Single-balloon catheter with concomitant vaginal misoprostol is the most effective strategy for labor induction: a meta-review with network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have been conducted to summarize the evidence for the efficacy of various labor induction agents. However, the most effective agents or strategies have not been conclusively determined. We aimed to perform a meta-review and network meta-analysis of published systematic reviews to determine the efficacy and safety of currently employed pharmacologic, mechanical, and combined methods of labor induction. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using PubMed, EMBASE, and the Cochrane Central Register of Control Trials. We systematically searched electronic databases from inception to May 31, 2021. STUDY ELIGIBILITY CRITERIA: We considered systematic reviews and meta-analyses of randomized controlled trials comparing different agents or methods for inpatient labor induction. METHODS: We conducted a frequentist random-effects network meta-analysis employing data from randomized controlled trials of published systematic reviews. We performed direct pairwise meta-analyses to compare the efficacy of the various labor induction agents and placebo or no treatment. We performed ranking to determine the best treatment using the surface under the cumulative ranking curve. The main outcomes assessed were cesarean delivery, vaginal delivery within 24 hours, operative vaginal delivery, hyperstimulation, neonatal intensive care unit admissions, and Apgar scores of <7 at 5 minutes of birth. RESULTS: We included 11 systematic reviews and extracted data from 207 randomized controlled trials with a total of 40,854 participants. When assessing the efficacy of all agents and methods, the combination of a single-balloon catheter with misoprostol was the most effective in reducing the odds of cesarean delivery and vaginal birth >24 hours (surface under the cumulative ranking curve of 0.9 for each). Among the pharmacologic agents, low-dose vaginal misoprostol was the most effective in reducing the odds of cesarean delivery, whereas high-dose vaginal misoprostol was the most effective in achieving vaginal delivery within 24 hours (surface under the cumulative ranking curve of 0.9 for each). Single-balloon catheter (surface under the cumulative ranking curve of 0.8) and double-balloon catheter (surface under the cumulative ranking curve of 0.9) were the most effective in reducing the odds of operative vaginal delivery and hyperstimulation. Buccal or sublingual misoprostol (surface under the cumulative ranking curve of 0.9) and the combination of single-balloon catheter and misoprostol (surface under the cumulative ranking curve of 0.9) most effectively reduced the odds of abnormal Apgar scores and neonatal intensive care unit admissions. CONCLUSION: The combination of a single-balloon catheter with misoprostol was the most effective method in reducing the odds for cesarean delivery and prolonged time to vaginal delivery. This method was associated with a reduction in admissions to the neonatal intensive care unit.

Outpatient cervical ripening and labor induction with low-dose vaginal misoprostol reduces the interval to delivery: a systematic review and network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020. STUDY ELIGIBILITY CRITERIA: We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening. METHODS: We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation. RESULTS: We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 µg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9). CONCLUSION: When balancing efficacy and safety, vaginal misoprostol 25 µg represents the best method for outpatient cervical ripening.

Methods for the induction of labor: efficacy and safety.

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 µg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.

Water birth: a systematic review and meta-analysis of maternal and neonatal outcomes.

