Abstract
Aims/hypothesisThe 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.MethodsIn 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.ResultsHigher 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/interpretationHigher 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.
Highlights
Gestational diabetes mellitus (GDM) complicates up to 17% of pregnancies and is a major risk factor for maternal and fetal perinatal complications [1,2,3]
As maternal glucose levels before the diagnosis of GDM were not known in these studies, these findings are difficult to interpret in the context of the present study results
We observed that among non-diabetic women, higher maternal early-pregnancy non-fasting glucose levels across the full range were associated with decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards resulting in larger size at birth
Summary
Gestational diabetes mellitus (GDM) complicates up to 17% of pregnancies and is a major risk factor for maternal and fetal perinatal complications [1,2,3]. Recent studies suggest that these associations are present for higher maternal glucose levels below the threshold of GDM [4,5,6]. A meta-analysis of 25 prospective studies showed that higher maternal glucose levels in mid-pregnancy and late pregnancy are related to increased risks of perinatal complications [7]. About the direct effects of an impaired maternal glucose metabolism from early pregnancy onwards on fetal growth and the risks of adverse birth outcomes in both diabetic and non-diabetic pregnant women [3]. We hypothesised that a maternal glucose metabolism already impaired in early pregnancy affects embryonic and placental development, subsequently leading to altered fetal growth and increased risks of adverse birth outcomes [2, 3, 12, 13]. Insight into the influence of maternal blood glucose levels from early pregnancy onwards on fetal development is important, as maternal blood glucose levels offer a major target for potential future interventions
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