Association of HDL cholesterol, apolipoprotein AI, and E concentrations with foetal growth and placental insufficiency.

AIMS: Foetal cholesterol is primarily carried by high-density lipoprotein (HDL) enriched with apolipoprotein E (apoE) and the foetus depends on a maternal-placental supply in early gestation until foetal de novo synthesis is established. We aimed to examine HDL cholesterol (HDL-C), apoE, and apolipoprotein AI (apoAI) concentrations in early life and the association with foetal growth and placental insufficiency.

METHODS AND RESULTS: We used data from the Copenhagen Baby Heart and COMPARE study cohorts, including cord- (n = 13 353) and parallel child and maternal venous blood samples at birth (n = 444), 2- (n = 364), and 14-16 months (n = 156) after birth. HDL-C, apoAI, and apoE concentrations were higher in female vs. male newborns (P < 0.001). During the first 14-16 months of life, concentrations of HDL-C and apoAI increased (P < 0.02), apoE decreased (P < 0.001), and the HDL-C-apoAI correlation increased (Spearman's rho: 0.71, 0.87, 0.90), while the HDL-C-apoE correlation decreased (Spearman's rho: 0.58, 0.18). Small (SGA), appropriate (AGA), and large (LGA) for gestational age showed a stepwise increase in cord blood concentrations of HDL-C and apoE, but not apoA1, from SGA to LGA (P < 0.001). We found higher risk of low cord blood concentrations (<20th percentile) of HDL-C and apoE associated with placental insufficiency [odds ratio 1.39 (95% confidence interval 1.16-1.65) and 1.46 (1.22-1.75)], low pregnancy-associated plasma protein A (PAPP-A) [1.82 (1.47-2.25) and 1.50 (1.19-1.88)), preeclampsia (1.62 (1.28-2.04) and 1.39 (1.09-1.78)], hypertension (1.35 (1.05-1.73) and 1.28 (0.99-1.67)), body mass index (BMI) ≥ 25 kg/m2 [1.29 (1.17-1.43) and 1.13 (1.02-1.25)], and smoking [1.79 (1.43-2.23) and 1.38 (1.09-1.76)]. Only placental insufficiency [1.23 (1.03-1.48)], low PAPP-A [1.48 (1.18-1.85)], and smoking[(1.35 (1.06-1.72)] were associated with low cord blood apoAI.

CONCLUSION: During the first 14-16 months of life, the apolipoprotein profile of HDL approaches that of adults. Offspring concentrations of HDL-C and apoE at birth were positively associated with foetal growth and placental insufficiency was associated with increased risk of low HDL-C and apoE, suggesting these traits as markers of placental function.