Risk Of Spontaneous Preterm Birth Research Articles

Protective Effect of EBF Transcription Factor 1 (EBF1) Polymorphism in Sporadic and Familial Spontaneous Preterm Birth: Insights from a Case-Control Study.

This study investigated the potential role of specific single-nucleotide polymorphisms (SNPs) in the genes Astrotactin 1 (ASTN1), EBF Transcription Factor 1 (EBF1), Eukaryotic Elongation Factor, Selenocysteine-tRNA Specific (EEFSEC), Microtubule-Associated Serine/Threonine Kinase 1 (MAST1), and Tumor Necrosis Factor Alpha (TNF-α) to assess whether these genetic variants contribute to the risk of spontaneous preterm birth (sPTB). A case-control study was conducted involving 573 women from Croatia and Slovenia: 248 with sporadic sPTB (positive personal and negative family history of sPTB before 37 weeks' gestation), 44 with familial sPTB (positive personal and family history of sPTB before 37 weeks' gestation), and 281 control women. The analysis of ASTN1 rs146756455, EBF1 rs2963463, EBF1 rs2946169, EEFSEC rs201450565, MAST1 rs188343966, and TNF-α rs1800629 SNPs was performed using TaqMan real-time PCR. p-values were Bonferroni-adjusted for multiple comparisons. EBF1 SNP rs2963463 was significantly associated with sPTB (p adj = 0.03). Women carrying the CC genotype had a 3-4-times lower risk of sPTB (p adj < 0.0001). In addition, a significant difference in the frequency of the minor C allele was observed when comparing familial sPTB cases with controls (p adj < 0.0001). All other associations were based on unadjusted p-values. The minor T allele of EBF1 SNP rs2946169 was more frequent in sPTB cases overall than in controls, especially in sporadic sPTB (p = 0.045). Similarly, the CC genotype of ASTN1 SNP rs146756455 was more frequent in sporadic sPTB cases compared to controls (p = 0.019). Finally, the TNF-α SNP rs1800629 minor A allele and AA genotype were more common in the familial sPTB group compared to sporadic sPTB and controls (p < 0.05). The EBF1 SNP rs2963463 polymorphism showed a protective effect in the pathogenesis of sPTB, particularly in women carrying the CC genotype. Moreover, EBF1 SNP rs2946169 and ASTN1 SNP rs146756455, as well as TNF-α SNP rs1800629, were associated with an increased risk of sPTB, representing suggestive potential risk factors for sporadic and familial sPTB, respectively.

Transabdominal-transvaginal ultrasound cervical length sequential screening to predict the risk of spontaneous preterm birth in singleton pregnancy women with low risk of preterm birth

Objective: To investigate the feasibility of predicting the risk of spontaneous preterm birth in singleton pregnancy women with low risk of preterm birth by transabdominal-transvaginal ultrasound cervical length sequential screening in the second trimester. Methods: This prospective longitudinal cohort study included singleton pregnant women at 11-13+6 gestational weeks who were admitted to Nanjing Drum Tower Hospital from January 2023 to September 2023. Transabdominal and transvaginal cervical lengths were measured during the mid-trimester fetal ultrasound scan at 18-24 weeks, and pregnancy outcomes were obtained after delivery. A short cervix was defined as a transvaginal cervical length of ≤25 mm, and the outcomes were defined as spontaneous preterm birth occurs between 20 and 36+6 weeks and extremely preterm birth before 32 weeks. The area under the receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of predicting spontaneous preterm birth by transabdominal and transvaginal cervix length, as well as the effectiveness of predicting short cervix by transabdominal cervical length. The relationship between transabdominal and transvaginal cervical length was evaluated using a scatter plot. Results: A total of 562 cases were included in this study, comprising 33 cases of spontaneous preterm birth (7 cases occurring before 32 weeks) and 529 cases of term birth. (1) Compared to the term birth group, transabdominal cervical length (median: 37.6 vs 33.2 mm; Z=-3.838, P<0.001) and transvaginal cervical length (median: 34.0 vs 29.9 mm, Z=-3.030, P=0.002) in the spontaneous preterm birth group were significantly shorter. (2) The areas under the ROC curve for predicting spontaneous preterm birth by transabdominal and transvaginal cervical length were 0.699 (95%CI: 0.588-0.809) and 0.657 (95%CI: 0.540-0.774), respectively. The sensitivity, specificity and positive predictive value of transvaginal cervical length Conclusions: In singleton pregnancy women with low risk of preterm birth, transabdominal-transvaginal cervical length sequential screening can reduce unnecessary transvaginal ultrasounds by approximately 41% without missing the diagnosis of pregnant women with a short cervix. This method also enhances the effectiveness of transvaginal cervical length to spontaneous preterm birth.

