Diagnosis Of Preterm Labor Research Articles

Recent Advances and Challenges in the Early Diagnosis and Treatment of Preterm Labor.

Preterm birth (PTB) is the primary cause of neonatal mortality and long-term disabilities. The unknown mechanism behind PTB makes diagnosis difficult, yet early detection is necessary for controlling and averting related consequences. The primary focus of this work is to provide an overview of the known risk factors associated with preterm labor and the conventional and advanced procedures for early detection of PTB, including multi-omics and artificial intelligence/machine learning (AI/ML)- based approaches. It also discusses the principles of detecting various proteomic biomarkers based on lateral flow immunoassay and microfluidic chips, along with the commercially available point-of-care testing (POCT) devices and associated challenges. After briefing the therapeutic and preventive measures of PTB, this review summarizes with an outlook.

The effect of genital hygiene behaviors and vaginal douching of pregnant women on preterm labor.

To determine the effect of genital hygiene behavior (GHB) and vaginal douching (VD) of pregnant women on preterm labor (PTL). This study, which was conducted with 365 pregnant women, is a cross-sectional study. Data were collected using a questionnaire and the Genital Hygiene Behavior Inventory (GHBI) was applied. The ratios of PTL diagnosis and VD practice, and mean GHBI scores of the pregnant women were 35.1%, 9.6%, and 64.42 ± 10.44, respectively. The prevalence of receiving a diagnosis of PTL was significantly higher in those who changed their underwear two to three times a week, took baths while sitting, cleansed their perineum with water using their hands, removed pubic hair at intervals of 2 months or longer, and performed VD. It was found that poor GHB and VD practices increased the rate of PTL and, in particular, VD was found to increase the risk of PTL around eight-fold. These results can help pregnant women to understand the relationship between genital hygiene and PTL and show the importance of being educated by health professionals about this issue.

Study of Cervical Mucus Cytology and Serum Inflammatory Biomarkers in Preterm Labour Compared to Term Pregnancy Cases in a Tertiary Care Center of Western Uttar Pradesh (UP), India.

The onset of labor prior to 37 weeks of gestation is preterm labor. Incidence ranges from 5% to 7% of live births in developed countries, but higher in developing countries (10-13%). Preterm birth is a major threat in perinatal health care, as well as a risk factor for neurological impairment and disability. Considering that infection is the major risk factor for preterm labor in rural areas, this study was performed to assess the cytological changes in the cervical mucus of normal-term and preterm labor cases. A hospital-based cross-sectional observational study was conducted in the Department of Obstetrics and Gynecology at a tertiary care center in western Uttar Pradesh (UP), India. The sample size calculated was 90. The neutrophil-to-lymphocyte ratio (NLR) in cervical mucus, along with serum inflammatory biomarkers such as CRP and serum alkaline phosphatase, were compared in both groups. The incidence of preterm labor increased with an increase in parity, and progression to preterm delivery is faster in the higher parity group. C-reactive protein (CRP) (pvalue= < 0.001) and serum alkaline phosphatases (taking 220IU/L as the cutoff value), as well as the NLR (pvalue < 0.001) in cervical mucus in preterm labor, are significantly higher than those in term labor cases, which can be used to predict preterm labor. Higher levels of serum alkaline phosphatase (> 220 IU/L) and CRP positivity can be used as prognostic markers. Using a cutoff value of 5 for the NLR in the cervical mucusof preterm labor patients proved to be a highly accurate predictor (82.2%) for preterm labor diagnosis.

50 Years of Antenatal Corticosteroids: A Systematic Review

Summary The administration of antenatal corticosteroids (ACS) to accelerate fetal lung maturation is considered one of the most valuable antenatal therapies in preterm labour. Although early indications that administering antenatal corticosteroids has a positive impact on fetal lung maturation and despite the widespread recommendations to use this treatment in women at risk of preterm birth, there is still some uncertainty regarding its effectiveness, particularly in lower-resource settings and in high-risk groups such as women with hypertension or multiple pregnancies. The optimal timing of administration has not improved in over 50 years. This assessment aimed to evaluate the effects of administering a course of corticosteroids to women before anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and the child’s health later in life. It is advised that clinicians only administer a single course of ACS in high-risk cases of preterm birth likely to occur within the next seven days, and the gestational age is between 22+0 and 33+6 weeks. The diagnosis of preterm labour should be made based on available resources and expertise and supported by comprehensive protocols in the relevant setting.

