A Comparison of Neonatal Outcomes Between Obese and Nonobese Women With Preterm Prelabor Rupture of Membranes.

Introduction Preterm prelabor rupture of membrane (PPROM) contributes to increasing rates of preterm birth, causing greater health risks for newborns. While the mechanisms driving PPROM are not well understood, one hypothesis is that it is due to systemic inflammation, which can be caused by obesity defined as a BMI [Formula: see text]30 kg/m2. The specific aim of the study was to compare neonatal outcomes after PPROM between patients who were obese vs not obese in early pregnancy at a tertiary medical center serving an Appalachian population. Methods An observational, descriptive retrospective review was conducted of the medical records of patients who were diagnosed with PPROM from January 2017 through December 2020. Patients with a single gestation at the time of PPROM without evidence of clinical infection requiring immediate delivery were included. Maternal characteristics, latency management, and birth outcomes were compared between obese ([Formula: see text]30 BMI) and non-obese (<30 BMI) patients. Results Of the 214 women in the study, 129 (60.3%) were obese pre-pregnancy and 85 (39.7%) were not. Most PPROM occurred between 32 and 36 weeks of gestation (145 patients, 67.8%), with 19.2% occurring at 26-31 weeks (41 patients), and 13.2% at <26 weeks of gestation (28 patients). Latency, defined as the days between PPROM and delivery, ranged from 0 to 80 days with a mean of 4.9 + 10.9 days. At least one day of latency was achieved for most patients (144/214; 67.3%). When outcomes were compared between obese and nonobese patients, the obese patients experienced significantly more complications (10.1% vs 2.4%; p=0.031), which were accompanied by greater neonatal morbidity 67 of 129 ((51.9%) vs 30 of 85 (35.3%); p=0.018). Obese women had greater odds that their newborns would experience neonatal morbidity than nonobese women (odds ratio, 1.98; 95% confidence interval, 1.1-3.5). Conclusion This study of Appalachian women found that pre-pregnancy BMI [Formula: see text]30 increased the risk of complications and neonatal morbidity after PPROM. To improve birth outcomes, healthcare workers and policymakers must work together to decrease rates of obesity in Appalachian women at or near childbearing age.

Azithromycin Dosing and Preterm premature rupture of membranes Treatment (ADAPT): A randomized controlled Phase I trial.

BACKGROUND: Seven days of antibiotics are recommended in the setting of preterm premature rupture of membranes (PPROM) to promote latency. Azithromycin has generally replaced a seven-day course of erythromycin in current clinical practice. Azithromycin clears from plasma quickly and concentrates in local tissue which is why daily dosing is not always needed and local tissue, rather than plasma, concentrations are used to determine dosing. Based on limited pharmacokinetic studies in pregnancy, 1g one time dose of azithromycin may not maintain local (amniotic fluid) drug concentrations above minimum inhibitory concentrations (MIC50) for common genitourinary pathogens (50-500ng/ml). OBJECTIVE: We aim to compare the pharmacokinetics of one-time vs daily dosing of azithromycin in the setting of preterm pre-labor rupture of membranes (PPROM) STUDY DESIGN: This is a randomized clinical trial of singletons with PPROM randomized to 1gram oral azithromycin once or 500mg oral azithromycin daily x7 days. Primary outcome was amniotic fluid azithromycin concentrations over 8 days. Secondary outcomes included plasma azithromycin trough concentrations. Plasma was collected at time points 1-4hrs and 12-24hrs after first dose, and then every 24hrs through 8 days. Amniotic fluid was collected opportunistically throughout the day noninvasively with Always Flex-foam pads. We aimed to enroll 20 participants to achieve N=5 still pregnant through 8 days in each group. Continuous variables compared with Mann Whitney U test and relationship between azithromycin concentration and time assessed with linear regression. RESULTS: The study was halted after N=6 enrolled due to lagging enrollment, with 3 in each group. The mean gestational age of enrollment was 27.1±1.7weeks in the 1g group and 31.0±1.4 weeks in the 500mg daily group. One participant in each group had latency to delivery >7days. Regarding amniotic fluid azithromycin concentration, there was a difference in change in amniotic fluid azithromycin concentration over time between groups (p<0.001). Amniotic fluid concentration of azithromycin was relatively stable in the 1g once group (B=-0.07 (-0.44 - 0.31), p=0.71), in contrast, amniotic fluid concentration (ng/ml) increased over time (hours) in the 500mg daily group (B=1.3 (0.7 - 1.9), p<0.001). By ≥96hours median amniotic fluid levels of azithromycin were lower in the 1g once dosing group (median 11[7-56]) compared to 500mg daily (median 46 [23-196]), with a median difference -27 (-154 to -1), p=0.03. In plasma, there was higher azithromycin concentration during the first 24hrs with 1g once vs 500mg daily (median difference 637ng/ml (101-1547), p=0.01), however by ≥96hrs plasma azithromycin declined and was virtually undetectable in the 1g once group, while trough plasma levels in the 500mg remained elevated (median difference -207ng/ml (-271 to -155), p=0.03). CONCLUSION: 500mg daily dosing of azithromycin maintains higher amniotic fluid concentrations, and more consistently greater than common MICs, over eight days compared to 1g once in the setting of PPROM.