Automated Field of Interest Determination for Quantitative Ultrasound Analyses of Cervical Tissues: Toward Real-time Clinical Translation in Spontaneous Preterm Birth Risk Assessment

ObjectiveQuantitative ultrasound (QUS) analysis of the human cervix is valuable for predicting spontaneous preterm birth risk. However, this approach currently requires an offline processing step wherein a medically trained analyst manually draws a free-hand field of interest (Manual FOI) for QUS computation. This offline step hinders the clinical adoption of QUS. To address this challenge, we developed a method to determine automatically the cervical FOI (Auto FOI). This study's objective is to evaluate the agreement between QUS results obtained from the Auto and Manual FOIs and assess the feasibility of using the Auto FOI to replace the Manual FOI for cervical QUS computation. MethodsThe auto FOI method was developed and evaluated using cervical ultrasound data from 527 pregnant women, using Manual FOIs as the reference. A deep learning model was developed using the cervical B-mode image as the input to determine automatically the FOI. ResultsQuantitative comparison between the Auto and Manual FOIs yielded a high pixel accuracy of 97% and a Dice coefficient of 87%. Further, the Auto FOI yielded QUS biomarker values that were highly correlated with those obtained from the Manual FOIs. For example, the Pearson correlation coefficient was 0.87 between attenuation coefficient values obtained using Auto and Manual FOIs. Further, Bland–Altman analyses showed negligible bias between QUS biomarker values computed using the Auto and Manual FOIs. ConclusionThe results support the feasibility of using Auto FOIs to replace Manual FOIs in QUS computation, an important step toward the clinical adoption of QUS technology.

Perinatal outcomes with a copper intrauterine device in situ after 28 gestational weeks: A retrospective study of sole center in southeast China.

The purpose of this study was to investigate the pregnancy outcomes with a copper intrauterine device (IUD) in situ after 28 gestational weeks and the association between pregnancy with copper IUDs and neonatal congenital malformations. This retrospective study had compared the singleton pregnancies with the copper IUDs in situ and without after 28 gestational weeks in 1 delivery center of southeast China. The main exposure was a copper IUD in uterine cavity with pregnancy. The pregnant outcomes as preterm birth, premature rupture of membranes, infections were observed and compared. We had also compared neonatal congenital malformations in 2 groups. The statistical analysis was carried out using R (version 4.0.4; R Development Core Team) statistical software. Association between IUD use or duration of IUD use and adverse pregnancy outcomes were estimated using logistic model. Two-tailed P value < .05 was deemed statistically significant. A total of 148 pregnant women were included in our study, 74 with copper IUDs in situ were categorized into case group and 74 without IUDs during pregnancy into control group. No significant difference of maternal age, BMI, birth weight and gender were observed between 2 groups. In case group, the rates of preterm premature rupture of membranes (37.8%) and spontaneous preterm birth (23.0%) were significantly high compared to control group. Odds ratios of premature rupture of membranes and spontaneous preterm birth were 2.86 and 5.22 respectively. Women of elder age (≥35 years) in case group were more likely to experience premature rupture of membranes. The rates of neonatal congenital malformation were 10.8% (8/74) in case group and 1.4% (1/74) in control group respectively. We had found that pregnancy with copper IUD in situ increased the risk of premature rupture of membranes and spontaneous preterm birth after 28 gestation weeks, the risk of spontaneous preterm birth increased 5.22 times. Pregnancy with IUD in situ may be at increased risk of infection and neonatal malformation.

Effect of single blastocyst-stage versus single cleavage-stage embryo transfer on cumulative live births in women with good prognosis undergoing in vitro fertilization: Multicenter Randomized Controlled Trial

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643).

Maternal Plasma miRNAs as Early Biomarkers of Moderate-to-Late-Preterm Birth.

Globally, preterm birth (PTB) is a primary cause of mortality and morbidity in infants, with PTB rates increasing worldwide over the last two decades. Biomarkers for accurate early prediction of PTB before the clinical event do not currently exist. Given their roles in the development and progression of many disease states, there has been increasing interest in the utility of microRNAs (miRNAs) as early biomarkers for pregnancy-related disorders, including PTB. The present study was designed to examine potential differences in miRNA abundances in maternal plasma from mothers with infants born following a moderate to late (28-36 weeks' gestation, n = 54) spontaneous PTB (SPTB) compared to mothers with matched term infants (n = 54). Maternal plasma collected at 15 weeks' gestation were utilised from the Auckland and Adelaide cohorts from the Screening for Pregnancy Endpoints (SCOPE) study. miRNAs in plasma were quantified using the NanoString nCounter expression panel (800 miRNAs). The top four most abundant miRNAs were significantly decreased in the plasma of mothers in the SPTB group with results consistent across both cohorts and pathway analysis was undertaken to examine the biological processes linked to the dysregulated miRNAs. The top candidate miRNAs (miRs-451a, -223-3p, let-7a-5p, and -126-3p) were linked to gene pathways associated with inflammation, apoptosis, and mitochondrial biogenesis. Moreover, miRNAs were consistently less abundant in the plasma of mothers of preterm infants across both sites, suggesting potential global dysregulation in miRNA biogenesis. This was supported by a significant downregulation in expression of key genes that are involved in miRNA biogenesis (DROSHA, DICER, and AGO2) across both sites in the SPTB group. In summary, the present study has identified miRNAs in maternal plasma that may provide predictive utility as early biomarkers for the risk of later SPTB. Importantly, these observations were conserved across two independent cohorts. Further, our data provide evidence for a persistent decrease in miRNA abundance in mothers who later experienced an SPTB, which is likely to have widespread consequences for gene regulation and epigenetic processes.

Intrahepatic cholestasis of pregnancy: Introduction and overview 2024.

Considerable progress has been made to explain the aetiology of intrahepatic cholestasis of pregnancy (ICP) and of the adverse pregnancy outcomes associated with high maternal total serum bile acids (TSBAs). The reported thresholds for non-fasting TSBA associated with the risk of stillbirth and spontaneous preterm birth can be used to identify pregnancies at risk of these adverse outcomes to decide on appropriate interventions and to give reassurance to women with lower concentrations of TSBA. Data also support the use of ursodeoxycholic acid to protect against the risk of spontaneous preterm birth. A previous history of ICP may be associated with higher rates of subsequent hepatobiliary disease: if there is a suspicion of underlying susceptibility, clinicians caring for women with ICP should screen for associated disorders or for genetic susceptibility and, where appropriate, refer for ongoing hepatology review.

Uterocervical angle and cervical length measurements for spontaneous preterm birth prediction in low-risk singleton pregnant women: a prospective cohort study.

Preterm birth is the leading cause of early neonatal morbidity and mortality. Strategies to predict preterm birth risk can help improve pregnancy outcomes. Even pregnant women without known risk factors for preterm birth can also experience it. This study aimed to evaluate the ability of the uterocervical angle and cervical length to predict spontaneous preterm birth in low-risk singleton pregnant women. A prospective study on 1107 singleton pregnant women between 16+0 and 23+6weeks gestation at low risk for spontaneous preterm birth who were treated at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, between September 2020 and September 2021 was conducted. A single sonographer assessed the cervical length and the uterocervical angle using transvaginal ultrasonography. The patients were followed up until delivery to determine the main pregnancy outcome (spontaneous preterm birth before 37weeks gestation). The cut-off points for the uterocervical angle and cervical length were established by analyzing the receiver operating characteristic curve. The sensitivity, specificity, likelihood ratio, positive and negative predictive values, and accuracy of the uterocervical angle and cervical length for predicting spontaneous preterm birth were determined. A uterocervical angle ≥ 99° predicted spontaneous preterm birth at < 37weeks, with a sensitivity and specificity of 91% and 76%, respectively. A cervical length ≤ 33.8mm predicted preterm birth at < 37weeks with a sensitivity and specificity of 25% and 66%, respectively. A uterocervical angle ≥ 99° combined with a cervical length ≤ 33.8mm yielded the sensitivity, specificity, positive predictive value, likelihood ratio, and accuracy of spontaneous preterm birth prediction of 66%, 93%, 36%, 9, and 91%, respectively; thus provided a significant increase of specificity with an acceptable reduction of sensitivity as compared to cervical length alone. Besides the cervical length, the uterocervical angle can be considered a valuable ultrasound parameter for predicting spontaneous preterm birth in low-risk singleton pregnant women. Combining the uterocervical angle and cervical length yielded stronger spontaneous preterm birth prediction values.