Using Fetal Fibronectin Test to Reduce Hospital Admissions with Diagnosis of Preterm Labor: An Economic Evaluation Study.

Background: Preterm labor and delivery remain a major problem in obstetrics accounting for perinatal morbidity and mortality. The challenge is to identify those with true preterm labor to avoid unnecessary hospital admissions. The fetal fibronectin (FFN) test is a strong predictor of preterm birth and can help identify women with true preterm labor. However, its cost-effectiveness as a strategy for triaging women with threatened preterm labor is still debatable. Objective: To evaluate the effect of FFN test implementation on hospital resources by reducing the admission rate of threatened preterm labor in a tertiary hospital, Latifa Hospital, UAE. Methods: A retrospective cohort study of singleton pregnancies between 24 and 34 weeks of gestation who attended Latifa Hospital in the period of September 2015-December 2016, complaining of threatened preterm labor after the availability of an FFN test, and a historical cohort study for those who attended with threatened preterm labor before the availability of an FFN test. Data analysis was performed using a Kruskal-Wallis test, Kaplan-Meier, Fischer exact chi-square and cost analysis. The significance was set at p-value < 0.05. Results: In total, 840 women met the inclusion criteria and were enrolled. The relative risk of FFN for delivery at term was 4.35 times higher among the negative-tested compared to preterm delivery (p-value < 0.001). A total of 134 (15.9%) women were unnecessarily admitted (FFN tested negative, delivered at term) which yielded $107,000 in extra costs. After the introduction of an FFN test, a 7% reduction of threatened preterm labor admissions was recorded.

Reproducibility and usability assessment of the novel Fine Birth device for threatened preterm labor diagnosis

Preterm delivery is considered the leading cause of mortality worldwide in children under five. Forty-five million pregnant women are hospitalized yearly for Threatened Preterm Labor (TPTL). However, only 50% of TPTLs end in delivery before the estimated date, classifying the rest as false TPTL. The ability of current diagnostic methods to predict TPTL is low (low positive predictive value), ranging between 8-30%. This highlights the need for a solution that accurately detects and differentiates between false and real TPTLs in women who attend obstetric clinics and hospital emergency departments with delivery symptoms. This is a pilot study aiming at first, to assess the reproducibility and usability of a novel medical device, the Fine Birth, aimed at accurately diagnosing TPTL through the objective quantification of pregnant women's cervical consistency. Secondarily, we aimed to evaluate the impact of training and the incorporation of a lateral micro camera on the device's reliability and usability outcomes. 77 singleton pregnant women were recruited during their follow-up visit to the obstetric and gynecological departments at five Spanish hospitals. Eligibility criteria were: pregnant women ≥ 18 years old, with a normal fetus and uncomplicated pregnancy, without prolapse of membranes, uterine anomalies, previous cervical surgery or latex allergy, and signing the informed written consent. Cervical tissue stiffness was assessed using the Fine Birth device, whose technology is based on the propagation of torsional waves through the studied tissue. Cervical consistency measurements were taken for each woman until obtaining two valid measurements by two different operators. The intra-observer and inter-observer reproducibility of the Fine Birth measurements was assessed using the Intraclass Correlation Coefficients (ICC) with a 95% confidence interval (CI) and the F-test p-value. The usability was evaluated based on clinicians' and participants' feedback. There was a good intra-observer reproducibility (ICC=0.88, 95% CI 0.84 to 0.95; F-test p-value < 0.05). Since the results obtained for the inter-observer reproducibility did not reach the desired acceptable values (ICC<0.75), a lateral micro camera was added to the Fine Birth intravaginal probe, and the operators involved in the clinical investigation received the corresponding training with the modified device. Analysis of 16 additional subjects demonstrated an excellent inter-observer reproducibility (ICC=0.93, 95% CI 0.78 to 0.97) and a clear improvement after the intervention (p<0.0001). The robust reproducibility and usability results obtained after the insertion of a lateral micro camera and the corresponding training make the Fine Birth a promising novel device to objectively quantify the patient's cervical consistency, diagnose TPTL and thus, predict the risk of spontaneous preterm birth. Further research is needed to demonstrate the clinical utility of the device.

