夸大其词：儿童哮喘与早期对乙酰氨基酚暴露关系不大

《儿童疾病档案》（Archives of Disease in Childhood）近期发表的一份报告显示，早期对乙酰氨基酚暴露与儿童哮喘发病之间的关系较 “弱”，根据现有的证据这一推论“夸大”了两者的因果关系。

墨尔本大学M. Cheelo医生及其同事报告，该项综述对Embase和PubMed数据库中现有可用的数据进行检索整理，在分析了1967年至2013年间进行的1192篇相关研究后，纳入11项符合要求的研究。这11项研究中，有5项研究发现在孕早期暴露于对乙酰氨基酚可能导致哮喘发病的“可能性增加”（合并比值比，1.39）；但同时，这些研究试验间具有较高的异质性（I²=64.2%，P= 0.03）。

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剩下的6项研究观察了早期2年对乙酰氨基酚的暴露情况。其中3项研究发现了暴露与哮喘的“弱正相关”性，有4项研究直接对比了暴露于未暴露于对乙酰氨基酚中对儿童的影响。但仅一项研究调整了孕期上呼吸道感染因素，并得出“对乙酰氨基酚接触频率与儿童哮喘间的关联度有所下降。”因此，研究人员认为，“早期接触对乙酰氨基酚和哮喘发生间的关联证据常被夸大，而目前还没有足够证据支持该药物使用原则的变更。”在这5项研究中，只有2项研究探讨了孕中期时接触对乙酰氨基酚所产生的影响，结果大相径庭：2项研究所报告的比值比（OR）分别为1.06和2.15，后者I²=80%。2项研究发现在孕晚期接触对乙酰氨基酚接与哮喘发病“弱相关”，合并比值比1.17。3项研究观察了整个孕期接触对乙酰氨基酚的影响，但所有的研究结果都具有“显著的异质性”（OR =1.65，1.22，0.74，I²=89%）。只有一项研究调整了孕期呼吸道感染因素，但作者指出“所有研究均调整了早期呼吸道感染因素，并发现对乙酰氨基酚暴露和后续儿童哮喘的发生关联性降低”（Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]）。

研究所有作者报告无相关经济利益冲突。

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By: DEEPAK CHITNIS, Ob.Gyn. News Digital Network

FROM THE ARCHIVES OF DISEASE IN CHILDHOOD

VITALS

Key clinical point: Current evidence regarding purported link between early life exposure to acetaminophen and development of childhood asthma is weak and often overstated.

Major finding: Meta-analysis of 11 studies found disparate results linking acetaminophen exposure and childhood asthma, and these results generally were attenuated when adjusted for data related to respiratory tract infections during pregnancy and subsequent childhood asthma.

Data source: Meta-analysis of 11 observational cohort studies.

Disclosures: The authors reported no relevant financial conflicts of interest.

The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.

In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I2 = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.

Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I2 = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I2 = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).

The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

The authors reported no relevant financial conflicts of interest.