Absorption

An important and unique source of drug absorption, available until birth, is the placenta. Maternal drugs pass to the fetus and back again during pregnancy, but from delivery, any drugs present in the neonatal circulation can no longer be eliminated by that route and must be dealt with by the baby’s own systems. Important examples of maternal drugs which may adversely affect the newborn baby include opiates given for pain relief during labour, β-blockers given for pregnancy-induced hypertension and benzodiazepines for eclamptic seizures. In addition, a mother may be given a drug with the intention of treating not her but her fetus. An example of this is the use of corticosteroids to promote fetal lung maturation when preterm delivery is planned or expected. In this situation, betamethasone is normally the drug of choice as prednisolone is metabolised in the placenta and does not reach the fetus.

Enteral drug absorption is erratic in any newborn baby and unavailable in the ill baby because the stomach does not always empty effectively. Therefore, most drugs are given intravenously to ensure maximum bioavailability. Some drugs, such as paraldehyde and diazepam (for neonatal seizures) and paracetamol (for simple analgesia), can be given rectally. The trachea may be used as the preferred route of administration when surfactant administration is required or where adrenaline (epinephrine) is given for resuscitation. The buccal route may be used to administer glucose gel in the treatment of hypoglycaemia. In the very preterm baby of 28 weeks’ gestation or less, the skin is extremely thin and a poor barrier to water loss; consequently it is also permeable to substances in contact with it. This is harmful to the baby if there is prolonged skin contact with alcohol, as in chlorhexidine in 70% methylated spirit, which causes severe chemical burn and has resulted in systemic methyl alcohol poisoning. The intramuscular route is normally avoided in premature babies because of their small muscle bulk, although the notable exceptions to this are the administration of vitamin K and naloxone.

Distribution

Drugs are distributed within a baby’s body as a function of their lipid and aqueous solubility, as at any other time of life. The main difference in the neonate is that the size of the body water pool under renal control is related not to the baby’s surface area but to body weight. Furthermore, the absolute glomerular filtration rate increases logarithmically with postconceptional age irrespective of the length of a baby’s gestation. This has implications for predicting the behaviour of water-soluble drugs such as gentamicin. The amount of adipose tissue can vary substantially between different babies. Any baby born more than 10 weeks early, and babies of any gestation who have suffered intrauterine growth restriction, may have little body fat. Conversely, the infant of a diabetic mother may have a particularly large fat layer and this affects the retention of predominantly lipid-soluble drugs. Protein binding in the plasma is influenced by the amount of albumin available and this in turn is related to gestation, with albumin values found 12 weeks prior to term being only two-thirds of adult concentrations.

Metabolism

The metabolic fate of drugs in the newborn is not qualitatively different to that in the older child, for example, hydroxylation, oxidation and conjugation to sulphate or glucuronide. It is the efficiency with which these processes are carried out that distinguishes the baby from the older person. In addition to the immaturity of the metabolic pathways for drug disposal, drug metabolism is also affected by the physiological hyperbilirubinaemia of the newborn. The bilirubin can compete both for enzyme-binding sites and for glucuronate, and may thus affect drug metabolism for as long as unconjugated hyperbilirubinaemia persists.

Elimination

The relative immaturity of hepatic and renal function results in correspondingly slow elimination of most drugs from the neonate. This is not necessarily a problem, so long as due account is taken of the slow elimination and dose intervals are modified accordingly. It may even be a useful property, as with phenobarbital, which when given as a loading dose (usually 20 mg/kg) will remain in circulation for days in useful therapeutic quantities, often avoiding the need for further doses. On the other hand, drugs such as gentamicin and vancomycin, which have a relatively narrow therapeutic index, must be given far less frequently than in children or adults and serum drug levels must be assayed to avoid toxicity.

