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Use of metabolomics for predicting spontaneous preterm birth in asymptomatic pregnant women: protocol for a systematic review and meta-analysis.

ABSTRACT: INTRODUCTION:Preterm birth (PTB) is the leading cause of neonatal mortality and short- and long-term morbidity. The aetiology and pathophysiology of spontaneous PTB (sPTB) are still unclear, which makes the identification of reliable and accurate predictor markers more difficult, particularly for unscreened or asymptomatic women. Metabolomics biomarkers have been demonstrated to be potentially accurate biomarkers for many disorders with complex mechanisms such as PTB. Therefore, we aim to perform a systematic review of metabolomics markers associated with sPTB. Our research question is 'What is the performance of metabolomics for predicting spontaneous preterm birth in asymptomatic pregnant women?' METHODS AND ANALYSIS:We will focus on studies assessing metabolomics techniques for predicting sPTB in asymptomatic pregnant women. We will conduct a comprehensive systematic review of the literature from the last 10 years. Only observational cohort and case-control studies will be included. Our search strategy will be carried out by two independent reviewers, who will scan title and abstract before carrying out a full review of the article. The scientific databases to be explored include PubMed, MedLine, ScieLo, EMBASE, LILACS, Web of Science, Scopus and others. ETHICS AND DISSEMINATION:This systematic review protocol does not require ethical approval. We intend to disseminate our findings in scientific peer-reviewed journal, the Preterm SAMBA study open access website, specialists' conferences and to our funding agencies. PROSPERO REGISTRATION NUMBER:CRD42018100172.

SUBMITTER: Souza RT

PROVIDER: S-EPMC6429842 | biostudies-other | 2019 Mar

REPOSITORIES: biostudies-other

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Use of metabolomics for predicting spontaneous preterm birth in asymptomatic pregnant women: protocol for a systematic review and meta-analysis.

Souza Renato T RT Galvão Rafael Bessa RB Leite Debora Farias Batista DFB Passini Renato R Baker Philip P Cecatti Jose Guilherme JG

BMJ open 20190304 3

<h4>Introduction</h4>Preterm birth (PTB) is the leading cause of neonatal mortality and short- and long-term morbidity. The aetiology and pathophysiology of spontaneous PTB (sPTB) are still unclear, which makes the identification of reliable and accurate predictor markers more difficult, particularly for unscreened or asymptomatic women. Metabolomics biomarkers have been demonstrated to be potentially accurate biomarkers for many disorders with complex mechanisms such as PTB. Therefore, we aim t ...[more]

PMID: 30837257

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Project description:OBJECTIVES:Perturbation of the choriodecidual space before the onset of spontaneous preterm birth (sPTB) could lead to a concomitant rise in both cervicovaginal fluid (CVF) cytokine and fetal fibronectin (FFN), and assessing the concentrations of both markers could improve the prediction of sPTB (delivery before 37 completed weeks of gestation). Therefore, we prospectively determined mid-trimester changes in CVF cytokine and FFN concentrations, and their predictive capacity for sPTB in asymptomatic pregnant women. STUDY DESIGN:CVF collected at 20+0-22+6 weeks (n?=?47: Preterm-delivered?=?22, Term-delivered?=?25) and 26+0-28+6 weeks (n?=?50: Preterm-delivered?=?17, Term-delivered?=?33) from 63 asymptomatic pregnant women at risk of sPTB were examined. Cytokine and FFN concentrations were determined by multiplexed bead-based immunoassay and 10Q Rapid analysis (Hologic, MA, USA) respectively. The 20+0-22+6/26+0-28+6 weeks ratios of cytokines and FFN concentrations were compared between preterm- and term-delivered women using Receiver Operating Characteristics curves to predict sPTB. Also, bacterial 16S rDNA from 64 samples (20+0-22+6 weeks n?=?36, 26+0-28+6 weeks n?=?28) was amplified by polymerase chain reaction to determine associations between vaginal microflora, cytokine and FFN concentrations. RESULTS:Changes in RANTES and IL-1? concentrations between 20+0-22+6 and 26+0-28+6 weeks, expressed as a ratios, were predictive of sPTB, RANTES (AUC?=?0.82, CI?=?0.62-0.94) more so than IL-1? (AUC?=?0.71, CI?=?0.53-0.85) and FFN (not predictive). Combining these markers (AUC?=?0.83, CI?=?0.63-0.95) showed similar predictive capacity as RANTES alone. FFN concentrations at 26+0-28+6 weeks correlated with IL-1? (r?=?0.4, P?=?0.002) and RANTES (r?=?0.3, P?=?0.03). In addition, there was increased prevalence of vaginal anaerobes including Bacteroides, Fusobacterium and Mobiluncus between gestational time points in women who experienced sPTB compared to the term women (P?=?0.0006). CONCLUSIONS:CVF RANTES and IL-1? in mid-trimester of pregnancy correlate with quantitative FFN. The levels of CVF RANTES and IL-1? decline significantly in women who deliver at term unlike women who deliver preterm. This observation suggests that sPTB may be characterised by sustained choriodecidual inflammation and may have clinical value in serial screening for sPTB if confirmed by larger studies.

