A new study by researchers at Oxford Population Health’s National Perinatal Epidemiology Unit, the Department of Physiology, Anatomy, and Genetics, and the Nuffield Department of Primary Care Health Sciences has found that maternal anaemia in early pregnancy is associated with an increased risk of babies being born with congenital heart disease. The study was funded by the British Heart Foundation and published in BJOG: An International Journal of Obstetrics and Gynaecology.
In 2021, the same team found a link between anaemia during pregnancy and congenital heart disease in mice. Congenital heart defects are the most common birth defects and a leading cause of infant mortality. It is estimated that nearly a quarter of pregnant women in the UK, and over a third of pregnant women globally, have anaemia. The prevalence of maternal anaemia in low-and-middle income countries has been reported to be in excess of 50%.
In this study, researchers analysed anonymised data from a GP record database for over 2,700 mothers who had a child with congenital heart disease and around 14,000 mothers at the same GP practices whose children did not have congenital heart disease, but whose pregnancies started at similar times. Blood test results from the first 100 days of each pregnancy were used to determine whether the mothers had anaemia at the time.
The researchers found an increased risk of congenital heart disease among children whose mothers had anaemia in the first 100 days of pregnancy, a critical period for fetal heart development. In the group of mothers who had a child with congenital heart disease, 4.4 per cent had anaemia compared with 2.8 per cent anaemia among mothers who did not have a child with congenital heart disease.
It is the first study in a UK population to demonstrate a clear link between maternal anaemia in early pregnancy and congenital heart disease in offspring, demonstrating a 47% increase in odds of structural heart abnormality in the child. The researchers estimate that maternal anaemia may account for up to one in 20 congenital heart disease cases in the UK.
Manisha Nair, Senior Research Fellow at Oxford Population Health and first author of the paper said, ‘Between one-third to half of all pregnant women in low-and-middle income countries have anaemia. Thus preventing anaemia in the periconceptional period could result in a much higher reduction in the number of children born with congenital heart defects in countries that have a higher burden. Anaemia can be caused by multiple factors, so we are currently undertaking research to establish whether iron deficiency is the cause leading to the identified higher risk. our next steps will be to research whether taking iron supplements before and during early pregnancy could help to prevent some types of heart defects at birth.’
Duncan Sparrow, British Heart Foundation Senior Research Fellow at the Department of Physiology, Anatomy, and Genetics and senior author of the paper, said ‘We already know that the risk of congenital heart disease can be raised by a variety of factors, but these results develop our understanding of anaemia specifically and take it from laboratory studies to the doctors clinic. Knowing that early maternal anaemia is so damaging could be a gamechanger worldwide.’
Sonya Babu-Narayan, Clinical Director at the British Heart Foundation, said ‘If low iron turns out to be one of the culprits, then replenishing iron levels during early pregnancy when the baby's heart is forming could have significant benefit for a baby's lifelong heart health. Whilst observational studies like this can show us links, they cannot tell us about cause. Larger studies are needed to confirm the finding and determine which type of congenital heart disease may be linked to low iron. It is also important to note that the usual risk of having a child with a congenital heart disease is around 1 per cent, so even with the increase that this study suggests, the individual risk for people with no family history of congenital heart disease is still relatively small.’