The predictive role of second trimester uterocervical angle measurement in obstetric outcomes.

Objective:Uterocervical angle has been suggested as a marker to predict preterm birth. However, the literature has limited data about its predictive role in preterm delivery. Moreover, no evidence is present to clarify the role of second-trimester uterocervical angle in induction success and postpartum hemorrhage. Here, it was aimed to compare the role of uterocervical angle with cervical length in predicting preterm labor and assess the utility of the second-trimester uterocervical angle in induction success and postpartum hemorrhage.Materials and Methods:A total of 125 pregnant women, hospitalized with a diagnosis of preterm labor were included in the study. Sonographic measurements of cervical length and uterocervical angle were performed between 16 and 24 weeks of gestation. The demographic, obstetric, laboratory, and sonographic features of the participants were recorded. Patients were divided into subgroups as preterm and term; with and without induction success; with and without postpartum hemorrhage. Additionally, preterm cases were divided into subgroups as early and late preterm. Variables were evaluated between the groups.Results:Cervical length was shorter in the preterm group (30.74±6.37 and 39.19±5.36, p<0.001). The uterocervical angle was 100.85 (85.2-147) in preterm and 88 (70-131) degrees in terms that were statistically significant (p<0.001). Furthermore, the uterocervical angle was wider [126 (100.7-147) and 98 (85.2-114), p<0.001] in the early preterm group. When the groups with and without postpartum bleeding were compared, no significant difference was detected in terms of uterocervical angle [96.5 (71-131) and 88 (70-147), p=0.164]. Additionally, the uterocervical angle was wider in the successful induction group (p<0.001). An a uterocervical angle >85 degrees predicted preterm delivery with 100% sensitivity and 45.54% specificity [area under the curve (AUC)=0.743, p<0.001]. When the cervical length and uterocervical angle were evaluated together to predict preterm delivery, no significant difference was found (p=0.086). An a uterocervical angle >88 degrees predicted induction success with 84.78% sensitivity and 79.75% specificity (AUC=0.887, p<0.001).Conclusion:Our study revealed that the uterocervical angle can be a useful marker in predicting preterm labor and induction success, although it does not predict postpartum hemorrhage.

Fetal Fibronectin as a Predictor of Preterm Delivery: A Nigerian Cohort Study.

Background Fetal fibronectin is a useful biomarker in the diagnosis and management of preterm labour. Objectives To evaluate the relationship between cervical fetal fibronectin and preterm delivery and the association between cervical fetal fibronectin level and gestational age at delivery. Materials and Methods A prospective cohort study was performed in a tertiary hospital in Nigeria, involving equal number of pregnant women with (96) and without (96) preterm labour. Fetal fibronectin assay was done using solid-phase immunogold assay. The data were analysed using IBM SPSS version 24. Descriptive and inferential statistical analyses were done. The level of significance was p-value <0.05. Results Less than half (47.9%) of the women in the study group had preterm delivery while 13.09% of the women in the control group delivered preterm. Fetal fibronectin test had a sensitivity, specificity, positive predictive value and negative predictive value of 78%, 86.5%, 71.9%, and 89.0%, respectively, a positive likelihood ratio and negative likelihood ratio of 5.76(95% CI, 3.67 – 9.64) and 0.26(95% CI, 0.16 – 0.41), respectively. Conclusion The findings in our study value of fetal fibronectin in predicting preterm delivery. Its use will support less intervention for patients with negative results.

Identification of Preterm Labor Evaluation Visits and Extraction of Cervical Length Measures from Electronic Health Records Within a Large Integrated Health Care System: Algorithm Development and Validation.