There has been little study of pharmacodynamics in the term or preterm neonate. Most clinicians work on the assumption that the kinetics of drug behaviour are so different in this group of patients that the pharmacodynamic properties must follow the same pattern. In practice, the most important pharmacodynamic effect is probably that of the behaviour of opiates derived from the mother in labour. Pethidine and diamorphine are the opiates most likely to cause significant respiratory depression in the neonate. Such respiratory depression can be treated with naloxone, and a special neonatal preparation (20 µcg/mL) is available. However, after birth the opiates and their metabolites have a long serum half-life in the baby whereas the naloxone is rapidly eliminated. The initial dramatic effect of naloxone can give a false sense of security, as the baby may become narcosed after a few hours following transfer to the postnatal ward. To try to prevent this late-onset narcosis, adult naloxone (400 µcg/mL) may be given intramuscularly to ensure it remains active over several hours. Even when the respiratory effects have disappeared, opiates may have prolonged behavioural effects on both mother and baby.

Respiratory distress syndrome (RDS)

Among preterm babies the most commonly encountered disorder is RDS (also sometimes called hyaline membrane disease from its appearance on lung histology, or surfactant deficiency lung disease in recognition of the aetiology). The root cause of this disease is the lack of sufficient pulmonary surfactant at the time of birth. The condition is rare in babies born at or near term and becomes increasingly likely the more preterm a birth takes place. It is now quite unusual to see classical RDS because it is prevented both by the use of antenatal betamethasone in the mother and the postnatal administration of surfactant to babies at highest risk (see below).

Clinically, RDS is manifested by obvious difficulty with breathing, with nasal flaring, rib recession, tachypnoea and a requirement for oxygen therapy. The natural history is that RDS becomes worse over the first 2 days, reaches a plateau and then gradually improves. The use of antenatal steroid therapy to the mother, and surfactant therapy for the infant, has not only transformed the clinical course of this condition but also greatly reduced mortality.

A relatively big baby born around 32–34 weeks of gestation with mild RDS may need no more treatment than extra oxygen. In contrast, smaller, more premature or more severely affected babies need some degree of mechanical assistance: either continuous positive airway pressure by nasal prongs or full artificial ventilation through an endotracheal tube. A few babies require high inspired concentrations of oxygen (up to 100%) for several days. Fortunately, pulmonary oxygen toxicity is not as much a problem to the neonate as it is to the adult, though it may have a causal role in the development of bronchopulmonary dysplasia. The major concern is the damage that prolonged arterial hyperoxia can do to the retina, resulting in retinopathy of prematurity. The goal is to give enough inspired oxygen to keep the arterial partial pressure within a range of about 6–12 kPa.

Mechanical ventilation is not a comfortable experience, for adults or children, but it has taken a long time to appreciate that this may also be true for premature babies. Paralysing agents such as pancuronium are sometimes given to ventilated neonates but these only prevent the baby from moving and are not sedative. Pancuronium is widely used, partly because it wears off slowly so that the baby is not suddenly destabilised. Shorter acting agents such as atracurium are often used for temporary paralysis for intubation. Whether or not the baby is paralysed, morphine is commonly given either as intermittent doses or as an infusion, to provide narcosis and analgesia to reduce the distress of neonatal intensive care.

Antenatal steroids given to the mother reduce the incidence, severity and mortality of RDS caused by surfactant deficiency. Unfortunately, it is not possible to identify and treat all mothers whose babies could benefit. Babies of less than 32 weeks’ gestation gain most benefit because they are at greatest risk of death and disability from RDS. Optimum treatment is four oral doses of 6 mg betamethasone, each given 12-hourly, or two doses of 12 mg intramuscularly 24 h apart.

Similarly, the introduction of exogenous surfactant, derived from the pig or calf, has revolutionised the management of RDS. Natural surfactants derived from animals are currently more effective than artificial synthetic ones. The first dose should be given as soon as possible after birth since the earlier it is given, the greater the benefit (Soll, 1999).

