母亲流产史及辅助生育措施与儿童哮喘相关
2019/10/17
摘要
背景：导致采用辅助生殖技术(ART)出生儿童患哮喘风险更大的原因尚不清楚。
目的：阐明父母的生育能力低下及某些无法测量的混杂因素，在ART和儿童哮喘之间的关系，并揭示了找到父母的低生育能力和母亲流产史影响哮喘发病的共同机制的可能性。
方法：我们使用的数据来自于挪威国家健康登记处(n=474 402)和挪威母亲和儿童队列研究(MoBa) (n=75 797)。使用线性回归来估计总体关联，并使用固定效应回归模型来估计各子女之间的关联。
结果：ART后代有更高的患哮喘风险，在基于健康登记的队列中调整相对风险(aRR)为1.20 (95% CI 1.09至1.32)，在MoBa中为1.42 (95% CI 1.14至1.76)。虽然CI包含了空值，但在子女之间的分析同样得到了类似的关联结果。与受孕时间超过12个月的自然分娩后代相比，ART后代的患哮喘风险升高得到了缓解，aRR为1.22(95%可信区间为0.95 ~ 1.57)。患哮喘风险也可随着孕妇早期流产史(<12周)的增加而增加，一名孕妇的aRR为1.07 (95% CI 1.03至1.11)，两名孕妇的aRR为1.18 (95% CI 1.10至1.26)，而三名以上孕妇的aRR则增加到1.24 (95% CI 1.12至1.37)。
结论：我们的研究结果表明，父母的低生育能力及ART过程本身可能增加后代哮喘的风险，尽管这可能还需要在未来的研究中去证实。且进一步表明，父母低生育能力和反复流产的共同机制可能会影响后代哮喘的发病机理。
Magnus MC1,2,3, Karlstad Ø4, Parr CL4,5, Page CM1,6, Nafstad P4,7, Magnus P1, London SJ8, Wilcox AJ8, Nystad W4, Håberg SE1
Objective Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between ART and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis.
Methods We used data from national Norwegian health registries (n=474 402) and the Norwegian Mother and Child Cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings.
Results ART offspring had greater asthma risk, the adjusted relative risk (aRR) was 1.20 (95% CI 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% CI 1.14 to 1.76) in MoBa. The sibling analysis yielded similar associations, although the CI included the null value. The elevated asthma risk among ART offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, aRR 1.22 (95% CI 0.95 to 1.57). Asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an aRR of 1.07 (95% CI 1.03 to 1.11) for one, aRR 1.18 (95% CI 1.10 to 1.26) for two and aRR 1.24 (95% CI 1.12 to 1.37) for three or more.
Conclusion Our findings indicate that both parental subfertility and characteristics related to the ART procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis.
PMID:30514789 PMCID:PMC6467238 DOI:10.1136/thoraxjnl-2018-211886
背景：导致采用辅助生殖技术(ART)出生儿童患哮喘风险更大的原因尚不清楚。
目的：阐明父母的生育能力低下及某些无法测量的混杂因素，在ART和儿童哮喘之间的关系，并揭示了找到父母的低生育能力和母亲流产史影响哮喘发病的共同机制的可能性。
方法：我们使用的数据来自于挪威国家健康登记处(n=474 402)和挪威母亲和儿童队列研究(MoBa) (n=75 797)。使用线性回归来估计总体关联，并使用固定效应回归模型来估计各子女之间的关联。
结果：ART后代有更高的患哮喘风险，在基于健康登记的队列中调整相对风险(aRR)为1.20 (95% CI 1.09至1.32)，在MoBa中为1.42 (95% CI 1.14至1.76)。虽然CI包含了空值，但在子女之间的分析同样得到了类似的关联结果。与受孕时间超过12个月的自然分娩后代相比，ART后代的患哮喘风险升高得到了缓解，aRR为1.22(95%可信区间为0.95 ~ 1.57)。患哮喘风险也可随着孕妇早期流产史(<12周)的增加而增加，一名孕妇的aRR为1.07 (95% CI 1.03至1.11)，两名孕妇的aRR为1.18 (95% CI 1.10至1.26)，而三名以上孕妇的aRR则增加到1.24 (95% CI 1.12至1.37)。
结论：我们的研究结果表明，父母的低生育能力及ART过程本身可能增加后代哮喘的风险，尽管这可能还需要在未来的研究中去证实。且进一步表明，父母低生育能力和反复流产的共同机制可能会影响后代哮喘的发病机理。
（陆军军医大学第二附属医院（新桥医院） 杨睿 马千里）
Thorax. 2019 Feb;74(2):106-113. doi: 10.1136/thoraxjnl-2018-211886. Epub 2018 Dec 4.
Maternal history of miscarriages and measures of fertility in relation to childhood asthmaThorax. 2019 Feb;74(2):106-113. doi: 10.1136/thoraxjnl-2018-211886. Epub 2018 Dec 4.
Magnus MC1,2,3, Karlstad Ø4, Parr CL4,5, Page CM1,6, Nafstad P4,7, Magnus P1, London SJ8, Wilcox AJ8, Nystad W4, Håberg SE1
Abstract
Background It remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (ART).Objective Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between ART and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis.
Methods We used data from national Norwegian health registries (n=474 402) and the Norwegian Mother and Child Cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings.
Results ART offspring had greater asthma risk, the adjusted relative risk (aRR) was 1.20 (95% CI 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% CI 1.14 to 1.76) in MoBa. The sibling analysis yielded similar associations, although the CI included the null value. The elevated asthma risk among ART offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, aRR 1.22 (95% CI 0.95 to 1.57). Asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an aRR of 1.07 (95% CI 1.03 to 1.11) for one, aRR 1.18 (95% CI 1.10 to 1.26) for two and aRR 1.24 (95% CI 1.12 to 1.37) for three or more.
Conclusion Our findings indicate that both parental subfertility and characteristics related to the ART procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis.
PMID:30514789 PMCID:PMC6467238 DOI:10.1136/thoraxjnl-2018-211886
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