Associations of Maternal Early-Pregnancy Glucose Concentrations With Placental Hemodynamics, Blood Pressure, and Gestational Hypertensive Disorders

Abstract

Background: Gestational diabetes mellitus is associated with increased risks of gestational hypertension and preeclampsia. We hypothesized that high maternal glucose concentrations in early pregnancy are associated with adverse placental adaptations and subsequently altered uteroplacental hemodynamics during pregnancy, predisposing to an increased risk of gestational hypertensive disorders.

Methods: In a population-based prospective cohort study from early pregnancy onwards, among 6,078 pregnant women, maternal early-pregnancy non-fasting glucose concentrations were measured. Mid and late pregnancy uterine and umbilical artery resistance indices were assessed by Doppler ultrasound. Maternal blood pressure was measured in early, mid, and late pregnancy and the occurrence of gestational hypertensive disorders was assessed using hospital registries.

Results: Maternal early-pregnancy glucose concentrations were not associated with mid or late pregnancy placental hemodynamic markers. A 1 mmol/l increase in maternal early-pregnancy glucose concentrations was associated with 0.71 mm Hg (95% confidence interval 0.22-1.22) and 0.48 mm Hg (95% confidence interval 0.10-0.86) higher systolic and diastolic blood pressure in early pregnancy, respectively, but not with blood pressure in later pregnancy. Also, maternal glucose concentrations were not associated with the risks of gestational hypertension or preeclampsia.

Conclusions: Maternal early-pregnancy non-fasting glucose concentrations within the normal range are associated with blood pressure in early pregnancy, but do not seem to affect placental hemodynamics and the risks of gestational hypertensive disorders.

Keywords: Doppler; blood pressure; cohort; gestational hypertensive disorders; glucose; hypertension; placenta; pregnancy.

Figure 1.

Flowchart population for analysis.

Figure 2.

Longitudinal associations between tertiles of early-pregnancy glucose concentrations and blood pressure (n = 6,078). Blood pressure patterns in different maternal early-pregnancy glucose tertiles. (a) Systolic and (b) diastolic blood pressure in different maternal early-pregnancy glucose tertiles (n = 6,078). Results reflect the change in mm Hg in mothers with early-pregnancy glucose concentrations in the second (4.0–4.6 mmol/l) and third (4.6–10.3 mmol/l) tertiles, compared with those with glucose levels in the first tertile (0.3–4.0 mmol/l). (a) Systolic blood pressure = β₀ + β₁ × glucose tertile + β₂ × gestational age + β₃ × gestational age⁻² + β₄ × glucose tertile × gestational age. (b) Diastolic blood pressure = β₀ + β₁ × glucose tertile + β₂ × gestational age + β₃ × gestational age^0.5 + β₄ × glucose tertile × gestational age. The models were adjusted for gestational age at intake. The interaction term of maternal early-pregnancy glucose tertile with gestational age in weeks was not significant. Similarly, when glucose was used continuously in the models, no significant interaction of maternal early-pregnancy glucose concentration with gestational age in weeks was observed. Estimates are given in Supplementary Table S5 online.