Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

TLDR

The study examined how maternal glucose levels and cord serum C‑peptide relate to neonatal adiposity, testing the Pedersen hypothesis that maternal hyperglycemia drives fetal hyperinsulinemia and increased fat deposition. In a multinational cohort of 23,316 pregnant women, a 75‑g oral glucose tolerance test was performed at 24–32 weeks, and neonatal skin‑folds and cord C‑peptide were measured and analyzed with multivariable logistic regression adjusting for confounders. Higher maternal glucose and cord C‑peptide were strongly associated with increased neonatal adiposity, with odds ratios of 1.35–1.44 per standard‑deviation rise, confirming the Pedersen hypothesis.

Abstract

To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity.Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex.Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD.These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth.