Perinatal Energy Substrate Metabolism : Glucose Production and Lipolysis in Pregnant Women and Newborn Infants with Particular Reference to Intrauterine Growth Restriction (IUGR)

Glucose is the most important fetal nutrient and the production of this substrate increases in the pregnant woman. In the last trimester the increased insulin resistance directs energy substrates to the fetus. Fetal growth is sometimes disturbed, often without an obvious explanation. After birth the newborn infant must produce its own glucose, primarily for the brain. Fatty acids from lipolysis are also important energy substrates. Hypoglycaemia can be a problem, occurring frequently in preterm infants and infants born small for gestational age (SGA). In addition, SGA infants are at risk of developing the metabolic syndrome in adulthood. Neonatal medication can influence energy metabolism. One such medication is theophylline, administered in preterm infants to prevent apnoea. We investigated energy substrate production in women with normal and IUGR pregnancies, in preterm neonates, before and after theophylline treatment and in newborn SGA infants, using stable isotope-labelled compounds and gas chromatography-mass spectrometry. We found that late pregnancy was associated with an almost twofold increase in the rate of lipolysis. This provides substrates for maternal energy metabolism, which may spare glucose for the fetus. Even though glucose production was comparable in the two groups of pregnant women, those with IUGR had a lower rate of lipolysis. A reduced supply of energy substrates could be one factor underlying IUGR. In spite of the insulin resistance of late pregnancy, insulin still had a regulatory role in energy substrate production in the women with normal pregnancies, but not in those with IUGR. Although infants born preterm and/or SGA have limited energy stores, we demonstrated that they are capable of both lipolysis and glucose production. Theophylline had no adverse effects on energy substrate production. Data on insulin and IGFBP-1 in the SGA infants indicate that in such infants insulin sensitivity is increased peripherally but reduced in the liver