Project description:OBJECTIVE:Preterm birth (birth before 37 weeks of completed gestation) is the leading cause of neonatal death, and has an incidence of 5-13% which is believed to be on the rise. The objective of this study was to determine the rate of spontaneous preterm birth and investigate the relationship between preterm birth and cervical length in a pregnant Asian population. MATERIALS AND METHODS:A prospective observational study between September 2010 and November 2013 was performed at KK Women's and Children's Hospital, Singapore. 1013 women with single viable pregnancies were recruited at less than 14 weeks of gestation between September 2010 and November 2013, excluding those with multiple gestation, pre-existing autoimmune or renal disease or those with current pregnancies complicated by aneuploidy or fetal anomalies. Participant characteristics were obtained from an interviewer-administered questionnaire at the first recruitment visit. Cervical length was measured using ultrasound at each of the 4 antenatal visits (Visit 1: < 14 weeks, Visit 2: 18-22 weeks, Visit 3: 28-32 weeks and Visit 4: > 34 weeks) using the Fetal Medicine Foundation protocol. Data on pregnancy outcomes were obtained from obstetric case notes and records. The main outcome measure examined in this study was that of spontaneous preterm birth and its relationship to cervical length. RESULTS:There was a significantly shorter cervical length both in the 2nd trimester (18 to 22 weeks) and the 3rd trimester (28 to 32 weeks) in the preterm birth group compared to the term birth group (p = 0.028 and p < 0.001 respectively). In the first trimester (11 to 14 weeks), there was no statistically significant difference in cervical length between the two groups (p = 0.425). ROC curve analysis for cervical length in the preterm birth group for 18 to 22 weeks and 28 to 32 weeks showed an AUC of 0.605 and 0.725 respectively. At 28 to 32 weeks of gestation, a cut-off level at 2.49 cm has a sensitivity of 54.8%, specificity of 82.5%, negative predictive value of 97.9% and positive predictive value of 11.1%. CONCLUSION:There is a significantly shorter cervical length in the 2nd and 3rd trimester in the preterm birth group. Cervical length is a moderate predictor of preterm birth with good negative predictive value and a relatively good specificity. Ultrasound cervical length screening for pregnant Asian women between 18 and 22 weeks of gestation with a cutoff of ? 2.48cm can help to identify a group of women who are at risk for preterm birth.

Project description:Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions.To determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth.Longitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts.Posttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications.Preterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview.Recursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27-13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0-110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02-2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98-4.03]).Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.

Dataset Information

Use of metabolomics for predicting spontaneous preterm birth in asymptomatic pregnant women: protocol for a systematic review and meta-analysis.

Publications

Use of metabolomics for predicting spontaneous preterm birth in asymptomatic pregnant women: protocol for a systematic review and meta-analysis.

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