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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.

Elevated lipoprotein (a) (Lp[a]) is associated with cardiovascular disease (CVD) and is mainly genetically determined. Studies suggest a role of dietary fatty acids (FAs) in the regulation of Lp(a), however, no studies have investigated the association between plasma Lp(a) concentration and omega-6 FAs. We aimed to investigate whether plasma Lp(a) concentration was associated with dietary omega-6 FA intake, and plasma levels of arachidonic acid in subjects with familial hypercholesterolemia (FH). We included FH subjects with (n=68) and without (n=77) elevated Lp(a) defined as ≥75 nmol/L, and healthy subjects (n=14). Total fatty acid profile was analyzed by Gas Chromatography-Flame Ionization Detector analysis, and the daily intake of macronutrients (including the sum of omega-6 FAs: 18:2n-6, 20:2n-6, 20:3n-6 and 20:4n-6) were computed from completed food frequency questionnaires. FH subjects with elevated Lp(a) had higher plasma levels of arachidonic acid (AA) compared to FH subjects without elevated Lp(a) (P=0.03). Furthermore, both FH subjects with and without elevated Lp(a) had higher plasma levels of AA compared to controls (P<0.001). The multivariable analyses showed associations between dietary omega-6 FA intake and plasma levels of AA (P=0.02), and between plasma levels of Lp(a) and AA (P=0.006). Our data suggest a novel link between plasma Lp(a) concentration, dietary omega-6 FAs and plasma AA concentration, which may contribute to explain the small diet-induced increase in Lp(a) levels associated with lifestyle changes. Although the increase may not be clinically relevant, this association may be mechanistically interesting in understanding more of the role and regulation of Lp(a).