Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Paediatr Perinat Epidemiol. 2020 May;34(3):257-266. doi: 10.1111/ppe.12582. Epub 2019 Sep 15.
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.
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.
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).
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.
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. It is important that these results be tested using other datasets or methodologies before assuming that they are causal.
大多数关于扑热息痛(对乙酰氨基酚)在妊娠期间可能产生不良影响的流行病学研究都集中在儿童哮喘上。几项研究已经证实了最初的关联结果。最近,一些队列研究关注了特定的神经认知结果,其中一些表明与多动有关。
为了证实这些发现,需要进一步的信息和结果。在这里,我们使用大量人群评估妊娠 18 至 32 周时服用扑热息痛是否与儿童行为和认知结果有关。
通过阿冯纵向研究父母和孩子(ALSPAC)在 32 周妊娠时收集的数据,并参考从 18 周到 32 周的时间,确定 43.9%的女性服用过扑热息痛。我们首先使用暴露组分析来确定与孕妇服用该药相关的背景因素,然后允许这些因素评估与儿童结果的关联(使用回归分析进行评估)。
我们确定了在此期间与服用扑热息痛独立相关的 15 个变量,这些变量被用作潜在的混杂因素。在考虑的 135 个神经认知变量中,调整假阳性发现的可能性后,我们确定了 56 个可进行调整分析的结果。调整后发现 12 个结果与扑热息痛使用独立相关(P<.05),其中 4 个在 P<.0001 水平(均与母亲在 42 个月和 47 个月时报告的儿童行为有关;例如行为问题:调整后的平均得分+0.22(95%置信区间 0.10,0.33))。在 7-8 岁以后,无论是母亲还是老师报告,扑热息痛使用与行为或神经认知结果的关联都很少。
如果妊娠中期至晚期使用扑热息痛对儿童神经认知结果有不良影响,它似乎主要与学前时期有关。在假设这些结果具有因果关系之前,使用其他数据集或方法对这些结果进行测试非常重要。