Purpose: To assess whether polymorphisms of haptoglobin (Hp) modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia (IDA). Methods: This study analyzed 1430 singleton pregnant women aged 20 ~ ≤ 48 years from the 2017–2019 National Nutrition and Health Survey of Pregnant Women in Taiwan. Sociodemographic, blood biochemical, Hp phenotype, and 24-h dietary recall data were collected. Erythropoiesis-related total prenatal supplementation was defined as the reported use of multivitamins and minerals, vitamin B complex, folate, and iron. Results: Distributions of the Hp 1-1, Hp 2-1, and Hp 2-2 phenotypes were 13.6, 39.8, and 46.5%, respectively. Women with the Hp 1-1 phenotype had the lowest mean levels of serum ferritin (p-trend = 0.017), the highest prevalence of gestational ID (p-trend = 0.033) as well as the highest prevalence of gestational IDA (did not reach statistical differences, p-trend = 0.086). A gene–diet interaction on serum ferritin was observed between the Hp 1 and Hp 2 (2-1/2-2) alleles (p < 0.001). An adjusted multivariate logistic regression showed that compared to those with a normal blood iron status and who reported using erythropoiesis-related total prenatal supplements, those who did not had a 4.05-fold [odds ratio (OR) = 4.05 (95% confidence interval (CI) 2.63–6.24), p < 0.001] increased risk of gestational IDA. The corresponding ORs for carriers of the Hp 1 and Hp 2 alleles were 4.78 (95% CI 1.43–15.99) and 3.79 (95% CI 2.37–6.06), respectively. Conclusion: Pregnant women who are Hp 1 carriers are at increased risk for developing IDA if they do not meet the recommended dietary allowance for iron or use erythropoiesis-related prenatal supplements.
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