OBJECTIVE: This systematic review and meta-analysis aimed to conduct a thorough and contemporary assessment of maternal and neonatal outcomes associated with water birth in comparison with land-based birth. DATA SOURCES: We conducted a comprehensive search of PubMed, EMBASE, CINAHL, and gray literature sources, from inception to February 28, 2023. STUDY ELIGIBILITY CRITERIA: We included randomized and nonrandomized studies that assessed maternal and neonatal outcomes in patients who delivered either conventionally or while submerged in water. METHODS: Pooled unadjusted odds ratios with 95% confidence intervals were calculated using a random-effects model (restricted maximum likelihood method). We assessed the 95% prediction intervals to estimate the likely range of future study results. To evaluate the robustness of the results, we calculated fragility indices. Maternal infection was designated as the primary outcome, whereas postpartum hemorrhage, perineal lacerations, obstetrical anal sphincter injury, umbilical cord avulsion, low Apgar scores, neonatal aspiration requiring resuscitation, neonatal infection, neonatal mortality within 30 days of birth, and neonatal intensive care unit admission were considered secondary outcomes. RESULTS: Of the 20,642 articles identified, 52 were included in the meta-analyses. Based on data from observational studies, water birth was not associated with increased probability of maternal infection compared with land birth (10 articles, 113,395 pregnancies; odds ratio, 0.93; 95% confidence interval, 0.76-1.14). Patients undergoing water birth had decreased odds of postpartum hemorrhage (21 articles, 149,732 pregnancies; odds ratio, 0.80; 95% confidence interval, 0.68-0.94). Neonates delivered while submerged in water had increased odds of cord avulsion (10 articles, 91,504 pregnancies; odds ratio, 1.75; 95% confidence interval, 1.38-2.24) and decreased odds of low Apgar scores (21 articles, 165,917 pregnancies; odds ratio, 0.69; 95% confidence interval, 0.58-0.82), neonatal infection (15 articles, 53,635 pregnancies; odds ratio, 0.64; 95% confidence interval, 0.42-0.97), neonatal aspiration requiring resuscitation (19 articles, 181,001 pregnancies; odds ratio, 0.60; 95% confidence interval, 0.43-0.84), and neonatal intensive care unit admission (30 articles, 287,698 pregnancies; odds ratio, 0.56; 95% confidence interval, 0.45-0.70). CONCLUSION: When compared with land birth, water birth does not appear to increase the risk of most maternal and neonatal complications. Like any other delivery method, water birth has its unique considerations and potential risks, which health care providers and expectant parents should evaluate thoroughly. However, with proper precautions in place, water birth can be a reasonable choice for mothers and newborns, in facilities equipped to conduct water births safely.

Exploring the Limits of Artificial Intelligence for Referencing Scientific Articles.

OBJECTIVE: To evaluate the reliability of three artificial intelligence (AI) chatbots (ChatGPT, Google Bard, and Chatsonic) in generating accurate references from existing obstetric literature. STUDY DESIGN: Between mid-March and late April 2023, ChatGPT, Google Bard, and Chatsonic were prompted to provide references for specific obstetrical randomized controlled trials (RCTs) published in 2020. RCTs were considered for inclusion if they were mentioned in a previous article that primarily evaluated RCTs published by the top medical and obstetrics and gynecology journals with the highest impact factors in 2020 as well as RCTs published in a new journal focused on publishing obstetric RCTs. The selection of the three AI models was based on their popularity, performance in natural language processing, and public availability. Data collection involved prompting the AI chatbots to provide references according to a standardized protocol. The primary evaluation metric was the accuracy of each AI model in correctly citing references, including authors, publication title, journal name, and digital object identifier (DOI). Statistical analysis was performed using a permutation test to compare the performance of the AI models. RESULTS: Among the 44 RCTs analyzed, Google Bard demonstrated the highest accuracy, correctly citing 13.6% of the requested RCTs, whereas ChatGPT and Chatsonic exhibited lower accuracy rates of 2.4 and 0%, respectively. Google Bard often substantially outperformed Chatsonic and ChatGPT in correctly citing the studied reference components. The majority of references from all AI models studied were noted to provide DOIs for unrelated studies or DOIs that do not exist. CONCLUSION: To ensure the reliability of scientific information being disseminated, authors must exercise caution when utilizing AI for scientific writing and literature search. However, despite their limitations, collaborative partnerships between AI systems and researchers have the potential to drive synergistic advancements, leading to improved patient care and outcomes. KEY POINTS: · AI chatbots often cite scientific articles incorrectly.. · AI chatbots can create false references.. · Responsible AI use in research is vital..