Amnioinfusion compared with expectant management in oligohydramnios with intact amnions in the second and early third trimesters.

INTRODUCTION: Treatment of oligohydramnios in the mid-trimester is challenging, because of the high incidence of adverse perinatal outcomes mainly due to bronchopulmonary dysplasia. Antenatal amnioinfusion has been proposed as a possible treatment for oligohydramnios with intact amnions, but there are few relevant studies. This study aimed to evaluate the effectiveness of transabdominal amnioinfusion in the management of oligohydramnios without fetal lethal malformations in the second and early third trimesters. MATERIAL AND METHODS: It is a historical cohort study. A total of 79 patients diagnosed with oligohydramnios at 18-32 weeks gestation were enrolled. In the amnioinfusion group (n = 39), patients received transabdominal amnioinfusion with the assistance of real-time ultrasound guidance. In the expectant group (n = 41), patients were treated with 3000 mL of intravenous isotonic fluids daily. The perioperative complications and perinatal outcomes were analyzed. RESULTS: Compared with the expectant group, the delivery latency was significantly prolonged, and the rate of cesarean delivery was significantly reduced in the amnioinfusion group (p < 0.05). Although the rate of intrauterine fetal death was significantly reduced, the incidence of spontaneous miscarriage, premature rupture of membranes (PROMs), and threatened preterm labor were significantly higher in the amnioinfusion group than in the expectant group (p < 0.05). There was no significant difference in terms of perinatal mortality (28.9% vs. 41.4%, p > 0.05). Multivariate logistic regression revealed that amnioinfusion (odds ratio [OR] 0.162, 95% confidence interval [CI] 0.04-0.61, p = 0.008) and gestational age at diagnosis (OR 0.185, 95% CI 0.04-0.73, p = 0.016) were independently associated with neonatal adverse outcomes. Further subgrouping showed that amnioinfusion significantly reduced the frequency of bronchopulmonary hypoplasia for patients ≤26 weeks (26.7% vs. 75.0%, p = 0.021). The rates of other neonatal complications were similar in both groups. CONCLUSIONS: Amnioinfusion has no significant effect on improving the perinatal mortality of oligohydramnios in the second and early third trimesters. It may lead to a relatively high rate of PROM and spontaneous abortion. However, amnioinfusion may significantly improve the latency period, the rate of cesarean delivery, and neonatal outcomes of oligohydramnios, especially for women ≤26 weeks with high risk of neonatal bronchopulmonary hypoplasia.

A comparison of Mersilene tape versus braided suture in transvaginal cervical cerclage: A retrospective case-control study.

OBJECTIVE: Previous studies have indicated that there is an association between cervical cerclage and type of suture material. However, it is still unclear which suture material can provide the greatest benefit to patients who have undergone cerclage. This study investigated the effect of two different suture materials (Mersilene tape vs braided suture) used for transvaginal cervical cerclage placement on maternal outcomes of women with cervical insufficiency. METHODS: In this retrospective case-control study, 170 women who underwent history-, ultrasound-, or physical examination-indicated transvaginal cervical cerclage were categorized according to suture materials used for cerclage: a total of 96 received Mersilene tape and 74 received braided suture. Study participants received a transvaginal cervical cerclage before 28 weeks and were followed up until delivery to assess pregnancy and neonatal outcomes. The primary outcome was gestational age at delivery. Secondary outcomes included preterm premature rupture of membranes (PPROM), premature rupture of membranes (PROM), chorioamnionitis, neonatal survival rate, and neonatal morbidity. RESULTS: Out of 170 eligible women, 74 (43.5%) received braided suture while 96 (56.5%) received Mersilene tape. Baseline characteristics were similar between the two groups. The group that received braided suture had a lower incidence of gestational age at delivery <37 weeks (29.2% vs 54.2%, P = 0.046), PPROM (9.5% vs 21.9%, P = 0.029) and PROM (17.6% vs 32.3%, P = 0.028) compared to the group that received Mersilene tape. However, there were no significant differences between the two groups in average gestational age at delivery, the rate of gestational age at delivery <24, <28, <32, and < 34 weeks, chorioamnionitis, and neonatal survival rate, as well as neonatal morbidity. CONCLUSION: Compared to Mersilene tape, the utilization of braided suture has been significantly associated with a reduction in the incidence of gestational age at delivery <37 weeks, as well as a decreased risk of PPROM and PROM. However, the use of braided sutures did not result in discernible differences in the rates of chorioamnionitis or adverse neonatal outcomes.

