MicroRNA Associations with Preterm Labor-A Systematic Review.

This systematic review delves into the connections between microRNAs and preterm labor, with a focus on identifying diagnostic and prognostic markers for this crucial pregnancy complication. Covering studies disseminated from 2018 to 2023, the review integrates discoveries from diverse pregnancy-related scenarios, encompassing gestational diabetes, hypertensive disorders and pregnancy loss. Through meticulous search strategies and rigorous quality assessments, 47 relevant studies were incorporated. The synthesis highlights the transformative potential of microRNAs as valuable diagnostic tools, offering promising avenues for early intervention. Notably, specific miRNAs demonstrate robust predictive capabilities. In conclusion, this comprehensive analysis lays the foundation for subsequent research, intervention strategies and improved outcomes in the realm of preterm labor.

Effectiveness of Vitamin D supplementation in combination with calcium on risk of maternal and neonatal outcomes: A quasi-experimental clinical trial.

Objectives: We examined the effectiveness of combining Vitamin D supplementation with calcium on maternal and neonatal outcomes, as opposed to using Vitamin D supplements alone. Materials and Methods: Pregnant women in their third trimester were divided into two groups. The control group received a daily dose of 1000 IU of Vitamin D, but, the experimental group received a combined daily dosage of 1000 IU of Vitamin D and 500 mg of calcium, until delivery. Results: The women in the Vitamin D + calcium group were less likely to develop gestational diabetes (2.78%; vs. 19.51%; P = 0.0318), preeclampsia (2.78% vs. 26.83%; P = 0.004), newly onset gestational hypertension (11.11% vs. 46.34%; P = 0.001), proteinuria (5.56% vs. 39.02%; P = 0.0004), and impaired glucose tolerance (2.78% vs. 21.95%; P = 0.0163) and had lower blood pressure at 20th and 39th weeks of gestation. The newborns in the Vitamin D + calcium group were less likely to experience low birth weight (5.71% vs. 31.58%; P = 0.0066), low birth length (5.71% vs. 44.74%; P = 0.0007), were less likely to be admitted to the neonatal intensive care unit (14.29% vs. 42.11%; P = 0.0105), have a larger head circumference (35.00 vs. 33.63; P < 0.0001), longer gestational age at birth (40.0 vs. 37.56 weeks; P < 0.0001), and higher APGAR scores (9.58 vs. 6.31; P < 0.0001.) compared to Vitamin D group, respectively. Conclusions: Taking Vitamin D and calcium by pregnant women in the third trimester is an effective treatment to decrease maternal, fetal, and neonatal outcomes.

The effect of maternal undernutrition on adverse obstetric outcomes among women who attend antenatal care in Gedeo zone public hospitals, cohort study design.

