UNASSIGNED: Spontaneous preterm delivery is defined as the beginning of the birth process before the 37th week of pregnancy. The presence of microorganisms in the fetal membranes is accompanied by an increase in the production of prostaglandin, one of the important factors associated with the prevalence of preterm birth. The invasion of microorganisms leads to the production of protease, coagulase, and elastase, which directly stimulate the onset of childbirth. We investigated the role of genital infections in women with preterm birth.
UNASSIGNED: The present case-control study was conducted in the west of Iran on 100 women with spontaneous preterm delivery (following 24 weeks of gestation and before 36 weeks and 6 days) as the case group and 100 women with normal delivery as controls. A questionnaire was applied to collect the data. Polymerase chain reaction and pathological examination of the placenta were performed.
UNASSIGNED: The average age in women with normal delivery (30.92 ± 5.10) in women with spontaneous preterm delivery (30.27 ± 4.93). The prevalence of Chlamydia trachomatis, Neisseria gonorrhea, Listeria monocytogenes, and Mycoplasma genitalium infections was zero in both groups. The highest prevalence of Gardnerella vaginalis was 19 (19%) in the case group and Ureaplasma parvum 15 (15%) in the control group. Also, Placental inflammation was zero in controls and 7(7%) in the patient group. There was a significant relationship between Gardnerella vaginalis bacteria and spontaneous preterm delivery.
UNASSIGNED: The results of our study showed that except for Gardnerella vaginalis bacteria, there is no significant relationship between the above bacterial infections and spontaneous preterm birth. Moreover, despite the significant reduction in the prevalence of many sexually transmitted infections in this research, it is still suggested to increase the awareness of people, including pregnant women, about the ways it can be transmitted by gynecologists and health and treatment centers.

Brain injury and poor neurodevelopment have been consistently reported in infants and adults born before term. These changes occur, at least in part, prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not by neurosonography along with amniotic fluid brain injury biomarkers.
This study aimed to evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm premature rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a risk mediator.
In this prospective cohort study, fetal brain remodeling and injury were evaluated using neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm premature rupture of membranes between 24.0 and 34.0 weeks of gestation, with (n=41) and without (n=54) intra-amniotic inflammation. The controls for neurosonography were outpatient pregnant patients without preterm labor or preterm premature rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm premature rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin 6 concentrations of >13.4 ng/mL in preterm labor and >1.43 ng/mL in preterm premature rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. Neuron-specific enolase, protein S100B, and glial fibrillary acidic protein were selected as amniotic fluid brain injury biomarkers. Data were adjusted for cephalic biometrics, fetal growth percentile, fetal sex, noncephalic presentation, and preterm premature rupture of membranes at admission.
Fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes showed signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in the intra-amniotic inflammation, non-intra-amniotic inflammation, and control groups, the transcerebellar diameter measurements were 32.7 mm (interquartile range, 29.8-37.6), 35.3 mm (interquartile range, 31.2-39.6), and 35.0 mm (interquartile range, 31.3-38.3), respectively (P=.019), and the vermian height measurements were 16.9 mm (interquartile range, 15.5-19.6), 17.2 mm (interquartile range, 16.0-18.9), and 17.1 mm (interquartile range, 15.7-19.0), respectively (P=.041). Second, they presented a lower corpus callosum area (0.72 mm2 [interquartile range, 0.59-0.81], 0.71 mm2 [interquartile range, 0.63-0.82], and 0.78 mm2 [interquartile range, 0.71-0.91], respectively; P=.006). Third, they showed delayed cortical maturation (the Sylvian fissure depth-to-biparietal diameter ratios were 0.14 [interquartile range, 0.12-0.16], 0.14 [interquartile range, 0.13-0.16], and 0.16 [interquartile range, 0.15-0.17], respectively [P<.001], and the right parieto-occipital sulci depth ratios were 0.09 [interquartile range, 0.07-0.12], 0.11 [interquartile range, 0.09-0.14], and 0.11 [interquartile range, 0.09-0.14], respectively [P=.012]). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes had higher concentrations of neuron-specific enolase (11,804.6 pg/mL [interquartile range, 6213.4-21,098.8], 8397.7 pg/mL [interquartile range, 3682.1-17,398.3], and 2393.7 pg/mL [interquartile range, 1717.1-3209.3], respectively; P<.001), protein S100B (2030.6 pg/mL [interquartile range, 993.0-4883.5], 1070.3 pg/mL [interquartile range, 365.1-1463.2], and 74.8 pg/mL [interquartile range, 44.7-93.7], respectively; P<.001), and glial fibrillary acidic protein (1.01 ng/mL [interquartile range, 0.54-3.88], 0.965 ng/mL [interquartile range, 0.59-2.07], and 0.24 mg/mL [interquartile range, 0.20-0.28], respectively; P=.002).
Fetuses with preterm labor with intact membranes or preterm premature rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in fetuses with intra-amniotic inflammation.