BackgroundPreterm birth (PTB) represents a significant public health problem in the United States and throughout the world. Accurate identification of preterm labor (PTL) evaluation visits is the first step in conducting PTB-related research.ObjectiveWe aimed to develop a validated computerized algorithm to identify PTL evaluation visits and extract cervical length (CL) measures from electronic health records (EHRs) within a large integrated health care system.MethodsWe used data extracted from the EHRs at Kaiser Permanente Southern California between 2009 and 2020. First, we identified triage and hospital encounters with fetal fibronectin (fFN) tests, transvaginal ultrasound (TVUS) procedures, PTL medications, or PTL diagnosis codes within 240/7-346/7 gestational weeks. Second, clinical notes associated with triage and hospital encounters within 240/7-346/7 gestational weeks were extracted from EHRs. A computerized algorithm and an automated process were developed and refined by multiple iterations of chart review and adjudication to search the following PTL indicators: fFN tests, TVUS procedures, abdominal pain, uterine contractions, PTL medications, and descriptions of PTL evaluations. An additional process was constructed to extract the CLs from the corresponding clinical notes of these identified PTL evaluation visits.ResultsA total of 441,673 live birth pregnancies were identified between 2009 and 2020. Of these, 103,139 pregnancies (23.35%) had documented PTL evaluation visits identified by the computerized algorithm. The trend of pregnancies with PTL evaluation visits slightly decreased from 24.41% (2009) to 17.42% (2020). Of the first 103,139 PTL visits, 19,439 (18.85%) and 44,423 (43.97%) had an fFN test and a TVUS, respectively. The percentage of first PTL visits with an fFN test decreased from 18.06% at 240/7 gestational weeks to 2.32% at 346/7 gestational weeks, and TVUS from 54.67% at 240/7 gestational weeks to 12.05% in 346/7 gestational weeks. The mean (SD) of the CL was 3.66 (0.99) cm with a mean range of 3.61-3.69 cm that remained stable across the study period. Of the pregnancies with PTL evaluation visits, the rate of PTB remained stable over time (20,399, 19.78%). Validation of the computerized algorithms against 100 randomly selected records from these potential PTL visits showed positive predictive values of 97%, 94.44%, 100%, and 96.43% for the PTL evaluation visits, fFN tests, TVUS, and CL, respectively, along with sensitivity values of 100%, 90%, and 90%, and specificity values of 98.8%, 100%, and 98.6% for the fFN test, TVUS, and CL, respectively.ConclusionsThe developed computerized algorithm effectively identified PTL evaluation visits and extracted the corresponding CL measures from the EHRs. Validation against this algorithm achieved a high level of accuracy. This computerized algorithm can be used for conducting PTL- or PTB-related pharmacoepidemiologic studies and patient care reviews.

Noninvasive prediction models of intra-amniotic infection in women with preterm labor

Among women with preterm labor, those with intra-amniotic infection present the highest risk of early delivery and the most adverse outcomes. The identification of intra-amniotic infection requires amniocentesis, perceived as too invasive by women and physicians. Noninvasive methods for identifying intra-amniotic infection and/or early delivery are crucial to focus early efforts on high-risk preterm labor women while avoiding unnecessary interventions in low-risk preterm labor women. This study modeled the best performing models, integrating biochemical data with clinical and ultrasound information to predict a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days. From 2015 to 2020, data from a cohort of women, who underwent amniocentesis to rule in or rule out intra-amniotic infection or inflammation, admitted with a diagnosis of preterm labor at <34 weeks of gestation at the Hospital Clinic and Hospital Sant Joan de Déu, Barcelona, Spain, were used. At admission, transvaginal ultrasound was performed, and maternal blood and vaginal samples were collected. Using high-dimensional biology, vaginal proteins (using multiplex immunoassay), amino acids (using high-performance liquid chromatography), and bacteria (using 16S ribosomal RNA gene amplicon sequencing) were explored to predict the composite outcome. We selected ultrasound, maternal blood, and vaginal predictors that could be tested with rapid diagnostic techniques and developed prediction models employing machine learning that was applied in a validation cohort. A cohort of 288 women with preterm labor at <34 weeks of gestation, of which 103 (35%) had a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days, were included in this study. The sample was divided into derivation (n=116) and validation (n=172) cohorts. Of note, 4 prediction models were proposed, including ultrasound transvaginal cervical length, maternal C-reactive protein, vaginal interleukin 6 (using an automated immunoanalyzer), vaginal pH (using a pH meter), vaginal lactic acid (using a reflectometer), and vaginal Lactobacillus genus (using quantitative polymerase chain reaction), with areas under the receiving operating characteristic curve ranging from 82.2% (95% confidence interval, ±3.1%) to 85.2% (95% confidence interval, ±3.1%), sensitivities ranging from 76.1% to 85.9%, and specificities ranging from 75.2% to 85.1%. The study results have provided proof of principle of how noninvasive methods suitable for point-of-care systems can select high-risk cases among women with preterm labor and might substantially aid in clinical management and outcomes while improving the use of resources and patient experience.

