Seminars in neonatology : SN最新文献

The concentration of thyroid hormone in preterm infants is lower than that in term infants. This phenomenon is referred to as transient hypothyroxinaemia of prematurity. Low thyroid hormone levels after very preterm birth are associated with worse developmental outcome in childhood, but only one randomized controlled trial has been carried out in the surfactant era to find out whether thyroid hormone supplementation is beneficial for developmental outcome. More studies are required to find out whether thyroid hormone supplementation is beneficial, and if so, for which preterm group.

The measurement of thyrotropin or thyroxine from dried blood spots collected from neonates allows diagnosis before clinical manifestations develop, and prevents mental deficiency from congenital hypothyroidism. However, severely hypothyroid newborns remain at risk of cognitive problems that may be avoided if they are treated within two weeks of birth, hence the importance of a quick turnaround time of the screening programme. This also applies to screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency based on the measurement of 17-hydroxy-progesterone from dried blood; this was primarily designed to prevent neonatal deaths from acute adrenal insufficiency. This goal can be achieved by a high degree of clinical awareness of the diagnosis, but this has only been reported in a few jurisdictions. Furthermore, biochemical screening allows earlier treatment. On the other hand, there are many false positives, mostly in premature infants, so screening for 21-hydroxylase deficiency has not been universally adopted.

Diagnosis of glucose status requires knowledge of the homeostatic mechanisms that maintain the blood glucose concentration between the narrow range of 2.5 and 7.5 mmol/l during periods of eating or fasting. Hypoglycaemia occurring within the first few hours after eating is suggestive of hyperinsulinism. Most glucose is subsequently converted into glycogen in the liver, and hypoglycaemia occurring during this phase is suggestive of glycogenosis. During fasting, gluconeogenesis progressively replaces glycogen as the major source of blood glucose, and hypoglycaemia occurring during this period is suggestive of impaired gluconeogenesis or fatty acid disorders. Growth hormone, glucagon, cortisol and insulin-like growth factor 1 deficiencies may also play a role. Other causes of hypoglycaemia have also been identified recently, namely glucose transporter disorders, respiratory chain disorders and congenital disorders of glycosylation.

This article reviews the evidence for fetal and early origins of type 2 diabetes, insulin resistance, dyslipidaemia and obesity. Particular emphasis is given to the role of adipose tissue in catch-up growth and long-term metabolic complications following restricted fetal growth. To date, several pathways have been proposed to explain the development of insulin resistance following restricted fetal growth, but no precise mechanisms have been demonstrated. It appears that early postnatal growth may also be a critical step.

Disturbances in mineral homeostasis are common in the neonatal period, especially in premature infants and infants who are hospitalised in an intensive care unit. In many cases these disturbances are thought to be exaggerated responses to the normal physiological transition from the intrauterine environment to neonatal independence. By contrast, some disturbances in calcium homeostasis are the result of genetic defects, which in many instances can now be identified at the molecular level. In other cases hypocalcaemia or hypercalcaemia may result from pathological intrauterine conditions, birth trauma or stress, or fetal immaturity. Diagnosis and management of hypocalcaemia and hypercalcaemia in the neonate and infant requires specific knowledge of perinatal mineral physiology and the unique clinical and biochemical features of newborn mineral metabolism. In this chapter we will provide a brief overview of calcium metabolism with an emphasis on the neonatal transition, followed by discussion of the common causes of hypercalcaemia and hypocalcaemia.

Transient (TNDM) and permanent neonatal diabetes mellitus (PNDM) are rare conditions occurring in one in 400 000–500 000 live births. In TNDM, growth-retarded infants develop diabetes in the first few weeks of life only to go into remission in a few months with later relapse as permanent type 2 diabetes, often around the time of adolescence. We believe that pancreatic dysfunction in this condition is maintained throughout life with relapse initiated at times of metabolic stress such as puberty or pregnancy. The mechanisms involved in this rare condition may inform on fetal pancreatic development, islet cell physiology and predisposition to type 2 diabetes. In PNDM, insulin secretory failure occurs in the early postnatal period. A number of conditions are associated with PNDM, some of which have been elucidated at the molecular level. Insulin therapy is difficult to manage in the neonatal period, and in experienced hands, the insulin pump may provide a valuable tool to administer insulin.

While the fetus is completely dependent on his/her mother for glucose and other nutrient transfer across the placenta, the adult is completely independent, especially one who is neither pregnant nor diabetic. The neonate is considered to be in a transition between the complete dependence of the fetus and the complete independence of the adult. The heterogeneity that is the hallmark of neonatal glucose metabolism is illustrated by the observation that maintenance of euglycaemia in the sick and/or low-birthweight neonate is especially difficult. This reinforces the concept that the neonate is vulnerable to carbohydrate disequilibrium. In this discussion, we shall first evaluate the definition of euglycaemia by considering the ranges for hypo- and hyperglycaemia. We shall also review the considerable literature that has been published on measurement of the rate of glucose production and the rate of glucose utilization in the neonate. This review highlights where further work is necessary to understand the developing maturation (i.e. control) of glucose homeostasis in the neonate.

Under normal circumstances, the fetus is exposed to very low concentrations of cortisol until late in gestation. Perturbations of the intra-uterine environment resulting in fetal exposure to increased cortisol may have consequences not only in infancy, but also into adult life. In the postnatal period, developmental immaturity and/or the effects of critical illness on adrenal function may result in insufficient cortisol production to maintain homeostasis in the face of acute stress or illness, a situation that has been labelled ‘relative adrenal insufficiency’ in other acutely ill populations. The definition of inadequate adrenal function in the newborn and its possible relationship to adverse outcomes in both premature and term infants are only beginning to be characterized.