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Analysis of Neurodevelopment in Children Born Extremely Preterm Treated With Acid Suppressants Before Age 2 Years
Elizabeth T Jensen1, Joe Yi2, Wesley Jackson3
1Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Insights
Early acid suppressant use in extremely preterm infants is linked to lower IQ scores and increased risk of autism spectrum disorder and epilepsy. These findings suggest caution when prescribing these medications to vulnerable infants.
Area of Science:
- Pediatric Neurodevelopment
- Neonatal Pharmacology
- Longitudinal Cohort Studies
Background:
- Infants born preterm face higher risks of neurodevelopmental issues.
- Gastric acid suppression in infancy may impact neurodevelopmental outcomes.
- Vulnerability of preterm infants to medication effects necessitates careful evaluation.
Purpose of the Study:
- To investigate the association between early acid suppressant use and neurodevelopmental outcomes in extremely preterm infants.
- To assess cognitive, neurodevelopmental, and psychiatric sequelae at age 10 years.
- To inform clinical practice regarding the use of acid suppressants in this population.
Main Methods:
- Longitudinal cohort study of infants born before 28 weeks' gestational age (Extremely Low Gestational Age Newborn study).
- Assessment of acid suppressant use before 24 months via medical records and maternal questionnaires.
- Comprehensive neurodevelopmental assessments at age 10 years, including cognitive, autism, and ADHD evaluations.
Main Results:
- Early acid suppressant use was associated with lower full-scale, verbal, and nonverbal IQ z scores, and reduced working memory.
- Acid suppressant use correlated with an increased risk of autism spectrum disorder and epilepsy.
- No significant associations were found with inhibitory control, ADHD, anxiety, or depression.
Conclusions:
- Early-life acid suppressant use in extremely preterm infants may be associated with adverse neurodevelopmental outcomes.
- Findings support the need for cautious prescribing of acid suppressants in this high-risk group.
- Further research is warranted to elucidate mechanisms and long-term effects.
Importance:
Children born preterm are at increased risk of adverse neurodevelopmental outcomes and may be particularly vulnerable to the effects of gastric acid suppression during infancy.
Objective:
To assess whether early acid suppressant use in infants born extremely preterm is associated with poorer neurodevelopmental outcomes.
Design, Setting, And Participants:
The Extremely Low Gestational Age Newborn study was a multicenter, longitudinal cohort study of infants born before 28 weeks' gestational age between March 22, 2002, and August 31, 2004. The current analyses were performed from September 12, 2020, through September 22, 2022. Of the 1506 infants enrolled, 284 died before discharge and 22 died before 24 months of age. An additional 2 died before age 10 years, leaving 1198 (79.5%) eligible for a visit. Of these, 889 (74%) participated in the visit at age 10. At age 10 years, the association of early-life acid suppressant use with neurocognitive, neurodevelopmental, and psychiatric symptomatology was assessed.
Exposures:
Acid suppressant use before 24 months of age was determined from medical records and from questionnaires administered to mothers.
Main Outcomes And Measures:
Neurodevelopmental assessments at age 10 years included the School-Age Differential Ability Scales-II, the Developmental Neuropsychological Assessment-II, the Autism Diagnostic Observation Schedule-2, the Social Responsiveness Scale-2, and the Child Symptom Inventory-4 for attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety.
Results:
Of the 889 participants assessed at age 10 years (mean [SD] age, 9.97 [0.67] years; mean [SD] gestational age at birth, 26.1 [1.3] weeks; 455 [51.2%] male), 368 (41.4%) had received acid suppressants by 24 months of age. Associations were observed between acid suppressant use and decreased full-scale IQ z score (adjusted β, -0.29; 95% CI, -0.45 to -0.12), verbal IQ z score (adjusted β, -0.34; 95% CI, -0.52 to -0.15), nonverbal IQ z score (adjusted β, -0.22; 95% CI to -0.39 to -0.05), working memory z score (adjusted β, -0.26; 95% CI to -0.45, -0.08), autism spectrum disorder (adjusted relative risk, 1.84; 95% CI, 1.15-2.95), and epilepsy (adjusted relative risk, 2.07; 95% CI, 1.31 to 3.35). Results were robust to multiple sensitivity analyses. Use of acid suppressants was not associated with inhibitory control, ADHD, anxiety, or depression.
Conclusions And Relevance:
The results of this cohort study suggest that early-life use of acid suppressants in extremely preterm infants may be associated with poorer neurodevelopmental outcomes and add to evidence indicating caution in use of these agents.
