Study Finds More Heart Defects in Kids Conceived With ART

Kids born via assisted reproductive technology (ART) had higher risk of congenital heart defects (CHDs), though the absolute risk difference was small, an observational Nordic study of 7.7 million children found.

Major CHDs were detected in 1.84% of kids conceived after ART compared to 1.15% of spontaneously conceived kids (adjusted odds ratio [AOR] 1.36, 95% CI 1.31-1.41), reported Ulla-Britt Wennerholm, MD, PhD, of the department of obstetrics and gynecology at the University of Gothenburg in Sweden, and colleagues.

Rates of severe CHDs were comparable, with slightly higher rates among ART kids compared with spontaneously conceived kids (0.35% vs 0.26%; AOR 1.30, 95% CI 1.20-1.42), authors wrote in European Heart Journal.

Risk of CHD was higher in multiple gestations regardless of conception method, with an absolute risk of 2.47% for ART and 2.41% for spontaneous conception, which was significantly higher than for singletons in either category (P<0.001).

“I think that the small increased risk for ART children is mostly reassuring for parents and clinicians,” Wennerholm told MedPage Today. “The thing that can be done is to go for single embryo transfer, which may reduce the risk.” In most scenarios, the American Society for Reproductive Medicine recommends single embryo transfer.

Within ART, CHD rates were similar for intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), and for fresh and frozen embryo transfers.

CHDs are the most common birth defect, though still only occur in 1-2% of the population, which is why a large cohort is needed to assess trends. Wennerholm noted that Nordic countries have extensive health data registries which are helpful for population-based studies.

Ultimately, authors concluded that while kids born after ART had higher risk of CHD, the absolute risks were “modest and partly associated with multiple pregnancies, more prevalent in ART.”

In an accompanying editorial, Nathalie Auger, MD, of Health Innovation and Evaluation Hub at the University of Montreal Hospital Research Centre in Canada, and colleagues wrote that the study “confirms associations found in earlier reports” though some of its findings raised questions.

For instance, within ART, the risk of major CHD was seen among singletons only (OR 1.19, 95% CI 1.14-1.24) — not multiple births, (OR 0.94, 95% CI 0.88-1.01), which Auger pointed out is counterintuitive. Also, even though ICSI requires more gamete manipulation than IVF, it did not have a stronger association with CHD. And sensitivity analyses didn’t explain the association between ART and CHD.

Auger noted the potential for confounding, especially since people who use ART tend to differ from the general population, with potential underlying morbidities that affect fertility. Wennerholm and team found that women who conceived via ART were more likely to be primiparous, to be older at birth, to not smoke, and had slightly higher prevalence of pregestational diabetes. Additionally, kids born after ART were more often born preterm.

“Although the bias scenarios that we tested did not have to be severe to explain the association with heart defects, they do not necessarily negate a possible effect of assisted reproductive technology,” Auger wrote, also noting that more research focused on determining if ART has a direct effect on CHD is still needed.

This study included data from all liveborn children in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1987-2015). Of these, 171,735 kids were conceived after ART, and 7,575,902 were born after spontaneous conception. Researchers cross-linked national ART and medical birth registry data with other health and population registries. They looked at major CHDs, severe CHDs, six hierarchical CHD lesion groups, as well as 10 selected major CHDs, diagnosed prenatally through 1 year of age (Denmark, Finland, and Sweden) and prenatally or at birth (Norway).

They conducted sensitivity analyses on smoking, maternal education level, one restricted to infants born between 2006 and 2015, as well as one excluding what was later deemed minor CHDs.

The major limitation was that the group couldn’t include data on miscarriages, terminations, and stillbirths, Wennerholm noted. Additionally, CHD rates varied somewhat between countries, as did prenatal screening routines. In terms of future research, the group is working on new data linkage with follow-up through more recent years.