Acetaminophen use in pregnancy linked to children’s language delays

In a recent prospective study published in the journal Pediatric Research, researchers investigated the effect of acetaminophen, an analgesic considered safe during pregnancy, on language development in children. They found that an increased use of acetaminophen during pregnancy is potentially associated with language development issues in children.

Study: Examining the relationship of acetaminophen use during pregnancy with early language development in children. Image Credit: luchschenF / Shutterstock

Background

The widespread use of acetaminophen (paracetamol) during pregnancy, perceived to be safe for decades, is now raising concerns about potential adverse neurodevelopmental effects. Epidemiological evidence links prenatal acetaminophen exposure to attention problems, motor delay, behavioral issues, and language development delay, highlighting the need for further investigation into its safety during pregnancy.

The few previous studies on prenatal use of acetaminophen and language development have been limited by infrequent self-report measures, hindering accurate assessment of timing and potential impacts. The Illinois Kids Development Study (IKIDS) improved upon this by assessing acetaminophen use in six distinct pregnancy periods, allowing for better evaluation. In the present study, researchers evaluated the impact of acetaminophen use on language development using the data from IKIDS and specific questionnaires.

About the study

IKIDS is a prospective pregnancy and birth cohort in the United States of America aimed at investigating the impact of gestational exposure to phenols and phthalates on neurodevelopment. Participants were recruited at 8–14 weeks gestation between 2013 and 2020. The inclusion criteria were <15 weeks of singleton pregnancy, age 18–40 years, willingness to provide samples, and residing close to the University of Illinois. They reported the number of times they consumed acetaminophen during the three trimesters of pregnancy. They also provided demographic, health, medication, pregnancy, and lifestyle-related data through interviews.

Data from 532 children born during the study were collected between 2016 and 2022. MacArthur-Bates Communicative Development Inventories (CDI) were filled by participants when their children (n = 298, 147 males) reached the age of 26.5–28.5 months. It is a parental form measuring expressive vocabulary, language complexity, and mean length of the longest three utterances (M3L). At 36–38 months, they filled the Speech and Language Assessment Scale (SLAS), a short questionnaire (n = 254, 121 males). It assesses responsiveness, semantics, assertiveness, syntax, and articulation. Socio-demographic factors and maternal stress and depression scores were considered as covariates, with child sex included as a potential modifier in continuous outcome models. Statistical analysis involved the use of multivariable generalized linear regression models and sensitivity analysis.

Results and discussion

Most participants consuming acetaminophen were found to be white and non-Hispanic. Demographic and exposure data were found to be similar among those filling the CDI and SLAS. About 70.9% of participants reportedly used acetaminophen-containing medications at least once during pregnancy, a higher proportion compared to previous studies. Few participants reported using other analgesics. Acetaminophen use was most common during the first trimester, with most participants using it for pain relief. There was no difference in acetaminophen use between subsets with CDI or SLAS data and the full sample. As per the CDI analysis, females demonstrated more advanced language development compared to males. Similarly, as per the SLAS analysis, females showed higher scores than males, but without statistical significance.

At 26.5–28.5 months, higher acetaminophen intake during pregnancy, especially in the second and third trimesters, was linked to reduced vocabulary size and M3L in children, with consistent effects across genders. Specifically, each increase in acetaminophen use during these trimesters was associated with a decrease in vocabulary size by 0.58 and 1.83 words, respectively, and a slight decrease in M3L. At 36–38 months of age, increased acetaminophen use during pregnancy, especially in the second and third trimesters, was found to correlate with lower total SLAS scores across genders. Males showed significantly lower SLAS scores with third-trimester exposure. Sensitivity analyses confirmed both these results.

Strengths of the study include its utilization of data from an ongoing, prospective birth cohort, multiple assessments of acetaminophen use during pregnancy, robustness to sensitivity analyses, and the use of comprehensive measures of language development in children. On the other hand, the study is limited by potential inaccuracies due to lack of correction for multiple comparisons, homogeneity of the cohort, loss to follow-up, potential error in self-reporting, lack of dosage information, and inability to assess the indications for acetaminophen use.

Conclusion

This is the first study to use a standardized measure of language development to evaluate the effect of prenatal acetaminophen exposure on neurodevelopmental outcomes in children. In conclusion, evidence from the present study links increased acetaminophen use during pregnancy to poorer language development. The study warrants further research to understand this association’s mechanisms and potentially establish causality. The researchers emphasize the importance of more extensive and more diverse cohort studies in the future to investigate prenatal acetaminophen exposure and its impact on neurodevelopment.