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Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding.

ABSTRACT: Importance:Acetaminophen (paracetamol) is used by a large proportion of pregnant women. Research suggests that acetaminophen use in pregnancy is associated with abnormal fetal neurodevelopment. However, it is possible that this association might be confounded by unmeasured behavioral factors linked to acetaminophen use. Objective:To examine associations between offspring behavioral problems and (1) maternal prenatal acetaminophen use, (2) maternal postnatal acetaminophen use, and (3) partner's acetaminophen use. Design, Setting, and Participants:From February 2015 to March 2016, we collected and analyzed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort. We studied 7796 mothers enrolled in ALSPAC between 1991 and 1992 along with their children and partners. Exposures:Acetaminophen use was assessed by questionnaire completion at 18 and 32 weeks of pregnancy and when the child was 61 months old. Main Outcomes and Measures:Maternal reports of behavioral problems using the Strengths and Difficulties Questionnaire (SDQ) when the children were 7 years old. We estimated risk ratios for behavioral problems in children after prenatal, postnatal, and partner's exposure to acetaminophen and mutually adjusted each association. Results:Maternal prenatal acetaminophen use at 18 (n?=?4415; 53%) and 32 weeks of pregnancy (n?=?3381; 42%) was associated with higher odds of having conduct problems (risk ratio [RR], 1.42; 95% CI, 1.25-1.62) and hyperactivity symptoms (RR, 1.31; 95% CI, 1.16-1.49), while maternal acetaminophen use at 32 weeks was also associated with higher odds of having emotional symptoms (RR, 1.29; 95% CI, 1.09-1.53) and total difficulties (RR, 1.46; 95% CI, 1.21-1.77). This was not the case for maternal postnatal (n?=?6916; 89%) or partner's (n?=?3454; 84%) acetaminophen use. We found the associations between maternal prenatal acetaminophen use and all the SDQ domains unchanged even after adjusting for maternal postnatal or partner's acetaminophen use. Conclusions and Relevance:Children exposed to acetaminophen prenatally are at increased risk of multiple behavioral difficulties, and the associations do not appear to be explained by unmeasured behavioral or social factors linked to acetaminophen use insofar as they are not observed for postnatal or partner's acetaminophen use. Although these results could have implications for public health advice, further studies are required to replicate the findings and to understand mechanisms.

SUBMITTER: Stergiakouli E

PROVIDER: S-EPMC5300094 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding.

Stergiakouli Evie E Thapar Anita A Davey Smith George G

JAMA pediatrics 20161001 10

<h4>Importance</h4>Acetaminophen (paracetamol) is used by a large proportion of pregnant women. Research suggests that acetaminophen use in pregnancy is associated with abnormal fetal neurodevelopment. However, it is possible that this association might be confounded by unmeasured behavioral factors linked to acetaminophen use.<h4>Objective</h4>To examine associations between offspring behavioral problems and (1) maternal prenatal acetaminophen use, (2) maternal postnatal acetaminophen use, and ...[more]

PMID: 27533796

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Project description:ImportanceLife-course determinants of insomnia, particularly the long-term association of childhood behavioral problems with insomnia later in life, are unknown. As childhood behaviors are measurable and potentially modifiable, understanding their associations with insomnia symptoms may provide novel insights into early intervention strategies to reduce the burden.ObjectiveTo investigate the association between behavioral problems at 5, 10, and 16 years of age and self-reported insomnia symptoms at 42 years of age.Design, setting, and participantsThis cohort study used data from the United Kingdom 1970 Birth Cohort Study, an ongoing large-scale follow-up study. Participants were followed up from birth (1970) to age 42 years (2012). Missing data were imputed via multiple imputation. Statistical analysis was performed from February 1 to July 15, 2019.ExposuresBehavior measured at 5, 10, and 16 years of age using the Rutter Behavioral Scale (RBS). Children's behavior was classified as normal (?80th percentile), moderate behavioral problems (>80th to ?95th percentile), and severe behavioral problems (>95th percentile) based on their RBS score.Main outcomes and measuresSelf-reported difficulties initiating or maintaining sleep (DIMS) were collected using a self-administered questionnaire at 42 years of age. Log-binomial logistic regression, adjusted for several potential confounders, was used to estimate the association of childhood behavioral problems with insomnia symptoms in adulthood. Sensitivity analyses were conducted to check robustness of the findings.ResultsParticipants were followed up from a baseline age of 5 years (n?=?8050; 3854 boys and 4196 girls), 10 years (n?=?9090; 4365 boys and 4725 girls), or 16 years (n?=?7653; 3575 boys and 4078 girls) until age 42 years. There was a 39% higher risk of DIMS (odds ratio [OR], 1.39; 95% CI, 1.04-1.84; P?=?.06 for trend) for participants with severe behavioral problems at 5 years of age compared with those with a normal RBS score. The odds of DIMS plus not feeling rested on waking (DIMS plus) in participants with severe behavioral problems at 5 years of age were 29% higher (odds ratio, 1.29; 95% CI, 0.97-1.70; P?=?.14 for trend) than participants with a normal RBS score, although this result was not statistically significant. Moderate and severe behavioral problems at 16 years of age were positively associated with DIMS and DIMS plus (moderate: OR, 1.28; 95% CI, 1.07-1.52; severe: OR, 1.67; 95% CI, 1.22-2.30; P?<?.001 for trend) and DIMS plus (moderate: OR, 1.32; 95% CI, 1.11-1.56; severe: OR, 1.47; 95% CI, 1.09-1.98; P?<?.001 for trend). Externalizing behavioral problems at 5 and 10 years of age were positively associated with insomnia symptoms at 42 years of age.Conclusions and relevanceThis study is the first to show associations of early-life behavioral problems, particularly early- and middle-childhood externalizing problems, with insomnia symptoms in adulthood. These findings underline the importance of addressing insomnia from a life-course perspective and considering the benefits of early behavioral intervention to sleep health.