Diabetes Mellitus as a Risk Factor for Spontaneous Preterm Birth in Women with a Short Cervix after Ultrasound-Indicated Cerclage.

Background: Preterm birth (PTB) is a significant challenge in contemporary obstetrics, affecting over one in ten infants worldwide and accounting for 75% of perinatal mortality. Short cervical length during mid-trimester is well known to be associated with an increased risk of spontaneous preterm birth (sPTB). Ultrasound-indicated cerclage (UIC) is recommended to prevent sPTB in women with a short cervix at mid-trimester and a history of sPTB. Objectives: This retrospective observational study aimed to examine the impact of diabetes and obesity on the occurrence of sPTB in women who underwent UIC due to mid-trimester cervical shortening. Methods/Results: The analysis revealed that cervical length at the time of operation, preoperative erythrocyte sedimentation rate levels, and diabetes were independent risk factors for sPTB. Additionally, the presence of diabetes, particularly when combined with obesity, significantly elevated the risk of sPTB. Women with pregestational diabetes or those requiring insulin treatment had a higher propensity for preterm delivery compared to those with gestational diabetes managed through diet control alone. Conclusions: These findings emphasize the importance of considering maternal metabolic factors, such as diabetes and obesity, in women with a short cervix when planning for UIC and highlight the crucial role of optimizing maternal glucose control and weight management in reducing the risk of sPTB.

Interpregnancy interval after vacuum delivery and subsequent perinatal outcomes.

To evaluate whether a short interpregnancy interval (IPI) after vacuum extraction (VE), poses similar perinatal risks in a subsequent pregnancy. This was a retrospective, single-center cohort study between 2011 and 2021. Nulliparous women with term, singleton VE deliveries and with known pregnancy outcomes in their subsequent pregnancy were eligible for inclusion in the study. Each woman was allocated into one of two groups based on the IPI, <18 months and between 18 and 60 months. The primary outcome was the risk of spontaneous preterm birth (PTB) <37 weeks in the consecutive birth. We included 1094 pregnancies: 212 (19.4%) with IPI <18 months and 882 (80.6%) with IPI between 18 and 60 months following the previous VE delivery. The VE characteristics were comparable between the groups. Young maternal age was a risk factor for a short IPI (28.0 ± 4.8 vs 30.3 ± 4 years, P < 0.01). Spontaneous PTB <37 weeks was significantly higher in the IPI <18 months group with 18-60 months (7.1% vs 2.6%, P = 0.002). Polynomial regression analysis also confirmed a significantly increased risk of preterm birth <37 weeks (P < 0.01). Short IPI <18 months was also associated with an increase in the risk of low birthweight <2500 g (6.1% vs 2.8%, P = 0.02) and admission to the neonatal intensive care unit (6.1% vs 2.6%, P = 0.013). The incidence of recurrent VE, albeit significant (2.3% vs 4.9%, P = 0.049), was low in both groups. No differences were noted in any of the other secondary outcomes. Short IPI (<18 months) following term VE delivery is associated with higher neonatal risks, particularly PTB, in the subsequent pregnancy. These findings are particularly important when counseling women planning an optimal IPI.

Indirect Effects of Neighbourhood Socioeconomic Status on Preterm Birth Risk in an Argentine Population.

Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to determine the indirect effects of neighbourhood socioeconomic status (NSES) on the risk of spontaneous PTB. We carried out a retrospective case-control study including sociodemographic and obstetric data of multigravid women who gave birth at a maternity hospital in Tucumán, Argentina, between 2005 and 2010: 949 women without previous PTB nor pregnancy loss who delivered at term and 552 who had spontaneous PTB. NSES was estimated from the Unsatisfied Basic Needs index of census data. Variables selected through penalised regressions were used to create a data-driven Bayesian network; then, pathways were identified and mediation analyses performed. Maternal age less than 20 years mediated part of the protective effect of high NSES on spontaneous PTB [natural indirect effect (NIE) -0.0125, 95% confidence interval (CI) (-0.0208, -0.0041)] and on few prenatal visits (< 5) [NIE - 0.0095, 95% CI (-0.0166, -0.0025)]. These pathways showed greater sensitivity to unobserved confounders that affect the variables mediator-outcome in the same direction, and exposure-mediator in the opposite direction. They did not show sensitivity to observed potential confounders, nor to the parameterization used to define NSES. Meanwhile, urinary tract infections showed a trend in mediating the effect of low NSES on spontaneous PTB [NIE 0.0044, 95% CI (-0.0006, 0.0093), P 0.0834]. High NSES has protective indirect effects on spontaneous PTB risk, mainly associated with a lower frequency of teenage pregnancy.