BACKGROUND: Undernutrition refers to an overall deficiency of nutrients due to an inadequate intake of a well-balanced diet. Undernourishment during pregnancy is an important contributor to maternal morbidity and mortality. It remains a persistent problem in developing countries, where women usually fall behind men in having access to food, health care, and education. Despite the high prevalence of maternal undernourishment, its direct impact on obstetric outcomes has not been studied in developing countries, including Ethiopia. OBJECTIVE: This study aimed to assess the effect of maternal undernutrition on adverse obstetric outcomes in Gedeo zone public hospitals. METHOD: A cohort study design was employed in Gedeo zone public hospitals from June 30, 2022, to February 28, 2023. This study included 721 pregnant women, 237 were exposed group whereas 484 were non-exposed. A systematic random sampling technique was used to select a non-exposed group and the exposed group was selected consecutively. Both groups were followed for 7 months, from 16 weeks of gestation to 24 h of delivery. The pretested interviewer-administered questionnaire and checklist were used. EpiData 4.4.1.2.version was used for data entry and analyzed using Stata version 16 software. A modified Poisson regression model with robust standard errors was used to determine relative risk, and the statistical association was declared at a p-value ≤ 0.05. Finally, the findings were reported in figures, tables, and words. RESULT: The incidence of adverse obstetrics outcomes among undernourished and normally nourished mothers was hypertensive disorder during pregnancy (HDDP) (7.49% vs. 3.19%), antepartum haemorrhage (7.49% vs. 3.19%), obstructed labor (1.53% vs. 3.49%), premature rupture of the membrane (2.5% vs. 3.33%), preterm labor (6.52% vs. 6.93%), instrumental vaginal delivery (1.8% vs. 4.3%), postpartum haemorrhage (5.95% vs. 3.88%), and sepsis (3.74% vs. 1.94%). The risk of adverse obstetric outcomes among undernourished women was hypertensive disorder during pregnancy (HDDP) (aRR) = 4.07, 95%CI: 2.53-6.55), antepartum haemorrhage (APH) (aRR = 5.0, 95% CI: 2.08-12.72), preterm labor (aRR = 1.8, 95%CI: 1.23-2.62), operative delivery (aRR = 1.24, 95%C: 0.87-1.78), postpartum haemorrhage (aRR = 3.02, 95%CI: 1.91-4.79), and sepsis/chrioaminitis (aRR = 3.55, 95%CI: 1.83-6.89) times higher than normally nourished women. CONCLUSION: The incidence rates of hypertensive disorder during pregnancy (HDDP), antepartum haemorrhage, postpartum haemorrhage, and sepsis were higher among undernourished women than normally nourished women. Undernourished women during pregnancy have an increased risk of adverse obstetrics outcomes including hypertensive disorder during pregnancy, antepartum, preterm labor, operative delivery, postpartum haemorrhage, and sepsis/chorioamnionitis.

Neutrophil Elastase as a Predictor of Delivery in Pregnant Women with Preterm Labour.

Background and objectives: No previous study has been conducted in Nigeria on the role of neutrophil elastase in predicting preterm birth. The present study aimed to determine the role of the neutrophil elastase test in predicting birth in women with preterm labor. Methods: The present prospective cohort study recruited 83 pregnant women with preterm labor between 28 and 36+6 weeks of gestation, and followed up these subjects for 14 days. The controls comprised 85 pregnant women without preterm labor. The cervicovaginal fluid was collected and tested using the neutrophil elastase test. Then, the sensitivity, specificity, and positive and negative predictive parameters were determined. Afterward, the data were scrutinized using the SPSS arithmetic software (Sort23). Results: Among the 168 pregnant women analyzed in the present study, 83 pregnant women were assigned to the preterm labor group, and 85 pregnant women were assigned to the control group. Furthermore, among the 83 pregnant women in the preterm labor group, 11 women had spontaneous preterm delivery, leading to a spontaneous preterm birth proportion of 13.3%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the neutrophil elastase test within 14 days post-enrollment were 93.8%, 61.2%, 36.6%, 97.6%, and 67.5%, respectively, for the general population, and 87.5%, 66.7%, 35.0%, 96.3%, and 70.2%, respectively, for subjects at <35 weeks of gestation. The positive and negative likelihood ratios for preterm birth prediction were 2.62 and 0.19, respectively. Conclusion: The neutrophil elastase test exhibited high predictive accuracy in pregnant women with preterm labor, when compared to the controls, based on the sensitivity and negative predictive value, but this had poor positive predictive values. The neutrophil elastase test may be used as a screening test, but not as a potential predictive test, in the routine clinical setting.

