The Impact of Maternal Pre-Pregnancy Body Weight and Gestational Diabetes on Markers of Folate Metabolism in the Placenta

Abstract

Dietary methyl donors, including folate, may modify the placenta and size at birth but the influence of maternal body weight has not been widely investigated. We therefore examined whether maternal or fetal folate status, together with indices of placental folate transport, were modulated by either maternal pre-pregnancy body mass index (BMI i.e., overweight: 25 ≤ BMI < 30 or obesity: BMI ≥ 30 kg/m²) and/or gestational diabetes mellitus (GD). We utilised a sub-sample of 135 pregnant women participating in the Spanish PREOBE survey for our analysis (i.e., 59 healthy normal weight, 29 overweight, 22 obese and 25 GD). They were blood sampled at 34 weeks gestation, and, at delivery, when a placental sample was taken together with maternal and cord blood. Placental gene expression of folate transporters and DNA methyltransferases (DNMT) were all measured. Folate plasma concentrations were determined with an electro-chemiluminescence immunoassay. Food diaries indicated that folate intake was unaffected by BMI or GD and, although all women maintained normal folate concentrations (i.e., 5⁻16 ng/mL), higher BMIs were associated with reduced maternal folate concentrations at delivery. Umbilical cord folate was not different, reflecting an increased concentration gradient between the mother and her fetus. Placental mRNA abundance for the folate receptor alpha (FOLR1) was reduced with obesity, whilst DNMT1 was increased with raised BMI, responses that were unaffected by GD. Multi-regression analysis to determine the best predictors for placental FOLR1 indicated that pre-gestational BMI had the greatest influence. In conclusion, the placenta's capacity to maintain fetal folate supply was not compromised by either obesity or GD.

Keywords: body mass index; folic acid; gestational diabetes; placenta.

Figure 1

Effects of maternal pre-pregnancy BMI and gestational diabetes on maternal and neonatal folate serum concentrations. Maternal samples were taken at 34 weeks gestation and at term/delivery i.e., c. 39 weeks of pregnancy, neonatal samples were taken from cord blood at birth. Open circles: normal weight (N: maternal, n = 59; cord, n = 33); open squares: overweight (OW: maternal, n = 29; cord, n = 15); open triangles: obese (O: maternal, n = 22; cord, n = 12); closed circles: gestational diabetic, normal weight (GDN: maternal, n = 14; cord, n = 7); closed triangles: gestational diabetic, obese women (GDO: maternal, n = 11; cord, n = 7). Values represent means ± S.E.M. Statistical differences between groups denoted at each time point by *, ** correspond to p < 0.05, p < 0.01 respectively compared to normal weight control group (independent t test for continuous variables).