Life after Ipradol

Genital mycoplasmas (GM), such as Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum, and Ureaplasma urealyticum are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of membranes (PPROM). This study determined the association between GM and such adverse pregnancy outcomes. We searched for studies published 1980–2019 in MEDLINE, EMBASE, and Web of Science. Studies were eligible when GM was detected during pregnancy. We included 93 and 51 studies in determining the prevalence and the inflammatory biomarkers associated with GM, respectively, using the “metafor” package within R. The protocol was registered with PROSPERO (registration no. CRD42016047297). Women with the studied adverse pregnancy outcomes had significantly higher odds of presence with GM compared to women who delivered at term. For PTB, the odds ratios were: M. hominis (OR: 2.25; CI: 1.35–3.75; I2: 44%), M. genitalium (OR: 2.04; CIL 1.18–3.53; I2: 20%), U. parvum (OR: 1.75; CI: 1.47–2.07; I2: 0%), U. urealyticum (OR: 1.50; CI: 1.08–2.07; I2: 58%). SPTL had significantly higher odds with M. hominis (OR: 1.96; CI: 1.19–3.23; I2: 1%) or U. urealyticum (OR: 2.37; CI: 1.20–4.70; I2: 76%) compared to women without SPTL. Women with PPROM had significantly higher odds with M. hominis (OR: 2.09; CI: 1.42–3.08; I2: 0%) than women without PPROM. However, our subgroup analysis based on the diagnostic test and the sample used for detecting GM showed a higher prevalence of GM in maternal samples than in fetal samples. GM presence of the cervix and vagina was associated with lower odds of PTB and preterm labor (PTL). In contrast, GM presence in the AF, fetal membrane, and placenta was associated with increased odds of PTB and PTL. However, genital mycoplasmas may not elicit the massive inflammation required to trigger PTB. In conclusion, GM presence in the fetal tissues was associated with significantly increased odds of PTB and PTL.

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB. Vaginal swabs were collected across gestation from pregnant women who ultimately underwent term birth, sPTL, or PPROM. Cytokines, chemokines, growth factors, and antimicrobial peptides in the samples were quantified via specific and sensitive immunoassays. Predictive models were constructed from immune mediator concentrations. Throughout uncomplicated gestation, the vaginal immunoproteome harbors a cytokine network with a homeostatic profile. Yet, the vaginal immunoproteome is skewed toward a pro-inflammatory state in pregnant women who ultimately experience sPTL and PPROM. Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative of macrophage and T-cell activation, and reduced antimicrobial proteins/peptides. The vaginal immunoproteome has improved predictive value over maternal characteristics alone for identifying women at risk for early (<34 weeks) sPTB. The vaginal immunoproteome undergoes homeostatic changes throughout gestation and deviations from this shift are associated with sPTB. Furthermore, the vaginal immunoproteome can be leveraged as a potential biomarker for early sPTB, a subset of sPTB associated with extremely adverse neonatal outcomes. This research was conducted by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, and NGL were supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.

Objective. Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI).Study design. This cross-sectional study included the following groups: (1) mid-trimester (n = 55); (2) normal pregnancy at term with (n = 50) and without (n = 50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm without IAI (n = 108); and (c) PTL with IAI (n = 84); and (4) preterm PROM with (n = 46) and without (n = 44) IAI. sHLA-G concentrations were determined by ELISA. Non-parametric statistics were used for analysis.Results. (1) Among patients with PTL, the median AF sHLA-G concentration was higher in patients with IAI than in those without IAI or women that delivered at term (p < 0.001 for both comparisons); (2) Similarly, patients with preterm PROM and IAI had higher median AF sHLA-G concentrations than those without IAI (p = 0.004); (3) Among patients with PTL and delivery, those with histologic chorioamnionitis and/or funisitis had a higher median AF sHLA-G concentration than those without histologic inflammation (p < 0.001); and (4) The median AF sHLA-G concentration did not change with advancing gestational age.Conclusions. AF sHLA-G concentrations are elevated in preterm parturition associated to IAI as well as in histologic chorioamnionitis. We propose that sHLA-G may participate in the regulation of the host immune response against intra-amniotic infection.

