Serum multiple cytokines for the prediction of spontaneous preterm birth in asymptomatic women: A nested case-control study

Huang, Lulu; Hou, Qingzhi; Huang, Yaling; Ye, Juan; Huang, Shengzhu; Tian, Jiarong; Tang, Rongjiang; Liu, Chaoqun; Liu, Yu; Qin, Xiaolian; Weng, Xunjin; Huang, Yifeng; Li, Mujun; Yang, Xiaobo; Mo, Zengnan

doi:10.1016/j.cyto.2019.02.007

Cited by 21 publications

(20 citation statements)

References 43 publications

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“…Maternal serum cytokine profiling can be used to gain detailed information about maternal inflammatory status, fetal stress, and early signs of immunological disturbance (13,17,21). To this end, immunological profiling by simultaneous measurement and analysis of multiple cytokines provides higher sensitivity and depicts ongoing inflammatory processes better than single cytokine measurements as cytokines comprise complex functional networks (17,(22)(23)(24). We have previously used serum cytokine profiling and multivariate statistics to reveal characteristic changes in cytokine patterns during the first half of pregnancy (13) and demonstrated deviant cytokine patterns before onset of clinical signs in hypertensive pregnancy disorders (21).…”

Section: Introductionmentioning

confidence: 99%

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

et al. 2021

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Pregnancy implies delicate immunological balance between two individuals, with constant changes and adaptions in response to maternal capacity and fetal demands. We performed cytokine profiling of 1149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum levels of 22 cytokines and C-reactive protein (CRP) followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptions. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus. These findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies.

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Section: Introductionmentioning

confidence: 99%

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

et al. 2021

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“…[33][34][35][36] More recently, investigations have examined mid-pregnancy biomarkers as "early warning signs" of risk for adverse birth outcomes. [37][38][39][40] Earlier studies that have considered inflammation in mid-pregnancy have focused on the relationship between individual cytokines and birth outcomes, [33][34][35][36] or have more recently used a multi-indicator approach, combining different biomarkers into composites. [37][38][39][40] However, two important considerations remain unaddressed.…”

Section: Introductionmentioning

confidence: 99%

“…[37][38][39][40] Earlier studies that have considered inflammation in mid-pregnancy have focused on the relationship between individual cytokines and birth outcomes, [33][34][35][36] or have more recently used a multi-indicator approach, combining different biomarkers into composites. [37][38][39][40] However, two important considerations remain unaddressed. First, the models used in the existing multiple indicator approaches do not sufficiently account for the complex interplay of inflammatory biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Using principal component analysis to examine associations of early pregnancy inflammatory biomarker profiles and adverse birth outcomes

Keenan-Devlin

Caplan

Freedman

et al. 2021

American J Rep Immunol

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Objective: Inflammation as a risk factor for preterm birth is well-established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of mid-pregnancy inflammation are significantly associated with risk for adverse birth outcomes. Study design:A multi-site prospective study was conducted in a socio-demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks' gestation, low-grade inflammation was measured via log-transformed serum concentrations of the biomarkers IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC).Results: Principal component analysis analysis yielded a two-factor solution, with the first factor (IF1) composed of IL-8, IL-10, IL-13, IFN-ɣ, and TNF-α, and the second

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“…Inflammatory cytokines and CRP are more strongly associated with sPTB in populations with high BMI [ 23 , 39 ], and that prediction using inflammatory biomarkers may be distinct in underweight and obese populations [ 28 , 72 ].…”

Section: Resultsmentioning

confidence: 99%

Is there a maternal blood biomarker that can predict spontaneous preterm birth prior to labour onset? A systematic review

2022

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Introduction The ability to predict spontaneous preterm birth (sPTB) prior to labour onset is a challenge, and it is currently unclear which biomarker(s), may be potentially predictive of sPTB, and whether their predictive power has any utility. A systematic review was conducted to identify maternal blood biomarkers of sPTB. Methods This study was conducted according to PRISMA protocol for systematic reviews. Four databases (MEDLINE, EMBASE, CINAHL, Scopus) were searched up to September 2021 using search terms: “preterm labor”, “biomarker” and “blood OR serum OR plasma”. Studies assessing blood biomarkers prior to labour onset against the outcome sPTB were eligible for inclusion. Risk of bias was assessed based on the Newcastle Ottawa scale. Increased odds of sPTB associated with maternal blood biomarkers, as reported by odds ratios (OR), or predictive scores were synthesized. This review was not prospectively registered. Results Seventy-seven primary research articles met the inclusion criteria, reporting 278 unique markers significantly associated with and/or predictive of sPTB in at least one study. The most frequently investigated biomarkers were those measured during maternal serum screen tests for aneuploidy, or inflammatory cytokines, though no single biomarker was clearly predictive of sPTB based on the synthesized evidence. Immune and signaling pathways were enriched within the set of biomarkers and both at the level of protein and gene expression. Conclusion There is currently no known predictive biomarker for sPTB. Inflammatory and immune biomarkers show promise, but positive reporting bias limits the utility of results. The biomarkers identified may be more predictive in multi-marker models instead of as single predictors. Omics-style studies provide promising avenues for the identification of novel (and multiple) biomarkers. This will require larger studies with adequate power, with consideration of gestational age and the heterogeneity of sPTB to identify a set of biomarkers predictive of sPTB.

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Serum multiple cytokines for the prediction of spontaneous preterm birth in asymptomatic women: A nested case-control study

Cited by 21 publications

References 43 publications

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Using principal component analysis to examine associations of early pregnancy inflammatory biomarker profiles and adverse birth outcomes

Is there a maternal blood biomarker that can predict spontaneous preterm birth prior to labour onset? A systematic review

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