Abstract 201: Maternal HDL-Cholesterol Levels in Women From the Gambia are Directly Related to Infant Birthweight

Abstract

Babies born with low birthweight are often at a health disadvantage. Previous studies have shown direct relationships between maternal plasma cholesterol and infant birthweight in resource-rich countries. As plasma cholesterol levels are often decreased in resource-poor countries, the purpose of these studies was to evaluate the relationship between plasma cholesterol and birthweight in women enrolled in the ENID trial (ISRCTN49285450) in rural Gambia, West Africa. Plasma was obtained at enrolment (13.6±3.3 wk) and at 20 and 30 weeks of gestation; samples were obtained from women with term infants that weighed <2.75 kg or >3.25 kg at birth. Women with lower HDL-cholesterol (HDL-C) concentrations in mid-pregnancy had lower birthweight infants compared to women with higher HDL-C concentrations. There was no significant association between LDL-C or total cholesterol concentrations and birthweight. The relationship with HDL-C and birthweight was maintained when maternal BMI was included in the model. To begin to elucidate the processes involved in the regulation of fetal growth, placental function was examined in mice with increasing maternal HDL-C concentrations based on apoA-I levels; mice were lacking apoA-I (apoA-I -/- ), were wildtype (apoA-I +/+ ), or had excess apoA-I (apoA-I tg/tg ). HDL decreased in size as plasma apoA-I levels increased, and there were no statistical differences in the proteins carried by HDL, except for apoA-I, in pregnant mice of different genotypes. However, pregnancy alone led to changes in the HDL proteome. Importantly, fetuses of mice with lower concentrations of maternal HDL-C had reduced growth rates, not due to a lack of fetal apoA-I. The murine fetal growth rates were directly related to nutrient uptake by and transport across the placenta. This work suggests that maternal HDL affects placental function leading to enhanced nutrient supply and improved growth in utero, making HDL a potential biomarker for fetal growth and putative target for intervention.