Intrapartum amnioinfusion reduces meconium aspiration syndrome and improves neonatal outcomes in patients with meconium-stained fluid: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to reassess the effect of prophylactic transcervical amnioinfusion for intrapartum meconium-stained amniotic fluid on meconium aspiration syndrome and other adverse neonatal and maternal outcomes. DATA SOURCES: From inception to November 2021, a systematic search of the literature was performed in PubMed, Embase, Web of Science, and Scopus databases and gray literature sources. STUDY ELIGIBILITY CRITERIA: We identified randomized controlled trials of patients with intrapartum moderate to thick meconium-stained amniotic fluid that evaluated the effect of amnioinfusion on adverse neonatal and maternal outcomes. METHODS: Of note, 2 reviewers independently abstracted data and gauged study quality by assigning a modified Jadad score. Meconium aspiration syndrome constituted the primary outcome. The secondary outcomes were meconium below the cords, Apgar scores of <7 at 5 minutes, neonatal acidosis, cesarean delivery, cesarean delivery for fetal heart rate abnormalities, neonatal intensive care unit admission, and postpartum endometritis. This study calculated the odds ratios with 95% confidence intervals for categorical outcomes and weighted mean differences with 95% confidence intervals for continuous outcomes. RESULTS: A total of 24 randomized studies with 5994 participants met the inclusion criteria. The overall odds of meconium aspiration syndrome was reduced by 67% in the amnioinfusion group (pooled odds ratio, 0.33; 95% confidence interval, 0.21-0.51). Except for postpartum endometritis, amnioinfusion was associated with a significant reduction in all secondary outcomes. CONCLUSION: Our study found that the use of intrapartum amnioinfusion in the setting of meconium-stained amniotic fluid significantly reduces the odds of meconium aspiration syndrome and other adverse neonatal outcomes.

Assessing the robustness of results from clinical trials and meta-analyses with the fragility index.

The fragility index has been increasingly used to assess the robustness of the results of clinical trials since 2014. It aims at finding the smallest number of event changes that could alter originally statistically significant results. Despite its popularity, some researchers have expressed several concerns about the validity and usefulness of the fragility index. It offers a comprehensive review of the fragility index's rationale, calculation, software, and interpretation, with emphasis on application to studies in obstetrics and gynecology. This article presents the fragility index in the settings of individual clinical trials, standard pairwise meta-analyses, and network meta-analyses. Moreover, this article provides worked examples to demonstrate how the fragility index can be appropriately calculated and interpreted. In addition, the limitations of the traditional fragility index and some solutions proposed in the literature to address these limitations were reviewed. In summary, the fragility index is recommended to be used as a supplemental measure in the reporting of clinical trials and a tool to communicate the robustness of trial results to clinicians. Other considerations that can aid in the fragility index's interpretation include the loss to follow-up and the likelihood of data modifications that achieve the loss of statistical significance.

A Low 50-gram, 1-hour Glucose Challenge Test Value Predicts Neonatal Birth Weight Less than the 10th Percentile: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to perform a systematic review with meta-analysis to investigate if women with a low 50-g, 1-hour glucose challenge test (GCT) value are at risk for having neonates with a birth weight less than the 10th percentile. STUDY DESIGN: A computerized literature search was conducted to identify studies that compared outcomes of pregnant women with a low GCT value versus women with a normal GCT value during routine screening for gestational diabetes. RESULTS: Sixteen cohort studies were included for analysis. Women with a low GCT value were noted to have a 43% increased odds of having neonates with birth weight less than the 10th percentile (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.28-1.60) and 30% increased odds of having neonates with a birth weight less than 2,500 g (OR: 1.3; 95% CI: 1.0-1.7) when compared with women with a normal GCT value. The rates of preterm delivery, neonatal intensive care unit (NICU) admission, pregnancy-induced hypertension (PIH)/preeclampsia, respiratory distress, NICU, and Apgar scores less than 7 were similar in the two groups. CONCLUSION: A low GCT value defined as less than 90 mg/dL identifies pregnancies at elevated risk for having neonates with a birth weight less than the 10th percentile.