Ultrasound assessment of the gravid cervix to assess for risk of spontaneous preterm birth: Introducing an evidence‐based clinical guideline for sonographers

AbstractThis article introduces a new evidence‐based clinical practice guideline (CPG) for sonographers; Ultrasound assessment of the gravid cervix to assess for risk of spontaneous preterm birth (sPTB). The purpose of this new CPG is to provide evidence‐based guidance for sonographers in Australia and New Zealand when making decisions on how and when they should sonographically assess the cervix in the gravid patient. Clinical questions relevant to the sonographic assessment of the gravid cervix were developed to inform the CPG. The primary sources to answer the clinical questions were relevant, existing CPGs. Recommendations in these existing CPGs were appraised for the level of evidence on which they were based and adapted for use in the new CPG. New recommendations were adapted from 19 existing CPGs rated as being based on best evidence and were applicable to three specific patient groups, each at different risk for sPTB. ‘How to Guidance’, statements about safety, acceptability, feasibility of ultrasound techniques, sonographer training and supplementary material were also developed using information from existing CPGs, relevant literature and the clinical experience of clinical guideline group members. The CPG recommendations, ‘how to guides’ and areas of future research are presented in this article. The full guideline and its supplementary materials are available at https://www.sonographers.org/resources-tools/clinical-guidance.

The Association Between Maternal Body Mass Index and Spontaneous Preterm Birth Among Patients Prescribed Vaginal Progesterone for Short Cervix [ID 2683530

INTRODUCTION: Vaginal progesterone decreases the risk of spontaneous preterm birth (sPTB) and adverse neonatal outcomes in patients with short cervix (cervical length [CL] &lt;2.5 cm) between 16 and 24 weeks. Few studies have assessed the efficacy of this intervention in patients with obesity. We evaluate the association between maternal body mass index (BMI) and sPTB among patients prescribed vaginal progesterone for short cervix. METHODS: This was an IRB-approved retrospective cohort study of patients prescribed vaginal progesterone for short cervix at Mount Sinai Hospital. Exclusion criteria included prior PTB, cerclage, or progesterone treatment in prior pregnancy, and multifetal gestation. Logistic regression models assessed the association between BMI categories (BMI less than 25, BMI 25.0–29.9, BMI 30 or higher) and PTB less than 37 weeks, PTB less than 34 weeks, and neonatal intensive care unit (NICU) admission adjusting for nulliparity, CL at diagnosis, and insurance status. RESULTS: Of the 210 patients included, 86 had BMI of less than 25 (41%), 72 had BMI of 25.0–25.9 (34.4%), and 52 had BMI of 30 or higher (24.8%), and 79 experienced sPTB (37.6%). Although BMI was not associated with sPTB less than 37 weeks, the odds of sPTB at less than 34 weeks among individuals with BMI of 30 or higher was 3.03 times the odds for those with BMI of less than 25 (95% CI, 1.13–8.14). The odds of NICU admission among those with BMI of 30 or higher is 2.82 times the odds among those with BMI of less than 25 (95% CI, 1.23, 6.46). CONCLUSION: This study demonstrates obesity is associated with sPTB at less than 34 weeks and NICU admission among those prescribed vaginal progesterone for short cervix. Larger studies are needed to evaluate the effect of BMI on efficacy of vaginal progesterone.

Utero-cervical angle to predict the risk of spontaneous preterm birth: a review of literature.

