiencies in the normal adult metabolic pathway. For example, glucuronidation accounts for up to 70% of the metabolic pathway of paracetamol in adulthood; however, in the early newborn period glucuronidation is deficient, accounting for less than 20% of paracetamol metabolism. This is compensated for by a more pronounced sulphate conjugation and this leads to an apparently normal half-life in newborns. Paracetamol appears to be less toxic in children than in adults and this may be in part explained by the compensatory routes of metabolism.