Project description:Previous studies have reported associations between prenatal cell phone use and child behavioral problems, but findings have been inconsistent and based on retrospective assessment of cell phone use. This study aimed to assess this association in a multi-national analysis, using data from three cohorts with prospective data on prenatal cell phone use, together with previously published data from two cohorts with retrospectively collected cell phone use data.We used individual participant data from 83,884 mother-child pairs in the five cohorts from Denmark (1996-2002), Korea (2006-2011), the Netherlands (2003-2004), Norway (2004-2008), and Spain (2003-2008). We categorized cell phone use into none, low, medium, and high, based on frequency of calls during pregnancy reported by the mothers. Child behavioral problems (reported by mothers using the Strengths and Difficulties Questionnaire or Child Behavior Checklist) were classified in the borderline/clinical and clinical ranges using validated cut-offs in children aged 5-7years. Cohort specific risk estimates were meta-analyzed.Overall, 38.8% of mothers, mostly from the Danish cohort, reported no cell phone use during pregnancy and these mothers were less likely to have a child with overall behavioral, hyperactivity/inattention or emotional problems. Evidence for a trend of increasing risk of child behavioral problems through the maternal cell phone use categories was observed for hyperactivity/inattention problems (OR for problems in the clinical range: 1.11, 95%CI 1.01, 1.22; 1.28, 95%CI 1.12, 1.48, among children of medium and high users, respectively). This association was fairly consistent across cohorts and between cohorts with retrospectively and prospectively collected cell phone use data.Maternal cell phone use during pregnancy may be associated with an increased risk for behavioral problems, particularly hyperactivity/inattention problems, in the offspring. The interpretation of these results is unclear as uncontrolled confounding may influence both maternal cell phone use and child behavioral problems.

Project description:BackgroundOver-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children.ObjectiveEstimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts.MethodsThe American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex.ResultsIn Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (β -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (β 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (β 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations.ConclusionsInconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.

Project description:BACKGROUND AND AIMS:Hazardous drinking (i.e. alcohol consumption that places drinkers at risk for adverse health outcomes) during pregnancy is associated with adverse child outcomes. To address whether the associations are causal, we aimed to estimate the effect of maternal hazardous drinking during the first trimester on offspring emotional and behavioural problems throughout the pre-school age. We adjusted for: (1) measured confounding (e.g. smoking), (2) familial risk factors by sibling control design and (3) non-shared environmental risk factors by using hazardous drinking the 3 months before pregnancy as an instrumental variable. DESIGN:Prospective cohort study. Participants were recruited between 1999 and 2009 at ultrasound examination offered to all pregnant women in Norway. Data were collected during the 17th and the 30th weeks of gestation, and when the children were aged 1.5, 3 and 5 years. SETTING:Norway, 1999-2015. PARTICIPANTS:The sample consisted of 14?639 mothers with 25 744 offspring siblings from the Norwegian Mother and Child Cohort Study. MEASUREMENTS:Respondents self-reported on: alcohol consumption, children's emotional problems (i.e. emotional reactive, anxiety/depression, somatic complaints) and children's behavioural problems (i.e. attention and aggressive behaviour) throughout pre-school age. We used longitudinal latent growth curve models to estimate the effect of maternal drinking during the first trimester on offspring emotional and behavioural problems. FINDINGS:Most associations were strongly reduced after controlling for both familial and measured environmental risk factors. After adjustment, exposed children were more emotionally reactive [? = 2.33; 95% confidence interval (CI) = 0.13-4.53] and had more somatic complaints (? = 1.93; 95% CI = 0.09-3.77) at age 3, but not at age 5. Exposed children were less aggressive than unexposed siblings at age 5 (? = -2.27; 95% CI = -4.02 to -0.52). CONCLUSIONS:Children exposed to their mothers' hazardous drinking during the first trimester appear to be more emotionally reactive and have more somatic complaints at age 3, but not at age 5, and are less aggressive at age 5 compared with unexposed siblings.

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Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding.

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Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding.

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