Vaginal Progesterone to Prevent Spontaneous Preterm Birth in Women With a Sonographic Short Cervix: The Story of the PREGNANT Trial.

The PREGNANT trial was a randomized, placebo-controlled, multicenter trial designed to determine the efficacy and safety of vaginal progesterone (VP) to reduce the risk of birth < 33 weeks and of neonatal complications in women with a sonographic short cervix (10 to 20 mm) in the mid-trimester (19 to 23 6/7 wk). Patients allocated to receive VP had a 45% lower rate of preterm birth (8.9% vs 16.1%; relative risk = 0.55; 95% CI: 0.33-0.92). Neonates born to mothers allocated to VP had a 60% reduction in the rate of respiratory distress syndrome. This article reviews the background, design, execution, interpretation, and impact of the PREGNANT Trial.

Accuracy of prenatal and postnatal biomarkers for estimating gestational age: a systematic review and meta-analysis.

Background: Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small for GA at a population level. Currently, the gold standard for pregnancy dating is measurement of the fetal crown rump length at 11-14 weeks of gestation. However, this is not possible for women first presenting in later pregnancy, or in settings where routine ultrasound is not available. A reliable, cheap and easy to measure GA-dependent biomarker would provide an important breakthrough in estimating the age of pregnancy. Therefore, the aim of this study was to determine the accuracy of prenatal and postnatal biomarkers for estimating gestational age (GA). Methods: Systematic review prospectively registered with PROSPERO (CRD42020167727) and reported in accordance with the PRISMA-DTA. Medline, Embase, CINAHL, LILACS, and other databases were searched from inception until September 2023 for cohort or cross-sectional studies that reported on the accuracy of prenatal and postnatal biomarkers for estimating GA. In addition, we searched Google Scholar and screened proceedings of relevant conferences and reference lists of identified studies and relevant reviews. There were no language or date restrictions. Pooled coefficients of correlation and root mean square error (RMSE, average deviation in weeks between the GA estimated by the biomarker and that estimated by the gold standard method) were calculated. The risk of bias in each included study was also assessed. Findings: Thirty-nine studies fulfilled the inclusion criteria: 20 studies (2,050 women) assessed prenatal biomarkers (placental hormones, metabolomic profiles, proteomics, cell-free RNA transcripts, and exon-level gene expression), and 19 (1,738,652 newborns) assessed postnatal biomarkers (metabolomic profiles, DNA methylation profiles, and fetal haematological components). Among the prenatal biomarkers assessed, human chorionic gonadotrophin measured in maternal serum between 4 and 9 weeks of gestation showed the highest correlation with the reference standard GA, with a pooled coefficient of correlation of 0.88. Among the postnatal biomarkers assessed, metabolomic profiling from newborn blood spots provided the most accurate estimate of GA, with a pooled RMSE of 1.03 weeks across all GAs. It performed best for term infants with a slightly reduced accuracy for preterm or small for GA infants. The pooled RMSEs for metabolomic profiling and DNA methylation profile from cord blood samples were 1.57 and 1.60 weeks, respectively. Interpretation: We identified no antenatal biomarkers that accurately predict GA over a wide window of pregnancy. Postnatally, metabolomic profiling from newborn blood spot provides an accurate estimate of GA, however, as this is known only after birth it is not useful to guide antenatal care. Further prenatal studies are needed to identify biomarkers that can be used in isolation, as part of a biomarker panel, or in combination with other clinical methods to narrow prediction intervals of GA estimation. Funding: The research was funded by the Bill and Melinda Gates Foundation (INV-000368). ATP is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre funding scheme. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, the Department of Health, or the Department of Biotechnology. The funders of this study had no role in study design, data collection, analysis or interpretation of the data, in writing the paper or the decision to submit for publication.

