Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC.
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Am J Obstet Gynecol. 2020 Nov;223(5):745.e1-745.e10. doi: 10.1016/j.ajog.2020.05.001. Epub 2020 May 7.
Extremely preterm infants whose placenta had histologic evidence of chorioamnionitis have early brain dysfunction, but little is known about neurologic development at 10 years of age.
We investigated the association between histologic chorioamnionitis and neurodevelopmental impairment at 10 years among children born <28 weeks' gestation (extremely preterm).
The multicenter Extremely Low Gestational Age Newborns study enrolled extremely preterm newborns from 2002 to 2004 at 14 hospitals in the United States. Chorioamnionitis was defined by histologic stage (early, moderate, and advanced) and grade (mild/moderate and severe) of chorionic plate and umbilical cord inflammation. The children were examined for cerebral palsy at 2 years and for autism spectrum disorder, cognitive impairment (intelligence quotient >2 standard deviations below the mean), and epilepsy at the age of 10 years by blinded evaluators using validated measures. Multivariable logistic regression with generalized estimating equations was used.
Among 805 placentas, 43% (347/805) had histologic chorioamnionitis by moderate or advanced maternal stage, 36% (286/805) by severe maternal grade, 18% (132/737) by moderate or advanced fetal stage, and 1% (10/737) by severe fetal grade. The frequencies of impairments were 11% (88/767) for cerebral palsy, 7% (56/773) for autism spectrum disorder, 15% (120/788) for cognitive impairment, and 7% (52/763) for epilepsy. After adjustment for maternal age, body mass index, race, insurance status, maternal education, tobacco use, infant sex, and multiple gestations, the adjusted odds ratio for the association between histologic chorioamnionitis and cerebral palsy years was increased with advanced maternal stage (adjusted odds ratio, 2.5; 95% confidence interval, 1.6-3.9), severe maternal grade (adjusted odds ratio, 2.0; 95% confidence interval, 1.2-3.4), moderate fetal stage (adjusted odds ratio, 2.20; 95% confidence interval, 2.1-2.2), and mild or moderate fetal grade (adjusted odds ratio, 1.5; 95% confidence interval, 1.0-2.2). Similarly, the adjusted odds ratio for the association between histologic chorioamnionitis and epilepsy was increased with advanced maternal stage (adjusted odds ratio, 1.5; 95% confidence interval, 1.3-1.6) and severe fetal grade (adjusted odds ratio, 5.9; 95% confidence interval, 1.9-17.8). In addition, the adjusted odds ratio for the association between histologic chorioamnionitis and autism spectrum disorder was increased with mild or moderate fetal grade (adjusted odds ratio, 1.7; 95% confidence interval, 1.0-2.9). Histologic chorioamnionitis was not associated with cognitive impairment. These findings held after adjustment for gestational age at delivery. In contrast to histologic chorioamnionitis, a clinical diagnosis of chorioamnionitis was not associated with neurodevelopmental impairment.
Histologic chorioamnionitis may be associated with some forms of neurodevelopmental impairment at 10 years of life among infants born <28 weeks' gestation.
胎盘组织学上有绒毛膜羊膜炎证据的极早产儿有早期脑功能障碍,但对于 28 周以下出生的儿童在 10 岁时的神经发育情况知之甚少。
我们研究了绒毛膜羊膜炎的组织学证据与极早产儿(<28 周)出生后 10 年神经发育障碍之间的关系。
多中心极早产儿新生研究于 2002 年至 2004 年在美国 14 家医院招募了极早产儿新生儿。绒毛膜羊膜炎通过绒毛膜和脐带炎症的组织学阶段(早期、中期和晚期)和分级(轻度/中度和重度)来定义。通过盲法评估者使用经过验证的测量方法,在 2 岁时对脑瘫进行检查,在 10 岁时对自闭症谱系障碍、认知障碍(智商>2 个标准差低于平均值)和癫痫进行检查。使用广义估计方程的多变量逻辑回归。
在 805 个胎盘组织中,43%(347/805)的胎盘组织有中度或晚期的母体阶段绒毛膜羊膜炎,36%(286/805)有严重的母体级绒毛膜羊膜炎,18%(132/737)有中度或晚期的胎儿阶段绒毛膜羊膜炎,1%(10/737)有严重的胎儿级绒毛膜羊膜炎。损伤的频率为脑瘫 11%(88/767)、自闭症谱系障碍 7%(56/773)、认知障碍 15%(120/788)和癫痫 7%(52/763)。在调整了母亲年龄、体重指数、种族、保险状况、母亲教育程度、吸烟状况、婴儿性别和多胎妊娠等因素后,与组织学绒毛膜羊膜炎相关的脑瘫年调整后优势比随着母体晚期阶段(调整后优势比,2.5;95%置信区间,1.6-3.9)、严重母体级(调整后优势比,2.0;95%置信区间,1.2-3.4)、中期胎儿阶段(调整后优势比,2.20;95%置信区间,2.1-2.2)和轻度或中度胎儿级(调整后优势比,1.5;95%置信区间,1.0-2.2)而增加。同样,与组织学绒毛膜羊膜炎相关的癫痫调整后优势比随着母体晚期阶段(调整后优势比,1.5;95%置信区间,1.3-1.6)和严重的胎儿级(调整后优势比,5.9;95%置信区间,1.9-17.8)而增加。此外,与组织学绒毛膜羊膜炎相关的自闭症谱系障碍调整后优势比随着轻度或中度胎儿级而增加(调整后优势比,1.7;95%置信区间,1.0-2.9)。组织学绒毛膜羊膜炎与认知障碍无关。这些发现在调整了分娩时的胎龄后仍然成立。与绒毛膜羊膜炎的组织学诊断不同,绒毛膜羊膜炎的临床诊断与 28 周以下出生的婴儿 10 岁时的神经发育损伤无关。
组织学绒毛膜羊膜炎可能与 28 周以下出生的婴儿 10 岁时的某些形式的神经发育障碍有关。