Mediators Linking Maternal Weight to Birthweight and Neonatal Fat Mass in Healthy Pregnancies

Abstract

Context Lifestyle interventions have not efficaciously reduced complications caused by maternal weight on fetal growth, requiring insight into explanatory mediators. Objective We hypothesized that maternal mediators, including adiponectin, leptin, insulin, and glucose, mediate effects of pregestational BMI (pBMI) and gestational weight gain (GWG) on birthweight and neonatal fat mass percentage (FM%) through placental weight and fetal mediators, including insulin levels ([I]fv) and venous-arterial glucose difference (Δ[G]fva). Hypothesized confounders were maternal age, gestational age, and parity. Design and setting A cross-sectional study of healthy mother-offspring-pairs (n=165) applying the 4-vessel in vivo sampling method at Oslo University Hospital, Norway. Methods We obtained pBMI, GWG, birthweight, and placental weight. FM% was available and calculated for a subcohort (n=84). We measured circulating levels of adiponectin, leptin, glucose, and insulin and performed path analysis and traditional mediation analyses based on linear regression models. Results The total effect of pBMI and GWG on newborn size was estimated to 30(16, 45)g birthweight and 0.17(0.04, 0.29)FM% per kg∙m -2 pBMI and 31(18, 44)g and 0.24(0.10, 0.37)FM% per kg GWG. The placental weight was the main mediator, mediating 25g birthweight and 0.11FM% per kg∙m -2 pBMI and 25g birthweight and 0.13FM% per kg GWG. The maternal mediators mediated a smaller part of the effect of pBMI (3.8g birthweight and 0.023FM% per kg∙m -2 pBMI) but not GWG. Conclusions Placental weight was the main mediator linking pBMI and GWG to birthweight and FM%. The effect of pBMI, but not GWG, on birthweight and FM%, was also mediated via the maternal and fetal mediators.

Maternal body mass index and placental weight: a role for fetal insulin, maternal insulin and leptin

“…Combined with the previously observed close association between maternal glucose and fetal insulin [12], these observations support the glucose steal hypothesis [63]. Fetal insulin is well recognized to promote fetal growth [12,22]. However, our observations support the hypothesis that fetal insulin may also promote placental growth [20,64].…”

“…The 4-vessel method study was a cross-sectional in vivo study of women scheduled for cesarean sections between 2012 and 2015. The current study included a subsample ( n = 165 of 179), previously described, including flow charts for the inclusion of participants [ 12 ].…”

“…The 4-vessel sampling method is a unique and specialized blood sampling method previously described and illustrated [ 12 ]. Briefly, blood samples were collected during a planned cesarean section procedure, and the women were in a fasting state (>8 h).…”

“…In a recent study [ 12 ], we found that PW mediates over 80% of the effect of pBMI and gestational weight gain (GWG) on birthweight after taking into account maternal glucose, insulin, leptin, and adiponectin, as well as fetal insulin and glucose uptake. Similarly, other previous studies have shown that adjustment for PW strongly reduces the estimated effect of maternal BMI on indicators of fetal growth [ 3 , 13 , 14 ].…”

“…Hence, the link between BMI and PW may include fetal factors. In previous publications, fetal insulin has been reported to be closely related to maternal glucose levels [ 12 , 22 , 23 ]. Furthermore, fetal insulin has been shown to stimulate villous endothelial proliferation, and thus promote placental growth [ 20 ].…”