Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center (Radboudumc), Nijmegen, The Netherlands.
Department of Surgery-Paediatric surgery, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
Birth Defects Res. 2019 Jan 15;111(2):62-69. doi: 10.1002/bdr2.1429. Epub 2018 Dec 19.
Chronic respiratory diseases and use of antiasthmatic medication during pregnancy may both play a role in the etiology of congenital anorectal malformations (ARM). However, it is unclear, whether the medication use or the underlying condition would be responsible. Therefore, our aim was to unravel the role of maternal chronic respiratory diseases from that of antiasthmatic medication in the etiology of ARM.
We obtained 412 ARM patients and 2,137 population-based controls from the Dutch AGORA data- and biobank. We used maternal questionnaires and follow-up telephone interviews to obtain information on chronic respiratory diseases, antiasthmatic medication use, and potential confounders. Multivariable logistic regression analyses were performed to estimate odds ratios (ORs) with 95% confidence intervals (95% CI).
We observed higher risk estimates among women with chronic respiratory diseases with and without medication use (1.4 [0.8-2.7] and 2.0 [0.8-5.0]), both in comparison to women without a chronic respiratory disease and without medication use. Furthermore, increased ORs of ARM were found for women using rescue medication (2.4 [0.8-7.3]) or a combination of maintenance and rescue medication (2.5 [0.9-6.7]). In addition, increased risk estimates were observed for women having nonallergic triggers (2.5 [1.0-6.3]) or experiencing exacerbations during the periconceptional period (3.5 [1.4-8.6]).
Although the 95% CIs of most associations include the null value, the risk estimates all point towards an association between uncontrolled chronic respiratory disease, instead of antiasthmatic medication use, with ARM in offspring. Further in-depth studies towards mechanisms of this newly identified risk factor are warranted.
慢性呼吸系统疾病和孕期使用抗哮喘药物都可能在先天性肛门直肠畸形(ARM)的病因中发挥作用。然而,尚不清楚是药物使用还是潜在疾病起主要作用。因此,我们的目的是厘清母体慢性呼吸系统疾病与抗哮喘药物在 ARM 病因学中的作用。
我们从荷兰 AGORA 数据和生物库中获得了 412 名 ARM 患者和 2137 名基于人群的对照。我们使用母亲问卷和随访电话访谈来获取慢性呼吸系统疾病、抗哮喘药物使用和潜在混杂因素的信息。多变量逻辑回归分析用于估计比值比(OR)及其 95%置信区间(95%CI)。
我们观察到,患有慢性呼吸系统疾病(无论是否使用药物)的女性的风险估计值更高(1.4 [0.8-2.7] 和 2.0 [0.8-5.0]),与没有慢性呼吸系统疾病且未使用药物的女性相比均如此。此外,我们还发现使用急救药物(2.4 [0.8-7.3])或维持药物和急救药物联合使用(2.5 [0.9-6.7])的女性的 ARM 比值比也有所增加。此外,我们还观察到非过敏性触发因素(2.5 [1.0-6.3])或在围孕期出现恶化(3.5 [1.4-8.6])的女性风险估计值也有所增加。
虽然大多数关联的 95%CI 都包含零值,但所有风险估计值都表明,未得到控制的慢性呼吸系统疾病而不是抗哮喘药物的使用与后代的 ARM 之间存在关联。需要进一步深入研究这个新发现的风险因素的机制。