Metabolic adaptation at birth

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Summary

After birth, the neonate must make a transition from the assured continuous transplacental supply of glucose to a variable fat-based fuel economy. The normal infant born at term accomplishes this transition through a series of well-coordinated metabolic and hormonal adaptive changes. The patterns of adaptation in the preterm infant and the baby born after intrauterine growth restriction are, however, different to that of a full-term neonate, with the risk for former groups that there will be impaired counter-regulatory ketogenesis. There is much less precise linkage of neonatal insulin secretion to prevailing blood glucose concentrations. These patterns of metabolic adaptation are further influenced by feeding practices.

Introduction

Birth poses major metabolic challenges for the emerging neonate. With the severance of the umbilical cord, the assured continuous transplacental supply of glucose is abruptly disrupted, and the neonate must now switch on the endogenous production of glucose until exogenous nutritional intake becomes established. The neonate then has to adjust to alternating periods of feeding and fasting. These challenges are met through well-orchestrated metabolic and hormonal adaptive changes that ensure a continuing supply of energy fuels and constitute the neonatal metabolic adaptation. Although not as dramatic as adaptive changes in the cardiorespiratory system, this adaptation is equally complex and essential for survival in the extrauterine environment.

Section snippets

Fetal metabolism

Before birth, the fetus is entirely dependent on continuous transplacental nutrient transfer from the maternal circulation, and no significant production of glucose by the fetus has been demonstrated. Glucose crosses the placenta along a concentration gradient between maternal and fetal plasma, facilitated by specific placental glucose transporters. Measurements of circulating fuels in fetal blood samples obtained at midgestation (18–21 weeks) by fetoscopy and cordocentesis show that the fetal

Changes at birth

The cascade of events in successful adaptation to extrauterine life has unique characteristics in the biology of the human life cycle. In essence, these changes consist of an endocrine stress response, in which the roles of insulin and glucagon differ significantly from those in the adult, driving metabolic changes such as hepatic glycogenolysis, lipolysis, fatty acid β-oxidation with generation of ketone bodies, and proteolysis that generates lactate and other substrates for gluconeogenesis.

Metabolic fuels for the newborn infant

Endogenous glucose production has been estimated to be 4–5 mg kg/min in the first few hours after birth,7, 8 and is two- to three-fold greater per unit body weight in 1-day-old newborns than older subjects.9 There is a linear relationship between glucose production and estimated brain weight, with a particularly high cerebral glucose consumption in the neonate due to its greater brain mass (10–12% of total body weight).9 Although many other tissues (e.g. astrocytes) store glucose in the perinatal

Immediate postnatal changes

At birth, the blood glucose concentration in the umbilical venous blood is 80–90% of that in the maternal venous blood.19 Blood glucose concentration falls rapidly after birth, reaching a nadir by 1 h of age and then rising to stabilize by 3 h of age even in the absence of any exogenous nutritional intake (Fig. 1).19, 20 During this period, plasma insulin levels fall and there is a marked surge in plasma immunoreactive glucagon levels.21, 22 Mechanisms other than hypoglycaemia seem to be

Patterns of metabolic adaptation

The pattern of subsequent changes in the metabolic and hormonal milieu differs according to the gestational maturity, intrauterine growth characteristics and postnatal feeding practices. In contrast to the wealth of information available about the changes in blood glucose concentration immediately after birth, there is a paucity of data on the concentrations and interactions of metabolic substrates in subsequent neonatal metabolic adaptation. Such research is limited by ethical considerations

Conclusion

It is through an understanding of the physiology of metabolic adaptation that rational approaches to nutrition and the identification and management of hypoglycaemia can be developed. Yet there is still much unknown and unexplored: the physiology of human neonatal adaptation has too often been studied in the baby alone rather than as a component of the mother–infant dyad, and many of the mysteries of the properties of human breast milk in relation to adaptation remain unsolved.

Practice points

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