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

ABSTRACT

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.