Prenatal exposure to acid-suppressive drugs elevates risk of childhood asthma
Children born to mothers who used acid-suppressive drugs, including histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), during pregnancy are at greater risk of developing asthma, according to a systematic review and meta-analysis.
Specifically, pooled data from eight population-based studies showed that acid-suppressive drug use in pregnancy increased the risk of childhood asthma in offspring by 45 percent (relative risk [RR], 1.45; 95 percent CI, 1.35–1.56; I2, 0 percent; p<0.00001). [Pediatrics 2018;doi:10.1542/peds.2017-0889]
In a subgroup analysis by type of acid-suppressive drug, prenatal exposure to PPIs was associated with a 34-percent increased risk of asthma in childhood (RR, 1.34; 1.18–1.52; I2, 46 percent; p<0.00001), whereas prenatal exposure to H2RAs increased the risk by 57 percent (RR, 1.57; 1.46–1.69; I2, 0 percent; p<0.00001).
Because of the risk of asthma in offspring, clinicians and parents need to exercise caution when considering the use of acid-suppressive drugs during pregnancy, the investigators said.
“In adults, the use of acid-suppressive drugs may alleviate asthma in patients with GERD [gastro-oesophageal reflux disease], but the drugs are also associated with allergic sensitization,” they added.
Although the mechanism by which acid-suppressive drug exposure during pregnancy contributes to the development of asthma in children is unclear, evidence from previous animal and human studies suggests that PPIs or H2RAs may interfere with the denaturation of food antigens in the stomach, making food proteins act like allergens and thereby causing allergic sensitization. [Allergy 2011;66:469-477; FASEB J 2007;21:1264-1270]
The investigators explained that allergic sensitization could, in turn, lead to food-specific immunoglobulin-E induction and the development of T helper cell-2–biased hypersensitivities in pregnant women.
Aside from prenatal exposures, such as the use of acid-suppressive drugs, antibiotics, paracetamol or folic acid, maternal smoking and/or passive smoking are also believed to contribute to asthma in offspring. [Am J Clin Nutr 2013;98:1272-1281; Pediatr Allergy Immunol 2015;26:756-764; Am J Hum Genet 2016;98:680-696]
Despite the strengths of the analysis, including the detailed examination of the association of acid-suppressive drugs with childhood asthma by stratifying by agent type and carrying out a sensitivity analysis, the investigators acknowledged several limitations. One is that most of the studies included in the analysis were observational in nature. Another is the lack of individual data on dose-response relationships that may have affected gastric acid production.
“On the basis of this study, researchers in future studies examining the early origins of childhood asthma need to account for the impact of prenatal, maternal, acid-suppressive drug use,” they said.