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in twin gestations: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations. DATA SOURCES: MEDLINE, Embase, LILACS, and CINAHL (from their inception to January 31, 2023), Cochrane databases, Google Scholar, bibliographies, and conference proceedings. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a twin gestation. METHODS: The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was preterm birth <34 weeks of gestation. Secondary outcomes included adverse perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in each included study, heterogeneity, publication bias, and quality of evidence, and performed subgroup and sensitivity analyses. RESULTS: Eleven studies (3401 women and 6802 fetuses/infants) fulfilled the inclusion criteria. Among all twin gestations, there were no significant differences between the vaginal progesterone and placebo or no treatment groups in the risk of preterm birth <34 weeks (relative risk, 0.99; 95% confidence interval, 0.84-1.17; high-quality evidence), <37 weeks (relative risk, 0.99; 95% confidence interval, 0.92-1.06; high-quality evidence), and <28 weeks (relative risk, 1.00; 95% confidence interval, 0.64-1.55; moderate-quality evidence), and spontaneous preterm birth <34 weeks of gestation (relative risk, 0.97; 95% confidence interval, 0.80-1.18; high-quality evidence). Vaginal progesterone had no significant effect on any of the perinatal outcomes evaluated. Subgroup analyses showed that there was no evidence of a different effect of vaginal progesterone on preterm birth <34 weeks of gestation related to chorionicity, type of conception, history of spontaneous preterm birth, daily dose of vaginal progesterone, and gestational age at initiation of treatment. The frequencies of preterm birth <37, <34, <32, <30, and <28 weeks of gestation and adverse perinatal outcomes did not significantly differ between the vaginal progesterone and placebo or no treatment groups in unselected twin gestations (8 studies; 3274 women and 6548 fetuses/infants). Among twin gestations with a transvaginal sonographic cervical length <30 mm (6 studies; 306 women and 612 fetuses/infants), vaginal progesterone was associated with a significant decrease in the risk of preterm birth occurring at <28 to <32 gestational weeks (relative risks, 0.48-0.65; moderate- to high-quality evidence), neonatal death (relative risk, 0.32; 95% confidence interval, 0.11-0.92; moderate-quality evidence), and birthweight <1500 g (relative risk, 0.60; 95% confidence interval, 0.39-0.88; high-quality evidence). Vaginal progesterone significantly reduced the risk of preterm birth occurring at <28 to <34 gestational weeks (relative risks, 0.41-0.68), composite neonatal morbidity and mortality (relative risk, 0.59; 95% confidence interval, 0.33-0.98), and birthweight <1500 g (relative risk, 0.55; 95% confidence interval, 0.33-0.94) in twin gestations with a transvaginal sonographic cervical length ≤25 mm (6 studies; 95 women and 190 fetuses/infants). The quality of evidence was moderate for all these outcomes. CONCLUSION: Vaginal progesterone does not prevent preterm birth, nor does it improve perinatal outcomes in unselected twin gestations, but it appears to reduce the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality in twin gestations with a sonographic short cervix. However, more evidence is needed before recommending this intervention to this subset of patients.

Vaginal progesterone for the prevention of preterm birth: who can benefit and who cannot? Evidence-based recommendations for clinical use.

Vaginal progesterone (VP) has been recommended to prevent preterm birth (PTB) in women at high-risk. However, there is controversy as to whether VP is efficacious in some subsets of high-risk women. In this review, we examined the current best evidence on the efficacy of VP to prevent PTB in several subsets of high-risk women and provided recommendations for its clinical use. Compelling evidence indicates that VP reduces the risk of PTB and improves perinatal outcomes in singleton gestations with a short cervix (≤25 mm), both with and without a history of spontaneous PTB. VP appears promising to reduce the risk of PTB in twin gestations with a short cervix (≤25 mm) and in singleton gestations conceived by assisted reproductive technologies, but further research is needed. There is no convincing evidence that supports prescribing VP to prevent PTB in singleton gestations based solely on the history of spontaneous preterm birth. Persuasive evidence shows that VP does not prevent PTB nor does it improve perinatal outcomes in unselected twin gestations and in singleton gestations with a history of spontaneous PTB and a cervical length >25 mm. There is no evidence supporting the use of VP to prevent PTB in triplet or higher-order multifetal gestations, singleton gestations with a positive fetal fibronectin test and clinical risk factors for PTB, and gestations with congenital uterine anomalies or uterine leiomyoma. In conclusion, current evidence indicates that VP should only be recommended in singleton gestations with a short cervix, regardless of the history of spontaneous PTB.

Effectiveness of a novel bubble CPAP system for neonatal respiratory support at a referral hospital in the Philippines.

