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将视黄醇与出生体重联系起来的遗传证据:一项双样本孟德尔随机化研究。

Genetic evidence linking retinol to birth weight: A two-sample Mendelian randomization study.

作者信息

Mu Fangxiang, Wang Kexin, Jiang Lu, Wang Fang

机构信息

Department of Reproductive Medicine, Lanzhou University Second Hospital, Lanzhou 730030, China.

Department of Reproductive Medicine, Lanzhou University Second Hospital, Lanzhou 730030, China.

出版信息

Reprod Toxicol. 2024 Dec;130:108739. doi: 10.1016/j.reprotox.2024.108739. Epub 2024 Oct 28.

Abstract

This study aims to clarify the potential causal effects of dietary antioxidant vitamins on pregnancy outcomes (miscarriage, preterm labor, and birth weight) using Mendelian randomization (MR). Our instrumental variables (IVs) were single-nucleotide polymorphisms (SNPs) linked to retinol, vitamin C, carotene, and vitamin E (P < 5×10). The summary statistics for miscarriage, preterm labor, and birth weight were extracted from genome-wide association studies (GWASs), with a sample size of 56,172, 5480, and 261,932, respectively. The present MR study primarily used the inverse-variance weighted method, with additional sensitivity analyses conducted to evaluate the robustness of the findings. We found that retinol was closely related to the birth weight (β=0.091, 95 %CI: 0.009-0.172, P=0.028), and sensitivity analyses showed similar results (MR-RAPS: OR=1.101, 95 %CI: 1.027-1.180; maximum likelihood: OR=1.098, 95 %CI: 1.011-1.194). While the relationship of retinol with miscarriage or preterm labor was not statistically significant. Additionally, our study did not reveal an association between the carotene, vitamin E, and vitamin C and pregnancy-related outcomes, miscarriage, preterm labor, and birth weight (all P > 0.05). In conclusion, our findings indicated a causal effect between retinol and birth weight and suggested that maintaining retinol at normal levels during pregnancy can prevent low birth weight. Therefore, it would be beneficial to measure retinol levels in pregnant women and to supplement with vitamin A in cases of deficiency, as these could be valuable strategies for improving pregnancy outcomes.

摘要

本研究旨在利用孟德尔随机化(MR)阐明膳食抗氧化维生素对妊娠结局(流产、早产和出生体重)的潜在因果效应。我们的工具变量(IVs)是与视黄醇、维生素C、胡萝卜素和维生素E相关的单核苷酸多态性(SNPs)(P<5×10)。流产、早产和出生体重的汇总统计数据分别从样本量为56172、5480和261932的全基因组关联研究(GWASs)中提取。本MR研究主要采用逆方差加权法,并进行了额外的敏感性分析以评估研究结果的稳健性。我们发现视黄醇与出生体重密切相关(β=0.091,95%CI:0.009-0.172,P=0.028),敏感性分析显示了相似的结果(MR-RAPS:OR=1.101,95%CI:1.027-1.180;最大似然法:OR=1.098,95%CI:1.011-1.194)。而视黄醇与流产或早产之间的关系无统计学意义。此外,我们的研究未发现胡萝卜素、维生素E和维生素C与妊娠相关结局、流产、早产和出生体重之间存在关联(所有P>0.05)。总之,我们的研究结果表明视黄醇与出生体重之间存在因果效应,并表明孕期维持视黄醇在正常水平可预防低出生体重。因此,测量孕妇的视黄醇水平并在缺乏时补充维生素A可能是有益的,因为这些可能是改善妊娠结局的有价值策略。

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