High maternal early-pregnancy blood glucose levels are associated with altered fetal growth and increased risk of adverse birth outcomes

Abstract

Aims/hypothesis: The study aimed to assess the associations of maternal early-pregnancy blood glucose levels with fetal growth throughout pregnancy and the risks of adverse birth outcomes.

Methods: In a population-based prospective cohort study among 6116 pregnant women, maternal non-fasting glucose levels were measured in blood plasma at a median 13.2 weeks of gestation (95% range 9.6-17.6). We measured fetal growth by ultrasound in each pregnancy period. We obtained information about birth outcomes from medical records and maternal sociodemographic and lifestyle factors from questionnaires.

Results: Higher maternal early-pregnancy non-fasting glucose levels were associated with altered fetal growth patterns, characterised by decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, resulting in an increased length and weight at birth (p ≤0.05 for all). A weaker association of maternal early-pregnancy non-fasting glucose levels with fetal head circumference growth rates was present. Higher maternal early-pregnancy non-fasting glucose levels were also associated with an increased risk of delivering a large-for-gestational-age infant, but decreased risk of delivering a small-for-gestational-age infant (OR 1.28 [95% CI 1.16, 1.41], OR 0.88 [95% CI 0.79, 0.98] per mmol/l increase in maternal early-pregnancy non-fasting glucose levels, respectively). These associations were not explained by maternal sociodemographic factors, lifestyle factors or BMI. Maternal early-pregnancy non-fasting glucose levels were not associated with preterm birth or delivery complications.

Conclusions/interpretation: Higher maternal early-pregnancy non-fasting glucose levels are associated with decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, and an increased risk of delivering a large-for-gestational-age infant. Future preventive strategies need to focus on screening for an impaired maternal glucose metabolism from preconception and early pregnancy onwards to improve birth outcomes.

Keywords: Adverse birth outcomes; Fetal growth; Gestational diabetes mellitus; Maternal glucose; Maternal hyperglycaemia; Prospective cohort.

Fig. 1

Study participant flow chart

Fig. 2

Differences in fetal growth rates per change in glucose levels. Data are SDS values (95% CI) from repeated measurement regression models that reflect the differences in gestational age-adjusted growth rates in SDS of head circumference (circles), length (triangles) and weight (squares) at mid-pregnancy, late pregnancy and at birth per 1 mmol/l change in maternal early-pregnancy glucose levels. As a measure of skeletal length growth from mid-pregnancy onwards, we used fetal femur length SDS in mid-pregnancy and late pregnancy and total body length SDS at birth within the repeated measurements model. All fetal biometry measurements for each pregnancy period were taken at the same time point. The models were adjusted for gestational age at intake. p <0.05 for interaction with gestational age for all models

Fig. 3

Associations of maternal early-pregnancy glucose levels in mmol/l with fetal biometry measurements (N = 6116). Data are SDS values (95% CI) from linear regression models that reflect the differences in growth characteristics in SDSs in (a) early pregnancy, (b) mid-pregnancy, (c) late pregnancy and (d) at birth, per 1 mmol/l change in maternal early-pregnancy glucose levels. Analyses with crown–rump length were based on subgroup analyses (n = 1470). Estimates are from multiple imputed data. Squares show basic model: adjusted for gestational age at assessment. Circles show maternal pregnancy-related factors model: basic model additionally adjusted for maternal ethnicity, age, parity, educational level, daily total energy intake, smoking, alcohol consumption and folic acid supplement use. Triangles show BMI model: maternal pregnancy-related factors model additionally adjusted for maternal pre-pregnancy BMI