Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial.

BACKGROUND: Variability in the FADS2 gene, which codifies the Delta-6 Desaturases and modulates the conversion of essential n-3 and n-6 fatty acids into long-chain polyunsaturated fatty acids, might modify the impact of prenatal supplementation with n-3 docosahexaenoic acid (DHA) on neurodevelopment. OBJECTIVE: To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years. DESIGN: We conducted a post-hoc interaction analysis of the POSGRAD randomized controlled trial (NCT00646360) of prenatal supplementation with algal-DHA where 1094 pregnant women originally randomized to 400 mg/day of preformed algal DHA or a placebo from gestation week 18-22 through delivery. In this analysis, we included offspring with information on maternal genotype and neurodevelopment at 5 years (DHA = 316; Control = 306) and used generalized linear models to assess interactions between FADS2 SNPs rs174602 or rs174575 and prenatal DHA on neurodevelopment at 5 years measured with McCarthy Scales of Children's Abilities (MSCA). RESULTS: Maternal and offspring characteristics were similar between groups. At baseline, mean (±standard deviation) maternal age was 26 ± 5 years and schooling was 12 ± 4 years. Forty-six percent (46%) of the children were female. Maternal minor allele frequencies were 0.37 and 0.33 for SNPs rs174602 and rs174575, respectively. There were significant variations by SNP rs174602 and intervention group (p for interactions <0.05) where children in the intervention group had higher MSCA scores on the quantitative (DHA: mean ± SEM = 22.6 ± 0.9 vs. Control = 19.1 ± 0.9, mean difference (Δ) = 3.45; p = 0.01) and memory (DHA = 27.9 ± 1.1 vs. Control = 23.7 ± 1.1, Δ = 4.26; p = 0.02) scales only among offspring of TT (minor allele homozygotes). CONCLUSIONS: Maternal FADS2 SNP rs174602 modified the effect of prenatal DHA on cognitive development at 5 years. Variations in the genetic make-up of target populations could be an important factor to consider for prenatal DHA supplementation interventions.

Prenatal exposure to environmental pollutants and child development trajectories through 7 years.

BACKGROUND: Prenatal exposure to environmental pollutants such as mold, lead, pesticides, tobacco, and air pollutants has been suggested to impair cognitive development. Evidence is needed from longitudinal studies to understand their joint impact on child development across time. OBJECTIVE: To study associations between exposure to indoor environmental pollutants or outdoor air pollution during pregnancy and offspring cognitive development trajectories through 7 years. METHODS: We included 718 Mexican mother-child pairs. Prenatal exposure to indoor environmental pollutants (mold, ventilation, pesticides, tobacco smoke, and use of vidiartred clay pots) was self-reported by the mothers and integrated into an index, or objectively measured in the case of outdoor air pollutants (nitrogen oxides, benzene, toluene, and xylene). Child global cognitive development was measured at 12, 18, 60, or 84 months. Using Latent Class Growth Analysis, we identified three developmental trajectories (positive = 108, average = 362, low = 248). We used multinomial logistic models to test associations between environmental pollutant score (EPS) or outdoor air pollutants, and cognitive development trajectories. RESULTS: After adjustment for sociodemographic covariates, EPS was associated with the average (OR = 1.26 95%CI = 1.01, 1.55) and low (OR = 1.41 95%CI = 1.11, 1.79) trajectories compared to positive; where a unit increase in EPS means an additional prenatal exposure to a pollutant. There was no association between outdoor air pollutants and cognitive development trajectories. CONCLUSION: Children of women who reported higher exposure to indoor environmental pollutants during pregnancy were more likely to follow worse developmental trajectories through 7 years. These results support the development and testing of interventions to reduce exposure to environmental pollutants during pregnancy and early childhood as a potential strategy to improve long-term cognitive development.