The incidence of infantile hypertrophic pyloric stenosis and its association with folic acid supplementation during pregnancy: A nested case-control study

Background and rationale: Several studies have suggested that the incidence of infantile hypertrophic pyloric stenosis (IHPS) has decreased in recent decades. This decrement is controversial and not fully explained. Concurrently, there has been a major increase in folic acid consumption by pregnant women to prevent neural tube defects. We aimed to describe IHPS incidence in Israel in recent years and to assess its potential association with folic acid consumption.

Methods: Using the electronic medical database of a 2.1 million member health organization in Israel, we identified all cases (n = 1899) of IHPS occurring between 1999 and 2015. Cases were individually matched with up to 5 controls (n = 7350) by birth date, sex, and region. Odds ratios and 95% confidence intervals by tertiles of cumulative dose of supplemented folic acid between three months prior to pregnancy and up to birth of index child were calculated using conditional logistic regression.

Results: During the study period IHPS incidence declined from 4.3 in 1999 to 2.1 per 1000 live births in 2015(p < 0.0001). No significant (p = 0.81) association was observed between folic acid intake during pregnancy and risk of IHPS incidence. Preterm birth and infant's use of macrolides during first 3 postnatal months were significantly (p < 0.01) associated with increased risk of IHPS.

Conclusions: Similar to other countries, IHPS incidence in Israel has decreased in recent years. The decrement cannot be explained by increased use of folic acid.

Type of study: Case Control Study.

Level of evidence: Level III.

Summary: Using linkage to a large electronic patient database, this study investigated the association between the decrease in infantile hypertrophic pyloric stenosis and maternal exposure to folic acid during pregnancy.