Effect of Acetaminophen use during pregnancy on adverse pregnancy outcomes: a systematic review and meta-analysis

ABSTRACT

Introduction

A high number of women are exposed to acetaminophen during pregnancy worldwide. This drug safety during pregnancy regarding preterm birth, birth weight, and fetal development has not been well described. This study investigated the effect of acetaminophen use during pregnancy on selected adverse pregnancy outcomes.

Areas covered

Databases were searched to identify studies reporting the effects of acetaminophen use during pregnancy on preterm birth, low birth weight, and small for gestational age. The studies’ quality was assessed by the Newcastle-Ottawa Scale and the Methodological Index for Non-Randomized Studies. Risk ratios with 95% confidence intervals were estimated using a fixed or random‐effects model. Six studies were included for final review, four cohort and two case‐control studies. We found no increased risk of preterm birth (RR 0.97; 95% CI 0.59–1.58), and decreased risks of low birth weight (RR 0.65; 95% CI 0.59–0.72) and small for gestational age (RR 0.69; 95% CI 0.50–0.97). Acetaminophen exposure during the third trimester revealed non-significantly in the outcomes.

Expert opinion

Exposure to acetaminophen during pregnancy appears to not increase the risk of the outcomes analyzed. However, there is a lack of information regarding the exposure dose and frequency of acetaminophen use.

KEYWORDS:

• Acetaminophen
• low birth weight
• meta-analysis
• pregnancy
• preterm birth
• small for gestational age
• systematic review

Article highlights

• Acetaminophen is the most used drug for pain and fever in pregnancy.

• The safety and consequences of this drug use during pregnancy regarding pregnancy duration and fetus development are not well described.

• This systematic review demonstrated that acetaminophen use during pregnancy was not associated with an increased risk of preterm birth, low birth weight, or small for gestational age.

• No evidence of an increased risk for adverse pregnancy outcomes in women exposed to acetaminophen in the third trimester was found in our analysis.

This box summarizes key points contained in the article.

Author contributions

C.T. Castro and D.B. Santos conceived the study. C.T. Castro and D.B. Santos contributed to the study design, data analysis, and data interpretation. C.T. Castro and R.S. Gama contributed to the study selection, data extraction, and interpretation of data. C.T. Castro, D.B. Santos, M. Pereira, M.G. Oliveira, T.S. Dal-Pizzol, and M.L. Barreto were involved in drafting the manuscript and revised it critically. All authors read and approved the final manuscript.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2022.2020246.

Additional information

Funding

This study was supported by Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) (Grant No. BOL0401/2019). The funders had no role in study design, study selection and data extraction, data analysis, decision to publish, or preparation of the manuscript.