Use of Acetaminophen (Paracetamol) During Pregnancy and the Risk of Attention-Deficit/Hyperactivity Disorder in the Offspring

Andrade, Chittaranjan

doi:10.4088/jcp.16f10721

Cited by 14 publications

(6 citation statements)

References 12 publications

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“…Although previous reports have suggested 45,46 the presence of bias, the results of sensitivity analysis for unmeasured confounding of the meta-analysis.…”

Section: Principal Findingsmentioning

confidence: 80%

Acetaminophen use during pregnancy and the risk of attention deficit hyperactivity disorder: A causal association or bias?

Masarwa

Platt

Filion

2020

Paediatric Perinatal Epid

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Background:The association between acetaminophen use during pregnancy and the development of attention deficit hyperactivity disorder (ADHD) in the offspring may be due to bias. Objectives:The primary objective was to assess the role of potential unmeasured confounding in the estimation of the association between acetaminophen use during pregnancy and the risk of ADHD, through bias analysis. The secondary objective was to assess the roles of selection bias and exposure misclassification. Data sources:We searched MEDLINE, Embase, Scopus, and the Cochrane Library up to December 2018. Study selection and data extraction:We included observational studies examining the association between acetaminophen use during pregnancy and the risk of ADHD. Synthesis:We meta-analysed data across studies, using random-effects model. We conducted a bias analysis to studies that did not adjust for important confounders, to explore systematic errors related to unmeasured confounding, selection bias, and exposure misclassification. Results:The search resulted in seven studies included in our meta-analysis. When adjusted estimates were pooled across all studies, the risk ratio (RR) for ADHD was 1.35 (95% confidence interval [CI] 1.25, 1.46; I 2 = 48%). Sensitivity analysis for unmeasured confounding in this meta-analysis showed that a confounder of 1.69 on the RR scale would reduce to 10% the proportion of studies with a true effect size of RR >1.10. Unmeasured confounding bias analysis decreased the point estimate in five of the seven studies and increased in two studies, suggesting that the observed association could be confounded by parental ADHD. Unadjusted and bias-corrected risk ratios (bcRRs) were: RR = 1.34, bcRR = 1.13; RR = 1.51, bcRR = 1.17; RR = 1.63, bcRR = 1.38; RR = 1.44, bcRR = 1.17; RR = 1.16, bcRR = 1.18; RR = 1.25, bcRR = 1.05;and RR = 0.99, bcRR = 1.18. Conclusions:Bias analysis suggests that the previously reported association between acetaminophen use during pregnancy and an increased risk of ADHD in the offspring may be due to unmeasured confounding. Our ability to conclude a causal association is limited. K E Y W O R D Sacetaminophen, ADHD, bias, confounding, pregnancy

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“…Although previous reports have suggested 45,46 the presence of bias, the results of sensitivity analysis for unmeasured confounding of the meta-analysis.…”

Section: Principal Findingsmentioning

confidence: 80%

Acetaminophen use during pregnancy and the risk of attention deficit hyperactivity disorder: A causal association or bias?

Masarwa

Platt

Filion

2020

Paediatric Perinatal Epid

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“…With ADHD as the outcome of interest, whereas exposure was indeed associated with a very small but statistically significantly increased risks (HR, 1.07 or lower), causality is unproven because confounding, such as confounding by indication, by maternal genetic factors, and by environmental factors, has been identified in observational designs. 10,12 Even if our finding for ADHD risk is true in the population, it is unlikely to be of clinical significance because the increase in risk was small and because ADHD is an uncommon event.…”

Section: Implications Of the Findingsmentioning

confidence: 76%

“…10,11 Whereas significant associations were identified, it appeared that the risks were driven by parental genetic factors, family environmental variables, and confounding by indication. 12 Although there have been 2 systematic reviews in the field, 13,14 there has been no metaanalysis of data to quantify the associations. Furthermore, studies have been published after these systematic reviews, one of which 10 had a more than tenfold larger number of exposed subjects than that in all previous studies pooled.…”

Section: Introductionmentioning

confidence: 99%

Gestational exposure to benzodiazepines or z‐hypnotics and neurodevelopmental disorders in offspring: Systematic review and meta‐analysis

Andrade,

Varadharajan,

Bascarane

et al. 2024

Acta Psychiatr Scand

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IntroductionBenzodiazepine (BDZP) and/or z‐hypnotic dispensing during pregnancy has increased globally, as have rates of autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD). This systematic review and meta‐analysis aimed to estimate the association between gestational exposure to BDZP and/or z‐hypnotics and diagnosis of ASD or ADHD in offspring.MethodsWe searched MEDLINE, EMBASE, and SCOPUS from inception till December 2023 for relevant English‐language articles. Outcomes of interest were risk of ASD and ADHD, two independent primary outcomes, in children exposed anytime during pregnancy to BDZP and/or z‐hypnotics versus those unexposed. Secondary outcomes were trimester‐wise analyses. Using a random effects model, we pooled the overall and trimester‐wise hazard ratios (HRs), with 95% confidence intervals (CIs), separately for risk of ASD and ADHD.ResultsWe found six eligible retrospective cohort studies and no case–control studies. There was no increased risk of ASD associated with anytime gestational BDZP and/or z‐hypnotic exposure (primary outcome, HR, 1.10; 95% CI, 0.81–1.50; 4 studies; n = 3,783,417; 80,270 exposed, 3,703,147 unexposed) nor after first trimester exposure (HR, 1.15; 95% CI, 0.83–1.58; 3 studies; n = 1,539,335; 70,737 exposed, 1,468,598 unexposed) or later trimester exposures. A very small but significantly increased risk of ADHD was noted with anytime gestational exposure to these drugs (primary outcome, HR, 1.07; 95% CI, 1.03–1.12; 4 studies; n = 2,000,777; 78,912 exposed, 1,921,865 unexposed) and also with (only) second trimester exposure (HR, 1.07; 95% CI, 1.03–1.12; 3 studies; n = 1,539,281; 33,355 exposed, 1,505,926 unexposed). Findings were consistent in sensitivity analyses.ConclusionGestational exposure to benzodiazepines or z‐hypnotics was not associated with an increased risk of ASD and with only a marginally increased risk of ADHD in offspring. Given the likelihood of confounding by indication and by unmeasured variables in the original studies, our findings should reassure women who need these medications for severe anxiety or insomnia during pregnancy.

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“…There is accumulating evidence that the use of paracetamol during pregnancy is not as safe as has been thought earlier, e.g. in some studies, it has been linked to an increased risk of autism, ADHD and lower IQ in the developing fetus [27][28][29] . Because paracetamol is a frequently used drug, more information is urgently needed about the consumption of paracetamol during pregnancy, especially its role in preeclampsia.…”

Section: Discussionmentioning

confidence: 98%

Maternal use of drugs and preeclampsia

Sahlman

Koponen

El‐Nezami

et al. 2019

Brit J Clinical Pharma

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Use of Acetaminophen (Paracetamol) During Pregnancy and the Risk of Attention-Deficit/Hyperactivity Disorder in the Offspring

Cited by 14 publications

References 12 publications

Acetaminophen use during pregnancy and the risk of attention deficit hyperactivity disorder: A causal association or bias?

Acetaminophen use during pregnancy and the risk of attention deficit hyperactivity disorder: A causal association or bias?

Gestational exposure to benzodiazepines or z‐hypnotics and neurodevelopmental disorders in offspring: Systematic review and meta‐analysis

Maternal use of drugs and preeclampsia

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