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.

Maternal Pre-pregnancy Body Mass Index Categories and Infant Birth Outcomes: A Population-Based Study of 9 Million Mother–Infant Pairs

“…Maternal prepregnancy BMI categories at both upper and lower extremes may affect infant adverse birth outcomes in several ways. First, prepregnancy overweight and obesity usually cause metabolic abnormalities during pregnancy [such as gestational hypertension and diabetes (6, 7)] which may lead to placental abnormalities (27)(28)(29)(30)(31), and ultimately affect adverse birth outcomes. Second, excessive or poor maternal periconceptional weight status may increase the risk of abnormal growth and development of the offspring through epigenetic imprinting or methylation (32)(33)(34).…”

Diabetic Uterine Environment Leads to Disorders in Metabolism of Offspring

“…At the crucial period of epigenetic reprogramming, adverse uterine environment may influence the establishment and maintenance of methylation in mice. For example, Martino et al reported that placental mRNA abundance for the folate receptor alpha (FOLR1) and DNA methyltransferases (DNMT1) were influenced with raised BMI ( Martino et al, 2018 ). Although the mechanisms remain to be clarified, the alterations of the methylation patterns and expressions of the imprinted genes in mid-gestational placental tissues ( Ge et al, 2013a ) may influence the postnatal metabolism of offspring ( Crespi, 2019 ).…”

Maternal obesity during pregnancy leads to derangements in one-carbon metabolism and the gut microbiota: implications for fetal development and offspring wellbeing

“…In particular, low levels of vitamin B12 and folate are associated with high BMI [40][41][42] and it is known that, despite regular folic acid supplement use, obese women retain low fasting serum folate levels and have a lower folate absorption phase compared to normal-weight women [19,43]. These observations are also seen in early, mid and late pregnancy, where obese women tend to have lower serum vitamin B12 and folate concentrations, and higher odds of vitamin B12 and folate deficiency compared to non-obese pregnant women [40,[44][45][46][47][48][49][50][51][52]. In fact, offspring of obese women have a two-fold higher risk of being born with NTDs despite maternal folic-acid supplement use [53].…”