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

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.

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.

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.