Universal cervical length screening and risk of spontaneous preterm birth: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the risk of spontaneous preterm birth with or without universal transvaginal ultrasound cervical length screening at the time of midtrimester scan. DATA SOURCES: Medline, Embase, ClinicalTrials.gov, and Web of Science were systematically searched from the inception of the databases to November 12, 2023, using combinations of the relevant medical subject heading terms, key words, and word variants that were considered suitable for the topic. STUDY ELIGIBILITY CRITERIA: Studies including individuals with singleton gestations at 16-25 weeks of gestation screened or not screened with universal transvaginal ultrasound cervical length screening were considered eligible. Primary outcome was spontaneous preterm birth <37 weeks; secondary outcomes were spontaneous preterm birth <34 and <32 weeks. METHODS: Random effect head-to-head analyses were used to directly compare each outcome, expressing the results as summary odds ratio and relative 95% confidence interval. The quality of the included studies was independently assessed by 2 reviewers, using the Newcastle-Ottawa scale for cohort studies and the Cochrane risk-of-bias tool for randomized controlled studies. The study was registered on the prospective register of systematic reviews database (PROSPERO) (registration number: CRD42022385325). RESULTS: Eight studies, including 447,864 pregnancies, were included in the meta-analysis (213,064 screened with transvaginal ultrasound cervical length and 234,800 unscreened). In the overall analysis, universal transvaginal ultrasound cervical length did not significantly decrease the spontaneous preterm birth rates <37 weeks (odds ratio, 0.92 [95% confidence interval, 0.84-1.01], P=.07) and <34 weeks (odds ratio, 0.87 [95% confidence interval, 0.73-1.04], P=.12), but was significantly associated with a lower risk of spontaneous preterm birth <32 weeks (odds ratio, 0.84 [95% confidence interval, 0.76-0.94], P=.002). Individuals without a prior spontaneous preterm birth had a significantly lower risk of spontaneous preterm birth <37 weeks (odds ratio, 0.88 [95% confidence interval, 0.79-0.97], P=.01) and a lower trend of spontaneous preterm birth <32 weeks (odds ratio, 0.82 [95% confidence interval, 0.66-1.01], P=.06) when screened with transvaginal ultrasound cervical length, compared with no screening. CONCLUSION: Universal transvaginal ultrasound cervical length screening usually <24 weeks in singletons without a prior spontaneous preterm birth, is associated with a significant reduction in spontaneous preterm birth <37 weeks, compared with no screening.

Obstetric and maternal outcomes of IVF and oocyte donation pregnancies among women ages 40-45-a large cohort study.

PURPOSE: To analyze the perinatal and maternal outcomes of women ranging in age from 40 to 45 years who gave birth after in vitro fertilization or oocyte donation, compared to spontaneous conception. METHODS: This retrospective cohort study used electronic data from a national healthcare service from 2000 through 2019. Three groups were compared: spontaneous pregnancy (SC), in vitro fertilization (IVF) utilizing autologous oocytes, and pregnancies resulting from oocyte donation (OD). The primary study outcomes were preterm labor (PTL) before 37 weeks of gestation, and infants classified as small for gestational age (SGA). RESULTS: The cohort included 26,379 SC, 2237 IVF pregnancies, and 300 OD pregnancies for women ages 40-45 years at delivery. Women with OD or IVF had a higher incidence of PTL < 37 weeks compared to women with SC (19.7% vs. 18% vs. 6.9%, p = 0.001), PTL < 34 (7% vs. 4.5% vs. 1.4%, p = 0.001), PTL < 32 (3.7 vs. 2.1 vs. 0.6, p = 0.001). A multivariable logistic regression for PTL < 37 weeks demonstrated that age (OR = 1.18) and hypertensive diseases (OR = 3.4) were statistically significant factors. The OD group had a lower rate of SGA compared to SC (1% vs. 4.3%, p = 0.001), while the IVF group had a higher rate of SGA compared to SC (9.1% vs. 4.3%, p = 0.001). Hypertensive diseases in pregnancy were significantly higher among the OD group and the IVF group compared to SP pregnancies (3.3% vs. 1%, p = 0.002; 2.3% vs. 1%, p = 0.001, respectively). CONCLUSIONS: Women ages 40-45 undergoing IVF or OD have a greater risk of PTL, possibly due to higher rates of hypertensive disorders of pregnancy.

Systemic lupus erythematosus is associated with an increased frequency of spontaneous preterm births: systematic review and meta-analysis.

