In animal models, mothers deficient in iron had a significantly increased risk of having offspring with congenital heart disease (CHD).
A team of researchers from the University of Oxford, funded by the British Heart Foundation, has identified a brand new risk factor for congenital heart disease (CHD). Using an animal model system, the researchers showed that if the mother suffers from severe iron deficiency and is anemic during early pregnancy, it greatly increases the risk of her offspring suffering from heart defects.
Coronary artery disease is the most common human birth defect, affecting 12 babies born every day in the UK. Babies with coronary artery disease are born with one or more structural defects caused when the heart does not develop properly in the womb. It is a major cause of infant mortality and requires continuous medical treatment throughout life. Yet despite the prevalence of the disease, we don’t always know why it happens.
Coronary artery disease can be caused by a genetic defect inherited from one or both parents, such as a genetic mutation. Yet while more than 100 genes have been linked to individual cases of the disease, mutations in these genes can only explain about a third of cases. The cause of coronary heart disease in the other two-thirds of cases is often unknown. In many of these unknown cases, coronary artery disease is most likely caused by exposure of the embryo to an abnormal environment in the uterus during early pregnancy. However, coronary artery disease is not routinely detected until after 20 weeks of pregnancy, so it has long been difficult to collect data on maternal physiology in the first trimester to establish new risk factors for birth defects. .
Duncan Sparrow, associate professor at the University of Oxford, principal investigator at BHF and principal investigator of the study, said: “Severe iron deficiency in the mother during the second and third trimesters is well known to increase the risk of having a low birth weight baby. and premature delivery. However, we are specifically looking for the first time for maternal iron deficiency in the first trimester, and we show in mice that maternal iron deficiency can cause serious cardiovascular abnormalities in her offspring.
This finding is supported by a 2020 epidemiological study in China which suggests that the risk of having a child with coronary heart disease could be tripled in women who have low iron intake during early pregnancy.
Professor Sparrow said: “Anemia is a major global health problem, affecting 20-40% of women of childbearing age, a total of over 500 million people, and half of these are due to to iron deficiency. So, if our results are applicable to humans, this may explain why congenital heart disease is relatively common around the world.
Research has also shown that the risk of coronary heart disease can be significantly reduced if the mother is given iron supplements, as long as it happens very early in the pregnancy before the heart forms in the embryo.
According to Dr. Jacinta Kalisch-Smith, first author of the article, “In humans, the heart forms between weeks 3 and 9. Our results from the animal study suggest that iron supplementation should probably be given before. week 3 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 global health priority of ensuring women of childbearing age are not iron deficient. In fact, the WHO recommends that supplementation start as early as possible and continue throughout pregnancy. ‘
Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation, said: “Congenital heart disease remains the most common birth defect, although we don’t always know why congenital heart disease develops. In this research study, iron deficiency in the mother caused severe birth defects in the offspring of mice, but if left untreated, the baby’s heart developed normally.
“Iron supplementation is an inexpensive and safe treatment for women with low iron levels and this research suggests that it can have significant benefits for a baby’s heart health if taken during early pregnancy. when the baby’s heart is forming. “
The team also studied the impact of genetic factors when combined with iron deficiency in the mother. About half of people with Down syndrome have congenital heart disease. A chromosomal abnormality is known to cause the development of coronary heart disease in these cases. The team hypothesized that this genetic change in combination with the environmental factor of iron deficiency may increase the likelihood of coronary heart disease. Their results showed that mouse embryos with chromosomal duplication modeling Down syndrome are particularly vulnerable to the effects of maternal iron deficiency, resulting in a higher risk of developing severe heart defects in the womb.
The research team hopes their findings can be translated into clinical practice to ultimately reduce the birth prevalence of coronary heart disease worldwide “in a manner similar to the impact of folate supplementation which reduced the prevalence to. the birth of neural tube defects of more than 60% in the past 30 years. ‘