There are several other important ways of treating babies in respiratory failure. Inhaled nitric oxide dilates pulmonary arterioles and lowers the excessive pulmonary blood pressure which often complicates respiratory failure. Persistent pulmonary hypertension may also complicate early onset septicaemia and meconium aspiration syndrome; in term and near-term babies, nitric oxide is both more effective than the previous drug therapies and much less likely to lead to systemic hypotension. However, it does not reduce mortality or major complications when used in babies with birth weights less than 1500 g (Van Meurs et al., 2005).

For some babies of at least 34 weeks of gestation and at least 2 kg birth weight, extracorporeal membrane oxygenation (ECMO), in which a baby is in effect put on partial heart–lung bypass for a few days, may be life-saving when ventilation and nitric oxide fails (ECMO Collaborative Trial Group., 1996).

Patent ductus arteriosus (PDA)

PDA can be a problem in the recovery phase of RDS, and usually shows itself as a secondary increase in respiratory distress and/or ventilatory requirement, an increasing oxygen requirement, wide pulse pressure and a characteristic heart murmur. Physiologically, as pressure in the pulmonary artery falls, an open duct allows blood from the aorta to flow into the pulmonary artery, which engorges the lungs and reduces their compliance, while putting strain on the heart. Echocardiography is used to confirm the clinical suspicion. About one-third of all babies with birth weights less than 1000 g will develop signs of PDA, for example, the characteristic heart murmur, but treatment is only needed when the baby is haemodynamically compromised. When treatment is needed the options are either medical treatment (with indometacin or ibuprofen) or surgical ligation.

Indometacin is usually given intravenously in the UK, because when given enterally its absorption is unpredictable and it may need to be given before the baby has started enteral feeds. The alternative is intravenous ibuprofen. Potential serious side effects of both drugs include renal impairment, gastric haemorrhage and gut perforation. Surgery is considered when one or more courses of medical treatment fail to close the PDA or if drugs are contraindicated for any reason. There are no good randomised controlled trials to guide clinicians on the best approach to managing PDA.

Bronchopulmonary dysplasia (BPD)

BPD, also sometimes generically known as chronic lung disease of prematurity, most frequently occurs in very immature babies who have undergone prolonged respiratory support. The factors predisposing to BPD are the degree of prematurity, the severity of RDS, infection, the occurrence of PDA, oxygen toxicity and probably intrinsic genetic factors. BPD can be defined as oxygen dependency lasting more than 28 days from birth, but this definition is not very useful in that many babies born at less than 28 weeks of gestation require oxygen for 28 days or more, but few still need it after 8 weeks. A more useful functional and epidemiological definition of established BPD is oxygen dependency at 36 weeks of postmenstrual age, in a baby born before 32 weeks.

Established BPD not severe enough to need continuing mechanical ventilation is either treated with nasal continuous positive airway pressure with or without oxygen supplementation, or if less severe again is treated with oxygen through nasal cannulae. Enough oxygen must be used to maintain an oxygen saturation high enough to control pulmonary artery pressure, while avoiding chronic low-grade hyperoxia which could contribute to retinopathy of prematurity. Optimum oxygen saturations in these babies have not been rigorously defined but the outcome of several large trials is awaited.

A chronic inflammatory process is part of the pathology of BPD, and for this reason much attention has been given to the role of corticosteroids in treating it. Steroid use generally results in a rapid fall in oxygen requirements, but does not improve mortality. Indeed, there is evidence that when dexamethasone is used within the first 1 or 2 weeks there may even be an increased rate of cerebral palsy, so one of the principal indications for steroid use is when a baby remains ventilator dependent at the age of 4 weeks or more. A wide variety of treatment regimens has been tested in trials and there is no standard approach; both the initial dose (usually between 50 and 250 μcg/kg) and the rate of reduction of dose are generally individualised to the baby. Side effects such as hypertension and glucose intolerance are common, although mostly reversible, but the effects on growth can be more serious if steroids are given for a long time.

