Treating hyperglycemia in early pregnancy: a randomized controlled trial

Abstract

Background: Treating women with gestational diabetes mellitus in the third trimester improves perinatal outcomes. It is unknown whether treating women with mild glucose intolerance earlier in pregnancy would be beneficial in the reduction of maternal and neonatal morbidities.

Objective: In women with hyperglycemia (hemoglobin A1c ≥5.7% and/or fasting glucose ≥92 mg/dL) in early pregnancy, we sought to determine whether immediate treatment improved maternal and neonatal outcomes.

Study design: This unblinded randomized controlled trial enrolled women with hyperglycemia at ≤15+0 weeks gestation between 2013 and 2015. Participants were assigned randomly to early pregnancy or third-trimester treatment of hyperglycemia that included nutrition counseling, glucose monitoring, and medications as needed. Participants underwent a blinded 2-hour glucose tolerance test at 24-28 weeks gestation. Exclusion criteria were pregestational diabetes mellitus and multiple gestations. The primary outcome was the proportion of infants with neonatal umbilical cord C-peptide >1.77 nmoL (90th percentile). Secondary outcomes were neonatal fat mass, infant World Health Organization weight-for-length percentile at birth, maternal gestational weight gain, and diagnosis of gestational diabetes mellitus on glucose tolerance test. Mann-Whitney-Wilcoxon test and Fisher's exact test were used, as appropriate.

Results: A total of 202 women were assigned randomly; 45 women dropped out before delivery, which left cases 157 for analysis (82 with early pregnancy and 75 with third-trimester treatment). The trial was terminated early because of low enrollment. Baseline characteristics were similar between groups. There was no difference in C-peptide >90th percentile between groups (1 [1.5%] vs 4 [6.7%]; P=.19) in the early pregnancy and third-trimester groups, respectively). There was also no difference in fat mass (0.37±0.16 vs 0.36±0.17 kg; P=.91), weight-for-length percentile at birth (25% vs 25%; P=.46), or macrosomia (1.5 vs 5.0%; P=.84). Maternal gestational weight gain was 22.6±12.9 lb and 23.9±11.2 lb in the early pregnancy and third-trimester groups, respectively (P=.88). Gestational diabetes mellitus was diagnosed in 19.0% of the cohort and did not differ between groups (14.2% vs 25.8%; P=.17).

Conclusion: In this population of women with hyperglycemia, treatment in early pregnancy did not appear to improve maternal or neonatal outcomes significantly. Given comparable results in both groups, caution should be used in the initiation of an intensive diabetes mellitus treatment protocol for women with the diagnosis of hyperglycemia in early gestation.

Keywords: diabetes mellitus; gestational diabetes mellitus; gestational weight gain; hemoglobin A1c; hyperglycemia; neonatal fat mass; prediabetes; umbilical cord C-peptide.