Acetaminophen use in pregnancy: Examining prevalence, timing, and indication of use in a prospective birth cohort

Bandoli, Gretchen; Palmsten, Kristin; Chambers, Christina D.

doi:10.1111/ppe.12595

Cited by 41 publications

(34 citation statements)

References 28 publications

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“…Therefore, the potential effect of this bias in the observed null associations cannot be ruled out at all. Second, the relatively high prevalence of paracetamol use in our study population (36.8–61.7%) was similar to other observational studies; for example, 58% of pregnant women from the MotherToBaby study (USA) [ 27 ] or 47% of women included in the Danish National Birth Cohort [ 25 ]. However, our study did not consider other relevant variables regarding paracetamol use such as the specific doses, medical prescription or combination with other mild analgesics.…”

Section: Discussionsupporting

confidence: 86%

Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort

Navarro-Lafuente

Arense-Gonzalo

Adoamnei

et al. 2021

IJERPH

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Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred—the recall of paracetamol intake independent of AGD measurements—introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.

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Section: Discussionsupporting

confidence: 86%

Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort

Navarro-Lafuente

Arense-Gonzalo

Adoamnei

et al. 2021

IJERPH

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“…Residual confounding is a third source of bias, and in our representation (panel A, Figure ), the most likely to cause bias away from the null, or an overestimation of the true effect. Acetaminophen presents a difficult confounding problem, since it is used to treat a wide range of conditions, including pain and fever, but as observed in several studies, it is also used in greater amounts by pregnant women who report more psychiatric diagnoses, or more depressive or anxiety symptoms . This suggests that the underlying indications and causes of exposure are complex and points to a potential for heritable or familial confounding by susceptibility to psychiatric co‐morbidities.…”

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confidence: 99%

Associations between prenatal acetaminophen exposure and child neurodevelopment: Truth, bias, or a bit of both?

Wood

2020

Paediatric Perinatal Epid

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What are we to make of a recent flood of studies suggesting that prenatal exposure to acetaminophen is associated with neurodevelopmental problems in toddlers and young children? Neurodevelopment is a notoriously slippery outcome to define, as it encompasses multiple phenotypes, including cognition and intelligence, psychiatric diagnoses, developmental milestone attainment, behavioural problems, motor and communication skills, and emotional regulation.Others have noted that many of the survey-based instruments used to measure neurodevelopment have uncertain predictive value for clinically relevant developmental problems. 1 Even assuming that studies have selected outcome measures that capture important neurodevelopmental phenotypes, studying the effect of acetaminophen on these outcomes is extraordinarily challenging. Nonetheless, acetaminophen is one of the most commonly used medications among pregnant women, and if prenatal exposure truly has a causal effect on neurodevelopment, even if this effect is small, it is important to understand it.Consider the hypothetical case where acetaminophen has a true causal effect on neurodevelopment, but affects only impulsivity, and only for exposures occurring between gestational weeks 17 and 20.Acetaminophen is highly subject to exposure misclassification, both in terms of confusion with other drugs and with respect to timing of use. Many studies rely on maternal report for both the exposure and the outcome, which can introduce dependent measurement error. Acetaminophen is taken for a wide range of reasons and severity, including pain, inflammation, and fever, making confounding by indication very difficult to understand and control, either through design or analysis. Ascertainment of neurodevelopmental problems often requires follow-up over the course of years, leaving the sample vulnerable to bias from selection, especially if parents of children with more behavioural problems are less likely to sustain their participation in a long-term study, and if participation is also associated with exposure. Considered singly, any one of these sources of bias should worry conscientious researchers, but taken together, a picture of multiple competing biases emerges, making the task of identifying a true causal effect very challenging. The figure depicts the classic threats to validity-information, selection, and confounding bias-in terms of how they are likely to move effect estimates in studies of prenatal exposure to acetaminophen and neurodevelopmental outcomes in children (panel A), and a possible directed acyclic graph (panel B) suggests a possible causal mechanism through which these biases may act.

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“…Taken together, these findings underscore the importance of indication information for interpretation of any findings observed. Bandoli and colleagues greatly informed the scope of factors that should be considered in this process by identifying specific factors associated with frequency, timing, and duration of prenatal acetaminophen use. These include chronic medical conditions (any use) and fevers (short‐term use) as well as sleeping difficulties and arthritis (longer‐term use).…”

mentioning

confidence: 99%

“…However, impacts of chronic or longer‐duration use (often defined as >28 days or administrations) may be worthy of further investigation given this aspect of acetaminophen exposure was most reliably associated with child behavioural outcomes. That said, as Bandoli and colleagues illustrate, confounding by indication represents a viable alternative explanation if factors specifically associated with long‐duration use are not assessed and incorporated into analysis. We must also consider any risks associated with pregnant women not using acetaminophen for pain or fever relief.…”

mentioning

confidence: 99%

Prenatal acetaminophen exposure and neurodevelopment: State of the evidence

Talge

2020

Paediatric Perinatal Epid

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The developing brain is a fascinating enigma-it is vulnerable to the impacts of deleterious exposures, yet it simultaneously exhibits a remarkable capacity for resilience and adaptation. This apparent paradox can be explained by the concept of sensitive periods, timeframes in which the presence or absence of particular experiences shape brain development in ways that are resistant to subsequent change. Brain regions/networks vulnerable at any given point in time tend to be those undergoing rapid development. In the perinatal period, depending upon the timing, dose, and duration of exposure, overall brain size, subcortical development, and connectivity between subcortical and cortical regions may be particularly vulnerable. 1 In con

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Acetaminophen use in pregnancy: Examining prevalence, timing, and indication of use in a prospective birth cohort

Cited by 41 publications

References 28 publications

Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort

Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort

Associations between prenatal acetaminophen exposure and child neurodevelopment: Truth, bias, or a bit of both?

Prenatal acetaminophen exposure and neurodevelopment: State of the evidence

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