Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism

Abstract

Objective: This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.

Research design and methods: HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10-14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT.

Results: Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased.

Conclusions: Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes.

Figure 1

Child glucose levels across categories of maternal glucose levels. Mean levels of child fasting (A), 30-min (B), 1-h (C), and 2-h (D) glucose levels, sum of glucose z scores (E) and A1C (F) across categories of fasting, 1-h, and 2-h PG are shown. Glucose categories are defined as follows: fasting PG level—category 1, <4.2 mmol/L; category 2, 4.2–4.4 mmol/L; category 3, 4.5–4.7 mmol/L; category 4, 4.8–5.0 mmol/L; and category 5, ≥5.1 mmol/L; 1-h PG level—category 1, ≤5.8 mmol/L; category 2, 5.9–7.3 mmol/L; category 3, 7.4–8.6 mmol/L; category 4, 8.7–9.9 mmol/L; and category 5, ≥10.0 mmol/L; and 2-h PG level—category 1, ≤5.0 mmol/L; category 2, 5.1–6.0 mmol/L; category 3, 6.1–6.9 mmol/L; category 4, 7.0–8.4 mmol/L; and category 5, ≥8.5 mmol/L.

Figure 2

Child glucose outcomes across categories of maternal glucose levels. The frequency of childhood IFG (A) and IGT (B) and means of the Matsuda index (C), insulinogenic index (D), and disposition index (E) across categories of fasting, 1-h, and 2-h PG is shown. Glucose categories are defined as follows: fasting PG level—category 1, <4.2 mmol/L; category 2, 4.2–4.4 mmol/L; category 3, 4.5–4.7 mmol/L; category 4, 4.8–5.0 mmol/L; and category 5, 5.1 mmol/L or more; 1-h PG level—category 1, 5.8 mmol/L or less; category 2, 5.9–7.3 mmol/L; category 3, 7.4–8.6 mmol/L; category 4, 8.7–9.9 mmol/L; and category 5, ≥10.0 mmol/L; and 2-h PG level—category 1, ≤5.0 mmol/L; category 2, 5.1–6.0 mmol/L; category 3, 6.1–6.9 mmol/L; category 4, 7.0–8.4 mmol/L; and category 5, ≥8.5 mmol/L.

Figure 3

Estimated latent class trajectories of maternal glucose levels from the HAPO OGTT during pregnancy. Best fit trajectories included a quadratic term and adjustment for maternal BMI during pregnancy and estimated three latent classes: class A (87.8% [3,652 of 4,160]), class B (9.0% [376 of 4,160]), and class C (3.2% [132 of 4,160]). OR (95% CIs) for IGT, in addition to maternal pregnancy BMI already included in trajectory estimates, included adjustments for all other model 4 covariates.