Gastric acid suppression in preemies carries neurodevelopmental risks

Exposure to acid suppressants during infancy may have adverse, long-term neurodevelopmental consequences in extremely preterm infants, as shown in a study.

Acid suppressant use in the first 24 months of life was associated with multiple adverse neurocognitive and neurodevelopmental outcomes at age 10 years, including lower scores on measures of IQ (–4.35 points on full scale IQ, 95 percent confidence interval [CI], 6.75–1.80), executive function (verbal IQ: adjusted β, −0.34, 95 percent CI, −0.52 to −0.15; nonverbal IQ: adjusted β, −0.22, 95 percent CI, −0.39 to −0.05), and working memory (adjusted β, −0.26; 95 percent CI −0.45 to −0.08). [JAMA Netw Open  2022;5:e2241943]

Moreover, exposed infants were more likely to develop autism spectrum disorder (adjusted relative risk [aRR], 1.84, 95 percent CI, 1.15–2.95) and epilepsy (aRR, 2.07, 95 percent CI, 1.31–3.27).

The associations observed persisted in multiple sensitivity analyses. Meanwhile, acid suppressant use had no effect on other outcomes such as inhibitory control, attention deficit hyperactivity disorder, anxiety, and depression.

“Although the specific mechanisms underlying these associations are uncertain, acid suppressant use has been associated with changes in the intestinal microbiome and dysbiosis, which in turn has been associated with neurocognitive outcomes,” according to the investigators. [Microbiome 2017;5:10]

In a previous study in infants, the use of a proton pump inhibitor (PPI) led to a decrease in the abundance of Lactobacillus and Stenotrophomonas species and a parallel increase in the abundance of Haemophilus strains. This, according to the investigators, suggests that intestinal dysbiosis in the preterm infant may be particularly detrimental to neurodevelopment. [Front Cell Infect Microbiol 2017;7:444]

The present analysis used data from the longitudinal study Extremely Low Gestational Age Newborn and included 1,198 infants born before 28 weeks of gestational age. Among the 889 infants (mean age 9.97 years, mean gestational age at birth 26.1 weeks, 51.2 percent boys) who participated at the follow-up, 368 (41.4 percent) had received acid suppressants by 24 months of age.

Despite the presence of several limitations, “the present study has implications for the possible adverse effects of acid suppressants on neurodevelopment in children born extremely preterm, who generally experience intense physiological stress and may thus be particularly sensitive to [such] medications,” the investigators said.

They acknowledged that despite the increased awareness of the lack of benefit of acid suppression therapy, such as PPI, in the NICU, postdischarge use remains frequent. [JAMA 2018;319:2009-2020; Basic Clin Pharmacol Toxicol 2019;124:704-710; Lancet Reg Health Eur 2021;7:100129; Clin Pediatr   2016;55:712-716]

In light of the frequent use of acid suppressants in extremely preterm infants, the investigators called for additional investigation into the observed associations.