Iron intake and iron status during pregnancy and risk of congenital heart defects: A case-control study

Yang, Jun-Song; Kang, Yijun; Cheng, Yue; Zeng, Lingxia; Shen, Yuan Li; Shi, Guoshuai; Liu, Yezhou; Qu, Pengfei; Zhang, Ruo; Yan, Hong; Dang, Shaonong

doi:10.1016/j.ijcard.2019.11.115

Cited by 29 publications

(49 citation statements)

References 36 publications

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“…Poor maternal nutrition during pregnancy is a major cause of adverse birth outcomes including birth defects [14]. Previous studies have found that maternal low intakes of iron, folate, riboflavin, and niacin were associated with an increased CHD risk [4][5][6]. In the present study, we observed that maternal daily intakes of micronutrients during pregnancy were higher in the adequate DDS group than in the inadequate DDS group.…”

Section: Discussionsupporting

confidence: 54%

“…As an important modifiable factor, maternal diet can be easily intervened with low cost and low risk. Previous studies have reported that maternal low intakes of iron, folate, riboflavin, and niacin increased CHD risk [4][5][6]. Unfortunately, maternal diets during pregnancy are typically monotonous and predominantly plant-based with little consumption of micronutrient-dense animal-based foods in most parts of China, especially in Northwest China [7].…”

Section: Introductionmentioning

confidence: 99%

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Maternal dietary diversity during pregnancy and congenital heart defects: a case-control study

et al. 2020

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Background/objectives Maternal diet is critical to fetal development. This study aimed to explore the association between maternal dietary diversity during pregnancy and congenital heart defects (CHD) in Chinese population. Methods A hospital-based case-control study was conducted including 474 cases and 948 controls in Northwest China. We recruited eligible women waiting for delivery in the hospital and gathered their diets during the whole pregnancy by a validated food frequency questionnaire. According to the FAO Minimum Dietary Diversity for Women (MDD-W) guideline, the participants were categorized into "inadequate dietary diversity score (DDS)" (DDS < 5) and "adequate DDS" (DDS ≥ 5) groups. The association between dietary diversity and CHD was estimated using the mixed logistic regression models. Results Case mothers had a lower DDS during pregnancy than the controls (P < 0.001). The proportions of women consuming all the ten defined food groups were lower in the inadequate DDS group than in the adequate DDS group among both cases and controls (all P < 0.001). The prevalence of inadequate micronutrient intake was higher in the inadequate DDS group than in the adequate DDS group among both cases and controls (all P < 0.05). Women in the adequate DDS group had reduced risks of having fetuses with total CHD (OR = 0.62, 95% CI = 0.45-0.84) and ventricular septal defects (OR = 0.58, 95% CI = 0.38-0.88). Conclusions Adequate DDS during pregnancy might be associated with a lower risk of CHD in offspring. Efforts to promote dietary diversity during pregnancy need to be strengthened to reduce the prevalence of CHD in Chinese population.

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Section: Discussionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Maternal dietary diversity during pregnancy and congenital heart defects: a case-control study

et al. 2020

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“…Our results suggest that all women of child-bearing age should be advised to maintain optimal iron levels. This conclusion is supported by a recent study suggesting that low iron intake during early pregnancy in humans increases the risk of offspring CHD by up to 5-fold 10 . Iron supplementation during pregnancy is unlikely to have a deleterious effect on embryonic development.…”

Section: Discussionsupporting

confidence: 66%

“…In humans, at least half of all cases of anaemia result from ID 4 . Furthermore, low iron intake during pregnancy in humans may increase the risk of intrauterine growth restriction 9 and CHD 10 . To investigate further, we used our previously published model of maternal ID 11 .…”

Section: Maternal Iron Deficiency Perturbs Embryonic Developmentmentioning

confidence: 99%

Maternal iron deficiency perturbs embryonic cardiovascular development

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Szumska

et al. 2020

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Congenital heart disease (CHD) is the most common type of birth defect, with a global prevalence of 0.9% of live births. Most research in the last 30 years has focused on finding genetic causes of CHD. However, despite the association of over 100 genes with CHD, mutations in these genes only explain ~30% of cases. Many of the remaining cases of CHD are caused by in utero exposure to environmental factors. Here we have identified a completely new environmental teratogen causing CHD: maternal iron deficiency. In humans, iron deficiency anaemia is a major global health problem. 38% of pregnant women worldwide are anaemic4, and at least half of these are due to iron deficiency, the most prevalent micronutrient deficiency. We describe a mouse model of maternal iron deficiency anaemia that causes severe cardiovascular defects in her offspring. We show that these defects likely arise from increased retinoic acid signalling in iron deficient embryos, probably due to reduced activity of the iron-dependent retinoic acid catabolic CYP26 enzymes. The defects can be prevented by maternal iron administration early in pregnancy, and are also greatly reduced in offspring of mothers deficient in both iron and the retinoic acid precursor vitamin A. Finally, one puzzling feature of many genetic forms of CHD in humans is the considerable variation in penetrance and severity of defects. We show that maternal iron deficiency acts as a significant modifier of heart and craniofacial phenotype in a mouse model of Down syndrome. Given the high incidence of maternal iron deficiency, peri-conceptional iron monitoring and supplementation could be a viable strategy to reduce the prevalence and severity of CHD in human populations worldwide.

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“…Secondly, maternal exposure to chronic mild hypoxia late in gestation, mimicking the effects of maternal anaemia, causes reduced RA signalling in her offspring's kidney post-natally 82 , that is, the opposite effect to our observations. Lastly, human epidemiological studies suggest that maternal anaemia only increases offspring CHD risk minimally (adjusted odds ratio (OR) 1.2 [83][84][85] ), whereas low iron intake in the first trimester (with or without overt anaemia) has an adjusted OR of offspring CHD of up to 5.0 11 . Our hypothesis that ID causes mildly increased RA signalling is supported by studies of the effects of exposure of pregnant mice to excess RA [67][68][69]86 .…”

Section: Discussionmentioning

confidence: 99%

Maternal iron deficiency perturbs embryonic cardiovascular development in mice

et al. 2021

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Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene–environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.

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Iron intake and iron status during pregnancy and risk of congenital heart defects: A case-control study

Cited by 29 publications

References 36 publications

Maternal dietary diversity during pregnancy and congenital heart defects: a case-control study

Maternal dietary diversity during pregnancy and congenital heart defects: a case-control study

Maternal iron deficiency perturbs embryonic cardiovascular development

Maternal iron deficiency perturbs embryonic cardiovascular development in mice

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