Acetaminophen Use During Pregnancy, Behavioral Problems, and Hyperkinetic Disorders
Acetaminophen Use During Pregnancy, Behavioral Problems, and Hyperkinetic Disorders
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DOI：
10.1001/jamapediatrics.2013.4914
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发表时间：
2014-04-01
期刊：
影响因子：
26.1
通讯作者：
Olsen, Jorn
中科院分区：
文献类型：
--
作者：
Liew, Zeyan;Ritz, Beate;Olsen, Jorn
重要性扑热息痛(扑热息痛)是许多国家最常用的治疗孕期疼痛和发烧的药物。研究数据表明，对乙酰氨基酚是一种激素干扰物，怀孕期间异常的激素暴露可能会影响胎儿的大脑发育。目的评估产前暴露于对乙酰氨基酚是否会增加儿童患注意力缺陷/多动障碍(ADHD)样行为问题或多动障碍(HKDS)的风险。研究对象我们研究了1996年至2002年在丹麦国家出生队列中登记的322名活产儿童和母亲。通过3次计算机辅助电话访谈，前瞻性地评估了孕期和婴儿出生后6个月对乙酰氨基酚的使用情况。主要结果和确定结果的措施我们使用(1)父母使用强项和困难问卷报告7岁儿童的行为问题；(2)从丹麦国家医院登记处或丹麦精神病学中央登记处检索2011年前的香港病症诊断；及(3)从丹麦处方登记处确定儿童ADHD处方(主要是利他林)。我们评估了接受HKD诊断或使用ADHD药物的风险比，以及产前暴露于扑热息痛后儿童行为问题的风险比。结果超过一半的母亲报告在怀孕期间使用扑热息痛。母亲在怀孕期间服用扑热息痛的儿童在7岁时被医院诊断为HKD(风险比=1.37；95%CI，1.19-1.59)、使用ADHD药物(风险比=1.29；95%CI，1.15-1.44)或有ADHD样行为(风险比=1.13；95%CI，1.01-1.27)的风险更高。妊娠期间服用扑热息痛超过1个月有更强的相关性，暴露反应趋势随妊娠期间扑热息痛使用频率的增加而增加(即HKD诊断、ADHD药物使用和ADHD样行为；P趋势及.001)。结果似乎没有受到母体炎症、孕期感染、母亲的精神健康问题或其他我们评估的潜在混杂因素的影响。结论母亲在孕期使用对乙酰氨基酚与儿童发生HKD和ADHD样行为的风险较高。由于暴露和结果是频繁的，这些结果与公共卫生有关，但需要进一步调查。版权所有2014美国医学会。版权所有。
IMPORTANCE Acetaminophen (paracetamol) is the most commonly used medication for pain and fever during pregnancy in many countries. Research data suggest that acetaminophen is a hormone disruptor, and abnormal hormonal exposures in pregnancy may influence fetal brain development.OBJECTIVE To evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD)-like behavioral problems or hyperkinetic disorders (HKDs) in children.DESIGN, SETTING, AND PARTICIPANTS We studied 64 322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002.EXPOSURES Acetaminophen use during pregnancy was assessed prospectively via 3 computer-assisted telephone interviews during pregnancy and 6 months after child birth.MAIN OUTCOMES AND MEASURES To ascertain outcome information we used (1) parental reports of behavioral problems in children 7 years of age using the Strengths and Difficulties Questionnaire; (2) retrieved HKD diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry prior to 2011; and (3) identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry. We estimated hazard ratios for receiving an HKD diagnosis or using ADHD medications and risk ratios for behavioral problems in children after prenatal exposure to acetaminophen.RESULTS More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at higher risk for receiving a hospital diagnosis of HKD (hazard ratio = 1.37; 95% CI, 1.19-1.59), use of ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk ratio = 1.13; 95% CI, 1.01-1.27). Stronger associations were observed with use in more than 1 trimester during pregnancy, and exposure response trends were found with increasing frequency of acetaminophen use during gestation for all outcomes (ie, HKD diagnosis, ADHD medication use, and ADHD-like behaviors; P trend < .001). Results did not appear to be confounded by maternal inflammation, infection during pregnancy, the mother's mental health problems, or other potential confounders we evaluated.CONCLUSIONS AND RELEVANCE Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcome are frequent, these results are of public health relevance but further investigations are needed. Copyright 2014 American Medical Association. All rights reserved.