Nulliparas at Term with Premature Rupture of Membranes and an Unfavorable Cervix: Labor Induction with Prostaglandin or Oxytocin? A Retrospective Matched Case Study.

Background: Induction of labor (IOL) in nulliparas with premature rupture of membranes (PROM) and an unfavorable cervix at term poses challenges. Our study sought to investigate the impact of prostaglandin E2 (PGE2) compared to oxytocin on the duration of IOL in this specific group of parturients. Methods: This was retrospective matched-case study. All nulliparas with term PROM who underwent induction between January 2006 to April 2023 at Shaare Zedek Medical Center were identified. Cases induced by either PGE2 or oxytocin were matched by the following criteria: (1) time from PROM to IOL; (2) modified Bishop score prior to IOL ≤ 5; (3) newborn birthweight; and (4) vertex position. The primary outcome was time from IOL to delivery. Results: Ninety-five matched cases were identified. All had a modified Bishop score ≤ 5. Maternal age (26 ± 4.7 years old, p = 0.203) and gestational age at delivery (38.6 ± 0.6, p = 0.701) were similar between the groups. Matched factors including time from PROM to IOL (23.5 ± 19.2 versus 24.3 ± 21.4 p = 0.780), birth weight of the newborn (3111 g versus 3101 g, p = 0.842), and occiput anterior position (present on 98% in both groups p = 0.687) were similar. Time from IOL to delivery was significantly shorter by 3 h and 36 min in the group induced with oxytocin than in the group induced with PGE2 (p = 0.025). Within 24 h, 55 (58%) of those induced with PGE2 delivered, compared to 72 (76%) of those induced with oxytocin, (p = 0.033). The cesarean delivery rates [18 (19%) versus 17 (18%)], blood transfusion rates [2 (2%) versus 3 (3%)], and Apgar scores (8.8 versus 8.9) were similar between the groups (PGE2 versus oxytocin, respectively), p ≥ 0.387. Conclusions: Induction with oxytocin, among nulliparas with term PROM and an unfavorable cervix, was associated with a shorter time from IOL to delivery and a higher rate of vaginal delivery within 24 h, with no difference in short-term maternal or neonatal adverse outcomes.

Relationship between first trimester physical activity and premature rupture of membranes: a birth cohort study in Chinese women.

OBJECTIVE: This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. METHODS: A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. RESULTS: Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58-0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59-0.81, OR = 0.70, 95% CI 0.60-0.82, OR = 0.62, 95% CI 0.53-0.73 and OR = 0.82, 95% CI 0.70-0.97, respectively). CONCLUSIONS: High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. TRIAL REGISTRATION: The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.

Knowledge, attitude, and practices of midwives on premature rupture of membranes (PROM): A cross-sectional study in Samosir and Toba, Indonesia.

Indonesia has a significantly higher maternal mortality ratio (MMR) than other countries in Southeast Asia, and infection is one of the most common causes of maternal deaths, of which premature rupture of membranes (PROM) can be the consequence of the infections. In primary healthcare settings, midwives play an important role in identifying and managing PROM appropriately; however, studies on their knowledge, attitudes, and practices related to PROM are limited. The aim of this study was to determine the midwives' knowledge, attitude and healthcare practice on PROM in Indonesia. A cross-sectional study was conducted among midwives at primary healthcare facilities in Samosir and Toba Regency, North Sumatra, Indonesia, from July to November 2022. The knowledge, attitude and practice towards PROM were assessed. Results showed that 57.5% of midwives had poor knowledge and 35.1% had poor attitude levels. There were 4.9% of midwives referred the patients immediately to the hospital. Our data indicated that aged 31-40 or 41-50 years, having a lower than bachelor degree and having a higher monthly number of referred PROM patients were significantly associated with poor knowledge compared to younger, having a bachelor degree, and lower monthly referral patient number, respectively. Similarly, younger, having higher degree and a having lower monthly referral number of PROM cases were associated with higher chances of having a sufficient-good attitude towards PROM. This study highlights that a significant percentage of midwives had poor levels of knowledge and attitude, and age, educational level and monthly referral number of PROM cases were associated with the level of knowledge and attitude.

