Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore.
Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Australia.
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.
在随机试验中，孕期补充 n-3（ω-3）长链多不饱和脂肪酸（LC-PUFA）可使出生体重增加，这归因于妊娠期延长。
我们使用孟德尔随机化方法，利用影响 LC-PUFA 代谢的脂肪酸去饱和酶（FADS）基因变异来检验这一发现。
作为新加坡一个三族裔母婴队列的一部分，在 898 名母亲和 1103 名后代中对 FADS1、FADS2 和 FADS3 中的 35 个遗传变异进行了基因分型。在妊娠 26-28 周时测量了母亲血浆中 n-3 和 n-6 PUFA 浓度。妊娠期从早孕超声检查和出生日期推算得出。出生时的身长和体重进行了测量。通过标记 SNP 方法选择了 8 个 FADS 变体，并通过校正族裔的线性回归和生存模型，评估这些变体与 PUFA 浓度、自发性分娩的妊娠持续时间以及出生时的体型之间的关系，该模型考虑了引产和剖宫产分娩的竞争风险。
母亲 FADS1 变体 rs174546 及其标记的 8 个位于 FADS1 和 FADS2 的其他变体与血浆 n-6 但与 n-3 LC-PUFA 浓度强烈相关。在有自发性分娩的女性中，后代和母亲的 FADS3 变体与妊娠持续时间有关：每个 rs174450 次要等位基因 C 的拷贝与 2.2 d（95%CI：0.9，3.4 d）和 1.9 d（0.7，3.0 d）的妊娠缩短有关，分别为母亲和后代变体。在生存模型中，与主要等位基因纯合子相比，rs174450 次要等位基因纯合子在自发性分娩后分娩时间缩短[母亲和后代的 HR（95%CI）分别为 1.51（1.18，1.95）和 1.51（1.20，1.89）]。
我们使用孟德尔随机化方法观察到 FADS 变体与妊娠持续时间之间存在关联。这表明 LC-PUFA 在妊娠持续时间中可能发挥作用。本试验在 http://www.clinicaltrials.gov 注册，编号为 NCT01174875。
