Severe iron deficiency and anaemia during early pregnancy may greatly increase the risk of the child having heart defects, new research suggests.
A team of University of Oxford researchers identified an entirely new risk factor for congenital heart disease (CHD) using mice models.
Affecting 12 babies born each day in the UK, CHD is the most common human birth defect.
Babies with CHD are born with one or more structural defects caused when the heart does not develop properly in the womb.
The condition is a major cause of infant mortality and requires ongoing medical treatment throughout life.
However, it is not always known why it occurs.
CHD can be caused by a genetic fault inherited from one or both parents, such as a gene mutation.
Mutations in these genes can only explain around one-third of cases, while more than 100 genes have been associated with individual cases of disease.
The cause of CHD in the other two-thirds of cases is often unknown.
In many of these unknown cases, it is most likely caused by the embryo being exposed to an abnormal environment in the womb during early pregnancy, researchers say.
However, the condition is not routinely detected until after 20 weeks in pregnancy, so it has been difficult to collect data on the mother’s physiology in the first trimester to establish new risk factors for birth defects.
Duncan Sparrow, associate professor at the University of Oxford, British Heart Foundation (BHF) senior research fellow and lead researcher on the study, said: “Severe maternal iron deficiency in the second and third trimesters is well known to increase the risk of having a low-birth weight baby and a premature delivery.
“However, we are specifically looking for the first time at maternal iron deficiency in the first trimester, and we show in mice that maternal iron deficiency can cause severe cardiovascular defects in her offspring.”
Researchers say their findings are supported by a 2020 epidemiological study in China that suggests the risk of having a child with CHD could be increased up to three-fold in women who have low iron intake during early pregnancy.
Prof Sparrow said: “Anaemia is a major global health problem, affecting 20-40% of women of child-bearing age, a total of more than 500 million individuals, and half of these are due to iron deficiency.
“Thus, if our results are applicable to humans, then this may explain why congenital heart disease is relatively common around the world.”
The research also indicates the risk of CHD can be greatly reduced if the mother is given iron supplements, provided this happens very early in pregnancy before the heart has formed in the embryo.
Dr Jacinta Kalisch-Smith, first author on the paper, said: “In humans, the heart forms between weeks three to nine.
“Our results from the animal study suggest that iron supplementation should probably be given before week three to be effective.
“Even better to take supplements while trying to conceive as women may not know they are pregnant at such an early stage.
“This adds more evidence supporting the WHO’s global health priority of making sure that women of child-bearing age are not iron-deficient.
“In fact, WHO recommends that supplementation should begin as early as possible and continue throughout pregnancy.”
The research team hope their findings can be translated to clinical practice to ultimately reduce the birth prevalence of CHD worldwide.
The research was funded by the British Heart Foundation (BHF).