BPD leads to increases in both pulmonary artery pressures and lung water content. The consequent strain on the heart can lead to heart failure, with excessive weight gain, increasing oxygen requirements and clinical signs such as oedema and a cardiac ‘gallop’ rhythm. The first-line treatment for heart failure, as in any age group, is with diuretics. Thiazides improve pulmonary mechanics as well as treating heart failure (Brion et al., 2002). Sometimes furosemide is used but its side effects are significant urinary loss of potassium and calcium, and renal calcification. An alternative is to combine a thiazide with spironolactone which causes less calcium and potassium loss. By reducing lung water content, diuretics can also improve lung compliance and reduce the work of breathing. However, BPD is not routinely treated with diuretics, since many babies do well without them. Systemic hypertension sometimes occurs among babies with BPD and may need treatment with antihypertensive drugs such as nifedipine.

For some babies with severe BPD, in whom echocardiography demonstrates pulmonary arterial pressures close to, or greater than, systemic pressure, many neonatologists try sildenafil, as there has been considerable experience using this drug off-label to prevent pulmonary hypertensive crises in babies after cardiac surgery. However, sildenafil has very variable pharmacokinetics in babies, so the dose is difficult to define, and the commonly recommended upper limit of 2 mg/kg four times a day may not be sufficient for some babies (Ahsman et al., 2010).

Significantly preterm babies still in oxygen at 36 weeks’ postmenstrual age are almost certain to need oxygen at home after discharge, and home oxygen programmes for ex-premature babies with BPD are now widespread. Most babies manage to wean off supplementary oxygen in a few months but a very few may need it for up to 2 years.

Infection

Important pathogens in the first 2 or 3 days after birth are group B β-haemolytic streptococci and a variety of Gram-negative organisms, especially Escherichia coli. Coagulase-negative staphylococci and Staphylococcus aureus are more important subsequently. In general, it is wise to use narrow-spectrum agents and short courses of antibiotics whenever possible, and to discontinue blind treatment quickly, for example, after 48 h if confirmatory evidence of bacterial infection, such as blood culture, is negative. The most serious neonatal infections are listed in Table 9.2.

Table 9.2 Serious neonatal infections and pathogens

Superficial candida infection is common in all babies, but systemic candida infection is a particular risk in very preterm babies receiving prolonged courses of broad-spectrum antibiotics, with central venous access, and receiving intravenous feeding. Increasingly, units are adopting policies of prophylaxis with either enteral nystatin or systemic fluconazole in the highest risk preterm babies.

It is usual to start antibiotics prophylactically whenever preterm labour is unexplained, where there has been prolonged rupture of the fetal membranes prior to delivery, and when a baby is ventilated from birth. A standard combination for such early treatment is penicillin G and an aminoglycoside, to cover group B streptococci and Gram-negative pathogens. Treatment can be stopped after 48 h if cultures prove negative. Blind treatment starting when a baby is more than 48 h old has to take account of the expected local pathogens, but will always include cover for S. aureus. Cephalosporins such as cefotaxime and ceftazidime have been heavily promoted for use in the blind treatment of neonatal infection on the grounds of their lower toxicity when compared to aminoglycosides, their wide therapeutic index and the absence of any need to monitor serum concentrations. Their main disadvantage is the breadth of their spectrum which may result in fungal overgrowth or the spread of resistance, although they compare favourably with ampicillin in this regard. Since courses of blind treatment are often only for 48 h, and the antibiotics can be stopped when cultures are negative, there is often no need to measure levels in babies receiving aminoglycosides, thereby negating much of the apparent advantage of cephalosporins. Moreover, there is now good evidence for giving gentamicin 24 hourly rather than more frequently, as it has similar efficacy and less potential for toxicity.

Methicillin-resistant S. aureus (MRSA) has emerged as a real problem in hospitals in recent years, but there is little evidence that neonatal units are a particularly hazardous environment.

