Congenital heart disease (CHD) is the most common form of birth defects with a prevalence of 1-2% of live births. Despite recent advances in our understanding of heart development, as well as diagnostic approaches, two-thirds of cases have an unknown aetiology, with some of these posited to result from the exposure to environmental teratogens in the critical, early stages of pregnancy (3-8 weeks post-conception).

In 2021, the team led by Dr Duncan Sparrow at the University of Oxford (UK) has identified maternal iron deficiency (ID) leading to anaemia has a potential teratogen causing CHD in mice (1). Briefly, the study showed that maternal ID in mice caused several developmental defects in her offspring including membranous and muscular ventricular septal defects, atrioventricular septal defects, double-outlet right ventricle or overriding aorta, and noncompacted myocardium. Mechanistically, these defects were suggested to arise from premature differentiation of a subset of cardiac progenitor cells due to dysregulated retinoic acid signalling. Importantly, dietary iron supplementation mid-gestation was found to rescue the cardiac defects in mice.

Now, in their follow-up report the Sparrow team describes the findings arising from their study of 2,776 women with CHD-diagnosed children against 13,880 matched controls, the first of this type in the UK (2). Specifically, the authors assessed whether maternal anaemia in early pregnancy, classified as <110 g/L haemoglobin, was associated with offspring CHD within 5 years of birth making use of data extracted from the UK Clinical Practice Research Datalink GOLD database of electronic health records. A strong association between maternal anaemia in early pregnancy and increased risk of offspring CHD was observed with the odds of giving birth to a CHD-diagnosed child being 47% higher among anaemic mothers, aligning with their previous evidence in mice.

Taken together, these findings highlight the need for further research on the role of iron deficiency. As approximately two-thirds of anaemia cases globally are due to iron deficiency, it is suggested that periconceptional iron supplementation may be a minimally invasive and low-cost intervention for the prevention of some forms of CHD. As such, the recent findings from the Sparrow group pave the way for clinical trials on iron supplementation.