Yoon B H, Romero R, Park J S, Kim C J, Kim S H, Choi J H, Han T R
Departments of Obstetrics and Gynecology, Pathology, Diagnostic Radiology, Pediatrics, and Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Korea.
Am J Obstet Gynecol. 2000 Mar;182(3):675-81. doi: 10.1067/mob.2000.104207.
The aim of this study was to determine whether fetal exposure to intra-amniotic inflammation and a systemic fetal inflammatory response (funisitis) are associated with the development of cerebral palsy at the age of 3 years.
This cohort study included 123 preterm singleton newborns (gestational age at birth, </=35 weeks) born to mothers who underwent amniocentesis and were followed up for >/=3 years. The presence of intra-amniotic inflammation was determined by elevated amniotic fluid concentrations of proinflammatory cytokines such as interleukins 6 and 8 and by amniotic fluid white blood cell count. Cytokine concentrations were measured with sensitive and specific immunoassays. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. Cerebral palsy was diagnosed by neurologic examination at the age of 3 years.
Newborns with subsequent development of cerebral palsy had a higher rate of funisitis and were born to mothers with higher median concentrations of interleukins 6 and 8 and higher white blood cell counts in the amniotic fluid compared with newborns without subsequent development of cerebral palsy (funisitis: 75% [9/12] vs 23% [24/105]; interleukin 6: median, 18.9 ng/mL; range, 0. 02-92.5 ng/mL; vs median, 1.0 ng/mL; range, 0.01-115.2 ng/mL; interleukin 8: median, 13.0 ng/mL; range, 0.1-294.5 ng/mL; vs median, 1.2 ng/mL; range, 0.05-285.0 ng/mL; white blood cell count: median, 198 cells/mm(3); range, 0->1000 cells/mm(3); vs median, 3 cells/mm(3); range, 0-19,764 cells/mm(3); P <.01 for each). After adjustment for the gestational age at birth, the presence of funisitis and elevated concentrations of interleukins 6 and 8 in amniotic fluid significantly increased the odds of development of cerebral palsy (funisitis: odds ratio, 5.5; 95% confidence interval, 1.2-24.5; interleukin 6: odds ratio, 6.4; 95% confidence interval, 1. 3-33.0; interleukin 8: odds ratio, 5.9; 95% confidence interval, 1. 1-30.7; P <.05 for each).
Antenatal exposure to intra-amniotic inflammation and evidence of a systemic fetal inflammatory response (funisitis) are strong and independent risk factors for the subsequent development of cerebral palsy at the age of 3 years.
本研究旨在确定胎儿暴露于羊膜内炎症和全身性胎儿炎症反应（脐带炎）是否与3岁时脑瘫的发生有关。
这项队列研究纳入了123例早产单胎新生儿（出生时孕周≤35周），其母亲接受了羊膜穿刺术，并随访≥3年。羊膜内炎症的存在通过羊水中促炎细胞因子如白细胞介素6和8浓度升高以及羊水白细胞计数来确定。细胞因子浓度通过灵敏且特异的免疫测定法进行测量。脐带炎在中性粒细胞浸润到脐血管壁或华通胶时被诊断。3岁时通过神经学检查诊断脑瘫。
与未继发脑瘫的新生儿相比，继发脑瘫的新生儿脐带炎发生率更高，其母亲羊水中白细胞介素6和8的中位数浓度更高，羊水白细胞计数也更高（脐带炎：75%[9/12]对23%[24/105]；白细胞介素6：中位数18.9 ng/mL；范围0.02 - 92.5 ng/mL；对中位数1.0 ng/mL；范围0.01 - 115.2 ng/mL；白细胞介素8：中位数13.0 ng/mL；范围0.1 - 294.5 ng/mL；对中位数1.2 ng/mL；范围0.05 - 285.0 ng/mL；白细胞计数：中位数198个细胞/mm³；范围0 ->1000个细胞/mm³；对中位数3个细胞/mm³；范围0 - 19764个细胞/mm³；每项P <.01）。在对出生时孕周进行调整后，脐带炎以及羊水中白细胞介素6和8浓度升高显著增加了脑瘫发生的几率（脐带炎：比值比5.5；95%置信区间1.2 - 24.5；白细胞介素6：比值比6.4；95%置信区间1.3 - 33.0；白细胞介素8：比值比5.9；95%置信区间1.1 - 30.7；每项P <.05）。
产前暴露于羊膜内炎症和全身性胎儿炎症反应（脐带炎）的证据是3岁时随后发生脑瘫的强大且独立的危险因素。
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