Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study

Abstract

Background Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99). Conclusions Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

Overweight or obesity in children born after assisted reproductive technologies in Denmark: A population-based cohort study

“…Additionally, we compared each type of embryo transfer to OI/IUI. We identified the following potential confounders from the literature: parental causes of infertility [34], maternal and paternal age at conception (restricted cubic splines with 3 knots) [35], maternal and paternal highest educational level at conception [36], maternal country of origin [37], maternal BMI (restricted cubic splines with 3 knots) [38], maternal smoking status [39], maternal and paternal hyperlipidemia or use of lipid-modifying drugs [40], maternal and paternal hypertension or use of antihypertensive drugs [41], presence/absence of diabetes (I or II) [42], parity [43], and year of conception [44]. To adjust for confounding, we used stabilized inverse probability of treatment weighting (IPTW) including the following steps [45]: For each child and each comparison, we used the listed potential confounders to compute a propensity score (i.e., the predicted probability of being exposed) using a logistic regression model and then graphically displayed the distribution of propensity scores across the various exposure and comparison cohorts (S1 Fig) . We then used the propensity score to reweight the population by stabilized IPTW and truncated the extreme weights (the 1st and 99th percentiles) [45].…”

Association between maternal serum lipid profiles in early pregnancy and the risk of congenital heart disease in offspring: a prospective cohort study

“…Apo A and Apo B play important roles in lipid metabolism, cholesterol transport, absorption, and metabolism. Several studies have shown the relationship between Apo A and Apo B levels during pregnancy and pregnancy outcomes 30. 32 Smedts et al and Cao L et al both found that maternal Apo B levels in early pregnancy were the best predictor of CHD in offspring, but this relationship weakened after adjusting for confounding factors in Cao L et al's study.…”

Plasma cholesterol levels in infancy: a neglected resource

“…Data from the Norwegian Mother, Father and Child Cohort Study showed that maternal pre-natal cholesterol levels also predicted offspring weight trajectories during childhood. 15 …”