New research suggests that children born via cesarean delivery are more likely to be hospitalized for allergies during their first 13 years. The study adds to evidence suggesting that the type of delivery at birth can have a long-lasting impact on the immune system.

“Our findings suggest that cesarean section may influence allergy development in children independent of environmental and genetic factors, and vaginal delivery may protect children against allergies,” said McGill University medical student Safiya Soullane, MSc, lead author of a study published in the Annals of Allergy, Asthma and Immunology, in an interview with Medscape Medical News.

Other studies have explored possible influences between cesarean delivery — which made up 31.7% of live US births in 2019 — and immune disorders. According to Soullane, “Exposure to vaginal flora is thought to help newborns develop a normal immune system and prevent allergies. Because of reduced exposure to maternal flora, cesarean delivery may increase the risk of developing allergies.”

A 2014 meta-analysis linked cesarean delivery to a 16% increase in the odds of children developing asthma, and a 2018 study suggested cesarean delivery could raise the risk for food allergies by 21%. On the other hand, a 2020 study failed to find any connection between cesarean delivery and higher rates of allergic rhinitis.

For the new study, researchers retrospectively tracked 954,754 children born at full term in hospitals in Quebec, Canada, from 2006 to 2019. Twenty-three percent were born by cesarean delivery, and 10% were born by operative vaginal delivery (ie, delivery with the assistance of forceps or vacuum). The rest were born vaginally without operative assistance.

Allergic hospitalizations were rare ― they occurred in 2.9% of those born by cesarean or operative vaginal delivery and in 2.6% of those born vaginally without operative assistance.

After adjusting their findings to account for various confounders, the researchers found that children who were born via cesarean delivery were more likely to be hospitalized for any allergy than were those born vaginally without operative assistance (hazard ratio [HR] = 1.13; 95% CI, 1.09 – 1.17). Those born vaginally with operative assistance were also more likely to be hospitalized for allergy (HR = 1.09; 95% CI, 1.04 – 1.15).

Children born by cesarean delivery were also more likely to be hospitalized for anaphylaxis (HR = 1.05; 95% CI, 0.91 – 1.22; HR = 0.91; 95% CI, 0.73 – 1.12).

The HRs for cesarean delivery remained steady or grew after the researchers used a statistical strategy to account for unknown variables that siblings share. Under this analysis, the increased risks were higher for any allergy (HR = 1.16; 95% CI,1.06 – 1.27; HR = 1.35; 95% CI, 0.94 – 1.94) and nonasthmatic allergy (HR = 1.27; 95% CI, 1.10 – 1.45). The excess risk went down a bit for allergic asthma (HR = 1.07; 95% CI, 0.96 – 1.20).

However, the excess risk for operative vaginal delivery in all categories — hospitalization for all allergies, asthmatic asthma, anaphylaxis, and nonasthmatic allergy — vanished when the statistical strategy was employed.

“It was surprising to see that cesarean section was associated with allergies even after accounting for environmental and genetic factors,” Soullane said. “In contrast, the association between forceps/vacuum delivery and child allergy disappeared when we accounted for these confounders.”

Regarding the study’s limitations, Soullane said, “We lacked data on paternal characteristics, breastfeeding, and nutrition.”

She said the study findings should not discourage women from undergoing cesarean delivery, “which remains a safe procedure that is lifesaving in many cases.” However, she said, “women who have the opportunity to attempt a vaginal delivery should be encouraged to do so.”

Pauline Mendola, PhD, an epidemiologist at the University of Buffalo, in Buffalo, New York, who has studied cesarean deliveries but was not involved in this study, said in an interview with Medscape Medical News that the study was “well done.” According to her, it tackles a topic — hospitalization for allergy — that is “a less common and more serious outcome than generally studied.”

She added that lack of exposure to vaginal flora might not be the only possible cause of an increased risk for immune disorders in children born via cesarean delivery. “Other potential links could be due to antibiotic use and the reduced stimulation of the infant, as they are not exposed to the hormonal and physical stresses of labor and vaginal delivery,” she said. “These early life events appear to be very important for the regulation of infant immune system development.”

Unanswered questions remain, she said. “Why will some offspring develop asthma/allergy after cesarean delivery while others do not? And related: what is the underlying biologic mechanism or combination of factors that most contribute to risk? Also, given that cesarean delivery can be lifesaving and medically necessary, are there interventions that could mitigate these potential offspring effects?”

The study was funded by the Canadian Institutes of Health Research and the Quebec Health Research Fund. Mendola and the study authors have disclosed no relevant financial relationships.

Ann Allergy Asthma Immunol. Published online April 21, 2021. Abstract

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