OBJECTIVE: Preterm birth is one of the most frequent complications of pregnancy in women with systemic lupus erythematosus. The high indicated preterm birth proportion due to hypertensive disorders of pregnancy and/or fetal growth restriction is well known, and preventive measures and screening for early detection are performed. The risk of spontaneous preterm birth is less well recognized. This study aimed to determine the proportions of spontaneous and indicated preterm birth in pregnancies of women with systemic lupus erythematosus. DATA SOURCES: A systematic literature search using Pubmed, Embase, Web of Science, and Google Scholar was performed in June 2021. STUDY ELIGIBILITY CRITERIA: Studies in pregnant women with systemic lupus erythematosus reporting spontaneous and indicated preterm birth rates were selected. Original research articles published from 1995 to June 2021 were included. METHODS: Quality and risk of bias of the included studies were assessed using the Newcastle-Ottawa quality assessment scale. To estimate the pooled event rates and 95% confidence intervals, meta-analysis of single proportions with a random-effects model was performed. RESULTS: We included 21 articles, containing data of 8157 pregnancies in women with systemic lupus erythematosus. On average, 31% (95% prediction interval, 0.14-0.50) of the pregnancies resulted in preterm birth, including 14% (95% prediction interval, 0.04-0.27) spontaneous and 16% (95% prediction interval, 0.03-0.35) indicated preterm birth. CONCLUSION: In pregnant women with systemic lupus erythematosus, spontaneous and indicated preterm birth proportions are high. This information should be applied in (prepregnancy) counseling and management in pregnancy. The knowledge obtained by this meta-analysis paves the way for further research of associated risk factors and development of interventions to reduce spontaneous preterm birth in systemic lupus erythematosus pregnancies.

Parturition at term: induction, second and third stages of labor, and optimal management of life-threatening complications-hemorrhage, infection, and uterine rupture.

Childbirth is a defining moment in anyone's life, and it occurs 140 million times per year. Largely a physiologic process, parturition does come with risks; one mother dies every two minutes. These deaths occur mostly among healthy women, and many are considered preventable. For each death, 20 to 30 mothers experience complications that compromise their short- and long-term health. The risk of birth extends to the newborn, and, in 2020, 2.4 million neonates died, 25% in the first day of life. Hence, intrapartum care is an important priority for society. The American Journal of Obstetrics & Gynecology has devoted two special Supplements in 2023 and 2024 to the clinical aspects of labor at term. This article describes the content of the Supplements and highlights new developments in the induction of labor (a comparison of methods, definition of failed induction, new pharmacologic agents), management of the second stage, the value of intrapartum sonography, new concepts on soft tissue dystocia, optimal care during the third stage, and common complications that account for maternal death, such as infection, hemorrhage, and uterine rupture. All articles are available to subscribers and non-subscribers and have supporting video content to enhance dissemination and improve intrapartum care. Our hope is that no mother suffers because of lack of information.

Efficient administration of a combination of nifedipine and sildenafil citrate versus only nifedipine on clinical outcomes in women with threatened preterm labor: a systematic review and meta-analysis.

BACKGROUND: Preterm labor (PTL) is a common and serious pregnancy disorder that can cause long-term neurological issues in the infant. There are conflicting studies concerning whether sildenafil citrate (SC) reduces preterm labor complications. Therefore, the meta-analysis aimed to examine the clinical outcomes in women with threatened PTL who received nifedipine plus SC therapy versus only nifedipine. METHODS: For the original articles, six databases were searched using relevant keywords without restriction on time or language until January 13, 2024. The Cochrane risk-of-bias tool for randomized trials (RoB) and the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) were both used to assess the risk of bias in randomized and non-randomized studies, and GRADE determined the quality of our evidence. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1. RESULTS: Seven studies with mixed quality were included in the meta-analysis. The study found that combining nifedipine and SC resulted in more prolongation of pregnancy (MD = 6.99, 95% CI: 5.32, 8.65, p < 0.00001), a lower rate of delivery in the 1st to 3rd days after hospitalization (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001), a higher birth weight (252.48 g vs. nifedipine alone, p = 0.02), and the risk ratio of admission to the neonatal intensive care unit (NICU) was significantly lower (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001) compared to nifidepine alone. The evidence was high for prolongation of pregnancy, delivery rate 24-72 h after admission, and NICU admission, but low for newborn birth weight. CONCLUSIONS: Given the effectiveness of SC plus nifedipine in increased prolongation of pregnancy and birth weight, lower delivery in the 1st to 3rd days after hospitalization, and NICU admission, Gynecologists and obstetricians are suggested to consider this strategy for PTL management, although additional article rigor is required to improve the quality of the evidence.