Effects of acute ambient pollution exposure on preterm prelabor rupture of membranes: A time-series analysis in Shanghai, China.

BackgroundMultiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications.MethodsProspective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes.ResultsAmong 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%).When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p < 0.01), higher gestational age at delivery (p < 0.01), Caucasian race (p 0.04), ART use (p < 0.01), gestational diabetes (p < 0.01), vaginal bleeding (p < 0.01), antenatal corticosteroids (p < 0.01), diagnosis of fetal growth restriction (FGR) (p < 0.01), and monochorionic (p < 0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p < 0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p < 0.01).ConclusionOur study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants’ prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications.

Outcomes after cerclage and preterm prelabor rupture of membranes: data from the international collaborative for cerclage longitudinal evaluation and research (IC-CLEAR).

Preterm prelabour rupture of membranes (PPROM) is a leading cause of preterm births. Its attendant contribution to maternal and perinatal morbidity and mortality makes it imperative to identify factors that may help prevent this condition. This study examined the association between plasma vitamin C concentration and the risk of (PPROM) amongst pregnant women in a tertiary hospital setting. This was a prospective cross sectional study conducted at the Obstetric and Gynaecology Department of University of Benin Teaching Hospital (UBTH), Benin City. The study was in two phases, first a pilot study to determine baseline plasma vitamin C concentration amongst pregnant women in UBTH was conducted. In the main study 80 pregnant women were recruited into two groups of those with PPROM (40 cases) and those without PPROM (40 controls) matched for gestational age. Plasma vitamin C concentration was determined for all study participants and their sociodemographic characters were used to generate a database for analysis. In the pilot study, plasma vitamin C concentration decreased with increasing gestational age of pregnancy. In the main study plasma vitamin C concentration was significantly lower in women with PPROM than controls without PPROM, 0.53 ± 0.05 vs. 0.58 ± 0.05 mg/dl; P = 0.0001. Both groups (case and control) were comparably matched in age, parity and social class. There was a significant association between low vitamin C levels and the occurrence of PPROM (95% CI 1.53-11.88; P = 0.008). Plasma vitamin C was found to be lower in women with PPROM. Low plasma vitamin C concentration may thus be an associated risk factor for PPROM. Hence improved dietary or drug supplements may be a useful adjunctive strategy to reducing the incidence of PPROM and its attendant adverse sequelae. While this intervention is advocated, further multicentre investigation of the effects of vitamin C on risk of preterm PROM is suggested.

Objective: To investigate risk factors of preterm labor (PTL) as a predictor model for preterm delivery (PTD) within seven days. Materials and Methods: The present study was a historical cohort study conducted at Bhumibol Adulyadej Hospital, Thailand between January 2018 and December 2023. Participants were singleton pregnant women who attended antenatal care and were diagnosed with PTL with a gestational age (GA) between the 24⁺⁰ and the 36⁺⁶ weeks. Participants that delivered within and outside the seven-day mark were divided into the study and control groups. Risk factors, namely maternal age, education level, family’s income, parity, history of PTD, GA at PTL, pre-pregnancy body mass index (PPBMI), nifedipine usage, preterm pre-labor rupture of membrane (PPROM), urinary tract infection (UTI), and vaginal bleeding were collected and analyzed to create predictive model of PTD within seven days (PD 7). Results: One thousand fifty-five pregnant women were recruited. The mean age of participants was 28.8 years. Significant factors for PTD including advanced maternal age (AMA), PPBMI, nifedipine usage, multiparity, PPROM, treated UTI, vaginal bleeding and history of PTD were used to generate the predictive model for PD 7. PD 7 scores greater than 26 predicted delivery within seven days with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+ and LR– of 72.7%, 78.5%, 77.9%, 73.4%, 3.4, and 0.4, respectively. Conclusion: AMA, higher GA, multiparity, PPROM, vaginal bleeding, treated UTI, and history of PTD were significant risk factors for PD 7. The PD 7 model demonstrated good predictive performance. The model can be applied as a clinical decision-support tool to guide appropriate corticosteroid administration and timely referral, reducing unnecessary interventions. Incorporation of the PD 7 model into antenatal care practice and hospital protocols may enhance perinatal outcomes and promote standardized management of PTL.

