背景:母体先兆子痫与后代自闭症谱系障碍(ASD)的风险相关。然而,与先兆子痫相关的ASD风险增加是由于先兆子痫发病还是先兆子痫发病后的临床管理,因为先兆子痫的临床预期治疗可使患有这种并发症的孕妇根据发病和严重程度保持妊娠数周。确定与先兆子痫发病和暴露相关的风险提供了证据,以支持高危妊娠的护理并减少对后代的不利影响。
目的:本研究旨在通过评估与先兆子痫发病的孕龄和先兆子痫发病至分娩的天数相关的儿童ASD风险来填补知识空白。
方法:这项基于人群的回顾性临床队列研究包括2001年至2014年在南加州一个大型综合医疗保健系统中的364,588对单胎母婴。孕产妇社会人口统计和怀孕健康数据,以及5岁儿童的ASD诊断,是从电子病历中提取的.Cox回归模型用于评估与先兆子痫首次发生的胎龄和从首次发生到分娩的天数相关的儿童ASD风险的风险比(HRs)。
结果:在364,588例妊娠中,有16,205例(4.4%)发生了先兆子痫;在16,205例妊娠中,2727(16.8%)首次发生在<34孕周,4466(27.6%)首次发生在34到37周之间,9012(55.6%)首次发生在≥37周。从先兆子痫发病到分娩的中位天数为4(IQR2,16)天,1(IQR1,3)天,首次发生在<34、34-37和≥37周的患者为1(IQR0,1)天,分别。先兆子痫早期发病与更高的ASD风险相关(P=.003);HR为1.62(95%CI1.33-1.98),1.43(95%CI1.20-1.69),和1.23(95%CI1.08-1.41),分别,在<34、34-37和≥37周发病,相对于未暴露的群体。在先兆子痫组中,从先兆子痫发病到分娩的天数与儿童ASD风险无关;校正先兆子痫发病的孕龄后,HR为0.995(95%CI0.986-1.004).
结论:妊娠期子痫前期与儿童ASD风险相关,发病越早,风险越大。然而,从首次先兆子痫发病至分娩的天数与儿童ASD风险无关.我们的研究表明,在标准临床实践中,先兆子痫的预期管理不会增加与先兆子痫相关的儿童的ASD风险。我们的结果强调需要确定预防先兆子痫发作的有效方法,尤其是在怀孕初期。需要进一步的研究来确认这一发现是否适用于不同的人群和临床环境。
BACKGROUND: Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring.
OBJECTIVE: This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery.
METHODS: This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery.
RESULTS: Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset.
CONCLUSIONS: Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.