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The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth

Danmeng Liu¹, Yue Cheng², Pengfei Qu¹

¹Translational Medicine Center, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China.

The Journal of Nutrition

|June 30, 2023

Background:

The effect of iron supplementation during pregnancy on birth outcomes may vary with maternal genetic background and needs more investigation.

Objectives:

This prospective study aimed to evaluate the interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes.

Methods:

This was a substudy from a community-based randomized control trial conducted in Northwest China, which included 860 women from the 2 micronutrient supplementation groups (folic acid [FA] and FA + iron group). Maternal peripheral blood, sociodemographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms in iron metabolism-related genes were genotyped. The alleles associated with decreased iron/hemoglobin status were used as the effect alleles. The genetic risk score (GRS) that reflected the genetic risk of low iron/hemoglobin status was estimated using the unweighted and weighted methods. Generalized estimating equations with small-sample corrections were applied to evaluate the interactions between iron supplementation and SNPs/GRS on birth outcomes.

Results:

There were significant interactions between maternal iron supplementation and rs7385804 (P = 0.009), rs149411 (P = 0.035), rs4820268 (P = 0.031), the unweighted GRS (P = 0.018), and the weighted GRS (P = 0.009) on birth weight. Compared with FA supplementation only, FA + iron supplementation significantly increased birth weight among women with more effect alleles in rs7385804 (β: 88.8 g, 95% CI: 9.2, 168.3) and the GRSs (the highest unweighted GRS, β: 135.5 g, 95% CI: 7.7, 263.4; the highest weighted GRS, β: 145.9 g, 95% CI: 43.4, 248.5); it had a trend of decreasing birth weight and increasing low birth weight risk among women with fewer effect alleles.

Conclusions:

In our population, maternal genetic background related to iron metabolism plays a significant role in determining the efficacy of iron supplementation. Routine iron supplementation could be more beneficial to fetal weight growth among mothers with higher genetic risk for low iron/hemoglobin status.

Keywords:

birth outcomes gene-nutrient interaction genetic risk score iron supplementation pregnancy single nucleotide polymorphisms

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