507: Intraamniotic inflammatory response to bacteria in preterm prelabor rupture of membranes pregnancies: analysis of multiple amniotic fluid proteins

Management of late preterm prelabor rupture of membranes between 34+0 and 36+6 weeks' gestation balances the risks of preterm birth with the risks of infection for both the mother and the neonate. Expectant management to prolong pregnancy showed similar risks of neonatal sepsis, but children at 2 years of age showed more neurodevelopmental delay when compared with induction of labor. Long-term outcomes on child development after 2 years of age are unknown. This study aimed to assess the long-term outcomes of children born after singleton pregnancies complicated by late preterm prelabor rupture of membranes managed by induction of labor in comparison with expectant management. This was a follow-up study of the Preterm Prelabor Rupture of Membranes Expectant Management Versus Induction of Labor (PPROMEXIL) trials (randomized controlled trials between 2007 to 2011) evaluating children at 10 to 12 years of age (Netherlands Trial Register 6953). The primary outcomes were cognition, motor function, and behavior as assessed by the Wechsler Intelligence Scale for Children-V-NL, Movement Assessment Battery for Children-2, and Child Behavior Checklist, respectively. The secondary outcomes were sensory processing, respiratory problems, educational attainment, and general health. Mild delay was defined as -1 standard deviation or corresponding percentile. The relative risk and confidence intervals were calculated using standard methods. This follow-up study invited 711 surviving children of the 714 singleton pregnancies randomized in the original trials. In total, 248 (35%) children participated (127 induction of labor, 121 expectant management). Children born after induction of labor had no significant differences in the primary outcomes when compared with those born after expectant management. Mild cognitive delay was observed in 7 of 122 (5.7%) children born after induction of labor in comparison with in 12 of 120 (10.0%) children born after expectant management (relative risk, 0.57; 95% confidence interval, 0.23-1.41). A mild delay in motor function was observed in 42 of 122 (34.4%) children born after induction of labor vs in 55 of 120 (45.8%) children born after expectant management (relative risk, 0.75; 95% confidence interval, 0.55-1.03). Mild abnormal behavior was observed in 37 of 125 (29.6%) children born after induction of labor compared with in 33 of 118 (28.0%) children born after expectant management (relative risk, 1.05; 95% confidence interval, 0.71-1.57). Secondary outcomes were also comparable between the induction of labor and the expectant management groups except that more children born after expectant management had a hospital admission (relative risk, 0.68; 95% confidence interval, 0.52-0.89) or a surgery (relative risk, 0.58; 95% confidence interval, 0.41-0.82). In children born after pregnancies with late preterm prelabor rupture of membranes, expectant management did not improve long-term outcomes at 10 to 12 years when compared with induction of labor.