Indomethacin Pharmacokinetics and Pharmacodynamics in Pregnancies With Preterm Labor: The Need for Dose-Ranging Trials.

The use of indomethacin to delay delivery in preterm labor (PTL) is widely accepted; however, the optimal dosage of indomethacin in pregnancy is unknown. Here, we perform population pharmacokinetic (PK) and pharmacodynamic (PD) analyses, characterize the plasma disposition of indomethacin in pregnant women with PTL, and relate indomethacin exposure to delayed delivery and maternal/neonatal safety. We analyzed plasma and urine samples collected from a multicenter, prospective, opportunistic PK/PD study of indomethacin in pregnant women 12-32 weeks gestation admitted with PTL. Ninety-four participants with 639 plasma concentrations for indomethacin were included in the analysis. The final population PK (popPK) model for indomethacin was a 2-compartment structural model with first-order absorption and elimination and a covariate effect of body mass index on apparent oral clearance. We observed a 21%-60% increase in apparent oral clearance observed during pregnancy. There was no clear association between indomethacin exposure and maternal or neonatal safety outcomes, or with the magnitude of delayed delivery; however, 96.7% of women treated with indomethacin had a delivery that was delayed at least 48 hours. Given the changes to indomethacin apparent oral clearance during pregnancy, and the lack of relationship between indomethacin exposure and safety, dose-finding studies of indomethacin in pregnant women with PTL may help clarify the most safe and efficacious dosage and duration of indomethacin.

Predictive potential of various plasma inflammation-, angiogenesis-, and extracellular matrix remodeling-associated mediators for intra-amniotic inflammation and/or microbial invasion of the amniotic cavity in preterm labor.

PURPOSE: To determine whether various inflammatory-, angiogenic/anti-angiogenic-, and extracellular matrix remodeling-associated proteins in plasma, alone or in combination with conventional blood-based markers, can predict intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with spontaneous preterm labor (PTL). METHODS: A total of 193 singleton pregnant women with PTL (23-33 weeks) were included in this retrospective cohort study. Plasma samples were obtained at the time of amniocentesis. Amniotic fluid (AF) was cultured for microorganism detection and consequent MIAC diagnosis. IL-6 levels were determined in AF and used to identify IAI (AF IL-6 ≥ 2.6 ng/mL). Endostatin, haptoglobin, IGFBP-2/3, LBP, M-CSF, MMP-2/8, pentraxin 3, PlGF, S100A8/A9, and VEGFR-1 levels were assayed in plasma samples by ELISA. CRP levels and neutrophil-to-lymphocyte ratio (NLR) were measured. RESULTS: Plasma LBP, MMP-8, and S100A8/A9 levels, CRP levels, and NLR were significantly higher, and plasma IGFBP-2 and MMP-2 levels were significantly lower in women with IAI/MIAC than in those without this condition, whereas no baseline variables differed significantly between the two groups. Using a stepwise regression analysis, a noninvasive prediction model for IAI/MIAC was developed, which included plasma LBP, MMP-2, and MMP-8 levels (area under the curve [AUC], 0.785). The AUC for this prediction model was significantly or borderline greater than that of any single factor included in the model. CONCLUSIONS: IGFBP-2, LBP, MMP-2, MMP-8, and S100A8/A9 may represent valuable plasma biomarkers for predicting IAI/MIAC in women with PTL. Combination of LBP, MMP-2, and MMP-8 expression data can significantly improve the predictive potential for IAI/MIAC.