The most important active viral infection in neonates is cytomegalovirus (CMV), and the most important one from which to protect babies in the UK is vertically transmitted human immuno-deficiency virus (HIV). For CMV, which is now thought to be a major factor in non-hereditary sensori-neural hearing loss, treatment is with intravenous ganciclovir and oral valganciclovir.

For HIV, the goal of management is to prevent ‘vertical’ transmission from mother to baby. The main strategy to combat this is to use aggressive maternal treatment throughout pregnancy to suppress the maternal viral load. Current practice is to give the baby zidovudine, as a single agent, for 4 weeks when the maternal viral load is low, or triple therapy if the load is high.

Necrotizing enterocolitis (NEC)

NEC is an important complication of neonatal intensive care, and can arise in any baby. However, it most commonly occurs in premature babies and those already ill. It is especially associated with being small for gestational age, birth asphyxia and the presence of a PDA. Since many sick babies have multiple problems, it has been difficult to disentangle causal associations from spurious links to conditions that occur anyway in ill infants, such as the need for blood transfusion. There is general agreement that the pathophysiology is related to damage of the gut mucosa, which may occur because of hypotension or hypoxia, coupled with the presence of certain organisms in the gastro-intestinal tract that invade the gut wall to give rise to the clinical condition. It almost never arises in a baby who has never been fed, whilst early ‘minimal’ feeding, and initiating feeding with human breast milk, appears to be protective. Probably the most important protection that can be given exogenously is enteral probiotics (AlFaleh & Bassler, 2008).

A baby who becomes ill with NEC is often septicaemic and may present acutely with a major collapse, respiratory failure and shock, or more slowly with abdominal distension, intolerance of feeds with discoloured gastric aspirates and blood in the stool. The medical treatment is respiratory and circulatory support if necessary, antibiotics, and switching to intravenous feeding for a period of time, usually 7–10 days. One of the most difficult surgical judgements is deciding if and when to operate to remove necrotic areas of gut or deal with a perforation.

The antibiotic strategy for NEC is to cover Gram-positive, Gram-negative and anaerobic bacteria. Metronidazole is used to cover anaerobes in the UK but clindamycin is preferred in some other countries. As with other drugs, metronidazole behaves very differently in neonates compared with older children and adults, having an elimination half-life of over 20 h in term babies. The elimination half-life is up to 109 h in preterm babies, partly due to poor hepatic hydroxylation in infants born before 35 weeks’ gestation. There is probably a case to be made for monitoring serum levels of this drug, but in practice this is seldom done.

Haemorrhagic disease of the newborn

Haemorrhagic disease of the newborn, better described as vitamin K-dependent bleeding, is very rare but it may cause death or disability if it presents with an intracranial bleed. Except in the case of malabsorption, it affects only breast-fed babies because they get very little vitamin K in maternal milk, and their gut bacteria do not synthesise it. Formula fed infants get sufficient vitamin K in their diet.

There are several possible strategies for giving vitamin K with a view to preventing haemorrhagic disease. An intramuscular injection of phytomenadione 1 mg (0.5 mL) can be given either to every newborn baby or selectively to babies who have certain risk factors such as instrumental delivery, preterm birth, etc. Vitamin K can be given orally, so long as an adequate number of doses is given, and this has been shown to be effective in preventing disease (Wariyar et al., 2000). Intramuscular injections are an invasive and unpleasant intervention for the baby since muscle bulk is small in the newborn, and particularly the preterm, and other structures such as the sciatic nerve can be damaged even if the intention is to give the injection into the lateral thigh. Intramuscular injections can be reserved for those babies with doubtful oral absorption, for example, all those admitted for special care, or at high risk because of enzyme-inducing maternal drugs such as anticonvulsants.

Apnoea

Apnoea is the absence of breathing. Babies (and adults) normally have respiratory pauses, but preterm babies in particular are prone to prolonged pauses in respiration of over 20 s which can be associated with significant falls in arterial oxygenation. Apnoea usually has both central and obstructive components, is often accompanied by bradycardia, and requires treatment to prevent life-threatening episodes of arterial desaturation.

