Background
Postpartum hemorrhage remains the leading cause of maternal mortality. However, there
is an insufficient understanding of atonic postpartum hemorrhage. Uterine atony is
the most common cause of postpartum hemorrhage. Although an association between myometrium
inflammatory cytokines and atonic postpartum hemorrhage has been demonstrated preliminarily,
it is not clinically useful in predicting postpartum hemorrhage. Plasma is more readily
available, and the assessment of its inflammatory status is more relevant to biological
markers of postpartum hemorrhage and might explain the pathophysiology of atonic postpartum
hemorrhage.
Objective
Our objective was to examine changes in maternal plasma cytokines in women with atonic
postpartum hemorrhage.
Study Design
This was a retrospective longitudinal case-control study of pregnant women with singleton
gestations at term undergoing vaginal delivery. Cases were women with atonic postpartum
hemorrhage, and 1:1 propensity-score matching was used to match the control group.
Maternal plasma was collected in the first trimester, early third trimester, and late
third trimester, and multiplex Luminex assay was used to determine the cytokine concentrations.
Multivariate logistic regressions were used to determine the association between maternal
cytokines at different stages of pregnancy and atonic postpartum hemorrhage.
Results
A total of 36 pregnant women met the clinical diagnostic criteria for atonic postpartum
hemorrhage, and 36 patients without postpartum hemorrhage were matched as the control
group. Concentrations were lower for most cytokines in the atonic postpartum hemorrhage
group in the first and early third trimester. However, in the late third trimester,
higher plasma concentrations of basic fibroblast growth factor, interleukin-1 alpha,
interleukin-1 beta, interleukin-1 receptor antagonist, interleukin-2 receptor alpha,
interleukin-16, interleukin-18, macrophage colony stimulating factor, macrophage inflammatory
protein-1 alpha, beta-nerve growth factor, tumor necrosis factor-related apoptosis-induced
ligand, and stem cell factor were significantly associated with increased risk of
atonic postpartum hemorrhage. Multiple testing correction showed that basic fibroblast
growth factor (P<.001; fold change [FC]=1.16), macrophage inflammatory protein-1 alpha (P<.001; FC=1.15), and stem cell factor (P=.001; FC=1.25) had the most significant difference (P<.001). The prediction model of atonic postpartum hemorrhage constructed by these
significantly changed cytokines had a high predictive efficiency (area under the curve,
0.84; sensitivity, 0.78; specificity, 0.83; +likelihood ratio, 4.66; −likelihood ratio,
0.27).
Conclusion
Higher concentrations of maternal plasma cytokines in the late third trimester are
associated with high risk of subsequent atonic postpartum hemorrhage. These indicators
may be potential biomarkers for predicting atonic postpartum hemorrhage.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Obstetrics & GynecologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global causes of maternal death: a WHO systematic analysis.Lancet Glob Health. 2014; 2: e323-e333
- Obstetrics Subgroup Chinese Society of Obstetrics and Gynecology Chinese Medical Association. Guideline of prevention and treatment about postpartum hemorrhage (2014]..Zhonghua Fu Chan Ke Za Zhi. 2014; 49 (641-646. [Chinese])
- Practice Bulletin No. 183: postpartum hemorrhage.Obstet Gynecol. 2017; 130: e168-e186
- Poor uterine contractility and postpartum hemorrhage among low-risk women: a case-control study of a large-scale database from Japan.Int J Gynaecol Obstet. 2021; 154: 17-23
- Risk factors for atonic postpartum hemorrhage: a systematic review and meta-analysis.Obstet Gynecol. 2021; 137: 305-323
- Antigen-presenting cells in pregnant and non-pregnant human myometrium.Am J Reprod Immunol. 2010; 64: 188-196
- A molecular signature of an arrest of descent in human parturition.Am J Obstet Gynecol. 2011; 204: 177.e15-177.e33
- Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term.J Perinat Med. 2010; 38: 617-643
