The interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes: a prospective study in Chinese

BACKGROUND

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

OBJECTIVE

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 sub-study from a cluster-randomized control trial conducted in Northwest China, which included 860 women from the two micronutrient supplementation groups (folic acid (FA) and FA + iron group). Maternal peripheral blood, socio-demographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms (SNPs) 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 equation 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. results CONCLUSION: 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.