de Fays Laurence, Van Malderen Karen, De Smet Karen, Sawchik Javier, Verlinden Veerle, Hamdani Jamila, Dogné Jean-Michel, Dan Bernard
Federal Agency for Medicines and Health Products (FAMHP), Brussels, Belgium.
Department of Pharmacy, Université de Namur, Namur, Belgium.
Dev Med Child Neurol. 2015 Aug;57(8):718-24. doi: 10.1111/dmcn.12745. Epub 2015 Apr 7.
Paracetamol (acetaminophen) remains the first line for the treatment of pain and fever in pregnancy. Recently published epidemiological studies suggested a possible association between paracetamol exposure in utero and attention-deficit-hyperactivity disorder/hyperkinetic disorder (ADHD/HKD) or adverse development issues in children. However, the effects observed are in the weak to moderate range, and limitations in the studies' design prevent inference on a causal association with ADHD/HKD or child neurological development. In parallel, recent animal data showed that cognition and behaviour may be altered following exposure to therapeutic doses of paracetamol during early development. These effects may be mediated by interference of paracetamol with brain-derived neurotrophic factor, neurotransmitter systems (including serotonergic, dopaminergic, adrenergic, as well as the endogenous endocannabinoid systems), or cyclooxygenase-2. However, no firm conclusion can be made on the relevance of these observations to humans. We conclude that additional well-designed cohort studies are necessary to confirm or disprove the association. In the context of current knowledge, paracetamol is still to be considered safe in pregnancy and should remain the first-line treatment for pain and fever.
对乙酰氨基酚仍是孕期疼痛和发热治疗的一线用药。最近发表的流行病学研究表明，子宫内接触对乙酰氨基酚与儿童注意力缺陷多动障碍/多动障碍（ADHD/HKD）或不良发育问题之间可能存在关联。然而，观察到的影响处于弱到中等范围，且研究设计的局限性妨碍了对与ADHD/HKD或儿童神经发育之间因果关联的推断。同时，最近的动物数据显示，在早期发育过程中接触治疗剂量的对乙酰氨基酚后，认知和行为可能会发生改变。这些影响可能是由对乙酰氨基酚干扰脑源性神经营养因子、神经递质系统（包括血清素能、多巴胺能、肾上腺素能以及内源性大麻素系统）或环氧合酶-2介导的。然而，无法就这些观察结果与人类的相关性得出确切结论。我们得出结论，需要进行更多精心设计的队列研究来证实或反驳这种关联。根据目前的知识，对乙酰氨基酚在孕期仍被认为是安全的，应继续作为疼痛和发热的一线治疗药物。
