Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years

Yoon, Bo Hyun; Romero, Roberto; Park, Joong Shin; Kim, Chong Jai; Kim, Seung Hyup; Choi, Jung-Hwan; Han, Tai Ryoon

doi:10.1067/mob.2000.104207

Cited by 779Preterm Birth and ChorioamnionitisNeonatal and fetal brain pathologyNeonatal and Maternal Infections

Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years

Yoon, Bo Hyun, Romero, Roberto, Park, Joong Shin, Kim, Chong Jai, Kim, Seung Hyup, Choi, Jung-Hwan, Han, Tai Ryoon·2000·American Journal of Obstetrics and Gynecology

DOI 10.1067/mob.2000.104207

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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/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).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.

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The fetal inflammatory response has been linked to the onset of preterm labour, fetal injury, and long-term handicap including periventricular leucomalacia, cerebral palsy, and chronic lung disease.
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From Epidemiology and causes of preterm birth (2008) · cites this paper as [93]

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Authors: Yoon, B. H., Romero, R., Park, J. S., Kim, C. J., Kim, S. H., Choi, J.-H., & Han, T. R.
Affiliations: Seoul National University (KR)
ORCID: Yoon, Bo Hyun
Romero, Roberto
Park, Joong Shin
Choi, Jung-Hwan
Han, Tai Ryoon
Venue: American Journal of Obstetrics and Gynecology
Publisher: Elsevier BV
Published: 2000-03
Volume: 182
Issue: 3
Pages: 675-681
ISSN: 0002-9378 (ISSN-L)
DOI: 10.1067/mob.2000.104207
OpenAlex: W1998952411
Cited by: 779
References: 26
Citations by year: 2026: 6 · 2025: 7 · 2024: 12 · 2023: 14 · 2022: 14 · 2021: 18 · 2020: 24 · 2019: 28 · 2018: 21 · 2017: 92 · 2016: 32 · 2015: 37 · 2014: 17 · 2013: 38 · 2012: 33
FWCI: 22.98
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: American Journal of Obstetrics and Gynecology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
Keywords: cerebral palsy, intra-amniotic inflammation, funisitis, fetal inflammatory response, amniotic fluid cytokines, interleukin-6, interleukin-8, preterm infants, umbilical cord, Wharton's jelly, amniocentesis, neurodevelopmental outcomes, neonatal inflammation, maternal infection
MeSH terms: Amniotic Fluid, Cerebral Palsy, Child, Preschool, Chorioamnionitis, Female, Humans, Leukocyte Count, Predictive Value of Tests, Pregnancy, Prenatal Exposure Delayed Effects, Interleukin-6, Multivariate Analysis, Interleukin-8

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Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years

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