Measurement of cervical length (CL) by transvaginal ultrasound (TVU) is predictive of preterm birth (PTB). It is unclear if this screening test is effective for prevention of PTB. To assess the effectiveness of antenatal management based on TVU CL screening for preventing PTB. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2008), MEDLINE (1966 to September 2008), and reviewed the reference list of all articles. Published and unpublished randomized controlled trials including pregnant women between the gestational ages of 14 to 32 weeks screened with TVU CL for risk of PTB. This review focuses exclusively on studies based on knowledge versus no knowledge of TVU CL results. All potential studies identified as in the search were assessed for inclusion by three independent review authors. We also analyzed studies for quality measures and extracted data. Of 12 trials identified, five were eligible for inclusion (n = 507). Three included singleton gestations with preterm labor (PTL); one included singleton gestations with preterm prelabour rupture of membranes (PPROM); and one included twin gestations without or with PTL.In the three trials of singleton gestations with PTL, 290 women were randomized; 147 to knowledge and 143 to no knowledge of TVU CL. Knowledge of TVU CL results was associated with a non-significant decrease in PTB at less than 37 weeks (22.3% versus 34.7%, respectively; risk ratio 0.59, 95% confidence interval (CI) 0.26 to 1.32). Delivery occurred at a later gestational age in the knowledge versus no knowlege groups (mean difference 0.64 weeks (CI 0.03 to 1.25)). All other outcomes for which there were available data (PTB at less than 34 or 28 weeks; birthweight less than 2500 grams; perinatal death; maternal hospitalization; tocolysis; and steroids for fetal lung maturity) were similar in the two groups.The trial of singleton gestations with PPROM (n = 92) evaluated as its primary outcome safety of TVU CL in this population, and not its effect on management. The incidence of maternal and neonatal infections was similar in the TVU CL and no TVU CL groups.In the trial of twin gestations with or without PTL (n = 125), PTB at less than 36, 34, or 30 weeks, gestational age at delivery, and other perinatal and maternal outcomes were similar in the TVU CL and the no TVU CL groups. Life table analysis revealed significantly less preterm birth at less than 35 weeks in the TVU CL group compared to the no TVU CL group (P = 0.02). Currently there is insufficient evidence to recommend routine screening of asymptomatic or symptomatic pregnant women with TVU CL. Since there is a non-significant association between knowledge of TVU CL results and a lower incidence of PTB at less than 37 weeks in symptomatic women, we encourage further research. Future studies should look at specific populations separately (eg singleton versus twins; symptoms of PTL or no such symptoms), report on all pertinent maternal and perinatal outcomes, and include cost-effectiveness analyses. Most importantly, future studies should include a clear protocol for management of women based on TVU CL results, so that it can be easily evaluated and replicated.

Objective To estimate the effect of speculum examination only versus digital cervical examination on maternal infectious morbidity in women with preterm prelabor rupture of membranes by performing a systematic review and meta-analysis. Materials and methods We explored MEDLINE, Scopus, Embase, CINAHL, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials for studies comparing the rate of a composite maternal infectious morbidity (either chorioamnionitis, endometritis or both) in women with preterm prelabor rupture of membranes that underwent a speculum only versus digital cervical examination at the time of diagnosis. Two reviewers separately ascertained studies, obtained data, and gauged study quality. The rate of a composite maternal infectious morbidity (either chorioamnionitis, endometritis or both) were compared and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Results Four cohort studies, reporting on 1213 women were identified. The median point prevalence of the composite maternal infectious morbidity was 26% (interquartile range 15–35%) in women who had a speculum examination only compared to 33% (interquartile range 22–42%) in women who underwent a digital examination. The overall maternal composite infectious morbidity rate in women that had a speculum examination only was less compared to women that had undergone a digital examination (pooled OR 0.75, 95% CI 0.58–0.98, I 2 17%). The weighted mean length of latency in women with preterm prelabor rupture of membranes was longer in individuals evaluated by speculum only versus digital examination, 6.6 d versus 2.9 d (mean difference 4.5 d, 95% CI 1.4 to 7.8, I 2 99%). Conclusion Speculum examination only in women with preterm prelabor rupture of membranes is associated with less maternal infectious morbidity and longer latency periods.

