PMID- 35724639
OWN - NLM
STAT- MEDLINE
DCOM- 20230210
LR  - 20230211
IS  - 1619-3997 (Electronic)
IS  - 0300-5577 (Print)
IS  - 0300-5577 (Linking)
VI  - 51
IP  - 2
DP  - 2023 Feb 23
TI  - Maternal plasma cytokines and the subsequent risk of uterine atony and postpartum 
      hemorrhage.
PG  - 219-232
LID - 10.1515/jpm-2022-0211 [doi]
AB  - OBJECTIVES: To determine whether the maternal plasma concentrations of cytokines 
      are higher in pregnant women with postpartum hemorrhage (PPH) compared to 
      pregnant women without PPH. METHODS: A retrospective case-control study included 
      36 women with PPH and 72 matched controls. Cases and controls were matched for 
      gestational age at delivery, labor status, delivery route, parity, and year of 
      sample collection. Maternal plasma samples were collected up to 3 days prior to 
      delivery. Comparison of the plasma concentrations of 29 cytokines was performed 
      by using linear mixed-effects models and included adjustment for covariates and 
      multiple testing. A false discovery rate adjusted p-value <0.1 was used to infer 
      significance. Random forest models with evaluation by leave-one-out and 9-fold 
      cross-validation were used to assess the combined value of the proteins in 
      predicting PPH. RESULTS: Concentrations of interleukin (IL)-16, IL-6, 
      IL-12/IL-23p40, monocyte chemotactic protein 1 (MCP-1), and IL-1beta were 
      significantly higher in PPH than in the control group. This difference remained 
      significant after adjustment for maternal age, clinical chorioamnionitis, and 
      preeclampsia. Multi-protein random forest proteomics models had moderate 
      cross-validated accuracy for prediction of PPH [area under the ROC curve, 0.69 
      (0.58-0.81) by leave-one-out cross validation and 0.73 (0.65-0.81) by 9-fold 
      cross-validation], and the inclusion of clinical and demographic information did 
      not increase the prediction performance. CONCLUSIONS: Pregnant women with severe 
      PPH had higher median maternal plasma concentrations of IL-16, IL-6, 
      IL-12/IL-23p40, MCP-1, and IL-1beta than patients without PPH. These cytokines could 
      serve as biomarkers or their pathways may be therapeutic targets.
CI  - (c) 2022 Walter de Gruyter GmbH, Berlin/Boston.
FAU - Gallo, Dahiana M
AU  - Gallo DM
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
FAU - Romero, Roberto
AU  - Romero R
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, 
      USA.
AD  - Department of Epidemiology and Biostatistics, Michigan State University, East 
      Lansing, MI, USA.
AD  - Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, 
      USA.
AD  - Detroit Medical Center, Detroit, MI, USA.
FAU - Bosco, Mariachiara
AU  - Bosco M
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
FAU - Chaiworapongsa, Tinnakorn
AU  - Chaiworapongsa T
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
FAU - Gomez-Lopez, Nardhy
AU  - Gomez-Lopez N
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
AD  - Department of Biochemistry, Microbiology and Immunology, Wayne State University 
      School of Medicine, Detroit, MI, USA.
FAU - Arenas-Hernandez, Marcia
AU  - Arenas-Hernandez M
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
FAU - Jung, Eunjung
AU  - Jung E
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
FAU - Suksai, Manaphat
AU  - Suksai M
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
FAU - Gotsch, Francesca
AU  - Gotsch F
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
FAU - Erez, Offer
AU  - Erez O
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, HaEmek Medical Center, Afula, Israel.
FAU - Tarca, Adi L
AU  - Tarca AL
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, United States 
      Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, and 
      Detroit, MI, USA.
AD  - Department of Obstetrics and Gynecology, Wayne State University School of 
      Medicine, Detroit, MI, USA.
AD  - Department of Computer Science, Wayne State University College of Engineering, 
      Detroit, MI, USA.
LA  - eng
GR  - Z01 HD002400/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20220621
PL  - Germany
TA  - J Perinat Med
JT  - Journal of perinatal medicine
JID - 0361031
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Pregnancy
MH  - Female
MH  - Humans
MH  - *Postpartum Hemorrhage/diagnosis/etiology
MH  - *Uterine Inertia
MH  - Cytokines
MH  - Retrospective Studies
MH  - Case-Control Studies
MH  - Interleukin-6
MH  - Interleukin-12
PMC - PMC9768104
MID - NIHMS1818283
OTO - NOTNLM
OT  - CCL2
OT  - IL-12/IL-23p40
OT  - IL-16
OT  - IL-1beta
OT  - IL-6
OT  - MCP-1
OT  - biomarker
OT  - inflammation
OT  - interleukin (IL)
OT  - maternal proteins
COIS- Competing interests: The authors state no conflicts of interest.
EDAT- 2022/06/21 06:00
MHDA- 2023/02/11 06:00
PMCR- 2023/02/09
CRDT- 2022/06/20 18:25
PHST- 2022/05/02 00:00 [received]
PHST- 2022/05/23 00:00 [accepted]
PHST- 2022/06/21 06:00 [pubmed]
PHST- 2023/02/11 06:00 [medline]
PHST- 2022/06/20 18:25 [entrez]
PHST- 2023/02/09 00:00 [pmc-release]
AID - jpm-2022-0211 [pii]
AID - 10.1515/jpm-2022-0211 [doi]
PST - epublish
SO  - J Perinat Med. 2022 Jun 21;51(2):219-232. doi: 10.1515/jpm-2022-0211. Print 2023 
      Feb 23.