Much to HAPO FUS About: Increasing Maternal Glycemia in Pregnancy Is Associated With Worsening Childhood Glucose Metabolism.

Abstract

The initial purpose of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was to examine the associations of increasing degrees of untreated maternal glycemia, less severe than overt diabetes, with adverse pregnancy and neonatal outcomes and bring a unified approach to the diagnosis of gestational diabetes mellitus (GDM). The HAPO study (1) demonstrated linear increases in the risk of the primary outcomes of neonatal birth weight, cord C-peptide >90th percentile, neonatal hypoglycemia, and primary cesarean delivery with increasing maternal glycemia on a one-step 75-g 2-h oral glucose tolerance test (OGTT). The secondary outcomes including neonatal skinfold thicknesses >90th percentile, preterm delivery, preeclampsia, and shoulder dystocia had similar associations. In two long-term offspring follow-up studies published in this issue of Diabetes Care (2,3), risks of adverse outcomes related to this continuum of maternal glycemia in pregnancy are now demonstrated to persist into early adolescence. The long-term risk of maternal hyperglycemia to the offspring exposed in utero has been an ongoing concern for decades. In 1954, Pedersen (4) proposed that excessive glucose in mothers with diabetes is available for trans-placental passage, resulting in fetal hyperinsulinemia and excess fat accretion. In his Banting lecture, Norbert Freinkel (5) proposed the concept that fetal exposures to altered levels of maternal fuels, after organogenesis, may result in long-range adverse anatomical and metabolic changes in the offspring, which he called “fuel-mediated teratogenesis.” A related “fetal programming” hypothesis proposed by Barker and Osmond (6) holds that nutritional (and other environmental) exposures during critical developmental windows may induce changes in tissue development and function that contribute to long-term chronic disease risk. Based on studies in animal models and in …