The aim of this paper was to evaluate the predictive role of the uterocervical angle (UCA) in spontaneous preterm birth (sPTB). A systematic review of the literature was performed including all studies reporting the association between UCA and sPTB. Searches were performed with the use of a combination of keywords: "cervical length," "uterocervical angle," and "preterm birth" from inception of each database to March 2022. The statistical evaluations were carried out using the Comprehensive Meta-Analysis version 3 (Biostat Inc. USA). Sixteen studies all conducted on the second trimester UCA as well as its association with sPTB were included in this study. In all studies the measurements of cervical length (CL) and UCA were performer in the second trimester, except in one that in the third trimester. In most studies the CL is greater than 30 mm and the UCA is greater than 110 °. In seven studies women with symptoms were considered while in 8 studies the women were asymptomatic. It is too early for it to reach a firm conclusion on UCA utilization in clinical settings. A higher UCA measurement (greater than 150°) is an important risk factor for deliveries before 37 weeks' gestation. It provides a higher diagnostic performance in high risk patients than the CL measurement. However, the most relevant ultrasound parameter for the prediction of delivery within the next few data in women with preterm delivery remains the cervical length. There is a need to consider both markers and create protocols so that the values obtained with UCA and those with CL can make a real contribution to decisions to be made rather than using only CL.

The dosing regimen for 17-hydroxyprogesterone caproate was suboptimal: lessons for future pharmacotherapy for pregnant women

BackgroundMakena (17-hydroxyprogesterone caproate) was FDA approved for prevention of recurrent spontaneous preterm birth in 2011 under the accelerated approval pathway but fundamental pharmacokinetic or pharmacodynamic (phase1 and phase 2) studies were not performed. At the time, there were no dose-response or concentration-response data. The therapeutic concentration was not known. The lack of such data questions whether the dosing regimen for 17-hydroxyprogesterone caproate was optimized. ObjectiveThe purpose of this study was to evaluate the dosing regimen for 17-hydroxyprogesterone by analyzing three data sets that evaluated 17-hydroxyprogesterone caproate pharmacology: the Maternal-Fetal Medicine Omega 3 study, the Obstetric-Fetal Pharmacology Research Units study and the Obstetrical-Fetal Pharmacology Research Centers study. If an inappropriate dosing regimen could be identified, such information could inform future studies of pharmacotherapy in pregnancy. Study DesignData from the Omega 3 study were utilized to determine if plasma concentration was related to spontaneous preterm birth risk and if a threshold concentration could be identified. Data from the Obstetric-Fetal Pharmacology Research Units study were used to determine the half-life of 17-hydroxyprogesterone caproate and to develop a model to simulate drug concentrations with various dosing regimens. Data from the Obstetrical-Fetal Pharmacology Research Centers study were used to determine the relationship between dose and safety outcomes. ResultsAnalysis of the Omega 3 dataset indicated that the risk of spontaneous preterm birth decreased as the log of 17-hydroxyprogesterone caproate increased [odds ratio (95%CI) 0.04 (0.00 - 0.90)]. A steady state concentration> 9 ng/ml (equivalent to > 8 ng/ml at 25-28 weeks) was associated with the lowest risk of spontaneous preterm birth [hazard ratio (95%CI) 0.52 (0.27-0.98, p=0.04)]; this concentration was not achieved in 25% of subjects receiving the 250 mg weekly dose. In the Obstetrical-Fetal Pharmacology Research Units study, the adjusted half-life (median and IQR) of 17-hydroxyprogesterone caproate was 14.0 (11.5-17.2) days. Simulations indicated that with the 250 mg weekly dose, > 5 weekly injections were required to reach the 9 ng/ml target; however, those with the shortest half-life (corresponding to higher clearance), never reached the targeted 9 ng/ml concentration. In 75% of subjects, a loading dose of 500 mg weekly for 2 weeks followed by 250 mg weekly achieved and maintained the 9 ng/ml concentration within two weeks but in those 25% with the shortest half-life, concentrations exceeded the 9 ng/ml target for only 3 weeks. In the Obstetrical-Fetal Pharmacology Research Centers study, all 65 subjects receiving a weekly dose of 500 mg exceeded the 9 ng/ml steady state. ConclusionsThe dosing regimen for 17-hydoxyprogesterone caproate was inadequate. There is a significant inverse relationship between drug concentration and spontaneous preterm birth. Risk is lowest when concentration exceeds 9 ng/ml but 25% of women receiving the 250 mg weekly dose will never reach and maintain this concentration. The drug’s long half-life necessitates a loading dose to achieve therapeutic concentrations rapidly. The omission of basic pharmacologic studies to determine the proper dosing may have compromised the effectiveness of 17-hydroxyprogesterone caproate. Future pharmacotherapy trials in pregnancy must first complete fundamental pharmacology studies.

