Maternal anemia in early pregnancy linked to higher risk of congenital heart disease in offspring

Maternal anemia in pregnancy linked to higher risk of congenital heart disease in offspring | Image Credit: © BazziBa - stock.adobe.com.

A recent study conducted in the United Kingdom has revealed a significant association between maternal anemia in early pregnancy and the increased risk of congenital heart disease (CHD) in offspring. The matched case-control study, utilizing data from the Clinical Practice Research Datalink (CPRD) GOLD database, provides new insights into potential risk factors for CHD, the most common class of birth defects.¹

The research, published in the BJOG: An International Journal of Obstetrics & Gynaecology, highlights the importance of maternal health in the early stages of pregnancy for the development of the fetal heart.

Study design and methods

Researchers extracted data from the July 2022 release of the CPRD GOLD database. Access to these datasets was granted through the standard CPRD application process. The CPRD is a person-level database that includes anonymized primary care records for over 21 million patients from 986 GP practices in the UK. The study period spanned from January 1998 to October 2020.

The study focused on identifying mother-baby pairs. Cases were defined as mother-baby pairs in which the child had a diagnosis of CHD within the first five years after birth. Controls were mother-baby pairs where the child had not been diagnosed with CHD in the same period. Maternal anemia was classified based on the World Health Organization's definition, using a hemoglobin cut-off of less than 110 g/L.

Conditional logistic regression analyses were conducted to examine the association between maternal anemia in the first 100 days of pregnancy and CHD in offspring, adjusting for potential confounders. Potential confounders included maternal socioeconomic status, ethnicity, age, body mass index (BMI), smoking and alcohol consumption, and pre-existing type 1 or type 2 diabetes mellitus.

Key findings

The study included 2,776 cases and 13,880 matched controls. The researchers found that 4.4% of mothers in the case group had anemia, compared to 2.8% of mothers in the control group.

The analysis revealed a statistically significant association between maternal anemia and offspring CHD. In the unadjusted analysis, the odds of CHD in offspring were 60% higher if the mother had anemia in the first 100 days of pregnancy. After adjusting for confounders, the odds of offspring CHD were still 47% higher among mothers who had anemia (adjusted OR 1.47, 95% CI 1.18, 1.83, p = 0.0006).

The most common type of CHD among the cases was ventricular septal defect (VSD), accounting for 32% of cases, followed by atrial septal defect (ASD) at 23% and patent ductus arteriosus (PDA) at 14%.

Implications and limitations

The authors concluded that the study provides evidence of an association between maternal anemia in early pregnancy and an increased risk of CHD in offspring. These findings support previous experimental animal research that identified maternal iron deficiency anemia as a risk factor for offspring CHD.

The researchers suggest that periconceptional iron supplementation could potentially be a minimally invasive and low-cost intervention for preventing some cases of CHD, especially given that approximately two-thirds of anemia cases globally are due to iron deficiency. However, they emphasize that a clinical trial is needed to confirm this.

The study acknowledges several limitations. Due to data limitations, the study could not determine whether iron deficiency was the cause of anemia in the study population. Iron deficiency is typically measured using serum ferritin, but this was only available for a small percentage of the study population.

“We already know that the risk of congenital heart disease can be raised by a variety of factors, but these results develop our understanding of anemia specifically and take it from lab studies to the clinic. Knowing that early maternal anemia is so damaging could be a gamechanger worldwide,” said corresponding author Duncan B. Sparrow, PhD, of the University of Oxford. “Because iron deficiency is the root cause of many cases of anemia, widespread iron supplementation for women—both when trying for a baby and when pregnant—could help prevent congenital heart disease in many newborns before it has developed.”²

References:

1. Nair, M., Drakesmith, C.W., Smith, M., Bankhead, C.R. and Sparrow, D.B. (2025), Maternal Anaemia and Congenital Heart Disease in Offspring: A Case–Control Study Using Linked Electronic Health Records in the United Kingdom. BJOG. https://doi.org/10.1111/1471-0528.18150

2. Wiley. Does anemia during pregnancy affect newborns’ risk of heart defects?. Eurekalert. April 23, 2025. Accessed April 23, 2025. https://www.eurekalert.org/news-releases/1080977