[Impact of the mode of follow-up of preterm premature rupture of membranes before 36 weeks of gestation on the latency period]. / Impact du mode de suivi des ruptures prématurées des membranes avant 36 SA sur la durée de latence.

INTRODUCTION: Preterm premature rupture of membranes (PPROM) is the main cause of premature delivery, complicating 1-3% of all pregnancies. Conventional hospitalization (CH) is the most frequent mode of follow-up, but homecare (HC) seems to be an alternative. OBJECTIVES: Study of the impact of the monitoring mode on the duration of the latency period and on the latency ratio after PPROM, and analysis of the risk factors modifying this ratio. METHODS: This was a bicentric retrospective cohort study here-abouts including patients who presented a PPROM between 24 and 36weeks of gestation from 2016 to 2018. Patients had a follow-up in HC at Lille University Hospital center (UHC) and in CH at Nantes UHC according to two different follow-up protocols. The latency ratio corresponded to the real latency period divided by the latency period to theoretical term. RESULTS: We included 154 patients: 102 in HC and 52 in CH. The mean latency period was significantly higher in HC: 36.9±21.8 days, corresponding to an 85.5±23.7% latency ratio versus 20.2±12 days, corresponding to an 66.9±29.8% latency ratio in CH (P<0.001). The latency ratio in CH was correlated with term at PPROM (P=0.001). CONCLUSIONS: The duration of the latency period seems prolonged for PPROM followed by HC management versus CH in selected populations. This study suggests a benefit to HC in stable patients.

Value of fetal echocardiographic examination in pregnancies complicated by preterm premature rupture of membranes.

OBJECTIVES: Cardiopulmonary and infectious complications are more common in preterm newborns after preterm premature rupture of membranes (pPROM). Fetal echocardiography may be helpful in predicting neonatal condition. Our aim was to assess the cardiovascular changes in fetuses from pregnancies complicated by pPROM and possible utility in predicting the intrauterine or neonatal infection, and neonatal heart failure (HF). METHODS: It was a prospective study enrolling 46 women with singleton pregnancies complicated by pPROM between 18+0 and 33+6 weeks of gestation and followed until delivery. 46 women with uncomplicated pregnancies served as a control group. Fetal echocardiographic examinations with the assessment of cardiac structure and function (including pulmonary circulation) were performed in all patients. RESULTS: Mean gestational age of pPROM patients was 26 weeks. Parameters suggesting impaired cardiac function in fetuses from pPROM were: higher right ventricle Tei index (0.48 vs. 0.42 p<0.001), lower blood flow velocity in Ao z-score (0.14 vs. 0.84 p=0.005), lower cardiovascular profile score (CVPS), higher rate of tricuspid regurgitation (18.2 % vs. 4.4 % p=0.04) and pericardial effusion (32.6 vs. 0 %). Intrauterine infection was diagnosed in 18 patients (39 %). 4 (8.7 %) newborns met the criteria of early onset sepsis (EOS). HF was diagnosed in 9 newborns. In fetal echocardiographic examination HF group had shorter mitral valve inflow time and higher left ventricle Tei index (0.58 vs. 0.49 p=0.007). CONCLUSIONS: Worse cardiac function was observed in fetuses from pPROM compared to fetuses from uncomplicated pregnancies.

Changes in serum inflammatory factors in group B streptococcal infection and their predictive value for premature rupture of membranes complicated by chorioamnionitis.

Objective: The aim of this study as to unveil changes in serum inflammatory factors in pregnant women with genital tract group B Streptococcus (GBS) infection and their predictive value for premature rupture of membranes (PROM) complicated by chorioamnionitis (CS) and adverse pregnancy outcomes. Methods: The value of serum inflammatory factor levels in predicting PROM complicating CS and adverse pregnancy outcomes in GBS-infected pregnant women was evaluated by ELISA. Results: Serum IL-6, TNF-α, PCT and hs-CRP levels were higher in pregnant women with GBS infection. The combined diagnosis of these factors had excellent diagnostic value in PROM complicating CS and adverse pregnancy outcomes. Conclusion: Joint prediction of IL-6, TNF-α, PCT and hs-CRP has the best predictive value for PROM complicating CS and adverse pregnancy outcomes.