Semi-quantitative metalloproteinase-8 rapid test for the prediction of adverse pregnancy outcomes in patients with preterm premature rupture of membranes

ObjectiveWe aimed to determine whether the semi-quantitative metalloproteinase-8 (MMP-8) bedside test is a worthwhile indicator in reflecting the severity of of intra-amniotic inflammation (IAI) and in predicting adverse pregnancy outcomes. Study DesignThis retrospective cohort study comprised 76 singleton-pregnant women admitted to the Seoul National University Bundang Hospital with a diagnosis of preterm premature rupture of membranes (preterm PROM) between 20 weeks 0 days and 33 weeks 6 days of gestation who underwent trans-abdominal amniocentesis to confirm intra-amniotic infection by positive results for aerobic/anaerobic bacteria, fungi, and genital mycoplasma and evaluate lung maturity. The semi-quantitative MMP-8 rapid test kit employs a colourimetric assay to quantify MMP-8 levels in amniotic fluid (AF), expressing results from 0 to 100 percent. Participants were divided into three groups: group 1, including negative MMP-8 test with colour scale of 0 % (negative, n = 17); group 2, including positive MMP-8 test with colour scale < 51 % (weak positive, n = 21); and group 3, including positive MMP-8 test with colour scale of 51 %–100 % (strong positive, n = 38). ResultsApproximately 78 % (59/76) of the participants showed a positive MMP-8 test result; all culture-proven AF samples (33.3 % [25/75]) yielded positive MMP-8 test, categorizing these patients into either group 2 or group 3. A significant trend was observed where the rate of positive culture-proven samples increased with the progression from group 1 (negative) to group 3 (strong positive). Both white blood cell counts in AF and maternal serum C-reactive protein levels were found to escalate with the progression of test results from negative to strong positive. This progression was associated with an increased risk of spontaneous preterm birth within 48 h, 7 days, and 14 days from amniocentesis and within 34 weeks of gestation. ConclusionThe more the test results progress from negative to strong positive, the shorter the interval from amniocentesis to delivery becomes, and the higher the risk of intra-amniotic infection, spontaneous preterm delivery, and other perinatal complications. This relationship highlights the critical value of the semi-quantitative MMP-8 rapid test in predicting adverse pregnancy outcomes in patients with preterm PROM.

Noninvasive factors predicting the maintenance of pregnancy for more than 4 weeks after rescue cerclage in singleton pregnancies with cervical dilatation and prolapsed membrane.

Studies on noninvasive factors and predicting the maintenance of pregnancy, and those comparing the usefulness of these factors with invasive amniotic fluid markers in predicting the maintenance of pregnancy following rescue cerclage, are lacking. Therefore, this study aimed to determine whether C-reactive protein (CRP) levels, White blood cell (WBC) count, absolute neutrophil count (ANC), and platelet-to-lymphocyte ratio (PLR) in maternal blood, which are noninvasive and readily available clinical markers, can predict the maintenance of pregnancy following rescue cerclage in patients with cervical insufficiency (CI). A total of 142 singleton pregnant women (15-28 wk) who underwent rescue cerclage for CI were retrospectively evaluated. The interleukin (IL)-6 concentration in the amniotic fluid; CRP levels, WBC count, ANC, and PLR in the maternal peripheral blood; and degree of cervical dilatation were evaluated before cerclage. The primary outcome was whether the pregnancy was maintained for >4 weeks after rescue cerclage. Among the 142 patients, prolonged pregnancy for >4 weeks following emergent cerclage was observed in 107 (75.35%), while 35 (24.65%) gave birth within 4 weeks. This study demonstrated that the degree of cervical dilatation at diagnosis; WBC count, ANC, and CRP levels in the maternal peripheral blood; and IL-6 concentration in the amniotic fluid significantly differed between the successful and failure groups (all P < .05). The area under the curve (AUC) of the amniotic fluid IL-6 concentration was .795 for the prediction of spontaneous preterm birth within 4 weeks after rescue cerclage. Additionally, the AUC of the CRP level, cervical dilatation, WBC count, ANC, and PLR were .795, .703, .695, .682, and .625, respectively. These findings suggest that the preoperative CRP levels can be considered a useful noninvasive marker comparable to amniotic fluid IL-6 concentration for identifying pregnant women with CI at high risk of spontaneous preterm birth following rescue cerclage.

