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Maternal anaemia during pregnancy is associated with an increase in the risk of offspring congenital heart disease: a case-control study using linked electronic health records in England
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  • Manisha Nair,
  • Cynthia Drakesmith W,
  • Margaret Smith,
  • Clare Bankhead R,
  • Duncan Sparrow B
Manisha Nair
University of Oxford Nuffield Department of Population Health
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Cynthia Drakesmith W
University of Oxford Nuffield Department of Primary Care Health Sciences
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Margaret Smith
University of Oxford Nuffield Department of Primary Care Health Sciences
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Clare Bankhead R
University of Oxford Nuffield Department of Primary Care Health Sciences
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Duncan Sparrow B
University of Oxford Department of Physiology Anatomy and Genetics

Corresponding Author:duncan.sparrow@dpag.ox.ac.uk

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Abstract

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
22 Nov 2024Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
23 Nov 2024Submission Checks Completed
23 Nov 2024Assigned to Editor
23 Nov 2024Review(s) Completed, Editorial Evaluation Pending
25 Nov 2024Reviewer(s) Assigned
07 Feb 2025Editorial Decision: Revise Major