Fetus-Placenta-Newborn
Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years*,**

Presented at the Nineteenth Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, California, January 18-23, 1999.
https://doi.org/10.1067/mob.2000.104207Get rights and content

Abstract

Objective: 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. Study Design: 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. Results: 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/mm3; range, 0->1000 cells/mm3; vs median, 3 cells/mm3; range, 0-19,764 cells/mm3; 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). Conclusion: 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. (Am J Obstet Gynecol 2000;182:675-81.)

Section snippets

Study design

We examined the relationship between the occurrence of cerebral palsy at age 3 years and the presence of funisitis, amniotic fluid concentrations of interleukin 6 (IL-6) and interleukin 8 (IL-8), and amniotic fluid white blood cell count. The cohort consisted of patients who delivered preterm neonates at Seoul National University Hospital between January 1993 and December 1995 and who met the following criteria: (1) preterm singleton birth (gestational age at birth ≤35 weeks), (2)

Results

During the study period 340 women delivered singleton preterm newborns (gestational age at birth, 26-35 weeks). Among these, 172 underwent transabdominal amniocentesis, and cerebral palsy was subsequently diagnosed in 14 of their children. Among 168 patients who did not undergo amniocentesis, cerebral palsy was diagnosed in 6 of their children. There was no significant difference in the rate of cerebral palsy between patients who underwent amniocentesis and those who did not (8.1% [14/172] vs

Comment

Our data clearly demonstrate that amniotic fluid concentrations of specific cytokines (IL-6 and IL-8) and amniotic fluid white blood cell count are significantly higher in fetuses with subsequent development of cerebral palsy than in those without subsequent development of cerebral palsy, an association that remained significant after adjustment for gestational age at birth. Moreover, we report here that the presence of a systemic fetal inflammatory response (funisitis) is associated with both

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    *

    Supported by grant 03-96-050 from Seoul National University Hospital Research Fund, grant of KISTEP (Korea Institute of Science & Technology Evaluation and Planning), and grant 97-04-03-08-01-3 from the Korea Science and Engineering Foundation.

    **

    Reprint requests: Bo Hyun Yoon, MD, PhD, Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, 110-744, Korea.

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