Aim: To examine the impact of introducing and implementing the Vayu bubble continuous positive airway pressure (bCPAP) system on neonatal survival and neonatal respiratory outcomes in a neonatal intensive care unit (NICU) in the Philippines. Methods: We compared clinical outcomes of 1,024 neonates before to 979 neonates after introduction of Vayu bCPAP systems into a NICU. The primary outcome was survival to discharge. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Analyses were undertaken separately for the entire NICU population and for neonates who received any form of respiratory support. Results: The introduction of the Vayu bCPAP system was associated with (1) significant reductions in intubation (aOR: 0.75; 95% CI: 0.58-0.96) and in the use of nasal intermittent positive-pressure ventilation (NIPPV) (aOR: 0.69; 95% CI: 0.50-0.96) among the entire NICU population and (2) a significant increase in survival to discharge (aOR: 1.53; 95% CI: 1.09-2.17) and significant reductions in intubation (aOR: 0.52; 95% CI: 0.38-0.71), surfactant administration (aOR: 0.60; 95% CI: 0.40-0.89), NIPPV use (aOR: 0.52; 95% CI: 0.36-0.76), and a composite neonatal adverse outcome (aOR: 0.60; 95% CI: 0.42-0.84) among neonates who received any form of respiratory support. Conclusion: The use of the Vayu bCPAP system in a NICU in the Philippines resulted in significant improvement in neonatal respiratory outcomes.

Does vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations with a history of spontaneous preterm birth. DATA SOURCES: MEDLINE, Embase, LILACS, and CINAHL (from their inception to February 28, 2022), Cochrane databases, Google Scholar, bibliographies, and conference proceedings. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a singleton gestation and a history of spontaneous preterm birth. METHODS: The primary outcomes were preterm birth <37 and <34 weeks of gestation. The secondary outcomes included adverse maternal and perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in the included studies, heterogeneity (I2 test), small-study effects, publication bias, and quality of evidence; performed subgroup and sensitivity analyses; and calculated 95% prediction intervals and adjusted relative risks. RESULTS: Ten studies (2958 women) met the inclusion criteria: 7 with a sample size <150 (small studies) and 3 with a sample size >600 (large studies). Among the 7 small studies, 4 were at high risk of bias, 2 were at some concerns of bias, and only 1 was at low risk of bias. All the large studies were at low risk of bias. Vaginal progesterone significantly decreased the risk of preterm birth <37 weeks (relative risk, 0.64; 95% confidence interval, 0.50-0.81; I2=75%; 95% prediction interval, 0.31-1.32; very low-quality evidence) and <34 weeks (relative risk, 0.62; 95% confidence interval, 0.42-0.92; I2=66%; 95% prediction interval, 0.23-1.68; very low-quality evidence), and the risk of admission to the neonatal intensive care unit (relative risk, 0.53; 95% confidence interval, 0.33-0.85; I2=67%; 95% prediction interval, 0.16-1.79; low-quality evidence). There were no significant differences between the vaginal progesterone and the placebo or no treatment groups in other adverse perinatal and maternal outcomes. Subgroup analyses revealed that vaginal progesterone decreased the risk of preterm birth <37 weeks (relative risk, 0.43; 95% confidence interval, 0.33-0.55; I2=0%) and <34 weeks (relative risk, 0.27; 95% confidence interval, 0.15-0.49; I2=0%) in the small but not in the large studies (relative risk, 0.98; 95% confidence interval, 0.88-1.09; I2=0% for preterm birth <37 weeks; and relative risk, 0.94; 95% confidence interval, 0.78-1.13; I2=0% for preterm birth <34 weeks). Sensitivity analyses restricted to studies at low risk of bias indicated that vaginal progesterone did not reduce the risk of preterm birth <37 weeks (relative risk, 0.96; 95% confidence interval, 0.84-1.09) and <34 weeks (relative risk, 0.90; 95% confidence interval, 0.71-1.15). There was clear evidence of substantial small-study effects in the meta-analyses of preterm birth <37 and <34 weeks of gestation because of funnel plot asymmetry and the marked differences in the pooled relative risks obtained from fixed-effect and random-effects models. The adjustment for small-study effects resulted in a markedly reduced and nonsignificant effect of vaginal progesterone on preterm birth <37 weeks (relative risk, 0.86; 95% confidence interval, 0.68-1.10) and <34 weeks (relative risk, 0.92; 95% confidence interval, 0.60-1.42). CONCLUSION: There is no convincing evidence supporting the use of vaginal progesterone to prevent recurrent preterm birth or to improve perinatal outcomes in singleton gestations with a history of spontaneous preterm birth.

