Bernard JY, Pan H, Aris IM, Moreno-Betancur M, Soh SE, Yap F, Tan KH, Shek LP, Chong YS, Gluckman PD, Calder PC, Godfrey KM, Chong MF, Kramer MS, Karnani N, Lee YS. “Long-chain polyunsaturated fatty acids, gestation duration, and birth size: a Mendelian randomization study using fatty acid desaturase variants”. Am J Clin Nutr. 2018 Jul 1;108(1):92-100. doi: 10.1093/ajcn/nqy079.
In randomized trials, supplementation of n-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy has resulted in increased size at birth, which is attributable to longer gestation.
We examined this finding by using a Mendelian randomization approach utilizing fatty acid desaturase (FADS) gene variants affecting LC-PUFA metabolism.
As part of a tri-ethnic mother-offspring cohort in Singapore, 35 genetic variants in FADS1, FADS2, and FADS3 were genotyped in 898 mothers and 1103 offspring. Maternal plasma n-3 and n-6 PUFA concentrations at 26-28 wk of gestation were measured. Gestation duration was derived from an ultrasound dating scan in early pregnancy and from birth date. Birth length and weight were measured. Eight FADS variants were selected through a tagging-SNP approach and examined in association with PUFA concentrations, gestation duration among spontaneous labors, and birth size with the use of ethnicity-adjusted linear regressions and survival models that accounted for the competing risks of induced labor and prelabor cesarean delivery.
Maternal FADS1 variant rs174546, tagging for 8 other variants located on FADS1 and FADS2, was strongly related to plasma n-6 but not n-3 LC-PUFA concentrations. Offspring and maternal FADS3 variants were associated with gestation duration among women who had spontaneous labor: each copy of rs174450 minor allele C was associated with a shorter gestation by 2.2 d (95% CI: 0.9, 3.4 d) and 1.9 d (0.7, 3.0 d) for maternal and offspring variants, respectively. In survival models, rs174450 minor allele homozygotes had reduced time to delivery after spontaneous labor compared with major allele homozygotes [HR (95% CI): 1.51 (1.18, 1.95) and 1.51 (1.20, 1.89) for mothers and offspring, respectively].
With the use of a Mendelian randomization approach, we observed associations between FADS variants and gestation duration. This suggests a potential role of LC-PUFAs in gestation duration. This trial was registered at http://www.clinicaltrials.gov as NCT01174875.
Supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC/TCR/004-NUS/2008, NMRC/TCR/012-NUHS/2014), the Singapore Institute for Clinical Sciences, the Agency for Science Technology and Research (A*STAR), and Nestec. The study sponsors were not involved in the study design, data collection, analysis and interpretation of data, manuscript writing, or the decision to submit the article for publication. PCC and KMG are supported by the National Institute for Health Research (NIHR) through the NIHR Southampton Biomedical Research Center, and KMG is supported by the European Union's Seventh Framework Program (FP7/2007-2013), project EarlyNutrition (grant 289346).
The full paper can be downloaded from the publisher's URL: https://doi.org/10.1093/ajcn/nqy079