Children conceived with infertility treatment may have higher asthma, allergy risks

Children conceived through infertility treatment had a higher risk for asthma and allergies, even after adjustment for parental asthma and atopy, according to a study published in Human Reproduction.

“Our research group is particularly interested in how early life exposures, like fertility treatments, may affect child development and health outcomes,” Kristen J. Polinski, PhD, a postdoctoral Intramural Research Training Award fellow in the epidemiology branch of the division of population health research at the Eunice Kennedy Shriver National Institute of Children and Human Development, told Healio.

“Asthma and allergic conditions are some of the most common chronic diseases affecting children with potential origins in early life,” Polinski said.

The researchers analyzed data from the Upstate KIDS Study, which was designed to examine these types of relationships among 6,171 children delivered between 2008 and 2010 and their 5,034 mothers from 57 counties in New York.

Mothers completed questionnaires about the health of their children at age 4, 8, 12, 18, 24, 30 and 36 months and again annually between 2016 and 2019. A subset of 2,056 children participated in middle childhood follow-up at ages 7 to 9 years, and a subset of 373 children participated in a study visit measuring their fractional exhaled nitric oxide between age 8 and 11 years (median, 9 years).

When looking at children based on a family level (n = 4,912), 756 families had children born after assisted reproductive technology (ART) treatment, 687 after ovulation induction with or without intrauterine insemination (OI/IUI) and 3,468 without treatment.

Mothers who received infertility treatment were more likely to be older, nulliparous, non-Hispanic white, married or cohabitating and of higher socioeconomic status. They also were more likely to report atopic conditions and were less likely to smoke during pregnancy compared with those who did not receive treatment.

At age 36 months, 10.8% of children had persistent wheeze, 28.2% had eczema or atopic dermatitis and 8.8% had allergies including food. In middle childhood, 16.4% had current asthma, 10.4% had eczema, 14.1% had physician-diagnosed allergies and 13.4% had prescriptions for allergy medications. Further, 46.6% of those children with persistent wheeze at age 36 months had current asthma in middle childhood.

The risk for persistent wheeze at age 36 months, however, was higher among children born after infertility treatment compared with children born with no treatment (adjusted RR = 1.55; 95% CI, 1.11-2.17).

Specifically, children born after OI/IUI treatment had an even greater risk for persistent wheeze (aRR = 1.69; 95% CI, 1.14-2.51) compared with those born following no treatment.

The researchers also found a borderline association for any atopy at age 36 months among children born after infertility treatment (aRR = 1.12; 95% CI, 0.98-1.28) but not for eczema/atopic dermatitis or for food allergies.

In middle childhood, children born after infertility treatment had a greater risk for asthma (aRR = 1.27; 95% CI, 0.96-1.68), any atopy (aRR = 1.52; 95% CI, 1.2=1.92) and eczema (aRR = 1.69; 95% CI, 1.19-2.39).

Children born following OI/IUI treatment had increased risks for physician-diagnosed asthma (aRR = 1.65; 95% CI, 1.04-2.62) when they were older compared with those who were born without any treatment.

There were positive associations between OI/IUI and eczema (aRR = 1.91; 95% CI, 1.32-2.78) and physician-prescribed allergy medications (aRR = 1.45; 95% CI, 1.04-2.02) among older children after covariate adjustment as well.

There were similar effect sizes for eczema (aRR = 1.45; 95% CI, 0.92-2.28) and physician-prescribed allergy medications (aRR = 1.46; 95% CI, 0.97-2.19) among older children who were born following ART, although the researchers noted these results had low precision.

The similar results following the different treatment approaches indicate that underlying parental subfertility or shared ovarian stimulation protocols may contribute to these risks and not the specific techniques used, the researchers wrote.

“We found similar results between fertility treatment types — in vitro fertilization, taking drugs that stimulate ovulation, and undergoing procedures that insert sperm into the uterus — suggesting that it might not be specific treatments that are contributing to risk but rather parental subfertility or shared protocols for ovarian stimulation,” Polinski said. “More research is needed to elucidate potential mechanisms.”

Noting that values below 20 parts per billion (ppb) were considered low, the average FeNO measurement among children conceived without infertility treatment was 12.93 ppb (standard deviation [SD], 12.5), and the average for children born following treatment was 13.49 ppb (SD, 13.14).

These results indicate no significant association between FeNO measurements and infertility treatment, although they do imply noneosinophilic or a lack of airway inflammation among these children, the researchers wrote. Neutrophilic airway inflammation, however, remains a possibility, the researchers continued.

The researchers acknowledged that parents who seek infertility treatment may be more likely to seek medical care for their children, although data on medication use may have indicated respiratory illnesses apart from asthma diagnosis.

Looking ahead, the researchers called for more studies of the underlying biological mechanisms of infertility treatment on asthma and atopy among children as a specific mechanism linking treatment to these conditions has yet to be confirmed.

“Until we have a better understanding of an underlying mechanism, the implications for clinical practice are limited,” Polinski said. “It may not be specific to treatments and could result from underlying risk factors. The implications for clinical practice are limited, as the study was not designed to prove cause and effect.”

Next, Polinski said, it will be important to determine this mechanism.

“A good place to start would be to clarify and disentangle the impacts of fertility medications or procedures themselves from underlying subfertility,” she said.

Reference:

• Asthma, allergy risk may be higher for children conceived with infertility treatment. https://www.nih.gov/news-events/news-releases/asthma-allergy-risk-may-be-higher-children-conceived-infertility-treatment. Posted April 21, 2022. Accessed April 22, 2022.

For more information:

Kristen J. Polinski, PhD, can be reached at kristen.polinski@nih.gov.