Membrane Inflammasome activation by Choriodecidual Ureaplasma parvum infection without intra-amniotic infection in an NHP model.

Intrauterine infection is a significant cause of preterm labor and neonatal morbidity and mortality. Ureaplasma parvum is the microorganism most commonly isolated from cases of preterm birth and preterm premature rupture of membranes (pPROM). However, the mechanisms during the early stages of ascending reproductive tract infection remain poorly understood. To examine inflammation in fetal (chorioamnionic) membranes in response to U. parvum infection, we utilized a non-human primate (NHP) model of choriodecidual infection. Eight chronically catheterized pregnant rhesus macaques underwent maternal-fetal catheterization surgery at ~105-112d gestation and choriodecidual inoculation with U. parvum (105cfu/mL, n = 4) or sterile media (Controls; n = 4) starting at 115-119d, repeated at 5d intervals until C-section at 136-140d (term = 167d). The average inoculation to delivery interval was 21d and Ureaplasma infection of the amniotic fluid (AF) was undetectable in all animals. Choriodecidual Ureaplasma infection resulted in increased fetal membrane protein and gene expression of MMP-9 and PTGS2, but did not result in preterm labor or increased concentrations of AF pro-inflammatory cytokines. However, membrane expression of inflammasome sensor molecules, NLRP3, NLRC4, AIM2 and NOD2, and adaptor protein ASC (PYCARD) gene expression were significantly increased. Gene expression of IL-1ß, IL-18, the IL-18R1 receptor, CASPASE-1 and pro-CASPASE-1 protein were increased with Ureaplasma infection. Downstream inflammatory genes MYD88 and NFKB were also significantly upregulated. These results demonstrate that at early stages of ascending reproductive tract Ureaplasma infection, activation of inflammasome complexes and pathways associated with degradation of membrane integrity, pPROM and preterm labor are initiated prior to microbes being detectable in the amniotic fluid.

The role of placental insufficiency in spontaneous preterm birth: A literature review.

Preterm Birth (delivery before 37 weeks of gestation) is the leading cause of childhood mortality and is also associated with significant morbidity both in the neonatal period and beyond. The aetiology of spontaneous preterm birth is unclear and likely multifactorial incorporating factors such as infection/inflammation and cervical injury. Placental insufficiency is emerging as an additional contributor to spontaneous preterm delivery; however, the mechanisms by which this occurs are not fully understood. Serum biomarkers and imaging techniques have been investigated as potential predictors of placental insufficiency, however none have yet been found to have a sufficient predictive value. This review examines the evidence for the role of the placenta in preterm birth, preterm prelabour rupture of the membranes and abruption as well as highlighting areas where further research is required.

