Prenatal paracetamol exposure and child neurodevelopment: A review

Bauer, Ann Z.; Kriebel, David; Herbert, Martha R.; Bornehag, Carl‐Gustaf; Swan, Shanna H.

doi:10.1016/j.yhbeh.2018.01.003

Cited by 98 publications

(98 citation statements)

References 129 publications

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“…It is noteworthy that the literature review of Bauer and colleagues did not find results of neurocognitive associations with prenatal paracetamol intake beyond the age of 7. In the present study, we have shown that the strongest relationships with child behaviour were identified at 42 and 47 months, and that the SDQ associations diminished as the children became older—this being especially true of the boys.…”

Section: Commentmentioning

confidence: 94%

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Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study

Golding

Gregory

Clark

et al. 2019

Paediatric Perinatal Epid

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Background:The majority of epidemiological studies concerning possible adverse effects of paracetamol (acetaminophen) in pregnancy have been focussed on childhood asthma. Initial results of a robust association have been confirmed in several studies.Recently, a few cohort studies have looked at particular neurocognitive outcomes, and several have implicated hyperactivity.Objectives: In order to confirm these findings, further information and results are required. Here, we assess whether paracetamol intake between 18 and 32 weeks gestation is associated with childhood behavioural and cognitive outcomes using a large population. Methods: Data collected by the Avon Longitudinal Study of Parents and Children(ALSPAC) at 32 weeks gestation and referring to the period from 18 to 32 weeks, identified 43.9% of women having taken paracetamol. We used an exposome analysis first to determine the background factors associated with pregnant women taking the drug, and then allowed for those factors to assess associations with child outcomes (measured using regression analyses). Results:We identified 15 variables independently associated with taking paracetamol in this time period, which were used as potential confounders. Of the 135 neurocognitive variables considered, adjusting for the likelihood of false discovery, we identified 56 outcomes for adjusted analyses. Adjustment identified 12 showing independent associations with paracetamol use at P < .05, four of which were at P < .0001 (all related to child behaviours reported by the mother at 42 and 47 months; eg conduct problems: adjusted mean score + 0.22 (95% confidence interval 0.10, 0.33)). There were few associations with behavioural or neurocognitive outcomes after age 7-8 years, whether reported by the mother or the teacher. Conclusions:If paracetamol use in mid-to-late pregnancy has an adverse effect on child neurocognitive outcome, it appears to mainly relate to the pre-school period.

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Section: Commentmentioning

confidence: 94%

“…Results from other longitudinal studies concerning neurocognitive outcomes have been reviewed by Bauer and colleagues in 2018 . They identified nine studies from five cohorts, the Norwegian MoBA and the Danish DNBC being the largest and most informative.…”

Section: Commentmentioning

confidence: 99%

Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study

Golding

Gregory

Clark

et al. 2019

Paediatric Perinatal Epid

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“…However, it has been reported that the long-term administration of paracetamol to the pregnant mother is implicated in the development of autism or autism spectrum disorder in children. 16 In contrast, however, one study reported that there were no differences in neurodevelopmental outcomes at 18 to 24 months, including on the Bayley Scales of Infant Development, second edition; the Mental Developmental Index; and the Psychomotor Developmental Index, with recommended adaptations suggested for visual and auditory impairments in preterm or low-birth weight infants exposed to paracetamol as compared with ibuprofen for PDA. 17 Importantly, because the quality of evidence of this study is low, long-term follow-up to at least 18 to 24 months after birth must be incorporated in any studies of paracetamol in the newborn population, including our previous and present case series.…”

Section: Discussionmentioning

confidence: 97%

Safety and Feasibility of Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-/Ibuprofen-Resistant or -Contraindicated Preterm Infants: A Case Series

Oshima

Matsumura

Iwatani

et al. 2020

AJP Rep

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Background Although indomethacin and ibuprofen are the standard treatments for hemodynamically significant patent ductus arteriosus (hsPDA), they are associated with renal impairment and gastrointestinal complications. Paracetamol for hsPDA closure does not provoke a peripheral vasoconstrictive effect and seems to have effects similar to those of indomethacin and ibuprofen. We have previously reported the safety of low-dose (7.5 mg/kg) intravenous paracetamol for preterm infants with hsPDA, who were indomethacin-resistant or -contraindicated but did not affect the need for surgical PDA ligation. However, reports considering the use of higher-dose (15 mg/kg) paracetamol for hsPDA have not been published in Japan. Cases In 16 premature infants in whom indomethacin or ibuprofen was contraindicated or ineffective, 15 mg/kg of paracetamol was intravenously administered every 6 hours for 3 days after obtaining parental consent. hsPDA closure or narrowing was observed in 14 infants (88%), with the need for surgical closure totally avoided in nine cases (56%). High plasma paracetamol levels were observed in three cases. No paracetamol-related side effects or adverse events were reported. Conclusion The intravenous administration of higher dose paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials to explore the optimized dose and timing of administration are needed.

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“…Determining the effect of prenatal paracetamol exposure on child neurodevelopment is challenging. The term “neurodevelopment” encompasses a wide range of domains, and though previous studies have focused mainly on attention deficit hyperactivity disorder (ADHD) and behavioural outcomes, other outcomes, such as communication skills and temperament, are also important domains within the realm of neurodevelopment. Moreover, bias and confounding are problems encountered with observational data .…”

Section: Introductionmentioning

confidence: 99%

Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children

Trønnes

Wood

Lupattelli

et al. 2019

Paediatric Perinatal Epid

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Background: Recent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.Objective: To examine the association between duration and timing of prenatal paracetamol exposure on parent-reported communication skills, behaviour, and temperament in preschool-aged children, with focus on the role of unmeasured confounding. Methods:We used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes. Results:Of the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively.Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β −0.62, 95% confidence interval [CI] −1.05, −0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β −0.32, 95% CI −0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null. Conclusions:Timing of exposure and short-term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool-aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings. K E Y W O R D Schild neurodevelopment, MoBa, paracetamol, pregnancy This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Prenatal paracetamol exposure and child neurodevelopment: A review

Cited by 98 publications

References 129 publications

Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study

Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study

Safety and Feasibility of Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-/Ibuprofen-Resistant or -Contraindicated Preterm Infants: A Case Series

Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool‐aged children

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