[Box: see text].

Causal associations between Helicobacter pylori infection and pregnancy and neonatal outcomes: a two-sample Mendelian randomization study.

Background: Observational studies have reported that Helicobacter pylori (H. pylori) infection is associated with a series of pregnancy and neonatal outcomes. However, the results have been inconsistent, and the causal effect is unknown. Methods: A two-sample Mendelian randomization (MR) study was performed using summary-level statistics for anti-H. pylori IgG levels from the Avon Longitudinal Study of Parents and Children Cohort. Outcome data for pregnancy (miscarriage, preeclampsia-eclampsia, gestational diabetes mellitus, placental abruption, premature rupture of membranes, postpartum hemorrhage) and neonates (birthweight, gestational age, and preterm birth) were sourced from genome-wide association meta-analysis as well as the FinnGen and Early Growth Genetics Consortium. Causal estimates were calculated by five methods including inverse variance weighted (IVW). The heterogeneity of instrumental variables was quantified by Cochran's Q test, while sensitivity analyses were performed via MR-Egger, MR-PRESSO, and leave-one-out tests. Results: IVW estimates suggested that genetically predicted anti-H. pylori IgG levels were significantly associated with increased risks of preeclampsia-eclampsia (odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.01-1.24, P = 0.026) and premature rupture of membranes (OR = 1.17, 95% CI 1.05-1.30, P = 0.004). Similar results were obtained for preeclampsia-eclampsia from the MR-Egger method (OR = 1.32, 95% CI 1.06-1.64, P = 0.027) and for premature rupture of membranes from the weighted median method (OR = 1.22, 95% CI 1.06-1.41, P = 0.006). No significant causal effects were found for other outcomes. There was no obvious heterogeneity and horizontal pleiotropy across the MR analysis. Conclusion: Our two-sample MR study demonstrated a causal relationship of H. pylori infection with preeclampsia-eclampsia and premature rupture of membranes. The findings confirm the epidemiological evidence on the adverse impact of H. pylori in pregnancy. Further studies are needed to elucidate the pathophysiological mechanisms and assess the effectiveness of pre-pregnancy screening and preventive eradication.

Analysis of cases of premature rupture of membranes and preterm births to identify effective management measures to prevent them.

OBJECTIVE: Aim: Based on retrospective analysis recognize the key factors of development of premature childbirth and elaborate highly specific criteria for individual prognosis to improve perinatal outcomes. PATIENTS AND METHODS: Materials and Methods: A retrospective analysis of the birth histories of 250 women and their newborns with spontaneous preterm births at 22-36 weeks was conducted using archival data from the department for pregnant women with obstetric pathology of the State Institution "Institute of Pediatrics, Obstetrics and Gynecology named by academician OM Lukianova of the National Academy of Medical Sciences of Ukraine". RESULTS: Results: Important risk factors for premature rupture of membranes (PROM) in preterm pregnancy include the presence of sexually transmitted diseases (χ2=31.188, p=0.001), bacterial vaginosis (χ2=30.913, p=0.0001), a history of abortion and/or preterm birth (χ2=16.62, p=0.0002), SARS during pregnancy (χ2=16.444, p=0.0002), chronic adnexitis in anamnesis (χ2=11.522, p=0.0031), inflammatory cervical disease (χ2=11.437, p=0.0032), anaemia (χ2=10.815, p=0.0044), isthmic-cervical insufficiency (ІСІ) (χ2=10.345, p=0.0057), chronic pyelonephritis with exacerbation (χ2=9.16, p=0.01), smoking during pregnancy (χ2=10.815, p=0.0044). CONCLUSION: Conclusions: The results of a retrospective analysis of 250 cases of preterm birth at 22 to 36 weeks allowed us to identify ways to effectively use existing diagnostic measures to determine readiness for pregnancy and the possibility of prolonging pregnancy to the viability of the newborn. Ways to improve the prevention of preterm birth and the design of further research were identified.

A Case of Consumptive Coagulopathy Before Cardiopulmonary Failure in Amniotic Fluid Embolism and Review of Literature: A Perspective of the Latent Onset and Progression of Coagulopathy.

