Adults who developed a low haemoglobin level (anaemia) in their mothers’ wombs may be at greater risk of heart problems, according to a ground-breaking study led by paediatrician and HRC Clinical Research Training Fellow Dr Alexandra Wallace.
The HRC-funded study measured the heart function, coronary blood flow and cardiovascular risk factors of adult survivors of severe rhesus haemolytic disease in New Zealand.
Rhesus disease occurs when antibodies in a pregnant woman’s blood destroy her baby’s red blood cells leading to the baby developing anaemia.
Just over half of the study’s 187 participants received an intrauterine blood transfusion to treat their rhesus disease-induced anaemia at National Women’s Hospital in Auckland between 1963 and 1992.
For comparison, the rest of the study participants were made up of their siblings who did not have rhesus disease. The participants’ ages ranged from 18 to 47, with an average age of 37.
The study is the first to look at the effects of anaemia in the womb and treatment with intrauterine blood transfusion on adult heart health.
“The number of heart cells you have when you’re born is essentially the number you have for life. Fetal anaemia exposes the developing heart to physiological stress, which may alter the replication and differentiation of these cells before birth,” says Dr Wallace.
The results from this study provide the first evidence that babies who have anaemia in the womb may have permanently altered heart structure and function – changes that could potentially have lifelong health consequences.
“Using cardiac MRI, we found that the participants who had anaemia in utero had smaller and thicker walled left ventricles than their unaffected siblings,” says Dr Wallace. “They also had lower levels of high-density lipoprotein (or HDL, the so-called ‘good cholesterol’) and increased sympathetic control of heart rate variability, both of which suggest increased cardiovascular risk. In addition, analysis of coronary blood flow at rest and with stress indicates that exposure to anaemia before birth may also impair coronary blood vessel function.”
Despite these differences, Dr Wallace says all findings for those exposed to anaemia before birth were within normal limits, so the absolute increase in cardiovascular risk for these individuals is likely to be very small at their current age. “Further review in 10 to 20 years’ time will help establish if they have earlier onset or more severe cardiovascular disease in later life.”
Dr Wallace also carried out a pilot study in sheep to help establish whether babies born preterm, who frequently become anaemic after birth, show similar changes to their heart structure and function as those who had anaemia in utero.
Almost all babies born preterm will become anaemic at some point, a condition known as anaemia of prematurity.
For the pilot study, anaemia was induced in sheep delivered preterm. This resulted in no long-term growth impairments, but these animals did have increased levels of haemoglobin in their blood as adults. There was a similar increase in haemoglobin levels in the anaemia-affected participants from the human study.
“This is a completely novel finding. We suspect that the cardiovascular changes as a result of anaemia have caused the body’s haematological system to undergo changes too. It might be the body’s way of trying to improve cardiac performance. The similarity of this finding in humans and sheep leads us to wonder whether anaemia before term equivalent age, whether experienced in- or ex utero, may have similar long-term health consequences.”
Further work by other members of Dr Wallace’s team is now underway to investigate the effects of anaemia following preterm birth on long-term heart structure and function.
Dr Wallace completed this study as part of her PhD at the University of Auckland’s Liggins Institute under the supervision of Distinguished Professor Jane Harding and Dr Stuart Dalziel. She would like to acknowledge the support of her collaborators, including Professor Brett Cowan and Associate Professor Alistair Young (Department of Anatomy with Radiology, University of Auckland) who performed the cardiac MRI scans and complex coronary blood flow analysis; Associate Professor Ian LeGrice and Professor Bruce Smaill (Auckland Bioengineering Institute); Auckland cardiologist Dr Nigel Lever; and Professor Kent Thornburg from the Oregon Health & Science University in the US.