Impact of the introduction of a low-cost uterine balloon tamponade (ESM-UBT) device for managing severe postpartum hemorrhage in India: A comparative before-and-after study.

OBJECTIVE: To evaluate the impact of introducing a uterine balloon tamponade (ESM-UBT) device for managing severe postpartum hemorrhage (PPH), mainly due to uterine atony, in health facilities in India on the rates of PPH-related maternal death and invasive procedures for PPH control. METHODS: We used a quasi-experimental, difference-in-difference (DID) design to compare changes in the rates of a composite outcome (PPH-related maternal death and/or artery ligation, uterine compression sutures, or hysterectomy) among women delivering in nine intervention facilities compared with those delivering in two control facilities, before and after the introduction of ESM-UBT. RESULTS: The study sample included 214 123 deliveries (n = 78 509 before ESM-UBT introduction; n = 47 211 during ESM-UBT introduction; and n = 88 403 after ESM-UBT introduction). After introduction of ESM-UBT, there was a significant decline in the rate of the primary composite outcome in intervention facilities (21.0-11.4 per 10 000 deliveries; difference -9.6, 95% confidence interval -14.0 to -5.4). Change in the rate of the primary composite outcome was not significant in control facilities (11.7-17.2 per 10 000 deliveries; difference 5.4, 95% confidence interval -3.9 to 14.9). DID analyses showed there was a significant reduction in the rate of the primary composite outcome in intervention facilities relative to control facilities (adjusted DID estimate -15.0 per 10 000 points, 95% confidence interval -23.3 to -6.8; P = 0.005). CONCLUSION: Introduction of the ESM-UBT in health facilities in India was associated with a significant reduction in PPH-related maternal death and/or invasive procedures for PPH control.

SARS-CoV-2 infection during pregnancy and risk of preeclampsia: a systematic review and meta-analysis.

OBJECTIVE: To examine the relationship between SARS-CoV-2 infection during pregnancy and the risk for preeclampsia. DATA SOURCES: MEDLINE, Embase, POPLINE, CINAHL, LILACS, and the World Health Organization COVID-19, Chinese, and preprint databases (all from December 1, 2019, to May 31, 2021). Google Scholar, bibliographies, and conference proceedings were also searched. STUDY ELIGIBILITY CRITERIA: Observational studies that assessed the association between SARS-CoV-2 infection during pregnancy and preeclampsia and that reported unadjusted and/or adjusted risk estimates and 95% confidence intervals or data to calculate them. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was preeclampsia. Secondary outcomes included preeclampsia with severe features, preeclampsia without severe features, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Two reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled unadjusted and adjusted odds ratios with 95% confidence intervals, and 95% prediction interval were calculated. Heterogeneity was quantified using the І2 statistic, for which І2≥30% indicated substantial heterogeneity. Subgroup and sensitivity analyses were performed to test the robustness of the overall findings. RESULTS: A total of 28 studies comprising 790,954 pregnant women, among which 15,524 were diagnosed with SARS-CoV-2 infection, met the inclusion criteria. The meta-analysis of unadjusted odds ratios showed that the odds of developing preeclampsia were significantly higher among pregnant women with SARS-CoV-2 infection than among those without SARS-CoV-2 infection (7.0% vs 4.8%; pooled odds ratio, 1.62; 95% confidence interval, 1.45-1.82; P<.00001; І2=17%; 26 studies; 95% prediction interval of the odds ratio, 1.28-2.05). The meta-analysis of adjusted odds ratios also showed that SARS-CoV-2 infection during pregnancy was associated with a significant increase in the odds of preeclampsia (pooled odds ratio, 1.58; 95% confidence interval, 1.39-1.80; P<.0001; І2=0%; 11 studies). There was a statistically significant increase in the odds of preeclampsia with severe features (odds ratio, 1.76; 95% confidence interval, 1.18-2.63; І2=58%; 7 studies), eclampsia (odds ratio, 1.97; 95% confidence interval, 1.01-3.84; І2=0%, 3 studies), and HELLP syndrome (odds ratio, 2.10; 95% confidence interval, 1.48-2.97; 1 study) among pregnant women with SARS-CoV-2 infection when compared to those without the infection. Overall, the direction and magnitude of the effect of SARS-CoV-2 infection during pregnancy on preeclampsia was consistent across most prespecified subgroup and sensitivity analyses. Both asymptomatic and symptomatic SARS-CoV-2 infections significantly increased the odds of developing preeclampsial; however, it was higher among patients with symptomatic illness (odds ratio, 2.11; 95% confidence interval, 1.59-2.81) than among those with asymptomatic illness (odds ratio, 1.59; 95% confidence interval, 1.21-2.10). CONCLUSION: SARS-CoV-2 during pregnancy is associated with higher odds of preeclampsia.

