母婴危险因素对儿童哮喘的相对重要性及叠加效应
2016/05/31
摘要
背景：子宫环境和生命早期的环境可能通过人类微生物组的改变使得儿童换上哮喘。本研究的目的是评估环境对儿童患上哮喘风险的累积效应和相对重要性的。
方法：我们进行了一项以基于人口出生的母子队列研究，这些孩子出生于1995和2003之间，连续参加了PRIMA（预防RSV：对发病率和哮喘的影响）。孕期孕妇尿路感染（UTI）的个体和累积影响，母体感染B组链球菌（GBS）、分娩方式、新生儿抗生素的使用，家里有哥哥姐姐，采用Logistic回归这些因素对儿童哮喘的风险进行估计。对孕期母体尿路感染的次数、婴幼儿抗生素的使用次数、家里哥哥姐姐的个数等持续危险因素所引起的儿童哮喘的剂量效应进行评估。我们进一步评估和比较这些暴露对哮喘风险的相对重要性。对一个儿童亚组中孕期母体抗生素的使用信息，以及其对儿童哮喘的影响进行了评估。
结果：在136,098例独生子女中，13.29%例发展为哮喘。在单因素和调整分析中，妊娠期间母体尿路感染（比值比[OR] 1.2，95%可信区间[CI] 1.18、1.25；调整比值比[AOR] 1.04，95% CI 1.02，1.07每增加一次UTI）和婴儿使用抗生素（OR 1.21，95% CI 1.20，1.22，AOR 1.16，95% CI 1.15，1.17，每多使用一次）与儿童哮喘的风险增加有关，而在家里有兄弟姐妹（OR 0.92，95% CI 0.91，0.93；AOR 0.85，95% CI 0.84，0.87，每增加一个哥哥或姐姐）与降低儿童哮喘的风险有关，且呈剂量依赖性。与阴道分娩相比，在单因素分析中，剖腹产增加儿童哮喘的几率可达34%（OR 1.34，95% CI 1.29，1.39），根据其它环境因素与协变量进行调整后，增加几率为11%（AOR 1.11，95% CI 1.06，1.15）。母体GBS与显著增加儿童哮喘的危险因素进行单因素分析时相关（OR 1.27，95% CI 1.19，1.35），但在调整后的分析中不相关（AOR 1.03，95% CI 0.96，1.10）。在获得了母亲的抗生素使用信息的儿童亚组中发现，产妇抗生素的使用与儿童哮喘的危险性增加在单因素相关分析和调整之后的相关分析时均呈现类似的剂量依赖性（OR 1.13，95% CI 1.12，1.15；95% CI 1.05，或1.06，1.08，每多使用一次抗生素）。与受暴露影响最小的婴儿（孕期无尿路感染、阴道分娩、家里至少5个哥哥姐姐、婴儿期不用抗生素）相比，受暴露影响最大的婴儿（孕期至少三次尿路感染、剖腹产、没有兄弟姐妹、婴儿期使用抗生素8次或更多）发展成哮喘的几率要增加7.77倍（AOR：7.77，95%可信区间：6.25，9.65）。最后，婴儿使用抗生素与妊娠期间尿路感染、生产方式和家中有无哥哥姐姐相比，对哮喘的风险影响最大。
结论：母体孕期尿路感染（母亲使用抗生素）、生产方式、婴儿使用抗生素、家中有哥哥姐姐这些生命早期的影响和儿童患哮喘风险增加相关，并成累计效应，对那些连续变量，呈现剂量效应。和在子宫内受到的影响相比，婴儿期受到的影响对儿童哮喘形成的风险的影响更大。
（杨冬 审校）
PLoS One. 2016 Mar 22;11(3):e0151705. doi: 10.1371/journal.pone.0151705. eCollection 2016.
Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.
Wu P1,2, Feldman AS1, Rosas-Salazar C3, James K4, Escobar G5,6, Gebretsadik T2, Li SX6, Carroll KN3, Walsh E6, Mitchel E7, Das S8, Kumar R9, Yu C2,Dupont WD2, Hartert TV1.
Author information
Abstract
BACKGROUND:Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma.
METHODS:We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated.
RESULTS:Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C-section delivery increased odds of childhood asthma by 34% (OR 1.34, 95%CI 1.29, 1.39) in the univariate analysis and 11% after adjusting for other environmental exposures and covariates (AOR 1.11, 95%CI 1.06, 1.15). Maternal GBS was associated with a significant increased risk of childhood asthma in the univariate analysis (OR 1.27, 95%CI 1.19, 1.35), but not in the adjusted analysis (AOR 1.03, 95%CI 0.96, 1.10). In the subgroup analysis of children whose maternal antibiotic use information was available, maternal antibiotic use was associated with an increased risk of childhood asthma in a similar dose-dependent manner in the univariate and adjusted analyses (OR 1.13, 95%CI 1.12, 1.15; AOR 1.06, 95%CI 1.05, 1.08 for every additional course). Compared with infants with the lowest number of exposures (no UTI during pregnancy, vaginal delivery, at least five older siblings at home, no antibiotics during infancy), infants with the highest number of exposures (at least three UTIs during pregnancy, C-section delivery, no older siblings, eight or more courses of antibiotics during infancy) had a 7.77 fold increased odds of developing asthma (AOR: 7.77, 95%CI: 6.25, 9.65). Lastly, infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home.
CONCLUSION:Early-life exposures, maternal UTI during pregnancy (maternal antibiotic use), mode of delivery, infant antibiotic use, and having older siblings at home, are associated with an increased risk of childhood asthma in a cumulative manner, and for those continuous variables, a dose-dependent relationship. Compared with in utero exposures, exposures occurring during infancy have a greater impact on the risk of developing childhood asthma.
PLoS One. 2016 Mar 22;11(3):e0151705. doi: 10.1371/journal.pone.0151705. eCollection 2016.
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韩国学龄儿童特应性皮炎的危险因素：2010年儿童哮喘和过敏的国际研究
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孕前口服避孕药与儿童患喘息、哮喘和过敏性鼻炎的风险
