Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Int J Epidemiol. 2022 Jan 6;50(6):1852-1863. doi: 10.1093/ije/dyab131. Epub 2021 Jun 28.
The contribution of adverse consequences of preterm birth to gestational-age-related risk of cerebral palsy (CP) has rarely been studied. We aimed to assess the potential mediating roles of neonatal morbidity on the association between gestational age and risk of CP.
In this Swedish population-based study, 1 402 240 singletons born at 22-40 gestational weeks during 1998-2016 were followed from day 28 after birth for a CP diagnosis until 2017. Potential mediators included asphyxia, respiratory-related, infection-/inflammatory-related and neurological-related diseases within 0-27 days of life. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Causal mediation analysis was performed to estimate the proportion of the association mediated through pathways involving the four sequential mediators.
We found an inverse dose-response relationship between gestational age and risk of CP, where the strongest association was observed for 22-24 weeks (HR 47.26, 95% CI 34.09-65.53) vs 39-40 weeks. Compared with non-diseased peers, children with neonatal morbidity, particularly those with neurological-related diseases (HR 31.34, 95% CI 26.39-37.21), had a higher risk of CP. The increased risk of CP was, at 24 weeks, almost entirely explained by neonatal morbidity (91.7%); this proportion decreased to 46.1% and 16.4% at 32 and 36 weeks, respectively. Asphyxia was the main mediating pathway from 22 to 34 weeks, and neurological-related neonatal diseases led the mediating pathways from 34 weeks onwards.
Neonatal morbidity mediates a large proportion of the effect of preterm birth on CP, but the magnitude declines as gestational age increases.
早产的不良后果对与胎龄相关的脑瘫（CP）风险的贡献很少被研究。我们旨在评估新生儿发病率在胎龄与 CP 风险之间的关联中的潜在中介作用。
在这项瑞典基于人群的研究中，我们对 1998 年至 2016 年间在 22-40 孕周出生的 1402240 名单胎进行了随访，随访时间从出生后第 28 天到 2017 年 CP 诊断。潜在的中介因素包括出生后 0-27 天内的窒息、与呼吸相关、感染/炎症相关和与神经相关的疾病。Cox 回归用于估计风险比（HR）和 95%置信区间（CI）。因果中介分析用于估计通过涉及四个连续中介的途径介导的关联比例。
我们发现胎龄与 CP 风险之间呈负剂量-反应关系，其中 22-24 孕周（HR 47.26，95%CI 34.09-65.53）与 39-40 孕周之间的关联最强。与无疾病的同龄人相比，患有新生儿发病的儿童，尤其是患有与神经相关的疾病的儿童（HR 31.34，95%CI 26.39-37.21），CP 风险更高。CP 的风险增加在 24 孕周时几乎完全由新生儿发病引起（91.7%）；这一比例在 32 周和 36 周时分别下降到 46.1%和 16.4%。窒息是从 22 周到 34 周的主要中介途径，而与神经相关的新生儿疾病则是从 34 周开始的主要中介途径。
新生儿发病在很大程度上解释了早产对 CP 的影响，但随着胎龄的增加，其影响程度下降。
