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More glucose crosses the placenta than any other substrate, but correlations between its concentration in maternal plasma and fetal growth are not found consistently. The accumulation of maternal fat depots and hyperlipidemia are the two principal changes in lipid metabolism during pregnancy. Although lipids cross the placenta with difficulty, maternal plasma triacylglycerols (TAG) and non-esterified fatty acids (NEFA) correlate with fetal lipids, fetal growth and fat mass under certain conditions. In intrauterine growth restriction, impaired placental transfer of lipophilic compounds (long-chain polyunsaturated fatty acids and lipophilic vitamins) seems to underpin metabolic dysfunction and decreased birth weight. In gestational diabetes mellitus (GDM), maternal TAG and NEFA levels correlate with neonatal anthropometric measures. In GDM, adipocyte fatty acid-binding protein in fetuses correlated with neonatal fat mass; changes in maternal or cord blood leptin, retinol binding protein 4 and adiponectin concentrations have been related to neonatal fat mass or birth weight, although their importance remains to be investigated. The angiopoietin-like protein 4 (ANGPTL-4) is secreted from adipose tissue, liver and placenta, and irreversibly inhibits lipoprotein lipase (LPL) activity. Maternal plasma ANGPTL-4 is decreased in GDM, and it has been proposed to be responsible for an increase in placental LPL activity, which would facilitate a greater fatty acid placental transfer, contributing to the higher fetal fat accumulation. Thus, while evidence suggesting major involvement of maternal lipid metabolism in fetal adiposity and growth exists, the precise mechanisms remain to be elucidated.

In normal pregnancies, in contrast to those with gestational diabetes, maternal lipids do not influence neonatal weight. Similar levels of maternal lipids in pregnancies with gestational diabetes and control pregnancies, but higher free fatty acids in the cord blood of those with gestational diabetes, indicate their enhanced placental transport and/or enhanced lipolysis as a result of decreased fetal insulin responsiveness.

OBJECTIVETo determine the concentrations of adipocyte fatty acid–binding protein (AFABP) and other adipocytokines in maternal and cord serum of pregnant women with gestational diabetes mellitus (GDM) and of control subjects and to relate them to indexes of insulin sensitivity.RESEARCH DESIGN AND METHODSIn 86 control and 98 GDM pregnant women, venous blood was collected before vaginal delivery and arterial blood from cord immediately after delivery. Serum insulin and adipocytokines were measured by enzyme-linked immunosorbent assay (ELISA).RESULTSGDM women had higher prepregnancy BMI, and data were adjusted for it. Maternal serum insulin, insulin-to-glucose ratio, homeostasis model assessment (HOMA), AFABP, and retinol-binding protein 4 (RBP4) were higher and adiponectin was lower in GDM than in control subjects, whereas serum glucose, insulin, insulin-to-glucose ratio, HOMA, nonesterified fatty acids, and RBP4 were higher and glycerol, AFABP, and adiponectin were lower in cord blood serum of GDM than of control subjects. AFABP and adiponectin in cord serum of control subjects were higher than in maternal serum; in GDM women no difference was found for AFABP in cord versus maternal serum, although adiponectin remained higher in cord. Values of leptin in both groups were lower in cord than in maternal serum, and those of RBP4 were lower in only GDM women.CONCLUSIONSIt is suggested that fetal tissues are the main source of cord arterial serum AFABP, and in GDM fetuses AFABP values correlate with adiposity markers. A downregulation of adiponectin and upregulation of RBP4 in GDM mothers and their fetuses may be related to their insulin-resistant condition, whereas changes in AFABP do not seem to be related.

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OBJECTIVE—Neonates of women with gestational diabetes mellitus (GDM) have reduced levels of arachidonic acid (AA) (20:4 n-6) and docosahexaenoic acid (DHA) (22:6 n-3). To assess whether this is the result of impaired placental transfer or endogenous fetal metabolism, fatty acids in umbilical venous and arterial plasma were analyzed in neonates of GDM women. RESEARCH DESIGN AND METHODS—Fatty acids were analyzed by gas chromatography in the plasma of 15 subjects with GDM and 30 healthy control subjects undergoing elective cesarean section and in vein and artery cord blood collected separately. RESULTS—The percentages of AA (20:4 n-6), DHA (22:6 n-3), and total n-6 or n-3 polyunsaturated fatty acids (PUFAs) as well as total PUFAs were lower in umbilical arterial but not in venous plasma of neonates of the GDM versus the control group. CONCLUSIONS—An altered handling or metabolism of long-chain PUFAs by the fetus rather than impaired placental transfer seems to be responsible for the lower proportion of those fatty acids in the plasma of neonates of GDM mothers.

In pregnant women without diabetes (control), maternal glycemia correlates with neonatal glycemia, neonatal body weight and fat mass. In pregnant women with gestational diabetes mellitus (GDM), maternal glucose correlates with neither neonatal glycemia, neonatal birth weight nor fat mass, but maternal triacylglycerols (TAG), non-esterified fatty acids (NEFA) and glycerol do correlate with birth weight and neonatal adiposity. The proportions of maternal plasma arachidonic (AA) and docosahexaenoic (DHA) acids decrease from the first to the third trimester of pregnancy, and at term these long-chain polyunsaturated fatty acids are higher in cord blood plasma than in mothers, indicating efficient placental transfer. In control or pregnant women with GDM at term, the maternal concentration of individual fatty acids does not correlate with neonatal body weight or fat mass, but cord blood fatty acid levels correlate with birth weight and neonatal adiposity-positively in controls, but negatively in GDM. The proportion of AA and DHA in umbilical artery plasma in GDM is lower than in controls but not in umbilical vein plasma. Therefore, an increased utilization of those two fatty acids by fetal tissues, rather than impaired placental transfer, is responsible for their smaller proportion in plasma of GDM newborns. In control pregnant women, maternal glycemia controls neonatal body weight and fat mass, whereas in mothers with GDM-even with good glycemic control-maternal lipids and their greater utilization by the fetus play a critical role in neonatal body weight and fat mass. We propose that altered lipid metabolism rather than hyperglycemia constitutes a risk for macrosomia in GDM.

In well-controlled GDM pregnancies, decreased maternal ANGPTL4 concentrations and a gradient of TAG toward the fetus are related with higher neonatal FM. However, in GDM fetuses with the highest FM, the potential effect of ANGPTL4 inhibiting adipose tissue LPL activity could be overcome by their hyperinsulinemia.