EFFECT OF LEIOMYOMA ON MATERNAL AND FETAL OUTCOMES DURING PREGNANCY

Aim: The study aimed to determine the effects of leiomyoma size, number, location, and type on obstetric and fetal outcomes, retrospectively.&#x0D; Materials and Method: A total of 292 singleton pregnancies, who were attended to perinatology unit of Zekai Tahir Burak Women’s Health Training and Research Hospital in Ankara as part of routine antenatal follow-up between January 2007 and 2014 and delivered at or beyond 24 weeks were included. The study group consisted of patients with leiomyoma of 4 cm or more. Patients who underwent myomectomy during cesarean delivery, who had co-morbidities, uterine anomalies, or fetal malformations were excluded from the study. Obstetric and fetal outcomes were recorded.&#x0D; Results: Vaginal delivery rate was significantly higher in patients with a single leiomyoma when compared to patients with 2 or more leiomyoma (p=0.009). Diagnosis of preterm labor was significantly higher in patients with leiomyoma size larger than 10 cm when compared to patients with leiomyoma sizes 4-7 cm and 7-10 cm (p =0.005 and p=0.002, respectively). The presentation anomaly rate was significantly higher in patients with leiomyoma sizes bigger than 10 cm when compared to patients with leiomyoma sizes 4-7 cm (p=0.008) and 7-10 cm (p =0.045). The need for transfusion was lower in the group with leiomyoma measuring 4-7 cm when compared to leiomyoma measuring 7-10 cm and those larger than 10 cm (p=0.010 and p = 0.011, respectively). Cesarean delivery rate was higher in patients with leiomyoma localized to the cervix and corpus in comparison to those localized to the corpus only (p =0.008). Vaginal delivery rate (40.9%) was higher in patients with intramural leiomyoma when compared to subserous (p=0.002) and combined (p=0.004) leiomyoma.&#x0D; Conclusion: The prevalence of leiomyoma during pregnancy is increasing due to women planning pregnancy later in life, the increasing incidence of fibroids with age, and the rise of cesarean delivery rates which enables us to diagnose more cases in recent years. Patients with leiomyoma should be placed on close surveillance for possible complications during pregnancy, delivery and postpartum.

Treatment of Chorioamnionitis with Piperacillin/Tazobactam and Clindamycin

Objective: Chorioamnionitis is a condition that bacteria infects the chorion and amnion and the amniotic fluid which can affect pregnant women. Infections may affect both the mother and fetus. Cervical insufficiency and chorioamnionitis cause preterm birth and perinatal morbidities. Case: A 37-year-old patient was referred to the clinic with the diagnosis of preterm labor and cervical insufficiency at 26 weeks + 4 days of pregnancy. Cervix was 3 cm dilated, effaced 70%, the amnion membrane intact, and there was a cerclage thread on the cervix. There was a single, viable fetus in the uterine cavity with fetal measurements compatible with 27-28 weeks on ultrasonography. Ampicillin and azithromycin treatments were started. On the seventh day of observation, leukocytes and C reactive protein values had increased, and there was an onset of serohemorrhagic vaginal discharge. Thereupon, intravenous treatment of piperacillin/tazobactam and clindamycin started. Signs of chorioamnionitis were resolved. The patient was delivered on day 38 of admission due to vaginal bleeding. The newborn and patient outcomes were good. Further studies are needed to evaluate the new treatment regime's efficacy in chorioamnionitis treatment.

Preterm Labor: A Comprehensive Review of Guidelines on Diagnosis, Management, Prediction and Prevention.