Povidone-iodine 1% is the most effective vaginal antiseptic for preventing post-cesarean endometritis: a systematic review and network meta-analysis.

BACKGROUND: Direct comparison metaanalyses have reported benefits with presurgical vaginal preparation before cesarean delivery for the reduction of endometritis. These reports did not perform a multitreatment comparison of the various antiseptic solutions assessed in previous studies. OBJECTIVE: The purpose of this study was to review the literature systematically and quantitate and summarize indirectly the comparative efficacy of antiseptic formulations and their concentrations that are used for the preparation of the vagina before cesarean delivery in the prevention of endometritis and other infectious complications. STUDY DESIGN: We used MEDLINE, EMBASE (from their inception to November 2018) and Cochrane databases, biographies, and conference proceedings. We used randomized clinical trials of patients who underwent surgical preparation of the vagina with antiseptic formulations before cesarean delivery with the aim of reducing the risk of infectious morbidity. Our systematic review was registered and followed the Preferred Reporting Items for Systematic Review and Meta-analysis Extension for network meta-analysis guidelines. Network meta-analysis was performed with computerized software and used user-written programs to assess consistency, inconsistency, ranking probabilities, and graphing results. Direct and indirect pairwise comparisons of the various formulations and their concentrations were performed with the use of multivariate random-effects models and metaregression. A frequentist inference method was employed for the fitted model to estimate the ranking probabilities. Subgroup analyses for patients in labor, not in labor, and with ruptured membranes were conducted. RESULTS: For the prevention of endometritis, we identified 23 studies that comprised 7097 women who were allocated to the following treatments: povidone-iodine (1%, 5%, 10%), chlorhexidine (0.2%, 0.4%), metronidazole gel, cetrimide, or normal saline solution/no treatment. Direct and indirect pairwise comparisons indicated that, when compared with saline solution or no treatment, all antiseptic formulations decreased rates of endometritis (5.2% vs 9.1%; odds ratio, 0.48; 95% confidence interval, 0.35-0.65; 22 studies/6994 women). Individually, povidone-iodine (odds ratio, 0.43; 95% confidence interval, 0.28-0.64; 16 studies/5968 women), cetrimide (odds ratio, 0.34; 95% confidence interval, 0.13-0.90; 1 study/200 women), and metronidazole (odds ratio, 0.38; 95% confidence interval, 0.16-0.90; 1 study/224 women) significantly reduced the risk of endometritis. Rankings of vaginal preparations indicated that povidone-iodine 1% had the highest probability (72.7%) of being the most effective treatment for the prevention of endometritis. For the secondary outcomes of postoperative wound infection and fever, a significant reduction was found only with povidone-iodine (odds ratio, 0.61; 95% confidence interval, 0.48-0.78; 16 studies/5968 women; and odds ratio, 0.58; 95% confidence interval, 0.40-0.83; 12 studies/4667 women). Subgroup analyses also found that povidone-iodine significantly reduced risk of endometritis for women in labor (odds ratio, 0.42; 95% confidence interval, 0.20-0.88; 5 studies/1211 women), with ruptured membranes(odds ratio, 0.21; 95% confidence interval, 0.10-0.44; 4 studies/476 women), and undergoing planned cesarean delivery (odds ratio, 0.39; 95% confidence interval, 0.27-0.57; 8 studies/1825 women). CONCLUSION: Among patients who underwent cesarean delivery, presurgical vaginal irrigation with povidone-iodine had the highest probability of reducing the risk of endometritis, postoperative wound infections, and fever.

Single abnormal value on 3-hour oral glucose tolerance test during pregnancy is associated with adverse maternal and neonatal outcomes: a systematic review and metaanalysis.

