Pregnancy Insulin, Glucose, and BMI Contribute to Birth Outcomes in Nondiabetic Mothers

OBJECTIVE—We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes. RESEARCH DESIGN AND METHODS—Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months. RESULTS—In the retrospective study, within the nondiabetic range (2.1–7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean ± SEM) 2.1 ± 0.8% (P = 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 ± 0.8% (P < 0.0001) rise in emergency cesarean delivery, a 3.1 ± 0.7% (P < 0.0001) rise in elective cesarean delivery, and a 46 ± 8 g (P < 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight >90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per +1 mmol/l [95% CI 1.15–5.93]) and prepregnancy BMI (1.10 per +1 kg/m2 [1.04–1.18]). The mother's higher fasting glycemia (P = 0.004), lower insulin sensitivity (P = 0.01), and lower insulin secretion (P = 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P < 0.05). CONCLUSIONS—Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.