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Gonzalez Casanova, I.* ; Schoen, M.P.* ; Tandon, S.* ; Stein, A.D.* ; Barraza Villarreal, A.* ; DiGirolamo, A.M.* ; Demmelmair, H.* ; Ramirez Silva, I.* ; Feregrino, R.G.* ; Rzehak, P.* ; Stevenson, I.* ; Standl, M. ; Schnaas, L.* ; Romieu, I.* ; Koletzko, B.* ; Ramakrishnan, U.*

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.

Clin. Nutr. 40, 5339-5345 (2021)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Child Development ; Docosahexaenoic Acid ; Essential Fatty Acids ; Fatty Acid Desaturases ; Gene–nutrient Interactions ; Prenatal Supplementation; Fish-oil Supplementation; Prefrontal Cortex; Gene-cluster; Fatty; Metabolism; Omega-3; Growth; Fads1; Size
ISSN (print) / ISBN 0261-5614
e-ISSN 0261-5614
Journal Clinical Nutrition
Quellenangaben Volume: 40, Issue: 10, Pages: 5339-5345 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Journal Production Dept, Robert Stevenson House, 1-3 Baxters Place, Leith Walk, Edinburgh Eh1 3af, Midlothian, Scotland
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Grants LMU University Hospitals
March of Dimes
Nutricia Foundation
CONACYT Mexico
Thrasher Research Fund
National Heart, Blood and Lung Institute
European Research Council
European Joint Programming Initiative Projects NutriPROGRAM and EndObesity
German Ministry of Education and Research, Berlin
German Research Council
Else Kroner-Fresenius Foundation
NIH