- Histological characteristics of the myometrium in the postpartum hemorrhage of unknown etiology: a possible involvement of local immune reactions.J Reprod Immunol. 2015; 110: 74-80
- Elevated bradykinin receptor type 1 expression in postpartum acute myometritis: possible involvement in augmented interstitial edema of the atonic gravid uterus.J Obstet Gynaecol Res. 2019; 45: 1553-1561
- Acute inflammation in the uterine isthmus coincides with postpartum acute myometritis in the uterine body involving refractory postpartum hemorrhage of unknown etiology after cesarean delivery.J Reprod Immunol. 2020; 139: 103116
- Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: a matched analysis using propensity scores.J Clin Epidemiol. 2001; 54: 387-398
- A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003.Stat Med. 2008; 27: 2037-2049
- Analysis of matched case-control data with incomplete strata: applying longitudinal approaches.Epidemiology. 2007; 18: 446-452
- Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.Biometrics. 1988; 44: 837-845
- Inflammatory processes in preterm and term parturition.J Reprod Immunol. 2008; 79: 50-57
- The enigma of spontaneous preterm birth.N Engl J Med. 2010; 362: 529-535
- Leukocytes are primed in peripheral blood for activation during term and preterm labour.Mol Hum Reprod. 2009; 15: 713-724
- Systemic increase in human maternal circulating CD14+CD16- MCP-1+ monocytes as a marker of labor.Am J Obstet Gynecol. 2014; 210: 70.e1-70.e9
- Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process.Hum Reprod. 1999; 14: 229-236
- Immunolocalization of proinflammatory cytokines in myometrium, cervix, and fetal membranes during human parturition at term.Biol Reprod. 2002; 66: 445-449
- Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term.Mol Hum Reprod. 2003; 9: 41-45
- Is myometrial inflammation a cause or a consequence of term human labour?.J Endocrinol. 2017; 235: 69-83
- Maternal inflammation in spontaneous term labor.Am J Obstet Gynecol. 2011; 204: 223.e1-223.e5
- Maternal inflammatory markers and term labor performance.Am J Obstet Gynecol. 2014; 210: 447.e1-447.e6
- Labor and inflammation increase the expression of oxytocin receptor in human amnion.Biol Reprod. 2011; 84: 546-552
- Oxytocin signaling in human myometrium is impaired by prolonged exposure to interleukin-1.Biol Reprod. 2000; 63: 846-850
- Transcriptional regulation of oxytocin receptor by interleukin-1beta and interleukin-6.Endocrinology. 2001; 142: 1380-1385
- Markedly elevated levels of inflammatory cytokines in maternal serum and peritoneal washing during arrested labor.Acta Obstet Gynecol Scand. 2004; 83: 358-363
- A protein microarray analysis of plasma proteins for the prediction of spontaneous preterm delivery in women with preterm labor.Reprod Sci. 2020; 27: 1187-1196
- Regulation of hematopoietic cell clusters in the placental niche through SCF/Kit signaling in embryonic mouse.Development. 2010; 137: 3941-3952
- Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.Am J Obstet Gynecol. 2018; 218: 345.e1-345.e30
- Placental expression of insulin-like growth factor-I, fibroblast growth factor-basic, and neural cell adhesion molecule in preeclampsia.J Matern Fetal Neonatal Med. 2008; 21: 831-838
- Fibroblast growth factor type 2 (FGF2) administration attenuated the clinical manifestations of preeclampsia in a murine model induced by L-NAME.Front Pharmacol. 2021; 12: 663044
Article Info
Publication History
Published online: December 15, 2021
Accepted:
December 6,
2021
Received in revised form:
December 3,
2021
Received:
May 21,
2021
Footnotes
The authors report no conflict of interest.
This research was supported by the National Key Research and Development Program (grant number 2016YFC1000400) and Cohort Construction Project of Peking University Third Hospital (grant number BYSYDL2019001).
Cite this article as: Jiang H, Shi H, Chen L, et al. Is there a relationship between plasma, cytokine concentrations, and the subsequent risk of postpartum hemorrhage? Am J Obstet Gynecol 2022;226:835.e1-17.
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
