Inflammatory predictors of neurologic disability after preterm premature rupture of membranes

Am J Obstet Gynecol. 2015 Feb;212(2):212.e1-9. doi: 10.1016/j.ajog.2014.09.016. Epub 2014 Sep 16.


Objective: The maternal-fetal inflammatory response contributes to both preterm premature rupture of membranes (PPROM) and adverse neurological outcomes. Additionally, cytokines associated with fetal placental inflammation can be detrimental to brain development regardless of inciting infection. We investigated whether differential patterns of cytokine markers in maternal and fetal plasma samples reflect subtypes of placental inflammation and neurological outcomes at 6 months in infants born to mothers with PPROM.

Study design: Within a prospective cohort study of 25 women with PPROM, plasma cytokines (interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor-α) were measured by enzyme-linked immunosorbent assay from maternal blood samples at rupture and delivery, and from fetal umbilical cord blood samples. Patterns of cytokine expression were correlated with specific placenta pathologies. Infants underwent cranial ultrasound after birth and standardized neurological examinations at 6 months' corrected gestational age. Predictors of inflammation and adverse neurological outcome were assessed by logistic regression, adjusting for gestational age at birth.

Results: Inflammation of the fetal side of the placenta was associated with elevated maternal IL-6 and IL-8 at delivery and fetal IL-1β, IL-6, IL-8, and tumor necrosis factor-α. Worse neurological outcome at 6 months was associated with inflammation of the fetal side of the placenta and shorter duration from rupture of membrane to delivery, independent of gestational age at birth or cranial ultrasound results.

Conclusion: Our findings support the connection between fetal inflammation with adverse neurological outcome with PPROM, regardless of cranial ultrasound results. Further longitudinal studies are needed to adequately examine these patterns, and will aid in risk assessment and intervention strategies.

Keywords: cerebral palsy; chorioamnionitis; cytokines; funisitis; placenta.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chorioamnionitis / immunology*
  • Chorioamnionitis / pathology
  • Cohort Studies
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fetal Blood / immunology*
  • Fetal Membranes, Premature Rupture / immunology*
  • Fetal Membranes, Premature Rupture / pathology
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Inflammation / immunology
  • Interleukin-1beta / immunology*
  • Interleukin-6 / immunology*
  • Interleukin-8 / immunology*
  • Male
  • Nervous System Diseases / immunology*
  • Nervous System Diseases / physiopathology
  • Placenta / pathology*
  • Pregnancy
  • Prospective Studies
  • Tumor Necrosis Factor-alpha / immunology*
  • Young Adult


  • CXCL8 protein, human
  • Cytokines
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha