Symptoms Of Preterm Birth Research Articles

Predicting Spontaneous Pre-term Birth Risk Is Improved When Quantitative Ultrasound Data Are Included With Historical Clinical Data.

Predicting women at risk for spontaneous pre-term birth (sPTB) has been medically challenging because of the lack of signs and symptoms of pre-term birth until interventions are too late. We hypothesized that prediction of the sPTB risk level is enhanced when using both historical clinical (HC) data and quantitative ultrasound (QUS) data compared with using only HC data. HC data defined herein included birth history prior to that of the current pregnancy as well as, from the current pregnancy, a clinical cervical length assessment and physical examination data. The study population included 248 full-term births (FTBs) and 26 sPTBs. QUS scans (Siemens S2000 and MC9-4) were performed by registered diagnostic medical sonographers using a standard cervical length approach. Two cervical QUS scans were conducted at 20 ± 2 and 24 ± 2 wk of gestation. Multiple QUS features were evaluated from calibrated raw radiofrequency backscattered ultrasonic signals. Two statistical models designed to determine sPTB risk were compared: (i) HC data alone and (ii) combined HC and QUS data. Model comparisons included a likelihood ratio test, cross-validated receiver operating characteristic area under the curve, sensitivity and specificity. The study's birth outcomes were only FTBs and sPTBs; medically induced pre-term births were not included. Combined HC and QUS data identified women at risk of sPTB with better AUC (0.68, 95% confidence interval [CI]: 0.57-0.78) compared with HC data alone (0.53, 95% CI: 0.40-0.66) and HC data+cervical length at 18-20 wk of gestation (average AUC=0.51, 95% CI: 0.38-0.64). A likelihood ratio test for significance of QUS features in the classification model was highly statistically significant (p < 0.01). Even with only 26 sPTBs among 274 births, value was added in predicting sPTB when QUS data were included with HC data.

Correlation of Qualitative Alpha1-microglobulin, Values of Interleukin 6, Cervicometry and Cervical Infection in Pregnant Women with Symptoms of Preterm Birth.

One of the problems in modern obstetrics is how to identify and select pregnant women who are most likely to give premature birth. In the last ten years, due to false-positive test results, i.e., tests with low positive predictive values, there is an increase in unnecessary hospitalization days as well as unnecessary therapy. The probability of preterm birth is 25% in a population of pregnant women with symptoms of preterm birth. The aim was to analyze diagnostic accuracy of tests for the purpose of predicting premature births in< 37th and <34th week of pregnancy.Incidence of preterm births in < 37th week of pregnancy was 28%, while the incidence of preterm births up until 34th week of pregnancy, was < 8%. We included two groups of pregnant women in a prospective study; one group with the symptoms of threatening preterm birth between 22nd and 37th week of pregnancyand the other one of the same gestation period with no symptoms. Each pregnant woman underwent test for placental alphamicroglobulin-1, cervical length screening, cervical sampling for microbiological analysis, blood sampling for IL6 and CRP analysis. There were 16% of preterm births, up until 7 days from hospitalization, and they were all PAMG-1 positive; There is 75% of preterm births if PAMG-1 is positive with cervical length under 25mm. Combining tests, we reached the best predictive accuracy with positive PAMG-1 test, cervical length under 15mm along with the increase of CRP values above 15.96%. Total number of hospitalization days was 29% with preterm births up to 71% with full term births regardless the symptomatology, which justifies further studies towards releasing the pressure from the health care system and from doctors as well in the process of reaching a decision on treatment of pregnant women with the signs of preterm birth.

Identification of a novel gene signature in second-trimester amniotic fluid for the prediction of preterm birth

Preterm birth affects approximately 5% to 7% of live births worldwide and is the leading cause of neonatal morbidity and mortality. Amniotic fluid supernatant (AFS) contains abundant cell-free nucleic acids (cfNAs) that can provide genetic information associated with pregnancy complications. In the current study, cfNAs of AFS in the early second-trimester before the onset of symptoms of preterm birth were analyzed, and we compared gene expression levels between spontaneous preterm birth (n = 5) and term birth (n = 5) groups using sequencing analysis. Differential expression analyses detected 24 genes with increased and 6 genes with decreased expression in the preterm birth group compared to term birth. Upregulated expressions of RDH14, ZNF572, VOPP1, SERPINA12, and TCF15 were validated in an extended AFS sample by quantitative PCR (preterm birth group, n = 21; term birth group, n = 40). Five candidate genes displayed a significant increase in mRNA expression in immortalized trophoblast HTR-8/SVneo cell with H2O2 treatment. Moreover, the expression of five candidate genes was increased to more than twofold by pretreatment with lipopolysaccharide in HTR-8/SVneo cells. Changes in gene expression between preterm birth and term birth is strongly correlated with oxidative stress and infection during pregnancy. Specific expression patterns of genes could be used as potential markers for the early identification of women at risk of having a spontaneous preterm birth.

Infection/inflammation-associated preterm delivery within 14 days of presentation with symptoms of preterm labour: A multivariate predictive model.

Multi-marker tests hold promise for identifying symptomatic women at risk of imminent preterm delivery (PTD, <37 week’s gestation). This study sought to determine the relationship of inflammatory mediators and metabolites in cervicovaginal fluid (CVF) with spontaneous PTD (sPTD) and delivery within 14 days of presentation with symptoms of preterm labour (PTL). CVF samples from 94 (preterm = 19, term = 75) singleton women with symptoms of PTL studied between 19+0–36+6 weeks’ gestation were analysed for cytokines/chemokines by multiplexed bead-based immunoassay, while metabolites were quantified by enzyme-based spectrophotometry in a subset of 61 women (preterm = 16, term = 45). Prevalence of targeted vaginal bacterial species was determined for 70 women (preterm = 14, term = 66) by PCR. Overall, 10 women delivered within 14 days of sampling. Predictive capacities of individual biomarkers and cytokine-metabolite combinations for sPTD and delivery within 14 days of sampling were analysed by logistic regression models and area under the receiver operating characteristic curve. Fusobacterium sp., Mubiluncus mulieris and Mycoplasma hominis were detected in more preterm-delivered than term women (P<0.0001), while, M. curtisii was found in more term-delivered than preterm women (P<0.0001). RANTES (0.91, 0.65–1.0), IL-6 (0.79, 0.67–0.88), and Acetate/Glutamate ratio (0.74, 0.61–0.85) were associated with delivery within 14 days of sampling (AUC, 95% CI). There were significant correlations between cytokines and metabolites, and several cytokine-metabolite combinations were associated with sPTD or delivery within 14 days of sampling (e.g. L/D-lactate ratio+Acetate/Glutamate ratio+IL-6: 0.84, 0.67–0.94). Symptomatic women destined to deliver preterm and within 14 days of sampling express significantly higher pro-inflammatory mediators at mid to late gestation. In this cohort, IL-6, Acetate/Glutamate ratio and RANTES were associated with delivery within 14 days of sampling, consistent with their roles in modulating infection-inflammation-associated preterm labour in women presenting with symptoms of preterm birth. Replication of these observations in larger cohorts of women could show potential clinical utility.

Is the Use of Antibiotics Useful in Patients with Preterm Birth Symptoms and Intact Membranes?

Preterm birth is the main contributor to perinatal morbidity/mortality and high costs associated to stays in neonatal intensive care units. Its frequency has increased especially by ascending bacterial infection. Antibiotic treatment in preterm birth symptoms with intact membranes has not shown benefits and associated to its use is the neurological disabilities found in children whose mothers received antibiotics. However another study showed benefits of the treatment with antibiotics in patients with endocervical inflammation, but without microbial invasion of the amniotic cavity. Further studies are needed to clarify the benefit of antibiotics in preterm birth with intact membranes with these conditions.

Qualitative assessment of attitudes and knowledge on preterm birth in Malawi and within country framework of care

BackgroundThe overarching goal of this study was to qualitatively assess baseline knowledge and perceptions regarding preterm birth (PTB) and oral health in an at-risk, low resource setting surrounding Lilongwe, Malawi. The aims were to determine what is understood regarding normal length of gestation and how gestational age is estimated, to identify common language for preterm birth, and to assess what is understood as options for PTB management. As prior qualitative research had largely focused on patient or client-based focused groups, we primarily focused on groups comprised of community health workers (CHWs) and providers.MethodsA qualitative study using focus-group discussions, incidence narrative, and informant interviews amongst voluntary participants. Six focus groups were comprised of CHWs, patient couples, midwives, and clinical officers (n = 33) at two rural health centers referring to Kamuzu Central Hospital. Semi-structured questions facilitated discussion of PTB and oral health (inclusive of periodontal disease), including definitions, perception, causation, management, and accepted interventions.ResultsEvery participant knew of women who had experienced “a baby born too soon”, or preterm birth. All participants recognized both an etiology conceptualization and disease framework for preterm birth, distinguished PTB from miscarriage and macerated stillbirth, and articulated a willingness to engage in studies aimed at prevention or management. Identified gaps included: (1) discordance in the definition of PTB (i.e., 28–34 weeks or less than the 8th month, but with a corresponding fetal weight ranging 500 to 2300 grams); (2) utility and regional availability of antenatal steroids for prevention of preterm infant morbidity and mortality; (3) need for antenatal referral for at-risk women, or with symptoms of preterm birth. There was no evident preference for route of progesterone for the prevention of recurrent PTB.ConclusionsQualitative research was useful in (1) identifying gaps in knowledge in urban and rural Malawi, and (2) informing the development of educational materials and implementation of programs or trials ultimately aimed at reducing PTB. As a result of this qualitative work, implementation planning was focused on the gaps in knowledge, dissemination of knowledge (to both patients and providers), and practical solutions to barriers in known efficacious therapies.

Preterm Labor: Understanding of the Mechanism Involved to Improve Prediction and Prevention

Preterm birth is a significant problem occurring in around 10% of all deliveries and its increase is remarkable, even in developed countries. Being born under 37 weeks, and most importantly under 32 weeks, is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. Recent advances in perinatology and neonatology have increased survival rates, particularly for the extremely preterm baby. The associated morbidity for these survivors' remains significant, and up to one-quarter will have at least one major disability. This special issue focused in some aspect of the physiopathology of the preterm labor and different strategies to predict the patient at risk in order to improve the prevention of this pathology. This issue highlights the diversity of the physiopathology of preterm labor by including different points of view, such as focusing in the expression of steroid receptor coactivators in fetal membranes and its relationship with preterm labor. Using immunohistochemistry, western blot analysis, and real-time PCR, they demonstrate that SRC-1, SCR-2, p300, and PCAF proteins are present in nuclear extracts and display tissue-specific and labor-associated differential expression. In another paper, the authors propose a novel putative target for the prevention of infection-triggered preterm labor. They suggest that uterotonic effects of endothelin-1 (E-1) are mediated via sphingosine kinase (SphK). E-1 is a molecule that exerts potent oxytocic effects and is elevated in amniotic fluid obtained from preterm births. SphK plays a key role in ET-1-induced myometrial contractions and may represent a potential target for tocolysis to prevent preterm birth. In terms of prediction, a review accessing the accuracy of transvaginal sonographic cervical length in predicting preterm birth in women with twin pregnancy and symptoms of preterm birth is presented. The authors present a meta-analysis, using bivariate regression analysis, accounting for correlation between sensitivity and specificity. Despite the large variation in definition of preterm birth and cut-off point of cervical length and gestational age, they concluded that there is insufficient evidence to recommend the measurement of cervical length as a predictor of preterm birth in women with a twin pregnancy and symptoms of preterm birth because specificity and sensibility are low. With respect to prevention of preterm birth, a systematic review of the use of cervical pessaries and adjunctive therapies to cerclage is presented. The aim of one study was to evaluate the effective use of the cervical pessary to prevent preterm birth before 28, 34, and 37 weeks of gestation. Interestingly, one randomized controlled trial demonstrated a lower delivery rate prior to 34 weeks in the pessary group. Other studies, however, showed no positive effect. The author concluded that the cervical pessaries represent an affordable, safe, and reliable alternative for prevention of preterm birth in selected at-risk pregnant women. Nevertheless, more randomized clinical trials are needed before this device can be used in clinical practice. In another study, the authors reviewed publications that assessed the efficacy of adjunctive therapies used in addition to cervical cerclage as a preventive measure for preterm birth. The adjunctive therapies identified were progesterone, reinforcing or second cerclage placement, tocolytics, antibiotics, bedrest, and pessary. Even though small numbers of patients limited the strength of the conclusions, none of the studies clearly show the benefit of any adjunctive therapy used. By compiling these papers, we hope to improve the knowledge of clinicians and researchers with respect to this important cause of perinatal morbidity and mortality. Increasing the understanding of the physiopathology of the preterm labor and the strategies to prevent it are essential steps to avoid the consequence of this disease. S. E. Illanes J. K. Nien G. E. Rice

Use of the fetal fibronectin assay to avert unnecessary hospitalization and bedrest in patients with preterm labor symptoms: a cost analysis

Objective: To model cost implications of the fetal fibronectin (fFN) assay in management of patients with symptoms of preterm labor based on data from a previously published multicenter trial. Study design: Data from a trial of fFN in 763 patients with symptoms of preterm birth was used to create a decision analytic model. Standard management in the trial was compared with a theoretic management plan using fFN results to guide decisions regarding hospitalization and use of bedrest. Average costs and durations of antepartum and delivery hospitalizations for patients with preterm labor were obtained from a data set of 404,466 patients delivered in California in 1993. Average bedrest costs were obtained using data from the US Bureau of Labor Statistics ($89 per day). A cost savings of $3,000 from the use of betamethasone prior to 34 weeks was assumed based on estimates from the NIH consensus conference. All patients were treated equally until fFN results were obtained. All fFN positive patients were admitted, given steroids, and discharged after an average of 2.5 days of bedrest. Results: Under baseline assumptions, theoretic management using fFN cost $3,900 per patient vs estimates of $4,820 in the trial. This resulted in savings of $919 per patient, which was robust under sensitivity analysis of all costs in the model. Conclusions: Addition of fFN management of threatened preterm labor has theoretic cost advantages when compared to existing patterns of clinical management.