First-trimester and early-second-trimester transvaginal cervical length before 16 weeks among women with preterm and term birth: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the differences in first-trimester and early-second-trimester transvaginal cervical length between patients with spontaneous preterm birth and those with term birth. DATA SOURCES: PubMed, MEDLINE, Embase, and the Cochrane Library were systematically searched through August 2023. STUDY ELIGIBILITY CRITERIA: Studies had to include (1) transvaginal cervical length measurement before 16+0 weeks of gestation and (2) transvaginal cervical length measurement in a population of patients who delivered preterm and at term. Abstracts, studies with duplicated data, and those with cervical length measured by transabdominal ultrasound scan were excluded. METHODS: K.W.C. and J.L. searched for, screened, and reviewed the articles independently. The quality of the studies was assessed using the Newcastle-Ottawa scale. Mean differences were calculated using a random-effects model and pooled through a meta-analysis. RESULTS: A total of 5727 published articles were identified. Only 10 studies (which analyzed 22,151 pregnancies) met the inclusion criteria. All studies excluded iatrogenic preterm birth. Transvaginal cervical length was significantly shorter in women with spontaneous preterm birth than in those who delivered at term (mean difference, -0.97; 95% confidence interval, -1.65 to -0.29; P=.005; I2=69%). When a linear technique was used to measure transvaginal cervical length, a significantly shorter transvaginal cervical length was associated with spontaneous preterm birth as opposed to term birth (mean difference, -1.09; 95% confidence interval, -1.96 to -0.21; P=.02; I2=77%). A shorter transvaginal cervical length measured by other techniques was also associated with spontaneous preterm birth before 34 to 35 weeks (mean difference, -1.87; 95% confidence interval, -3.04 to -0.70; P=.002; I2=0%). When studies where interventions were given for a "short" cervix or studies with a mean transvaginal cervical length ≥40 mm were excluded, a significantly shorter transvaginal cervical length was observed among those with spontaneous preterm birth (mean difference, -1.13; 95% confidence interval, -1.89 to -0.37; P=.004; mean difference, -0.86; 95% confidence interval, -1.67 to -0.04; P=.04; respectively). The optimal transvaginal cervical length cutoff was 38 to 39 mm, yielding pooled sensitivity of 0.80, specificity of 0.45, positive likelihood ratio of 1.16, negative likelihood ratio of 0.33, diagnostic odds ratio of 5.12, and an area under the curve of 0.75. CONCLUSION: Women with spontaneous preterm birth had significantly shorter transvaginal cervical length before 16 weeks of gestation compared with those who delivered at term. The linear method and the 2-line method are acceptable techniques for measuring transvaginal cervical length.

Development of progesterone electrospun nanofibers to coat Arabin pessaries as a dual preventive and therapeutic approach for preterm labor.

Preterm labor is a growing health problem that causes newborn death, and safe and effective therapy is significantly needed. Arabin pessaries and progesterone are preventive and therapeutic approaches that can be applied to managing the short cervix; hence, reducing the risk of preterm labor. The main goal of current work is to fabricate a novel nanofiber formulation based on polycaprolactone (PCL) and loaded with progesterone to coat for Arabin pessaries to be used as dual preventive and therapeutic approaches for local vaginal delivery. Several important criteria were considered in this study to assess the prepared nanofibers (i.e.; nanofiber diameter, progesterone loading efficiency, progesterone release profiles and in vitro cytotoxicity assessment). The results showed a dimeter of 397 ± 88 nm, drug loading of 142 ± 3 µg/mg and encapsulation efficiency of 99 ± 2 % for the progesterone-loaded nanofibers. Approximately, 17 % of progesterone was released from the nanofibers after 90 days. The in vitro assessment showed that the application of progesterone is safe upon 24 and 48-hours incubation on HFF-1 cell line at concentrations ≤ 32 µg/mL and within 72-hours at a dose of ≤ 8 µg/mL. To conclude, the data recommended that progesterone-loaded nanofibers can coat the Arabin pessaries with the potential of being a safe and effective dual preventive and therapeutic tool for preterm labor.

Is Parity a Risk Factor for Late Preterm Birth? Results from a Large Cohort Study.

Most preterm births occur in the late preterm period. While prematurity-related adverse outcomes are significantly diminished when birth occurs during this period, these infants are still at increased risk of complications. Parity affects the incidence of obstetric complications. The purpose of this study was to determine whether parity impacts the risk of spontaneous late preterm birth (SLPTB) and associated complications. A retrospective observational cohort study was conducted. Patients were divided into three study groups according to parity. The primary outcome was the rate of SLPTB in each group. Secondary outcomes were unplanned cesarean delivery (UCD), prolonged third stage of labor respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), intraventricular hemorrhage (IVH), neonatal hypoglycemia, duration of NICU admission, neonatal death, and composite adverse neonatal outcome (CANO). Primiparas were more likely to have SLPTB, UCD, and CANO compared to multiparas (2.6% vs. 1.9% OR 1.5 [1.3-1.7] p < 0.01) (4.1% vs. 1.3% OR 2.7 [1.2, 5.9] p < 0.01) (8.5% vs. 4.2 OR 2.1 [1.3-3.5] p = 0.002) and grandmultiparas (2.6% vs. 1.7% OR 1.4 [1.2-1.5] p < 0.001) 8.5% vs. 4.4% OR 2.0 [1.1, 3.8], p = 0.01) but no difference in UCD compared to grandmultiparas (4.1% vs. 3.3% OR 1.2 [0.6-2.7] p = 0.28). Primiparas are at increased risk of SLPTB and UCD, and this is accompanied by an increased risk of adverse neonatal outcomes.

Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes.

BACKGROUND: Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. OBJECTIVE: We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. STUDY DESIGN: In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. RESULTS: From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. CONCLUSION: Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.

Speculum-free portable preterm imaging system.

Significance: Preterm birth is defined as a birth before 37 weeks of gestation and is one of the leading contributors to infant mortality rates globally. Premature birth can lead to life-long developmental impairment for the child. Unfortunately, there is a significant lack of tools to diagnose preterm birth risk, which limits patient care and the development of new therapies. Aim: To develop a speculum-free, portable preterm imaging system (PPRIM) for cervical imaging; testing of the PPRIM system to resolve polarization properties of birefringent samples; and testing of the PPRIM under an IRB on healthy, non-pregnant volunteers for visualization and polarization analysis of cervical images. Approach: The PPRIM can perform 4×3 Mueller-matrix imaging to characterize the remodeling of the uterine cervix during pregnancy. The PPRIM is built with a polarized imaging probe and a flexible insertable sheath made with a compatible flexible rubber-like material to maximize comfort and ease of use. Results: The PPRIM device is developed to meet specific design specifications as a speculum-free, portable, and comfortable imaging system with polarized imaging capabilities. This system comprises a main imaging component and a flexible silicone inserter. The inserter is designed to maximize comfort and usability for the patient. The PPRIM shows high-resolution imaging capabilities at the 20 mm working distance and 25 mm circular field of view. The PPRIM demonstrates the ability to resolve birefringent sample orientation and full field capture of a healthy, non-pregnant cervix. Conclusion: The development of the PPRIM aims to improve access to the standard of care for women's reproductive health using polarized Mueller-matrix imaging of the cervix and reduce infant and maternal mortality rates and better quality of life.

Bitter taste receptors in the reproductive system: Function and therapeutic implications.

Type 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single-cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders.

Antibiotic therapy in patients with amniotic fluid sludge and risk of preterm birth: a meta-analysis.

PURPOSE: Amniotic Fluid Sludge (AFS) has been theorized to be sonographic evidence of an underlying infection/inflammation and studies have concluded that approximately 10% of the patients who show signs of preterm labor with intact membranes have an underlying intraamniotic infection, mostly subclinical, carrying an increased risk for preterm birth with its subsequent neonatal and maternal complications. The purpose of the present systematic review is to evaluate the impact of antibiotic therapy on preterm birth rates of women diagnosed with AFS. METHODS: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases for relevant articles published until the 30th of September 2022. Observational studies (prospective and retrospective) that evaluated the impact of antibiotics on preterm delivery rates of patients with AFS were considered eligible for inclusion. Statistical meta-analysis was performed with RStudio and we calculated pooled risk ratios (OR) and 95% confidence intervals (CI). To evaluate the information size, we performed trial sequential analysis (TSA) and the methodological quality of the included studies was assessed using RoBINS tools. RESULTS: Overall, four retrospective cohort studies were included in the present systematic review and 369 women were enrolled. We demonstrated that preterm delivery prior to 34, 32 and 28 weeks of gestational age was comparable among the groups of women that had antibiotics and those that did not (OR: 0.34, 95% CI 0.05, 2.14, 0.40 [0.09, 1.66], 0.35 [0.08, 1.58], respectively) but the statistical heterogenicity of the studies included was high for every gestational period that was examined. CONCLUSIONS: According to our study, we cannot conclude that the use of antibiotics in women with amniotic fluid sludge benefit the prognostic risk to deliver prematurely. It is quite clear that data from larger sample sizes and more well adjusted and designed studies are needed.