OBJECTIVE DATA: The purpose of this study was to determine whether women with 1 abnormal value on 3-hour 100-g oral glucose tolerance test are at an increased risk for adverse pregnancy outcomes. STUDY: Gestational diabetes mellitus is diagnosed by a 2-step method, with a 3-hour, 100-g oral glucose tolerance test that is reserved for women with an abnormal 1-hour, 50-g glucose challenge test. Although the increased maternal-fetal morbidity with gestational diabetes mellitus is well established, controversy remains about the risk that is associated with an isolated abnormal value during a 3-hour, 100-g oral glucose tolerance test. STUDY APPRAISAL AND SYNTHESIS METHODS: Prospective and retrospective studies that evaluated the maternal and perinatal impact of 1 abnormal glucose value during a 3-hour, 100-g oral glucose tolerance test were identified with the use of computerized databases. Data were extracted and quantitative analyses were performed. RESULTS: Twenty-five studies (7 prospective and 18 retrospective) that met criteria for metaanalysis included 4466 women with 1 abnormal glucose value on oral glucose tolerance test. Patients with 1 abnormal glucose value had significantly worse pregnancy outcomes compared with women with zero abnormal values with the following pooled odds ratios: macrosomia, 1.59 (95% confidence interval, 1.16-2.19); large for gestational age, 1.38 (95% confidence interval, 1.09-1.76); increased mean birthweight, 44.5 g (95% confidence interval, 8.10-80.80 g); neonatal hypoglycemia, 1.88 (95% confidence interval, 1.05-3.38); total cesarean delivery, 1.69 (95% confidence interval, 1.40-2.05); pregnancy-induced hypertension, 1.55 (95% confidence interval, 1.31-1.83), and Apgar score of <7 at 5 minutes, 6.10 (95% confidence interval, 2.65-14.02). There was also an increase in neonatal intensive care unit admission and respiratory distress syndrome. Similar results were seen that compared 1 abnormal glucose value to a population with a normal 1-hour 50-g glucose challenge test (normal glucose screen). With the exception of birthweight, outcomes of patients with 1 abnormal glucose value were similar to outcomes of patients with gestational diabetes mellitus. CONCLUSION: Women with 1 abnormal value on 3-hour, 100-g oral glucose tolerance test have a significantly increased risk for poor outcomes comparable with women who have gestational diabetes mellitus.

Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis.

OBJECTIVE: The purpose of this study was to provide an updated summary of the literature regarding the effects of tocolysis with indomethacin on neonatal outcome by systematically reviewing previously and recently reported data. STUDY DESIGN: All previously reported studies pertaining to indomethacin tocolysis and neonatal outcomes along with recently reported data were identified with the use of electronic databases that had been supplemented with references that were cited in original studies and review articles. Observational studies that compared neonatal outcomes among preterm infants who were exposed and not exposed to indomethacin were included in this systematic review. Data were extracted and quantitative analyses were performed on those studies that assessed the neonatal outcomes of patients that received antenatal tocolysis with indomethacin. RESULTS: Twenty-seven observational studies that met criteria for systematic review and metaanalysis were identified. These studies included 8454 infants, of whom 1731 were exposed to antenatal indomethacin and 6723 were not exposed. Relative risks with 95% confidence intervals were calculated for dichotomous outcomes with the use of random and fixed-effects models. Metaanalysis revealed no statistically significant differences in the rates of respiratory distress syndrome, patent ductus arteriosus, neonatal mortality rate, neonatal sepsis, bronchopulmonary dysplasia, or intraventricular hemorrhage (all grades). However, antenatal exposure to indomethacin was associated with an increased risk of severe intraventricular hemorrhage (grade III-IV based on Papile's criteria; relative risk, 1.29; 95% confidence interval, 1.06-1.56), necrotizing enterocolitis (relative risk, 1.36; 95% confidence interval, 1.08-1.71), and periventricular leukomalacia (relative risk, 1.59; 95% confidence interval, 1.17-2.17). CONCLUSION: The use of indomethacin as a tocolytic agent for preterm labor is associated with an increased risk for severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia.