# Neurodevelopmental Effect of Acetaminophen Exposures

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $530,371

## Abstract

Project Summary
Acetaminophen (N-acetyl-p-aminophenol or APAP) is recommended as a safe treatment to reduce pain and
fever during pregnancy. An estimated 45-65% of pregnant people reported intake of APAP in the U.S., but there
has been little data on safety for potential health effects in the prenatally exposed offspring. APAP
placental
can cross the
barrier reaching the fetus which has limited capacity to metabolize the compound in early development.
Recent experimental studies demonstrated compelling evidence suggesting APAP can induce anti-androgenic
effects potentially affecting fetal brain development. The Society for Maternal-Fetal Medicine and the U.S. Food
and Drug Administration have called for a more thorough investigation and better data to guide the safety of
APAP use in pregnancy. Our experienced and multidisciplinary team proposes to leverage the rich data collected
in the Danish National Birth Cohort (DNBC) and records from the Danish population medical registries to
investigate the potential effects of APAP exposures on fetal development. In Aim 1, we will study 64,322 mother-
child pairs enrolled in the DNBC and investigate the effects of prenatal exposure to APAP on a wide spectrum
of neurodevelopmental outcomes, ascertained at multiple time points from infancy through age 18. Six domains
of outcomes will be examined, including milestones in infancy, craniofacial markers, neurobehavioral disorders,
motor function, school performance, and mental health. A rich set of confounding factors, including maternal
illnesses and familial/genetic risks, will be examined in a robust multi-stage analytical framework. In addition, we
will evaluate the effect of post-natal APAP exposure on neurodevelopment (aim 1a), the effect of APAP
exposures on childhood ADHD, adjusting for the genetic risk of ADHD (aim 1b), and explore whether APAP
exposures affect distinct neuropsychiatric phenotypes and/or behavioral trajectories across childhood and
adolescence (aim 1c). In Aim 2, we will investigate the influence of prenatal co-medication exposures with APAP
and their impacts on neurodevelopment. We will examine whether medications that co-occur with APAP use
during pregnancy confound the associations between APAP exposure and child neurodevelopment. We will also
examine the joint effects of co-medications exposures. We will focus on a list of common medications (7 major
and 15 subclasses) that impact fetal growth and/or brain development documented in the literature. This timely
research project will provide strong and scientifically rigorous data to inform long-term health effects of early life
exposure to APAP on child neurodevelopment. This is also the most extensive cohort study investigating
maternal polypharmacy exposure effects on offspring neurodevelopment. Our findings will contribute to
regulatory recommendations and policymaking decisions for APAP, a widely consumed medication in pregnancy,
as well as related co-medication use.

## Key facts

- **NIH application ID:** 10736409
- **Project number:** 1R01HD109213-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Zeyan Liew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $530,371
- **Award type:** 1
- **Project period:** 2023-09-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10736409

## Citation

> US National Institutes of Health, RePORTER application 10736409, Neurodevelopmental Effect of Acetaminophen Exposures (1R01HD109213-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10736409. Licensed CC0.

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