Management of clinical chorioamnionitis: an evidence-based approach.

This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an evidence-based contemporary approach for the management of this condition. Most trials that assessed the use of antibiotics in clinical chorioamnionitis included patients with a gestational age of ≥34 weeks and in labor. The first-line antimicrobial regimen for the treatment of clinical chorioamnionitis is ampicillin combined with gentamicin, which should be initiated during the intrapartum period. In the event of a cesarean delivery, patients should receive clindamycin at the time of umbilical cord clamping. The administration of additional antibiotic therapy does not appear to be necessary after vaginal or cesarean delivery. However, if postdelivery antibiotics are prescribed, there is support for the administration of an additional dose. Patients can receive antipyretic agents, mainly acetaminophen, even though there is no clear evidence of their benefits. Current evidence suggests that the administration of antenatal corticosteroids for fetal lung maturation and of magnesium sulfate for fetal neuroprotection to patients with clinical chorioamnionitis between 24 0/7 and 33 6/7 weeks of gestation, and possibly between 23 0/7 and 23 6/7 weeks of gestation, has an overall beneficial effect on the infant. However, delivery should not be delayed to complete the full course of corticosteroids and magnesium sulfate. Once the diagnosis of clinical chorioamnionitis has been established, delivery should be considered, regardless of the gestational age. Vaginal delivery is the safer option and cesarean delivery should be reserved for standard obstetrical indications. The time interval between the diagnosis of clinical chorioamnionitis and delivery is not related to most adverse maternal and neonatal outcomes. Patients may require a higher dose of oxytocin to achieve adequate uterine activity or greater uterine activity to effect a given change in cervical dilation. The benefit of using continuous electronic fetal heart rate monitoring in these patients is unclear. We identified the following promising interventions for the management of clinical chorioamnionitis: (1) an antibiotic regimen including ceftriaxone, clarithromycin, and metronidazole that provides coverage against the most commonly identified microorganisms in patients with clinical chorioamnionitis; (2) vaginal cleansing with antiseptic solutions before cesarean delivery with the aim of decreasing the risk of endometritis and, possibly, postoperative wound infection; and (3) antenatal administration of N-acetylcysteine, an antioxidant and antiinflammatory agent, to reduce neonatal morbidity and mortality. Well-powered randomized controlled trials are needed to assess these interventions in patients with clinical chorioamnionitis.