Amniotic fluid embolism (AFE) induces cardiopulmonary insufficiency with consumptive coagulopathy. Previous studies reported that refractory coagulopathy has already advanced at the onset of maternal cardiovascular and/or respiratory symptoms. However, when the consumption of coagulation factors starts during the clinical course, AFE remains to be elucidated. We report an intrapartum AFE case of consumptive coagulopathy before dyspnea with hypotension developing during urgent cesarean delivery that was revealed by non-reassuring fetal heart rate tracing. The patient, a 42-year-old multiparous parturient, underwent induced labor after a premature rupture of membranes in week 39 of pregnancy. Coagulation screening was initially within the normal range. Fetal heart rate monitoring demonstrated bradycardia coincided with uterine tachysystole after three hours, which required urgent cesarean section with preoperative blood screening. The hemoglobin level was maintained at 129 g/L; however, the fibrinogen value reduced to 1.79 g/L with D-dimer elevation over 60 µg/mL. Ninety minutes later, she developed dyspnea with hypotension at suturing hysterotomy. At the end of surgery, her fibrinogen further decreased to below 0.3 g/L with prolonged prothrombin time. After vigorous intensive care, she was discharged without sequelae. Consumptive coagulopathy may initiate and progress before apparent cardiopulmonary symptoms in some AFE cases. Non-reassuring fetal heart rate tracing concomitant with abrupt uterine tachysystole and/or hypertonus may be an earlier time point for the detection and intervention of AFE-related coagulopathy.

Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm premature rupture of membranes.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Association Analysis Between Maternal Neutrophil Ratio and the Risk of Histological Chorioamnionitis in Pregnant Women with Premature Rupture of Membranes in Late Pregnancy.

Background: We aimed to investigate the association between maternal neutrophil ratio and histological chorioamnionitis (HCA) risk in pregnant women with premature rupture of membranes (PROM) in late pregnancy. Methods: A retrospective analysis was conducted on 95 cases of women with PROM in their late pregnancy between March 2018 and August 2021. These women were divided into two groups based on the presence of HCA. General clinical data and laboratory indicators were compared between the two groups. A generalized additive model was used for curve fitting, and a segmented regression model was used to explain further the non-linear relationship between neutrophil ratio and HCA risk. Results: After adjusting for confounding factors, the curve fitting showed a "U"-shaped curve relationship between the neutrophil ratio and the risk of HCA. When the neutrophil ratio was <76.3%, the risk of HCA exhibited a decreasing trend, but the difference was not statistically significant (adjusted OR = 0.884, 95% CI: 0.781-1.001, P = 0.053). However, when the neutrophil ratio was >76.3%, the HCA risk was significantly increased (adjusted OR = 1.339, 95% CI: 1.067-1.680, P = 0.012). Furthermore, we equally divided the neutrophil ratio into three groups. The risk of HCA was significantly increased in the low-ratio group (OR = 4.292, 95% CI: 1.247-14.706, P = 0.021) compared with the middle-ratio group, which was used as the reference group. Similarly, the HCA risk of the high-ratio group (OR = 13.145, 95% CI: 1.796-96.233, P = 0.011) was also significantly enhanced. However, there was no significant difference in HCA risk between the high-ratio and low-ratio groups (OR = 1.182, 95% CI: 0.357-3.909, P = 0.784). Conclusion: There was a significant "U"-shaped relationship between maternal neutrophil ratio and HCA risk in women with PROM in late pregnancy.

Outcome of prelabor rupture of membranes before or at the limit of viability: systematic review and meta-analysis.

