Seminars in neonatology : SN最新文献

The past decade has seen enormous progress in understanding the renal regulation of salt and water homeostasis. Most of the key transporters have been cloned, and their physiological importance has been revealed from studies of children with inherited diseases and from mutagenesis studies on a cellular level. We are beginning to understand the complexity with which the activity of these transporters is regulated by hormones. Studies on experimental animals have uniformly shown that the majority of renal salt and water transporters undergo profound changes in the postnatal period. There is generally a robust increase in the number of transporters expressed in a single tubular cell. Many of the transporters also shift their expression from one isoform to another with a somewhat different function. The short-term regulation of salt and water transporters, the key to a well-functioning homeostatic system, is often blunted in the early postnatal period. Taken together, these findings explain some phenomena well known in infants. The low urinary concentrating capacity can, for example, be at least partially attributed to immaturity of the expression of water channels, sodium losses in preterm infants to low expression of the energy generator for salt transport, Na⁺,K⁺-ATPase, and the disposition to acidosis to immaturity of the Na⁺/H⁺exchanger. We propose that further studies on how these transporters are regulated will lead to the improved prevention and treatment of salt water balance disorders in infants.

Substantial alterations take place in the quantity and distribution of body water compartments after birth. Clinical management must be tailored to the pace of postnatal adaptation, and the neonatal physician must be aware of these alterations in order to promote both normal physiological change and growth.

Advances in imaging have resulted in higher-quality resolution. Techniques formerly considered to give pure anatomic information are now providing functional data, but the functions provided are not those typically measured in pathophysiologic terms. Instead, the data provided demand that we incorporate this new information into the understanding of the pathologic processes that confront us in clinical practice. Ultrasound provides information about kidney volume, blood flow velocity and blood flow volume. Radioisotopes can show the ability of the proximal tubules to extract the tracer from the blood as well as the ability of the kidney to clear the tracer into the bladder. Magnetic resonance imaging provides information about water content of the kidney.

The fluid management of newborn babies can pose many problems. This article discusses the factors that affect fluid balance in the newborn infant, both term and preterm, and the special circumstances of the surgical neonate. The main determinants of management are: (1) an estimation of transepidermal water losses; (2) an awareness of glomerular filtration rate and how this is influenced by age, respiratory distress and medical intervention; and (3) knowledge of tubular function and its maturation and the processes of postnatal adaptation. This knowledge and appropriate monitoring are the mainstay of management of neonatal fluid balance.

Renal function in utero deals chiefly with urine production rather than the excretion of metabolites, which are cleared by the placenta. Fetal renal impairment (FRI) in bilateral renal disease thus presents as oligohydramnios or anhydramnios; this can lead to lung hypoplasia and early neonatal death. As in the adult, FRI can be divided into prerenal, renal and postrenal causes. Causes of prerenal FRI include intrauterine growth restriction, unbalanced intertwin transfusion in monochorionic twins and maternal drug ingestion. Bilateral renal agenesis, multicystic dysplasia and both the autosomal dominant and recessive forms of polycystic kidney disease are examples of renal causes, whereas postrenal etiologies are usually caused by lower urinary tract obstruction (LUTO). When both kidneys are affected and there is severe mid-trimester oligohydramnios, the prognosis is poor. Although animal studies have shown that prolonged LUTO leads to lung hypoplasia and renal damage, and that decompression of the fetal kidney in early pregnancy restores fetal pulmonary and renal function, the value of fetal therapy such as vesico-amniotic shunting remains controversial, with a high procedure-related complication rate and a high incidence of end-stage renal failure in childhood. Fetal cystoscopic treatment of posterior urethral valves in utero may obviate some of these difficulties but remains an investigational procedure.

Although volume expansion is liberally used in newborn intensive care, we know little about its effects on hemodynamics or outcomes. Given appropriately to a truly hypovolemic baby, it can be life-saving, but the clinical diagnosis of hypovolemia is probably very inaccurate. We know that volume expansion has less effect on blood pressure than dopamine, and although it seems to produce immediate increases in systemic blood flow, we do not know for how long these increases are sustained. There is evidence to show that the routine use of volume expansion in preterm babies has no effect on outcome, and there is little evidence to support its routine use during resuscitation or the treatment of metabolic acidosis. Whether crystalloids or colloids are preferable is also unclear in newborns. In situations of concern related to circulatory compromise, if possible, define the hemodynamics echocardiographically. Otherwise, if in doubt, some volume should be given, although it is probably unwise to keep expanding the volume if this is not improving physiologic (blood pressure and heart rate) or echocardiographic systemic blood flow parameters.

Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a significant mortality rate. Despite widespread prenatal diagnosis, few parameters have been well defined to aid in prediction of outcome of these infants. Antenatal maternal steroid administration and foetal surgery are not proven interventions. Postnatal treatment has changed over the last 10 years, with avoidance of hyperventilation and ventilator-induced lung injury resulting in improved survival. Therapies such as inhaled nitric oxide, exogenous surfactant administration and extracorporeal membrane oxygenation (ECMO) have undergone limited study, but show no clear benefit in this population. With improved outcome, principally due to avoidance of barotrauma, greater opportunity exists for long-term evaluation of survivors. To date, continuing problems with pulmonary function, nutrition and growth, effects of right ventricular hypertension and developmental issues have been identified. Through co-ordinated, multidisciplinary evaluation of CDH survivors, improved long-term outcome for these challenging patients can be attained.

Hyperinsulinism (HI) is the commonest cause of persistent or recurrent hypoglycaemia in childhood. HI is genetically and phenotypically diverse. Key management issues involve early diagnosis by insuring that appropriate investigations are undertaken at the point of hypoglycaemia, prevention of recurrent hypoglycaemia and clinical, biochemical and genetic characterisation of the HI syndrome. Children with persistent diazoxide resistant HI require investigation at specialist centres to differentiate those with a generalised disorder of the pancreas (diffuse HI; di-HI) from those with localised abnormalities within the pancreas (focal HI; fo-HI). Fo-HI may be managed by selective pancreatic resection of the focal abnormality. Di-HI is only managed by surgery if combination drug therapies are unable to prevent hypoglycaemia. Pancreatic β-cell dysfunction persists following subtotal pancreatectomy of di-HI.

In utero repair of open spina bifida or myelomeningocele (MMC) is now performed in selected patients and presents an additional alternative to obstetricians and neonatologists counselling expectant mothers carrying a foetus with MMC. Early foetal intervention may improve neurologic outcomes and reduce the hindbrain herniation associated with the Arnold-Chiari II malformation in open spina bifida. These changes may improve long-term neurologic function and limit requirements for shunt placements and other surgical interventions. Further research is needed to better understand the pathophysiology of MMC, the ideal timing and technique of repair, and the long-term impact of in utero intervention. A prospective, randomized clinical trial is planned comparing prenatal MMC repair with postnatal repair.