Congenital heart disease (CHD) is the most common birth defect and a leading cause of infant and child morbidity and mortality, affecting approximately 1% to 2% of live births globally. CHD occurs mainly due to genetic factors or environmental factors. Approximately 30% of cases are reported because of gene mutations. Environmental factors, such as certain medications (anti-convulsants, thalidomide, and retinoic acid), contaminants or pollutants, folate deficiency, and maternal diseases (hyperthermia and viral infections), are considered major risk factors. Â
Recently, maternal iron deficiency anemia was identified as a potential environmental cause affecting 36.5% of pregnant women globally. However, it’s still not clear how this anemia is associated with CHD, particularly in the early stages of pregnancy. This study, published in BJOG: An International Journal of Obstetrics and Gynaecology, explains this association in the UK population.
This matched case-control study used the UK Clinical Practice Research Datalink (CPRD) GOLD database’s Pregnancy Register, Mother-Baby Link, Hospital Episode Statistics (HES) admission data, Office of National Statistics (ONS) mortality records, and Index of Multiple Deprivation (IMD) scores, including pregnancies that started in January 1998 and will continue until October 2020. Mothers were excluded if they lacked a hemoglobin (Hb) measurement within the first 100 days of pregnancy, or those with CHD <1 year of up-to-standard (UTS) data at the time of pregnancy at their present primary care center.Â
A total of 2,776 cases of mothers with CHD-diagnosed children (median age at pregnancy start = 30.6 [26.2–34.4] years) were included in this study. These were matched with 13,880 controls of mothers without CHD-diagnosed children (median age at pregnancy start = 29 [24.8–33.0] years). Maternal anemia data were extracted from mothers’ health records. After adjusting for relevant maternal demographic and health-related confounders, a conditional logistic regression analysis was performed using Stata version 18. The median time from the start of pregnancy to Hb measurement was found to be 71 days (57-84) for cases and 71 days (58-84) for controls. A similar median maternal Hb level of 128 g/L (122–134) was observed in both the case and control groups.
Results showed that 4.4% of mothers in cases (123/2776) had anemia (Hb < 110 g/L) compared to 2.8% of controls (390/13880). The unadjusted analysis showed 60% higher odds of CHD in offspring when mothers had anemia during the first 100 days of pregnancy, with odds ratios (OR) of 1.60, 95% confidence interval (CI) 1.30–1.97, and p < 0.0001. After adjusting for potential confounders, maternal anaemia was associated with a 47% higher odds of CHD in offspring, with an adjusted odds ratio of 1.47 (95% CI: 1.18–1.83) and p = 0.0006. No significant association was found between maternal Hb and offspring CHD.
This study’s limitations include limited data on iron deficiency, the inability to assess iron supplementation before conception, potential bias due to missing data, and a lack of power to analyze specific CHD subtypes or socioeconomic and ethnic disparities.
In conclusion, this study suggests that maternal anemia in early pregnancy significantly increases the risk of CHD in offspring. Approximately two-thirds of anemia cases were due to iron deficiency. A clinical study on periconceptional iron supplementation may serve as a low-cost and minimally invasive intervention to prevent some cases of CHD when iron deficiency is confirmed as the cause. However, before clinical implementation, further validation of larger datasets is needed.
Reference: Nair M, Drakesmith CW, Smith M, Bankhead CR, Sparrow DB. Maternal anaemia and congenital heart disease in offspring: A case–control study using linked electronic health records in the United Kingdom. BJOG: Int J Obstet Gynaecol. 2025;0:1–8. doi:10.1111/1471-0528.18150
