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

Objective: To describe the processes used to establish and standardise a UK-India collaborative platform for maternal and perinatal health research (MaatHRI). Design: Hospital-based research platform. Setting: India Population: Pregnant women Methods: MaatHRI is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India – Assam, Meghalaya, Uttar Pradesh and Maharashtra. The Indian research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. The UK partners include clinicians and epidemiologists from the University of Oxford. MaatHRI has advanced standardisation of data and laboratory parameters, monitoring data and participant safety, and secure transfer of data. An integral component of MaatHRI is bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board which ensure equitable partnerships between the collaborating institutions. Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a low and middle income country (LMIC). The model used to develop the platform can be replicated in other LMICs. Funding: Medical Research Council Career Development Award to Manisha Nair (Ref:MR/P022030/1).