Preterm prelabour rupture of membranes (PPROM) is a common preterm birth antecedent. Preterm infants experience increased adverse newborn outcome risks. Infection is a risk factor for early birth in PPROM. Current management is antibiotic therapy, antenatal corticosteroids and to plan delivery at 37weeks gestation. The microbiota and probiotics are potentially protective and may improve outcomes. The primary aim is to evaluate whether oral probiotic therapy (Lactobacillus fermentum CECT5716) administered during PPROM between 24 and 34weeks gestation prolongs pregnancy duration. The secondary aim is to evaluate maternal and neonatal outcomes. This is a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial in Australia. The population will be women with a singleton pregnancy and PPROM less than 34weeks gestation. The intervention will be an oral probiotic therapy compared with a placebo control. The primary outcome will be the proportion of women still pregnant at seven days following PPROM. One-to-one randomisation will occur within 24h of PPROM. The trial is powered (80%, alpha=0.05) to detect an absolute percentage increase in the primary outcome of 30%, (from expected rate of 20% up to 50%). This trial will provide evidence for the effectiveness of the probiotic in prolonging pregnancy duration. Findings will inform the feasibility of a larger trial to examine the effect of oral probiotics on clinically important maternal and neonatal outcomes in PPROM.

To assess the neonatal outcome and four-year follow-up of pregnancies complicated by preterm prelabor rupture of membranes (PPROM) before 24 weeks. Retrospective study. University Hospital of Saint Etienne, tertiary level center, France. Obstetric and neonatal records of 38 pregnancies and 44 fetuses born between 1999 and 2004 (six years) with PPROM between 14 and 23 + 6 weeks of gestation were studied. We analyzed spontaneous (group A) and iatrogenic PPROM (Group B) cases, including maternal, fetal, placental, and neonatal characteristics. Surviving infants were followed until the age of four. Median gestational age at PPROM was 21 weeks [range 15-23 + 6]. Of the 38 women with PPROM, 22 (A) had spontaneous PPROM and 16 (B) underwent an invasive procedure during pregnancy. Expectant management was applied to 25 women: 12 (13 fetuses) from group A and 13 (16 fetuses) from group B. Median latency from PPROM to delivery was 35 days [range 1-163 days]. The two groups showed significant differences. The overall survival rate was 59% (17 fetuses) and three babies from group A died in the hospital. Survival rate of infants discharged from hospital was 48% (14/29). Of 14 surviving infants, 71% had a normal neurological and developmental outcome at four years. Only two infants from group A survived without obvious sequelae. Pregnancy after iatrogenic PPROM had a better prognosis than after spontaneous PPROM. Intensive management with corticosteroids and antibiotics appeared to be helpful. Neonatal survival in spontaneous PPROM before 24 weeks remained very poor and discussing pregnancy termination in these cases seems legitimate.

The objective of this study was to evaluate associations between adverse outcomes in twin pregnancies and preterm prelabour rupture of membranes (PPROM). A chart review of 246 consecutive twin pregnancies with confirmed PPROM was conducted. Regression analysis (beta [natural log of the odds ratio] and odds ratio [OR]) was performed to identify independent predictors. Two hundred and forty-six twin pregnancies, 492 liveborns, and 20 neonatal deaths. Mean (SD) PPROM gestational age (GA): 31.3 (3.8) wk; delivery GA: 32.0 (3.3) wk. PPROM < 30 wk was associated with increased parity (OR: 2.66), and log (admission leukocyte count) (OR: 9.99). Shortened latency was associated with PPROM GA (beta = -0.17) and chorioamnionitis (beta = 0.95). Neonatal sepsis was predicted by lower delivery GA (OR: 2.04). Adverse perinatal outcomes were protected against by older GA at PPROM (OR 0.53) and shortened latency (OR 0.73). It was concluded that increased leukocytosis and parity implies an infectious aetiology in earlier PPROM. Increased risk for neonatal sepsis at earlier delivery GA is consistent with gestation-dependent fetal immunocompetence. Early PPROM and long latencies were associated with increased adverse perinatal outcomes.