BACKGROUND: Preterm birth is a leading cause of infant morbidity and mortality worldwide. The burden of prematurity underscores the need for effective risk reduction strategies. The purpose of this study is to evaluate the efficacy of progesterone therapy, both intramuscular 17-α-hydroxyprogesterone caproate (IM 17-OHPC) and vaginal progesterone, in the prevention of recurrent spontaneous preterm birth (sPTB). The co-primary outcomes included: recurrent spontaneous PTB < 37 and < 34 weeks\' gestation.
METHODS: This retrospective cohort study included 637 pregnant patients that delivered at any of the three hospitals within the Los Angeles County healthcare system between October 2015 and June 2021. We compared frequencies of measured variables between each of the progesterone treated groups to no treatment using Pearson chi-squared tests and independent t-tests for categorical and continuous variables, respectively. We estimated crude and adjusted associations between each specific treatment (versus no treatment) and primary outcomes using logistic regression.
RESULTS: Recurrent sPTB < 37 weeks\' gestation occurred in 22.3% (n = 64) of those in the no treatment group, 29.1% (n = 86, p = .077) in the 17-OHPC group, and 14.3% (n = 6, p = 0.325) in the vaginal progesterone group. Recurrent sPTB < 34 weeks\' gestation was 6.6% (n = 19) in the no treatment group, 11.8% (n = 35, p = .043) in the 17-OHPC group, and 7.1% (n = 3, p = 1) in the vaginal progesterone group. Among all participants, neither 17-OHPC nor vaginal progesterone was significantly associated with a reduction in recurrent sPTB at any time point. Among those with a short cervix, IM 17-OHPC was positively associated with recurrent sPTB < 37 weeks\' gestation (aOR 5.61; 95% CI 1.16, 42.9).
CONCLUSIONS: Progesterone therapy of any type did not reduce the risk of recurrent sPTB < 34 or < 37 weeks\' gestation compared to no progesterone therapy.

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.
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.
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.
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.
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.

OBJECTIVE: To assess the potential of five inflammatory and six angiogenic/antiangiogenic plasma proteins for predicting imminent spontaneous preterm delivery (SPTD; ≤14 days of sampling), microbial invasion of the amniotic cavity and/or intraamniotic inflammation (MIAC/IAI), and composite neonatal morbidity and mortality (CNMM) in women with early preterm premature rupture of membranes (PPROM).
METHODS: This retrospective cohort study included 76 singleton pregnant women with early PPROM (23-30 weeks). Amniotic fluid obtained via amniocentesis was cultured for microorganism detection and assayed for interleukin-6 to define IAI (≥2.6 ng/mL). Plasma C4a, endoglin, endostatin, IGFBP-1, IGFBP-2, MMP-9, PlGF, S100A8, S100A9, S100 A8/A9, and VEGFR-1 levels were determined using ELISA.
RESULTS: Multivariate logistic regression analyses revealed significant associations between (i) high levels of plasma S100A8/A9, SPTD ≤14 days after sampling, and shorter sampling-to-delivery intervals; (ii) elevated plasma MMP-9, S100A9, and S100A8/A9 levels and MIAC/IAI, and (iii) decreased plasma endoglin levels and increased CNMM risk, while adjusting for gestational age at sampling (or delivery) and tocolytic use. The area under the curves of the aforementioned proteins ranged from 0.655 to 0.731 for each outcome. Notably, the SPTD risk increased significantly with increasing plasma S100A8/A9 levels (P for trend < .05).
CONCLUSIONS: Plasma S100A8/A9, MMP-9, S100A9, and endoglin may represent valuable biomarkers associated with SPTD, MIAC/IAI, and CNMM in women with early PPROM. Owing to their less invasive nature, repeatability, and fair-to-moderate diagnostic accuracy, these biomarkers may contribute to risk stratification of PPROM-related complications in the clinical setting.

Background Preterm delivery is a significant contributor to neonatal and infant morbidity and mortality. Preventive methods are preferable to treatment protocols for reducing perinatal mortality and morbidity. The calcium channel blocker nifedipine has the potential to be employed as a tocolytic, whereas the phosphodiesterase inhibitor sildenafil citrate promotes smooth muscle relaxation. Objective This study aims to examine the tocolytic effect of nifedipine in combination with sildenafil citrate in managing preterm labour (PTL). Methods After approval from the ethical board, 160 patients fulfilling the selection criteria were enrolled in the study from the outpatient and emergency department of obstetrics and gynaecology, University of Lahore, Pakistan. After taking written informed consent, their demographic profile, i.e., name, age, gestational age at presentation, parity, and expected date of delivery was noted. Patients were randomly assigned in a 1:1 ratio to two study groups (Group A: sildenafil citrate + nifedipine) and (Group B: nifedipine) using a computer-generated random number table to obtain a trial sequence. In group A, each patient was given nifedipine 20 mg orally, followed by 10 mg orally every eight hours for 48 hours and vaginal administration of sildenafil citrate, 25 mg at eight-hour intervals, for 48 hours. In group B, females were given nifedipine 20 mg orally, followed by 10 mg orally every 8 hours for 48 hours. They were kept admitted for 72 hours. SPSS Statistics version 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used to enter and analyse the collected data. Mean and standard deviation was calculated for quantitative variables like age, gestational age at presentation, gestational age at delivery, and BMI. Frequency and percentage were calculated for parity and preterm delivery. Results The study involved 160 patients, with the average age in Group A being 29.60±4.9 years and in Group B being 30.96±4.98 years. In terms of gestational age at delivery, Group A had an average of 34.16±1.7 weeks, while Group B had an average of 33.5±1.8 weeks (p-value<0.05). Preterm delivery was observed in 68.5% of Group A and 41.3% of Group B, with a significant p-value of 0.001. The study also discovered that the duration of prolonged pregnancy was significantly higher in Group A compared to Group B, with averages of 14.96±10.37 days and 10.24±8.97 days, respectively (p-value=0.002). Conclusion The results of this study suggest that the combination of sildenafil citrate and nifedipine may offer a promising new approach to improving pregnancy outcomes in cases of PTL. In the present study, sildenafil citrate plus nifedipine showed a significant effect in the management of PTL and prolongation in mean gestational age at delivery.

OBJECTIVE: To investigate the role of family history of preterm delivery (PTD) in the individual risk of spontaneous preterm delivery.
METHODS: A retrospective case-control study was conducted on 354 patients who delivered between 2018 and 2020. 177 women who delivered preterm were matched with 177 controls who had full-term delivery. A questionnaire was administered to investigate the family history of PTD of both the patient and her partner. Cases and controls were matched for the anamnestic risk factors for PTD.
RESULTS: Seventeen of 173 women (9.8%) in the PTD group reported being born preterm, compared to five of 169 women (2.9%) in the control group (p = 0.01), with an odds ratio (OR) of 3.57 (95% confidence interval, CI 1.29-9.92). Women who delivered preterm also reported more frequently having a sibling who was born preterm (12.4% vs. 4.2%, p = 0.01), with an OR of 3.18 (95% CI 1.31-7.7). No association was found between the partner\'s family history of premature delivery and the patient\'s risk of preterm delivery in the present pregnancy.
CONCLUSIONS: Pregnant patients who were born prematurely or who have siblings born preterm have an increased risk of preterm delivery in their own pregnancies. Assessment of female personal and family history of PTD should be used to identify women at risk of having a PTD in the present pregnancy.

Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value.
Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded.
This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381).
The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.

Objective The aim of this study is to compare the rate of spontaneous preterm delivery between gestational diabetes mellitus (GDM) and normal pregnancy. Pregnancy outcomes and associated risk factors for spontaneous preterm delivery were evaluated. Methods A retrospective cohort study was conducted on 120 GDM and 480 normal pregnant women. All women received GDM screening with 50-g glucose challenge test and 100-g oral glucose tolerance test at the first visit and repeated at 24-28 weeks. Data were retrieved from medical records and included baseline and obstetric characteristics, preterm risks, GDM risks, and pregnancy outcomes. Spontaneous preterm birth was defined as delivery before 37 completed weeks of gestation that had been preceded by spontaneous labor. Results GDM women were more likely to be ≥30 years (p=0.032) and have previous GDM (p=0.013). Incidence of overall preterm delivery was significantly higher in GDM women (17.5% vs. 8.5%, p=0.004), as well as the incidence of spontaneous preterm delivery (15.8% vs. 7.1%, p=0.004). GDM women had less gestational weight gain (p<0.001) and were less likely to have excessive weight gain (p=0.002). GDM women were more likely to deliver large for gestational age (LGA) (p=0.02) and macrosomic infants (p=0.027). Neonatal hypoglycemia was significantly more common among GDM women (p=0.013). Multivariate analysis showed that previous preterm birth and GDM independently increased the risk of spontaneous preterm delivery (adjusted OR: 2.56, 95% CI: 1.13-5.79, p=0.024, and adjusted OR: 2.15, 95% CI: 1.2-3.84, p = 0.010, respectively). Conclusion GDM and previous preterm birth significantly increased the risk of spontaneous preterm delivery. GDM also increased the risk of LGA, macrosomia, and neonatal hypoglycemia.

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.