Preterm labor (PTL) is one of the most common and serious pregnancy complications associated with significant perinatal morbidity and mortality, as well as long-term neurologic impairment in the offspring. The aim of this study was to review and compare the most recently published major guidelines on diagnosis, management, prediction, and prevention of this severe complication of pregnancy. A descriptive review of guidelines from the National Institute for Health and Care Excellence (NICE), the World Health Organization, the American College of Obstetricians and Gynecologists, the New South Wales Government, and the European Association of Perinatal Medicine (EAPM) on PTL was carried out. There is a consensus among the reviewed guidelines that the diagnosis of PTL is based on clinical criteria, physical examination, measurement of cervical length (CL) with transvaginal ultrasound (TVUS) and use of biomarkers, although there is disagreement on the first-line diagnostic test. The NICE and the EAPM are in favor of TVUS CL measurement, whereas the New South Wales Government mentions that fetal fibronectin testing is the mainstay for PTL diagnosis. Moreover, there is consistency among the guidelines regarding the importance of treating PTL up to 34 weeks of gestation, to delay delivery for 48 hours, for the administration of antenatal corticosteroids, magnesium sulfate, and in utero transfer to higher care facility, although several discrepancies exist regarding the tocolytic drugs of choice and the administration of corticosteroids and magnesium sulfate after 34 and 30 gestational weeks, respectively. Routine cesarean delivery in case of PTL is unanimously not recommended. Finally, the NICE, the American College of Obstetricians and Gynecologists, and the EAPM highlight the significance of screening for PTL by TVUS CL measurement between 16 and 24 weeks of gestation and suggest the use of either vaginal progesterone or cervical cerclage for the prevention of PTL, based on specific indications. Cervical pessary is not recommended as a preventive measure. Preterm labor is a significant contributor of perinatal morbidity and mortality with a substantial impact on health care systems. Thus, it seems of paramount importance to develop consistent international practice protocols for timely diagnosis and effective management of this major obstetric complication and subsequently improve pregnancy outcomes.

Serum vitamin D-binding protein (VDBP) concentration and rs7041 genotype may be associated with preterm labor

Purpose Vitamin D deficiency is common during pregnancy and may cause complications such as preterm labor (PTL). This study was aimed to investigate the effect of the vitamin D-binding protein (VDBP) rs7041 genotype, which has a significant effect on vitamin D metabolism and PTL. Methods This cross-sectional study was conducted with 32 pregnant women who had spontaneous PTL and 54 pregnant women who had no specific findings as a control group. Serum total vitamin D 25-hydroxy vitamin D (25(OH)D) levels were measured using the Elecsys Vitamin D Total Kit. VDBP was measured using a VDBP Quantikine ELISA Kit. The levels of bioavailable 25(OH)D were calculated based on the total 25(OH)D and VDBP concentrations. DNA was extracted using the DNeasy Blood and Tissue Kit. Single nucleotide polymorphisms (rs7041) in GC were analyzed using a TaqMan SNP Genotyping Assay Kit. The unpaired t-test, Chi-squared, and ANCOVA tests were performed. Firth’s penalized logistic regression was applied. The area under the curve (AUC) was calculated and the cutoff value was determined. All statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). Results Total 25(OH)D levels were not significantly different between the two groups. Bioavailable 25(OH)D was significantly decreased in PTL women (p= .011), and VDBP was significantly increased in PTL women (p= .004) compared to the controls. Bioavailable 25(OH)D was lower in women with GT/TG and TT rs7041 genotypes than in those with GG, with statistical significance in women with the TT allele (p= .048). VDBP was higher in women with GT/TG and TT than those with GG, but there was no statistical significance. In PTL prevalence, bioavailable 25(OH)D and VDBP, the odds ratio increased by 1.463 times in GT/TG (p= .728) and increased by 1.675 times in TT compared to the GG allele (p= .640). In receiver operating characteristic (ROC) analysis for bioavailable 25(OH)D and VDBP, the AUC was 0.665 and 0685, respectively. The optimum cutoff of bioavailable 25(OH)D and VDBP levels for the diagnosis of PTL was calculated as 0.6 ng/mL and 523 µg/mL, respectively. Conclusions Pregnant women with the VDBP rs7041(c.1296 T > G) T allele genotype had reduced serum levels of bioavailable 25(OH)D and were more likely to develop PTL. Therefore, if the T allele is found in the VDBP rs7041 SNP genotyping test before or during pregnancy, more careful prenatal care may be required because of the increased risk of PTL.