Maternal cobalt concentration and risk of spontaneous preterm birth: the role of fasting blood glucose and lipid profiles.

Spontaneous preterm birth (SPB) is a significant cause of neonatal mortality, yet its etiology remains unclear. Cobalt, an essential trace element, might be a risk factor for SPB. This study aims to investigate the relationship between maternal serum cobalt concentration and SPB, and to clarify the role of blood lipids and fasting blood glucose (FBG) in this relationship. We conducted a nested case-control study within the Beijing Birth Cohort Study. Serum samples were obtained from 222 pregnant women with SPB and 224 controls during the first (7-13 weeks of pregnancy) and third trimesters (32-42 weeks of pregnancy). Serum cobalt concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Fasting blood glucose and lipids levels were detected using a fully automated biochemical immunoassay instrument. Logistic regression models and linear regression models were established to explore the association between serum cobalt concentration and the risk of SPB in pregnant women, and to test the mediating effect of fasting blood glucose (FBG) and lipids. We found that the serum cobalt concentration in mothers with SPB and controls was similar in the first trimester, with values of 0.79 (0.58-1.10) ng/mL and 0.75 (0.51-1.07) ng/mL, respectively. However, in the third trimester, the cobalt concentration increased to 0.88 (0.59-1.14) ng/mL and 0.84 (0.52-1.19) ng/mL, respectively. In the logistic regression model, when considering the third trimester of pregnancy, after adjusting for ethnicity, pre-pregnancy body mass index (BMI), maternal age, education, income, and parity, it was observed that the medium level of cobalt concentration (0.63-1.07 ng/ml) had a negative correlation with the risk of SPB. The odds ratio (OR) was 0.56, with a 95% confidence interval of 0.34-0.90 ng/mL and a p-value of 0.02. This suggests that cobalt in this concentration range played a protective role against SPB. Additionally, it was found that FBG in the third trimester of pregnancy had a partial intermediary role, accounting for 9.12% of the association. However, no relationship between cobalt and SPB risk was found in the first trimester. During the third trimester, intermediate levels of maternal cobalt appear to offer protection against SPB, with FBG playing a partial mediating role. To further clarify the optimal cobalt concentrations during pregnancy for different populations, a multi-center study with a larger sample size is necessary. Additionally, exploring the specific mechanism of FBG's mediating role could provide valuable insights for improving the prevention of SPB.

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case-control study in China.

Few studies have evaluated the joint effect of trace elements on spontaneous preterm birth (SPTB). This study aimed to examine the relationships between the individual or mixed maternal serum concentrations of Fe, Cu, Zn, Se, Sr and Mo during pregnancy, and risk of SPTB. Inductively coupled plasma MS was employed to determine maternal serum concentrations of the six trace elements in 192 cases with SPTB and 282 controls with full-term delivery. Multivariate logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to evaluate the individual and joint effects of trace elements on SPTB. The median concentrations of Sr and Mo were significantly higher in controls than in SPTB group (P < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted OR (aOR) of 0·432 (95 CI < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted aOR of 0·432 (95 % CI 0·247, 0·756), 0·386 (95 % CI 0·213, 0·701), 0·512 (95 % CI 0·297, 0·883) and 0·559 (95 % CI 0·321, 0·972), respectively. WQSR revealed the inverse combined effect of the trace elements mixture on SPTB (aOR = 0·368, 95 % CI 0·228, 0·593). BKMR analysis confirmed the overall mixture of the trace elements was inversely associated with the risk of SPTB, and the independent effect of Sr and Mo was significant. Our findings suggest that the risk of SPTB decreased with concentrations of the six trace elements, with Sr and Mo being the major contributors.

Molybdenum Concentration and the Risk of Spontaneous Preterm Birth: A Nested Case-Control Study - Beijing Municipality, China, 2018-2020.

The level of molybdenum (Mo) in a mother's urine has been linked to the growth rate of the fetus and the blood pressure levels in children. We evaluated the variations in maternal plasma Mo concentrations throughout pregnancy and their potential association with the risk of spontaneous preterm birth (SPB). Future research must determine the Mo levels in pregnant women across various regions in China. Moreover, particular attention needs to be given to the potential increase in Mo concentration throughout pregnancy and its possible adverse impacts on the health of both the mother and the fetus.