OBJECTIVE: Counseling of pregnancies complicated by pre- and periviable premature rupture of membranes to reach shared decision-making is challenging, and the current limited evidence hampers the robustness of the information provided. This study aimed to elucidate the rate of obstetrical and neonatal outcomes after expectant management for premature rupture of membranes occurring before or at the limit of viability. DATA SOURCES: Medline, Embase, CINAHL, and Web of Science databases were searched electronically up to September 2023. STUDY ELIGIBILITY CRITERIA: Our study included both prospective and retrospective studies of singleton pregnancies with premature rupture of membranes before and at the limit of viability (ie, occurring between 14 0/7 and 24 6/7 weeks of gestation). METHODS: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Moreover, our study used meta-analyses of proportions to combine data and reported pooled proportions. Given the clinical heterogeneity, a random-effects model was used to compute the pooled data analyses. This study was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42022368029). RESULTS: The pooled proportion of termination of pregnancy was 32.3%. After the exclusion of cases of termination of pregnancy, the rate of spontaneous miscarriage or fetal demise was 20.1%, whereas the rate of live birth was 65.9%. The mean gestational age at delivery among the live-born cases was 27.3 weeks, and the mean latency between premature rupture of membranes and delivery was 39.4 days. The pooled proportion of cesarean deliveries was 47.9% of the live-born cases. Oligohydramnios occurred in 47.1% of cases. Chorioamnionitis occurred in 33.4% of cases, endometritis in 7.0%, placental abruption in 9.2%, and postpartum hemorrhage in 5.3%. Hysterectomy was necessary in 1.2% of cases. Maternal sepsis occurred in 1.5% of cases, whereas no maternal death was reported in the included studies. When focusing on neonatal outcomes, the mean birthweight was 1022.8 g in live-born cases. The neonatal intensive care unit admission rate was 86.3%, respiratory distress syndrome was diagnosed in 66.5% of cases, pulmonary hypoplasia or dysplasia was diagnosed in 24.0% of cases, and persistent pulmonary hypertension was diagnosed in 40.9% of cases. Of the surviving neonates, the other neonatal complications included necrotizing enterocolitis in 11.1%, retinopathy of prematurity in 27.1%, and intraventricular hemorrhage in 17.5%. Neonatal sepsis occurred in 30.2% of cases, and the overall neonatal mortality was 23.9%. The long-term follow-up at 2 to 4 years was normal in 74.1% of the available cases. CONCLUSION: Premature rupture of membranes before or at the limit of viability was associated with a great burden of both obstetrical and neonatal complications, with an impaired long-term follow-up at 2 to 4 years in almost 30% of cases, representing a clinical challenge for both counseling and management. Our data are useful when initially approaching such patients to offer the most comprehensive possible scenario on short- and long-term outcomes of this condition and to help parents in shared decision-making. El resumen está disponible en Español al final del artículo.

Significance of cervical secretion culture in predicting maternal and fetal outcome in pregnant women with premature rupture of membranes: a retrospective cohort study.

Background: To investigate the clinical value of cervical secretion culture in pregnant women with premature rupture of membranes (PROM) in predicting maternal and fetal outcomes. Methods: We retrospectively reviewed clinical records of pregnant women who underwent obstetric examination and delivered in Fujian Maternal and Child Healthcare from December 2013 to December 2016. Pregnant women with a clear diagnosis of PROM, who underwent cervical secretion culture immediately after hospital admission were selected for the study. The primary outcome was the occurrence of chorioamnionitis. The secondary outcome was neonatal admission to the neonatal intensive care unit (NICU). Correlation between maternal and fetal outcomes and the results of the cervical secretion culture was analyzed by one-way analysis and multifactorial analysis, respectively. The predictive efficacy of cervical secretion culture was evaluated using receiver operating characteristic curve (ROC), area under the curve (AUC) and the integrated discrimination improvement (IDI). Results: A total of 7,727 pregnant women with PROM were included in the study. Of them, 1812 had positive cervical secretion cultures (635 positive for mycoplasma infection, 475 for bacterial, 637 for fungal, and 65 for chlamydial infections). Pregnant women with positive mycoplasma and bacterial cultures had higher rates of developing chorioamnionitis compared to women with negative cervical secretion cultures (9%, 12% vs. 1%, respectively). Similarly, positive mycoplasma and bacterial cultures were associated with higher rate of the preterm (before 34 weeks) labor (3%, 3% vs. 1% in women with negative cultures, respectively), and neonatal admission to the NICU (9%, 11% vs. 7%, respectively). After adjusting for various confounding factors, our analysis demonstrated that a positive cervical secretion culture for mycoplasma or bacterial pathogens remained an independent risk factor for chorioamnionitis. Cervical secretion culture outcome was less effective in predicting chorioamnionitis (AUC 0.569) compared to white blood count (WBC) (AUC 0.626) and C-reactive protein (CRP) levels (AUC 0.605). The IDI of the combined predictive model incorporating WBC, CRP, maternal fever and cervical secretion culture results was 0.0029. Conclusion: Positive cervical secretion cultures, especially for mycoplasma and bacteria, are associated with higher incidence of adverse maternal and fetal outcomes. However, the predictive value of this test is poor, and cannot be efficiently used for predicting chorioamnionitis.

Albumin and C-reactive protein as diagnostic markers for neonatal sepsis: a retrospective study.

