Association of High-Density Lipoprotein Cholesterol, Apolipoprotein E and A1 Concentrations With Fetal Growth, Maturation, and Placental Insufficiency
Abstract Body: Introduction: Cholesterol is important for fetal growth and is in fetal life mainly carried by high density lipoprotein (HDL) cholesterol enriched with apolipoprotein E (apoE). The fetus is dependent on maternal/placental transport of cholesterol until de novo synthesis increases at 19 weeks of gestation. The association between HDL cholesterol concentrations and fetal growth, maturation, and placental insufficiency remains uncertain. Hypothesis: We hypothesized that HDL cholesterol, apoE, and apolipoproteinA1 (apoA1) concentrations are associated with fetal growth, maturation, and placental insufficiency. Methods: To examine this we used data from the Copenhagen Baby Heart and COMPARE studies including more than 12,600 umbilical cord blood samples and 360 corresponding venous samples at birth, with follow-up at 2 months. Results: HDL cholesterol concentrations correlated significantly with apoE and apoA1 at birth in both cord blood (Spearman’s correlation: 0.48 for apoE and 0.67 for apoA1, p-values <0.001) and venous blood (0.58 for apoE and 0.71 for apoA1, p-values<0.001) and at two months of age in venous blood (Spearman’s correlation: 0.18 for apoE (p=0.003) and 0.87 for apoA1(p<0.001)). From birth to two months of age venous blood concentrations of HDL cholesterol and apoA1 increased while apoE decreased (p<0.001). Gestational age adjusted HDL cholesterol and apoE concentrations in cord blood at birth were positively associated with birth weight (p<0.001), while apoA1 was only marginally significant (p=0.05). The clinical classification of intrauterine growth/maturation; small, appropriate, and large for gestational age, showed a significant, stepwise increase in cord blood for HDL cholesterol and apoE concentrations, but not for apoA1, from small to large for gestational age (p for trend <0.001). Multifactorially adjusted odds ratios (95% CI) for cord concentrations of HDL cholesterol, apoE, and apoA1 below the 20th percentile among newborns exposed to placental insufficiency was 1.39 (1.17-1.66) for HDL cholesterol, 1.47 (1.23-1.76) for apoE, and 1.19 (0.99-1.43) for apoA1. Conclusions: HDL cholesterol and apoE at birth are positively associated with intrauterine growth and maturation. Placental insufficiency increases risk of having low HDL cholesterol and apoE concentrations at birth, suggesting these lipid traits as markers of placental health.