A prognostic model, including quantitative fetal fibronectin, to predict preterm labour: the QUIDS meta-analysis and prospective cohort study.

The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth. To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness. The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an individual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin. The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres. Pregnant women at 22+0-34+6 weeks' gestation with signs and symptoms of preterm labour. Quantitative fetal fibronectin. Spontaneous preterm birth within 7 days. The individual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days. The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation. A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour. The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model. This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 52. See the NIHR Journals Library website for further project information.

Ultrasound Assessment of Fetal Adrenal Gland in Term and Preterm Labor Cases

Background: Preterm birth (PTB) remains a major cause of perinatal morbidity and mortality worldwide. Compared with term deliveries, early PTB (< 34 weeks' gestation) carries a 7-fold increased risk of neonatal death. Objective: To compare the Fetal Zone Depth (FZD) of fetal adrenal gland in term and preterm labor cases Patients and Methods: Thirty-three preterm pregnant women at 29-36 weeks of gestation with single pregnancy and clinical diagnosis of preterm labor and control group of 33 pregnant women at 37-40 weeks with term pregnancy were included in this study. FZD and Total Gland Depth (TGD) of fetal adrenal gland were ultrasonographically measured and FZD/TGD ratios were calculated and compared between the two groups. Results: No difference was found between the two groups in respect of age and number of pregnancies (P > 0.05). Yet, preterm birth history rupture of membrane, cervical dilatation and mode of delivery were higher in preterm group (P <0.05). Fetal adrenal gland FZD/TGD ratio was statistically significantly higher in preterm group compared to the term group (52% ± 5% vs. 29% ±9%; P <0.001). Conclusion: The growth in FZ as a fetal adaptation mechanism in increased fetal stress in preterm labor cases was at a significant level. Once supported by more comprehensive studies, we think that this result would be beneficial in the prediction of preterm labor in clinical practice.

MiR-373-3p Regulates Invasion and Migration Abilities of Trophoblast Cells via Targeted CD44 and Radixin.

Preterm labor (PTL) is one of the obstetric complications, and is known to be associated with abnormal maternal inflammatory response and intrauterine inflammation and/or infection. However, the expression of specific miRNAs associated with PTL is not clear. In this study, we performed combination analysis of miRNA array and gene array, and then selected one miRNA (miR-373-3p) and its putative target genes (CD44 and RDX) that exhibited large expression differences in term and PTL placentas with or without inflammation. Using qRT-PCR and luciferase assays, we confirmed that miR-373-3p directly targeted CD44 and RDX. Overexpression of miR-373-3p reduced the migration and invasion of trophoblast cells, while inhibition of miR-373-3p restored the migration and invasion abilities of trophoblast cells. Finally, we validated the expression of miR-373-3p and its target genes in clinical patients’ blood. miR-373-3p was increased in PTL patients’ blood, and was the most expressed in PTL patients’ blood with inflammation. In addition, by targeting the miR-373-3p, CD44 and RDX was decreased in PTL patients’ blood, and their expression were the lowest in PTL patients’ blood with inflammation. Taken together, these findings suggest that miR-373-3p and its target genes can be potential biomarkers for diagnosis of PTL.

Preterm labor: issues of prognosis, prevention and management (Literature rewiew)

