Cord blood biomarkers of the fetal inflammatory response

Karen Mestan; Yunxian Yu; Poul Thorsen; Kristin Skogstrand; Nana Matoba; Xin Liu; Rajesh Kumar; David M. Hougaard; Munish Gupta; Colleen Pearson; Katherin Ortiz; Howard Bauchner; Xiaobin Wang

doi:10.1080/14767050802609759

Cord blood biomarkers of the fetal inflammatory response

Karen Mestan^*, Yunxian Yu, Poul Thorsen, Kristin Skogstrand, Nana Matoba, Xin Liu, Rajesh Kumar, David M. Hougaard, Munish Gupta, Colleen Pearson, Katherin Ortiz, Howard Bauchner, Xiaobin Wang

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

Abstract

Objective. In current, neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. Methods. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age (GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR < 5, P < 0.001) to account for multiple comparisons. Results. Among 506 births GA 2342 weeks, IL-1β increased with FIR among preterm subgroups P 0.0001 for <32 weeks; P 0.0009 for 3336 weeks. IL-6 and IL-8 increased with FIR among preterm and full-term infants P < 0.0001. P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. Conclusion. We conclude that among 27 cord blood biomarkers, IL-1β, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.

Original language	English (US)
Pages (from-to)	379-387
Number of pages	9
Journal	Journal of Maternal-Fetal and Neonatal Medicine
Volume	22
Issue number	5
DOIs	https://doi.org/10.1080/14767050802609759
State	Published - 2009

Funding

The authors thank the nursing staff of Labor and Delivery at Boston Medical Center for their continuous support and assistance to the study and Lingling Fu for data management, and Ann Ramsay for administrative support. They particularly thank the outstanding expert consultants of the BMC Preterm Study team: Drs. Barry Zuckerman, Phillip Stubblefield, Jerome Klein, Milton Kotelchuck, John M. Kasznica and Paul Wise. They thank Drs. Michael Caplan and Isabelle DePlaen for their careful review of the manuscript. Finally, the authors thank all of the participating mothers and their families. The study was supported in part by grants from the National Institute of Child Health and Human Development (R01 HD41702), National Institute of Environmental Health Sciences (R01ES11682, R21ES11666) and March of Dimes Birth Defects Foundation (20-FY98-0701 and 20-FY02-56).

Keywords

Chorioamnionitis
Cytokines
Intrauterine infection
Placenta

ASJC Scopus subject areas

Obstetrics and Gynecology
Pediatrics, Perinatology, and Child Health

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10.1080/14767050802609759

Cite this

@article{0017b21676e646ea968f6227de17a7ea,

title = "Cord blood biomarkers of the fetal inflammatory response",

abstract = "Objective. In current, neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. Methods. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age (GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR < 5, P < 0.001) to account for multiple comparisons. Results. Among 506 births GA 2342 weeks, IL-1β increased with FIR among preterm subgroups P 0.0001 for <32 weeks; P 0.0009 for 3336 weeks. IL-6 and IL-8 increased with FIR among preterm and full-term infants P < 0.0001. P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. Conclusion. We conclude that among 27 cord blood biomarkers, IL-1β, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.",

keywords = "Chorioamnionitis, Cytokines, Intrauterine infection, Placenta",

author = "Karen Mestan and Yunxian Yu and Poul Thorsen and Kristin Skogstrand and Nana Matoba and Xin Liu and Rajesh Kumar and Hougaard, {David M.} and Munish Gupta and Colleen Pearson and Katherin Ortiz and Howard Bauchner and Xiaobin Wang",

note = "Funding Information: The authors thank the nursing staff of Labor and Delivery at Boston Medical Center for their continuous support and assistance to the study and Lingling Fu for data management, and Ann Ramsay for administrative support. They particularly thank the outstanding expert consultants of the BMC Preterm Study team: Drs. Barry Zuckerman, Phillip Stubblefield, Jerome Klein, Milton Kotelchuck, John M. Kasznica and Paul Wise. They thank Drs. Michael Caplan and Isabelle DePlaen for their careful review of the manuscript. Finally, the authors thank all of the participating mothers and their families. The study was supported in part by grants from the National Institute of Child Health and Human Development (R01 HD41702), National Institute of Environmental Health Sciences (R01ES11682, R21ES11666) and March of Dimes Birth Defects Foundation (20-FY98-0701 and 20-FY02-56).",

year = "2009",

doi = "10.1080/14767050802609759",

language = "English (US)",

volume = "22",

pages = "379--387",

journal = "Journal of Maternal-Fetal and Neonatal Medicine",

issn = "1476-7058",

publisher = "Informa Healthcare",

number = "5",

}

TY - JOUR

T1 - Cord blood biomarkers of the fetal inflammatory response

AU - Mestan, Karen

AU - Yu, Yunxian

AU - Thorsen, Poul

AU - Skogstrand, Kristin

AU - Matoba, Nana

AU - Liu, Xin

AU - Kumar, Rajesh

AU - Hougaard, David M.

AU - Gupta, Munish

AU - Pearson, Colleen

AU - Ortiz, Katherin

AU - Bauchner, Howard

AU - Wang, Xiaobin

N1 - Funding Information: The authors thank the nursing staff of Labor and Delivery at Boston Medical Center for their continuous support and assistance to the study and Lingling Fu for data management, and Ann Ramsay for administrative support. They particularly thank the outstanding expert consultants of the BMC Preterm Study team: Drs. Barry Zuckerman, Phillip Stubblefield, Jerome Klein, Milton Kotelchuck, John M. Kasznica and Paul Wise. They thank Drs. Michael Caplan and Isabelle DePlaen for their careful review of the manuscript. Finally, the authors thank all of the participating mothers and their families. The study was supported in part by grants from the National Institute of Child Health and Human Development (R01 HD41702), National Institute of Environmental Health Sciences (R01ES11682, R21ES11666) and March of Dimes Birth Defects Foundation (20-FY98-0701 and 20-FY02-56).

PY - 2009

Y1 - 2009

N2 - Objective. In current, neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. Methods. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age (GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR < 5, P < 0.001) to account for multiple comparisons. Results. Among 506 births GA 2342 weeks, IL-1β increased with FIR among preterm subgroups P 0.0001 for <32 weeks; P 0.0009 for 3336 weeks. IL-6 and IL-8 increased with FIR among preterm and full-term infants P < 0.0001. P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. Conclusion. We conclude that among 27 cord blood biomarkers, IL-1β, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.

AB - Objective. In current, neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. Methods. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age (GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR < 5, P < 0.001) to account for multiple comparisons. Results. Among 506 births GA 2342 weeks, IL-1β increased with FIR among preterm subgroups P 0.0001 for <32 weeks; P 0.0009 for 3336 weeks. IL-6 and IL-8 increased with FIR among preterm and full-term infants P < 0.0001. P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. Conclusion. We conclude that among 27 cord blood biomarkers, IL-1β, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.

KW - Chorioamnionitis

KW - Cytokines

KW - Intrauterine infection

KW - Placenta

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JO - Journal of Maternal-Fetal and Neonatal Medicine

JF - Journal of Maternal-Fetal and Neonatal Medicine

IS - 5

ER -

Cord blood biomarkers of the fetal inflammatory response

Abstract

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Keywords

ASJC Scopus subject areas

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