OBJECTIVE: To assess the applicability of albumin (ALB) and C-reactive protein (CRP) concentrations in the diagnosis of sepsis in neonates on the day of admission, and to help with early identification and intervention in the development of sepsis. METHODS: This retrospective study included all neonates who were admitted to the neonatal intensive care unit from January 2020 to June 2023. We studied 160 full-term neonates, including 80 with sepsis and 80 healthy controls. A multivariate analysis was conducted to evaluate the associations between ALB, CRP, and sepsis. RESULTS: CRP concentrations were significantly higher in neonates with sepsis than in controls (26.5 ± 8.6 vs. 3.6 ± 1.2 ng/L). At a cut-off point of 10.8 ng/L, CRP showed a sensitivity of 74.3% and a specificity of 80%. Moreover, ALB concentrations were significantly lower in neonates with sepsis than in controls (25.4 ± 2.5 g/L vs. 29.2 ± 2.6 g/L). At a cut-off point of 26.8, ALB showed a sensitivity of 75.6% and a specificity of 84.2%. CONCLUSIONS: Our findings suggest that ALB and CRP concentrations on the first day of admission are different between neonates who do and those who do not develop sepsis. Higher CRP concentrations and lower ALB concentrations may indicate an increased risk of sepsis.

Comparison of Misoprostol with Foley Catheter vs Misoprostol alone for Cervical Ripening and Induction of Labor in Patients with Premature Rupture of Membrane: A Randomized Clinical Trial Study.

Background: This study evaluates the effect of misoprostol alone in comparison with misoprostol with Foley catheter in preparing the cervix for induction of labor in women with premature rupture of the amniotic sac. Materials and Methods: This randomized clinical trial study was performed from 2017 to 2019 on 206 pregnant women with singleton pregnancy and gestational age more than 36 weeks, whose rupture of the amniotic sac had occurred less than 12 hours and had a Bishop score less than 4. These women were randomly assigned to two groups of Foley catheters with misoprostol (intervention group, P = 103) or misoprostol alone (control group, P = 103) to induce labor. In both groups, sublingual misoprostol (25 micrograms) was administered at intervals of 4-6 hours. The collected data were analyzed by SPSS.21 software. Results: There is no significant difference between age and Bishop score in the two groups (P = 0.19, P = 0.31, respectively). Lower doses (0 to 3) of misoprostol were used in the intervention group versus 0 to 5 doses in the control group (P = 0.001). Delivery time was shorter in the intervention group (10.83 hours vs. 13.10 hours in the control group, P = 0.001). Also, the probability of complications such as fever, tachysystole, and hospitalization of an infant in the neonatal intensive care unit (NICU) did not increase. Conclusion: An intracervical Foley catheter with misoprostol is more effective in inducing labor in pregnancies with premature rupture of the membranes than using misoprostol alone and can be a safe and effective option.

Role of NF-κB p65/TNF-α in Cell Apoptosis in the Fetal Membranes of Pregnant Women with Preterm Premature Rupture of Membranes.

OBJECTIVE: This study aimed to investigate the roles of nuclear factor-kappa B p65 (NF-[Formula: see text]B p65) and tumor necrosis factor-α (TNF-α) in cell apoptosis occurring in the fetal membranes of pregnant women who experience preterm premature rupture of membranes (PPROM). METHODS: This was a case-control study involving 57 pregnant women who delivered in the obstetric department of Affiliated Loudi Hospital, Hengyang Medical School, University of South China, from June 2021 to June 2022. Samples of fetal membrane tissue were collected from pregnant women with PPROM (n=27) and pregnant women who had normal deliveries (control group; n=30). The membrane tissue morphology of both groups was observed, and the expression of NF-[Formula: see text]B p65, p-NF-[Formula: see text]B p65, TNF-α, and caspase-3 was detected. Apoptosis in fetal membranes was examined. RESULTS: Morphological evaluation of the fetal membrane tissues obtained from patients with PPROM revealed an abnormal structure with a thin collagen fiber layer and cells with a largely vacuolar cytoplasm. There was a positive correlation between the expression of p-NF-[Formula: see text]B p65/NF-[Formula: see text]B p65 and cell apoptosis (r1 =0.89, R2 =0.805, P=0.00). Furthermore, TNF-α was positively correlated with fetal membrane cell apoptosis (r2 =0.93, R2=0.881, P=0.00). CONCLUSION: NF-[Formula: see text]B p65 is involved in the occurrence of PPROM by promoting the expression of TNF-α, which upregulates caspase-3 to cause apoptosis of fetal membrane cells.