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

Castro, Caroline Tianeze de; Gama, Romana Santos; Pereira, Marcos; Oliveira, Márcio Galvão; Dal-Pizzol, Tatiane S.; Barreto, Maurício L.; Santos, Djanilson Barbosa dos

doi:10.1080/14740338.2022.2020246

Cited by 5 publications

(1 citation statement)

References 67 publications

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“…The highest risk was conferred by the NSAID-APAP combination ( Zafeiri et al, 2021 ). Conversely, APAP exposure during the third trimester was not associated with an increased risk of preterm birth and low birth weight ( Castro et al, 2021 ). Similarly, APAP exposure from 4 weeks before pregnancy until delivery and during pubertal development has not been associated with male puberty disorders (based on the examination of secondary genital organs, pubic hair, adult voice, first ejaculation) in more than 7,000 boys.…”

Section: Nonsteroidal Anti-inflammatory Drugs and Analgesics: Use And...mentioning

confidence: 99%

Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health

et al. 2022

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Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin (acetylsalicylic acid), diclofenac and ibuprofen (IBU), and analgesic drugs, such as acetaminophen (APAP, or paracetamol), are widely used to treat inflammation and pain. APAP and IBU are over-the-counter drugs and are among the most commonly taken drugs in the first trimester of pregnancy, even in combination. Furthermore, these drugs and their metabolites are released in the environment, and can be frequently detected in wastewater, surface water, and importantly in drinking water. Although their environmental concentrations are much lower than the therapeutics doses, this suggests an uncontrolled low-dose exposure of the general population, including pregnant women and young children, two particularly at risk populations. Epidemiological studies show that exposure to these molecules in the first and second trimester of gestation can favor genital malformations in new-born boys. To investigate the cellular, molecular and mechanistic effects of exposure to these molecules, ex vivo studies with human or rodent gonadal explants and in vivo experiments in rodents have been performed in the past years. This review recapitulates recent data obtained in rodent models after in utero or postnatal exposure to these drugs. The first part of this review discusses the mechanisms by which NSAIDs and analgesics may impair gonadal development and maturation, puberty development, sex hormone production, maturation and function of adult organs, and ultimately fertility in the exposed animals and their offspring. Like other endocrine disruptors, NSAIDs and APAP interfere with endocrine gland function and may have inter/transgenerational adverse effects. Particularly, they may target germ cells, resulting in reduced quality of male and female gametes, and decreased fertility of exposed individuals and their descendants. Then, this review discusses the effects of exposure to a single drug (APAP, aspirin, or IBU) or to combinations of drugs during early embryogenesis, and the consequences on postnatal gonadal development and adult reproductive health. Altogether, these data may increase medical and public awareness about these reproductive health concerns, particularly in women of childbearing age, pregnant women, and parents of young children.

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Section: Nonsteroidal Anti-inflammatory Drugs and Analgesics: Use And...mentioning

confidence: 99%

Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health

et al. 2022

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The relationship of prenatal acetaminophen exposure and attention-related behavior in early childhood

Woodbury,

Geiger,

Schantz

2024

Neurotoxicology and Teratology

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Examining the relationship of acetaminophen use during pregnancy with early language development in children

Woodbury,

Cintora,

et al. 2023

Pediatr Res

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Background Acetaminophen is the only analgesic considered safe for use throughout pregnancy. Recent studies suggest that use during pregnancy may be associated with poorer neurodevelopmental outcomes in children, but few have examined language development. Methods The Illinois Kids Development Study is a prospective birth cohort in east-central Illinois. Between December 2013 and March 2020, 532 newborns were enrolled and had exposure data available. Participants reported the number of times they took acetaminophen six times across pregnancy. Language data were collected at 26.5–28.5 months using the MacArthur-Bates Communicative Development Inventories (CDI; n = 298), and 36–38 months using the Speech and Language Assessment Scale (SLAS; n = 254). Results Taking more acetaminophen during the second or third trimester was associated with marginally smaller vocabularies and shorter utterance length (M3L) at 26.5–28.5 months. More acetaminophen use during the third trimester was also associated with increased odds of M3L scores ≤25th percentile in male children. More use during the second or third trimester was associated with lower SLAS scores at 36–38 months. Third trimester use was specifically related to lower SLAS scores in male children. Conclusions Higher prenatal acetaminophen use during pregnancy may be associated with poorer early language development. Impact Taking more acetaminophen during pregnancy, particularly during the second and third trimesters, was associated with poorer scores on measures of language development when children were 26.5–28.5 and 36–38 months of age. Only male children had lower scores in analyses stratified by child sex. To our knowledge, this is the first study that has used a standardized measure of language development to assess the potential impact of prenatal exposure to acetaminophen on language development. This study adds to the growing body of literature suggesting that the potential impact of acetaminophen use during pregnancy on fetal neurodevelopment should be carefully evaluated.

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

Cited by 5 publications

References 67 publications

Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health

Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health

The relationship of prenatal acetaminophen exposure and attention-related behavior in early childhood

Examining the relationship of acetaminophen use during pregnancy with early language development in children

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