Manisha Nair

and 4 more

Abstract Objective Assessment of whether maternal anaemia in early pregnancy causes offspring congenital heart disease (CHD) Design Matched case-control study Setting January 1998 - October 2020, England Population Women with a haemoglobin measurement in the first 100 days of pregnancy and a CHD-diagnosed child Methods Data was extracted from the United Kingdom Clinical Practice Research Datalink GOLD database. 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 388 (2.8%) controls had anaemia. After adjusting for potential confounders, the odds of giving birth to a CHD-diagnosed child was 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 prevention of some CHD if iron deficiency anaemia is proven to be a cause. Funding: British Heart Foundation (FS/17/55/33100, FS/SBSRF/22/31022, RE/18/3/34214); the Medical Research Council (MR/W029294/1); the National Institute for Health and Care Research (NIHR00172). Keywords: Congenital Heart Disease; Anaemia; Haemoglobin; Case-control studies; Risk Factor; Clinical Practice Research Datalink