Episodes of apnoea and bradycardia can be treated in three ways: intubating and mechanically ventilating the baby, giving nasal continuous positive airway pressure (nCPAP) or giving respiratory stimulants such as caffeine or doxapram. The main goal of medical treatment is to reduce the number and severity of the episodes without having to resort to artificial ventilation. Caffeine both reduces apnoea in the short term, and improves long-term outcome (Schmidt et al., 2006). Doxapram is occasionally given as an adjunct to both caffeine and nCPAP, to avoid resorting to mechanical ventilation. Most clinicians stop giving respiratory stimulants when the baby is around 34 weeks of postmenstrual age, by which time most babies will have achieved an adequate degree of cardiorespiratory stability and no longer need even the most basic forms of monitoring device.

Seizures

Seizures may arise as part of an encephalopathy, when they are accompanied by altered consciousness, or as isolated events when the baby is neurologically normal between seizure episodes. Investigations are directed to finding an underlying cause but in about half of all term babies having fits without an encephalopathy, no underlying cause can be found.

Just as with children and adults, treatment may be needed to control an acute seizure which does not terminate quickly, or given long term to prevent the occurrence of fits. In the neonate, the first-choice anticonvulsant for the acute treatment of seizures is phenobarbital because it is effective, seldom causes respiratory depression, and is active for many hours or days because of its long elimination half-life. Diazepam is sometimes used intravenously or rectally but it upsets temperature control, causes unpredictable respiratory depression, and is very sedating compared to phenobarbital. Paraldehyde is occasionally used because it is easy to give rectally, is relatively non-sedating and short acting. It is excreted by exhalation and the smell can make the working environment quite unpleasant for staff. Phenytoin is often used when fits remain uncontrolled after two loading doses of phenobarbital (total 40 mg/kg) but is not usually given long term because of its narrow therapeutic index. When seizures are intractable, options include clonazepam, midazolam or lidocaine; the last two are given as infusions. There is little experience with intravenous sodium valproate in the neonate. Longer term treatment is commonly with phenobarbital but after the first few postnatal months, carbamazepine or sodium valproate is more suitable.

Hypoxic–ischaemic encephalopathy (HIE), which usually results either from intrapartum asphyxia or from an antepartum insult such as placental abruption, is an important cause of seizures. Convulsions are a marker of a more severe insult; they usually occur within 24 h of birth and may last for several days, after which they spontaneously resolve. The less severely affected babies quickly return to neurological normality. No drug has been shown to improve outcome when given after the insult has occurred, but cooling a baby to between 33 and 34 °C for 72 h has been shown to improve the degree of neuro-disability among survivors and has rapidly become standard therapy (Edwards et al., 2010).

The therapeutic dilemma lies in the degree of aggression with which convulsions should be treated, since no conventional anticonvulsant is very effective in reducing electrocerebral seizure activity, even when the clinical manifestations of seizures are abolished, and as stated before, convulsions tend naturally to cease after a few days. However, seizures which compromise respiratory function need to be treated to prevent serious falls in arterial oxygen tension and possible secondary neurological damage. Also, babies with frequent or continuous seizure activity are difficult to nurse and cause great distress to their parents. Therefore, in practice it is usual to try to suppress the clinical manifestation of seizure activity, and phenobarbital remains the most commonly used first-line treatment. Where a decision is taken to keep a baby on anticonvulsant medication, therapeutic drug monitoring can provide helpful information and may need to be repeated from time to time during follow-up.

