The association of cord serum cytokines with neurodevelopmental outcomes

Michael W. Varner, Nicole E. Marshall, Dwight J. Rouse, Kathleen A. Jablonski, Kenneth J. Leveno, Uma M. Reddy, Brian M. Mercer, Jay D. Iams, Ronald J. Wapner, Yoram Sorokin, John M. Thorp, Fergal D. Malone, Marshall Carpenter, Mary J. O'Sullivan, Alan M. Peaceman, Gary Hankins, Donald J. Dudley, Steve N. Caritis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Study Design Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO<inf>4</inf>) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO<inf>4</inf> exposure, gestational age, race/ethnicity, and sociodemographic differences. Results Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Conclusion Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.

Original languageEnglish (US)
Pages (from-to)115-121
Number of pages7
JournalAmerican Journal of Perinatology
Volume30
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Cerebral Palsy
Interleukin-8
Interleukin-1
Cytokines
Serum
Magnesium Sulfate
Umbilical Cord
Premature Birth
Fetal Blood
Premature Infants
Gestational Age
Case-Control Studies
Logistic Models
Regression Analysis
Clinical Trials

Keywords

  • cerebral palsy
  • cytokines
  • magnesium sulfate
  • neurodevelopmental outcomes
  • prematurity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Varner, M. W., Marshall, N. E., Rouse, D. J., Jablonski, K. A., Leveno, K. J., Reddy, U. M., ... Caritis, S. N. (2015). The association of cord serum cytokines with neurodevelopmental outcomes. American Journal of Perinatology, 30(2), 115-121. https://doi.org/10.1055/s-0034-1376185

The association of cord serum cytokines with neurodevelopmental outcomes. / Varner, Michael W.; Marshall, Nicole E.; Rouse, Dwight J.; Jablonski, Kathleen A.; Leveno, Kenneth J.; Reddy, Uma M.; Mercer, Brian M.; Iams, Jay D.; Wapner, Ronald J.; Sorokin, Yoram; Thorp, John M.; Malone, Fergal D.; Carpenter, Marshall; O'Sullivan, Mary J.; Peaceman, Alan M.; Hankins, Gary; Dudley, Donald J.; Caritis, Steve N.

In: American Journal of Perinatology, Vol. 30, No. 2, 2015, p. 115-121.

Research output: Contribution to journalArticle

Varner, MW, Marshall, NE, Rouse, DJ, Jablonski, KA, Leveno, KJ, Reddy, UM, Mercer, BM, Iams, JD, Wapner, RJ, Sorokin, Y, Thorp, JM, Malone, FD, Carpenter, M, O'Sullivan, MJ, Peaceman, AM, Hankins, G, Dudley, DJ & Caritis, SN 2015, 'The association of cord serum cytokines with neurodevelopmental outcomes', American Journal of Perinatology, vol. 30, no. 2, pp. 115-121. https://doi.org/10.1055/s-0034-1376185
Varner MW, Marshall NE, Rouse DJ, Jablonski KA, Leveno KJ, Reddy UM et al. The association of cord serum cytokines with neurodevelopmental outcomes. American Journal of Perinatology. 2015;30(2):115-121. https://doi.org/10.1055/s-0034-1376185
Varner, Michael W. ; Marshall, Nicole E. ; Rouse, Dwight J. ; Jablonski, Kathleen A. ; Leveno, Kenneth J. ; Reddy, Uma M. ; Mercer, Brian M. ; Iams, Jay D. ; Wapner, Ronald J. ; Sorokin, Yoram ; Thorp, John M. ; Malone, Fergal D. ; Carpenter, Marshall ; O'Sullivan, Mary J. ; Peaceman, Alan M. ; Hankins, Gary ; Dudley, Donald J. ; Caritis, Steve N. / The association of cord serum cytokines with neurodevelopmental outcomes. In: American Journal of Perinatology. 2015 ; Vol. 30, No. 2. pp. 115-121.
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abstract = "Objective To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Study Design Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. Results Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Conclusion Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.",
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AU - Varner, Michael W.

AU - Marshall, Nicole E.

AU - Rouse, Dwight J.

AU - Jablonski, Kathleen A.

AU - Leveno, Kenneth J.

AU - Reddy, Uma M.

AU - Mercer, Brian M.

AU - Iams, Jay D.

AU - Wapner, Ronald J.

AU - Sorokin, Yoram

AU - Thorp, John M.

AU - Malone, Fergal D.

AU - Carpenter, Marshall

AU - O'Sullivan, Mary J.

AU - Peaceman, Alan M.

AU - Hankins, Gary

AU - Dudley, Donald J.

AU - Caritis, Steve N.

PY - 2015

Y1 - 2015

N2 - Objective To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Study Design Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. Results Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Conclusion Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.

AB - Objective To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Study Design Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. Results Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Conclusion Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.

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KW - cytokines

KW - magnesium sulfate

KW - neurodevelopmental outcomes

KW - prematurity

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