Maternal Anaemia and Congenital Heart Disease in Offspring: A Case–Control Study Using Linked Electronic Health Records in the United Kingdom

Objective: Assessment of whether maternal anaemia in early pregnancy is associated with offspring congenital heart disease (CHD). Design: Matched case–control study. Setting: January 1998–October 2020, United Kingdom. Population: Women with a haemoglobin measurement in the first 100 days of pregnancy and a CHD-diagnosed child. Methods: Data were extracted from the United Kingdom Clinical Practice Research Datalink GOLD database of electronic health records. Cases were 2,776 women with a CHD-diagnosed child. These were compared to 13 880 matched controls, women without a CHD-diagnosed child. Anaemia was classified as < 110 g/L haemoglobin following the WHO definition. A conditional logistic regression analysis was conducted, adjusted for potential maternal demographic and health-related confounders. Main Outcome Measures: Offspring CHD diagnosed within 5 years of birth. Results: 123 (4.4%) cases and 390 (2.8%) controls had anaemia. After adjusting for potential confounders, the odds of giving birth to a CHD-diagnosed child were 47% higher among anaemic mothers (adjusted OR 1.47, 95% CI 1.18,1.83, p < 0.001). Conclusions: The observed association between maternal anaemia in early pregnancy and increased risk of offspring CHD supports our recent evidence in mice. Approximately two-thirds of anaemia cases globally are due to iron deficiency. A clinical trial of periconceptional iron supplementation might be a minimally invasive and low-cost intervention for the prevention of some CHD if iron deficiency anaemia is proven to be a cause.