Cervical pessary to prevent preterm birth in asymptomatic high-risk women: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials that have assessed the efficacy of cervical pessary to prevent preterm birth in asymptomatic high-risk women have reported conflicting results. OBJECTIVE: To evaluate the efficacy and safety of cervical pessary to prevent preterm birth and adverse perinatal outcomes in asymptomatic high-risk women. DATA SOURCES: MEDLINE, EMBASE, POPLINE, CINAHL, and LILACS (from their inception to October 31, 2019), Cochrane databases, Google Scholar, bibliographies, and conference proceedings. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared cervical pessary with standard care (no pessary) or alternative interventions in asymptomatic women at high risk for preterm birth. STUDY APPRAISAL AND SYNTHESIS METHODS: The systematic review was conducted according to the Cochrane Handbook guidelines. The primary outcome was spontaneous preterm birth <34 weeks of gestation. Secondary outcomes included adverse pregnancy, maternal, and perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. Quality of evidence was assessed using the GRADE methodology. RESULTS: Twelve studies (4687 women and 7167 fetuses/infants) met the inclusion criteria: 8 evaluated pessary vs no pessary in women with a short cervix, 2 assessed pessary vs no pessary in unselected multiple gestations, and 2 compared pessary vs vaginal progesterone in women with a short cervix. There were no significant differences between the pessary and no pessary groups in the risk of spontaneous preterm birth <34 weeks of gestation among singleton gestations with a cervical length ≤25 mm (relative risk, 0.80; 95% confidence interval, 0.43-1.49; 6 trials, 1982 women; low-quality evidence), unselected twin gestations (relative risk, 1.05; 95% confidence interval, 0.79-1.41; 1 trial, 1177 women; moderate-quality evidence), twin gestations with a cervical length <38 mm (relative risk, 0.75; 95% confidence interval, 0.41-1.36; 3 trials, 1128 women; low-quality evidence), and twin gestations with a cervical length ≤25 mm (relative risk; 0.72, 95% confidence interval, 0.25-2.06; 2 trials, 348 women; low-quality evidence). Overall, no significant differences were observed between the pessary and no pessary groups in preterm birth <37, <32, and <28 weeks of gestation, and most adverse pregnancy, maternal, and perinatal outcomes (low- to moderate-quality evidence for most outcomes). There were no significant differences in the risk of spontaneous preterm birth <34 weeks of gestation between pessary and vaginal progesterone in singleton gestations with a cervical length ≤25 mm (relative risk, 0.99; 95% confidence interval, 0.54-1.83; 1 trial, 246 women; low-quality evidence) and twin gestations with a cervical length <38 mm (relative risk, 0.73; 95% confidence interval, 0.46-1.18; 1 trial, 297 women; very low-quality evidence). Vaginal discharge was significantly more frequent in the pessary group than in the no pessary and vaginal progesterone groups (relative risks, ∼2.20; high-quality evidence). CONCLUSION: Current evidence does not support the use of cervical pessary to prevent preterm birth or to improve perinatal outcomes in singleton or twin gestations with a short cervix and in unselected twin gestations.

Uterine balloon tamponade for the treatment of postpartum hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy, effectiveness, and safety of uterine balloon tamponade for treating postpartum hemorrhage. STUDY DESIGN: We searched electronic databases (from their inception to August 2019) and bibliographies. We included randomized controlled trials, nonrandomized studies, and case series that reported on the efficacy, effectiveness, and/or safety of uterine balloon tamponade in women with postpartum hemorrhage. The primary outcome was the success rate of uterine balloon tamponade for treating postpartum hemorrhage (number of uterine balloon tamponade success cases/total number of women treated with uterine balloon tamponade). For meta-analyses, we calculated pooled success rate for all studies, and relative risk with 95% confidence intervals for studies that included a comparative arm. RESULTS: Ninety-one studies, including 4729 women, met inclusion criteria (6 randomized trials, 1 cluster randomized trial, 15 nonrandomized studies, and 69 case series). The overall pooled uterine balloon tamponade success rate was 85.9% (95% confidence interval, 83.9-87.9%). The highest success rates corresponded to uterine atony (87.1%) and placenta previa (86.8%), and the lowest to placenta accreta spectrum (66.7%) and retained products of conception (76.8%). The uterine balloon tamponade success rate was lower in cesarean deliveries (81.7%) than in vaginal deliveries (87.0%). A meta-analysis of 2 randomized trials that compared uterine balloon tamponade vs no uterine balloon tamponade in postpartum hemorrhage due to uterine atony after vaginal delivery showed no significant differences between the study groups in the risk of surgical interventions or maternal death (relative risk, 0.59; 95% confidence interval, 0.02-16.69). A meta-analysis of 2 nonrandomized before-and-after studies showed that introduction of uterine balloon tamponade in protocols for managing severe postpartum hemorrhage significantly decreased the use of arterial embolization (relative risk, 0.29; 95% confidence interval, 0.14-0.63). A nonrandomized cluster study reported that use of invasive procedures was significantly lower in the perinatal network that routinely used uterine balloon tamponade than that which did not use uterine balloon tamponade (3.0/1000 vs 5.1/1000; P < .01). A cluster randomized trial reported that the frequency of postpartum hemorrhage-related invasive procedures and/or maternal death was significantly higher after uterine balloon tamponade introduction than before uterine balloon tamponade introduction (11.6/10,000 vs 6.7/10,000; P = .04). Overall, the frequency of complications attributed to uterine balloon tamponade use was low (≤6.5%). CONCLUSION: Uterine balloon tamponade has a high success rate for treating severe postpartum hemorrhage and appears to be safe. The evidence on uterine balloon tamponade efficacy and effectiveness from randomized and nonrandomized studies is conflicting, with experimental studies suggesting no beneficial effect, in contrast with observational studies. Further research is needed to determine the most effective programmatic and healthcare delivery strategies on uterine balloon tamponade introduction and use.

Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.

BACKGROUND: Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome. OBJECTIVE: To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation. STUDY DESIGN: The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm3) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation. RESULTS: Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases. CONCLUSION: In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.

Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes.

BACKGROUND: Intra-amniotic infection is present in 10% of patients with an episode of preterm labor, and is a risk factor for impending preterm delivery and neonatal morbidity/mortality. Intra-amniotic inflammation is often associated with intra-amniotic infection, but is sometimes present in the absence of detectable microorganisms. Antibiotic treatment of intra-amniotic infection has traditionally been considered to be ineffective. Intra-amniotic inflammation without microorganisms has a prognosis similar to that of intra-amniotic infection. OBJECTIVE: To determine whether antibiotics can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. MATERIALS AND METHODS: The study population consisted of women who met the following criteria: 1) singleton gestation between 20 and 34 weeks; 2) preterm labor and intact membranes; 3) transabdominal amniocentesis performed for the evaluation of the microbiologic/inflammatory status of the amniotic cavity; 4) intra-amniotic infection and/or intra-amniotic inflammation; and 5) received antibiotic treatment that consisted of ceftriaxone, clarithromycin, and metronidazole. Follow-up amniocentesis was performed in a subset of patients. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed for Ureaplasma spp. Intra-amniotic infection was defined as a positive amniotic fluid culture or positive polymerase chain reaction, and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count or a positive result of a rapid test for matrix metalloproteinase-8. For this study, the final diagnosis of intra-amniotic inflammation was made by measuring the interleukin-6 concentration in stored amniotic fluid (>2.6 ng/mL). These results were not available to managing clinicians. Treatment success was defined as eradication of intra-amniotic infection and/or intra-amniotic inflammation or delivery ≥37 weeks. RESULTS: Of 62 patients with intra-amniotic infection and/or intra-amniotic inflammation, 50 received the antibiotic regimen. Of those patients, 29 were undelivered for ≥7 days and 19 underwent a follow-up amniocentesis. Microorganisms were identified by culture or polymerase chain reaction of amniotic fluid obtained at admission in 21% of patients (4/19) who had a follow-up amniocentesis, and were eradicated in 3 of the 4 patients. Resolution of intra-amniotic infection/inflammation was confirmed in 79% of patients (15/19), and 1 other patient delivered at term, although resolution of intra-amniotic inflammation could not be confirmed after a follow-up amniocentesis. Thus, resolution of intra-amniotic inflammation/infection or term delivery (treatment success) occurred in 84% of patients (16/19) who had a follow-up amniocentesis. Treatment success occurred in 32% of patients (16/50) with intra-amniotic infection/inflammation who received antibiotics. The median amniocentesis-to-delivery interval was significantly longer among women who received the combination of antibiotics than among those who did not (11.4 days vs 3.1 days: P = .04). CONCLUSION: Eradication of intra-amniotic infection/inflammation after treatment with antibiotics was confirmed in 79% of patients with preterm labor, intact membranes, and intra-amniotic infection/inflammation who had a follow-up amniocentesis. Treatment success occurred in 84% of patients who underwent a follow-up amniocentesis and in 32% of women who received the antibiotic regimen.