Preterm labor is the leading cause of neonatal mortality and the most common cause for antenatal hospitalization. Approximately 15 million babies are born preterm each year worldwide. Of those, one million babies die before the age of 5, which is 18% of all deaths of children at this age. 35% of early and late neonatal mortality (under 28 days of age) is associated with preterm birth.The pathophysiology of preterm labor includes at least four major pathogenetic mechanisms. The studied components of this process are premature activation of the maternal or fetal hypothalamic-pituitary-adrenal system, inflammation or infection, decidual hemorrhage and pathological overdistension of the uterus. The diagnosis of preterm labor is based on the determination of concomitant regular uterine contractions and cervical changes. Vaginal bleeding and/or rupture of the amniotic membranes only increase the likelihood of this diagnosis. To improve the accuracy of diagnosis and assess the potential risk of preterm birth in the presence of symptoms in pregnant women, it is proposed to use such diagnostic tests as transvaginal ultrasound to measure cervical length; detection in vaginal fluids of fetal fibronectin (fFN), phosphorylated protein-1, which binds insulin-like growth factor (IGFBP-1), placental alpha-microglobulin, the ratio of insulin-like growth factorebinding protein 4 (IBP4) and sex hormoneebinding globulin (SHBG) – PreTRM-test.Correct identification of women in the true preterm labor allows performing appropriate actions, which results in better outcomes for the newborn. These are using of corticosteroids to prevent respiratory distress syndrome (RDS) of the newborn; prevention of group B streptococcal infection; magnesium sulfate to protect the baby’s nervous system; transportation to the institution of the third level of perinatal care, which can provide a newborn with appropriate medical care. Preventative and therapeutic measures for women, which have a high risk of preterm labor, include taking progesterone, cervical cerclage and an application of obstetric pessary.

The impact of betamethasone on fetal pulmonary, umbilical and middle cerebral artery Doppler velocimetry and its relationship with neonatal respiratory distress syndrome

BackgroundPrenatal corticosteroid administration is known to be an effective strategy in improving fetal pulmonary maturity. This study aimed to evaluate the impact of maternal betamethasone administration on fetal pulmonary and other arteries Doppler velocity and the correlation between RDS development and Doppler indices results.MethodsFifty one singleton pregnancies between 26 and 34 gestational weeks with a diagnosis of preterm labor were included in the exposed group and received betamethasone. Fifty one uncomplicated pregnancies were included in the non-exposed group. Fetal pulmonary, umbilical and middle cerebral arteries Doppler parameters were evaluated before and 24 to 48 h after steroid administration in the exposed group and two times at same intervals in the non-exposed group. Maternal records were matched to neonatal charts if delivery happened, and demographic and outcome data were abstracted.ResultsWhen compared with the nonexposed group, fetuses treated with corticosteroids demonstrated significantly decreased umbilical artery Pulsatility index (PI) and significantly increased the middle cerebral artery PI, pulmonary artery Acceleration time (AT) and pulmonary artery AT/ET (Ejection time), while all other indices remained similar. We found significantly decreased pulmonary artery AT in the fetuses with respiratory distress syndrome (RDS) compared to those that did not.ConclusionsThe results of our study showed that maternal antenatal betamethasone administration caused significant changes in the fetus blood velocity waveforms and also affected the blood flow in the pulmonary artery which led to an increase in the pulmonary artery AT and AT/ET. Among those fetuses with RDS, we found a significant decrease in the pulmonary artery AT, but we did not observe any pulmonary artery AT/ET differences.

The Role Of Corticosteroid Administration On The Incidents Of Asphyxia Neonatorum Among Mothers With Preterm Delivery In Ponek Rsud Jombang

The causes of death for newborns 0-6 days in Indonesia are 36.9% respiratory disorders, 32.4% premature birth, 12% sepsis, 6.8% hypothermia, and 6.6% neonatal jaundice. A preliminary study in Comprehensive Emergency Services Neonatal Obstetric (PONEK) of Jombang Regional Public Hospital (RSUD Jombang) reported that the incidence of asphyxia neonatorum was 295 cases in 2016 and 341 cases in 2015. There were 98 cases of preterm delivery in 2016. This study aims to prove the effect of corticosteroid administration on neonatal asphyxia in mothers with preterm delivery. This study was an analytical study using a one-group after only design. The population was all women giving birth at RSUD Jombang with preterm labor diagnosis in January-May 2017, while the sample was 82. The instruments utilized questionnaires and checklists. The bivariate analysis applied the chi-square association test. Based on the results of the chi-square test χ2= 4.622&gt; χ2 table; p = 0.009 &lt;α (0.05). There was a correlation between corticosteroid administration and the incidence of asphyxia neonatorum in women with preterm delivery. This study's results could be an input for primary health care facilities to prevent neonatal asphyxia. Further research should develop other similar variables and increase the number of respondents.