Rapid growth

Once the need for intensive care has passed, the growth of a premature baby can be very rapid indeed if the child is being fed with a high-calorie formula modified for use with preterm infants. Indeed, most babies born at 27 weeks, and weighing around 1 kg, can be expected to double their birth weight by the time they are 8 weeks old. Since the dose of all medications is calculated on the basis of body weight, constant review of dose is necessary to maintain efficacy, particularly for drugs that may be given for several weeks such as respiratory stimulants, diuretics and anticonvulsants. Conversely, all that is necessary to gradually wean a baby from a medication is to hold the dose constant so that the baby gradually ‘grows out’ of the drug. This practice is frequently used with diuretic medication in BPD, the need for which becomes less as the baby’s somatic growth reduces the proportion of damaged lung in favour of healthy tissue.

Therapeutic drug monitoring

The assay of serum concentrations of various drugs has a place in neonatal medicine, particularly where the therapeutic index of a drug is narrow. It is routine to assay levels of antibiotics such as aminoglycosides and vancomycin, of which the trough measurement is of most value since it is accumulation of the drug which must be avoided. More rarely, it may be necessary to assay minimal inhibitory or bactericidal concentrations of antibiotics in blood or cerebrospinal fluid if serious infections are being treated, but constraints on sampling limit the frequency with which this may be undertaken.

Where phenobarbital or other anticonvulsants are given long term, intermittent measurement of serum levels can be a useful guide to increasing the dose. All these drugs have a long half-life, so it is most important that drug concentrations are not measured too early, or too frequently, to prevent inappropriate changes in dose being made before a steady state is reached.

Avoiding harm

Intramuscular injections are considered potentially harmful because of the small muscle bulk of babies. However, it is not always easy to establish venous access and occasionally it may be necessary to use the intramuscular route instead. For vaccines the intramuscular route is unavoidable.

For sick preterm infants ventilated for respiratory failure, handling of any kind is a destabilising influence, so the minimal necessary intervention should be the rule. Merely opening the doors of an incubator can destabilise a fragile baby. It is, therefore, a good practice to minimise the frequency of drug administration and to try to coordinate the doses of different medications.

Time-scale of clinical changes

In babies, the time-scale for starting drug treatments is very short because the clinical condition of any baby can change with great rapidity. For example, where a surfactant is required it should be given as soon as possible after birth to premature babies who are intubated and ventilated. Similarly, infection can be rapidly progressive, so starting antibiotics is a priority when the index of suspicion is high or where congenital bacterial infection is likely. The same applies for antiretroviral drugs when a baby is born to a mother positive for HIV, especially if the maternal viral load is high.

For the sick preterm infant, this model applies to a wide range of interventions. It is seldom possible to wait a few hours for a given drug, and this has obvious implications for the level of support required by a neonatal service.

Early urgent immunisation with hepatitis B vaccine and the administration of anti-hepatitis B immunoglobulin are very important in preventing vertical transmission of hepatits B when the mother is e-antigen positive. Of less urgency, but considerable importance, is making sure that premature babies who are still on the neonatal unit 8 weeks after birth get their routine immunisations, since these should be given according to chronological age irrespective of prematurity.

Patient and parent care

It is all too easy to take a mechanistic approach to neonatal medicine, on the grounds that premature infants cannot communicate their needs. Such an approach to therapy is inappropriate. Even when receiving intensive care, any infant who is not either paralysed or very heavily sedated does in fact respond with a wealth of cues and non-verbal communication in relation to their needs. Monitors, therefore, do not replace clinical skills, but provide supplementary information and advance warning of problems. Even the most premature babies show individual characteristics, which emphasises that individualised care is as important in this age group as in any other. In particular, neonatal pain and distress have effects on nociception and behaviour well into the childhood years.

Involvement of parents in every aspect of care is a necessary goal in neonatal clinical practice, and care is increasingly regarded as a partnership between professionals and parents rather than the province of professionals alone. Routine administration of oral medication is thus an act in which parents may be expected to participate, and for those whose baby has to be discharged home still requiring continuous oxygen, the parent will rapidly obtain complete control, with support from the hospital and the primary health care team. The growing number of babies who survive very premature birth but whose respiratory state requires continued support after discharge presents an increasing therapeutic challenge for the future.