Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Assessing the Clinical Significance of Third-Trimester Post-Coital Bleeding.

INTRODUCTION: This study aimed to evaluate the impact of third-trimester post-coital bleeding (PCB) on pregnancy outcomes. METHODS: A retrospective cohort study was conducted at two tertiary medical centers, including all pregnant women between 24 and 34 weeks of gestation referred due to vaginal bleeding over an 11-year period. The study population includes all singleton deliveries; within this population, women were further classified into three groups: those admitted due to vaginal bleeding related to PCB, those admitted due to vaginal bleeding not related to PCB, and those who did not report vaginal bleeding. The primary outcome measure was delivery prior to 37 weeks of gestation, while secondary outcome measures included maternal and neonatal complications. Baseline characteristics of the two groups were compared. RESULTS: During the study period, there were a total of 51,698 deliveries. Among these, 230 cases involved bleeding between 24 and 34 weeks of gestation, 34 (14.8%) were identified as PCB, and 196 as bleeding unrelated to intercourse. In addition, 51,468 pregnancies without bleeding were analyzed as the general population for comparison. The incidence of preterm labor before 37 weeks of gestation was notably higher in both women with PCB (14.7%) and those with bleeding unrelated to coitus (20.9%) compared to the general population (5.6%); however, there was no statistically significant difference between the two bleeding groups (p = 0.403) while both were significantly different from the general population (p < 0.001). The odds ratio for preterm birth before 37 weeks of gestation after PCB was 3.29 (95% CI: 1.26-8.56, p = 0.0149). There were no significant differences between the PCB and bleeding unrelated to intercourse groups in terms of maternal and neonatal complications. CONCLUSION: This study found that third-trimester PCB is a risk factor for preterm delivery, with rates similar to other causes of third-trimester bleeding but significantly higher than the general population without bleeding. These findings challenge the assumption that PCB is benign.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose.

BACKGROUND: Post-COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti-SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients. STUDY DESIGN: Serum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction-confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction-confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction-confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti-SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes. RESULTS: A total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy. CONCLUSION: Postinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

Birthweight difference between deliveries and the risk of obstetric anal sphincter injury in parous women.

INTRODUCTION AND HYPOTHESIS: While obstetric anal sphincter injury (OASI) is less frequent in parous compared to nulliparous women, it remains a major concern affecting quality of life of women worldwide. The aim of this study was to evaluate the association between birthweight (BW) difference between deliveries and risk of OASI in parous women. METHODS: We performed a retrospective case-control study including parous women with at least one previous vaginal delivery who were diagnosed with OASI. The control group consisted of parous women who did not have OASI during vaginal delivery. Controls were matched in a 1:2 ratio by year of birth, maternal age, and parity. Medical history, obstetric background, and current labor-related data were compared. Further univariate and multivariable analyses were performed, assessing for risk factors for OASI. RESULTS: One hundred eight parous women who had a diagnosis of OASI and a control group of 216 parturients who delivered without OASI were included in the final analysis. Differences between the current BW and the preceding and maximal previous BW were evaluated. There were significantly higher rates of women who had a larger neonate with > 500 g difference between the current and previous BW in the OASI group than in those with no OASI (28.7% vs. 12.30%, respectively; p < 0.001). Following a multivariable analysis for the dependent parameter of OASI, the following parameters were found to be independently associated with OASI outcome: previous operative vaginal delivery, BW ≥ 90th percentile, and current BW ≥ 500 g compared to previous maximal BW. CONCLUSIONS: In parous women, neonatal BW increase between deliveries of > 500 g is associated with OASI.

Uterine rupture risk in a trial of labor after cesarean section with and without previous vaginal births.

PURPOSE: Previous cesarean delivery (CD) is the main risk factor for uterine rupture when attempting a trial of labor. Previous vaginal delivery (PVD) is a predictor for the trial of labor after cesarean (TOLAC) success and a protective factor against uterine rupture. We aimed to assess the magnitude of PVD as a protective factor from uterine rupture. METHODS: A retrospective cohort study was conducted, including women who underwent TOLACs from 2003 to 2015. Women with and without PVD were compared. Inclusion criteria were one previous CD, trial of labor at ≥ 24 weeks' gestation, and cephalic presentation. We excluded pre-labor intrauterine fetal death and fetal anomalies. The primary outcome was a uterine rupture. Secondary outcomes were maternal and fetal complications. Logistic regression modeling was applied to analyze the association between PVD and uterine rupture while controlling for confounders. RESULTS: A total of 11,235 women were included, 6795 of which had a PVD. Women with PVD had significantly lower rates of uterine rupture (0.18% vs. 1.1%; OR 0.19, p < 0.001), were less likely to be delivered by an emergency CD (13.2% vs. 39.4%, OR 0.17, p < 0.0001), were more likely to undergo labor induction (OR 1.56, p < 0.0001), and were less likely to undergo an instrumental delivery (OR 0.14, p < 0.001). Logistic regression modeling revealed that PVD was the only independent protective factor, with an aOR of 0.22. CONCLUSION: PVD is the most important protective factor from uterine rupture in patients undergoing TOLAC. A trial of labor following one CD should therefore be encouraged in these patients.

Normal labor curve in twin gestation.

BACKGROUND: Failure to progress is one of the leading indications for cesarean delivery in trials of labor in twin gestations. However, assessment of labor progression in twin labors is managed according to singleton labor curves. OBJECTIVE: This study aimed to establish a partogram for twin deliveries that reflects normal and abnormal labor progression and customized labor curves for different subgroups of twin labors. STUDY DESIGN: This was a multicenter, retrospective cohort analysis of twin deliveries that were recorded in 3 tertiary medical centers between 2003 and 2017. Eligible parturients were those with twin gestations at ≥34 weeks' gestation with cephalic presentation of the presenting twin and ≥2 cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, major fetal anomalies, and fetal demise. The study group comprised twin gestations, whereas singleton gestations comprised the control group. Statistical analysis was performed using Python 3.7.3 and SPSS, version 27. Categorical variables were analyzed using chi-square tests. Student t test and Mann-Whitney U test were applied to analyze the differences in continuous variables, as appropriate. RESULTS: A total of 1375 twin deliveries and 142,659 singleton deliveries met the inclusion criteria. Duration of the active phase of labor was significantly longer in twin labors than in singleton labors in both nulliparous and multiparous parturients; the 95th percentile duration was 2 hours longer in nulliparous twin labors and >3.5 hours longer in multiparous twin labors than in singleton labors. The cervical dilation progression rate was significantly slower in twin deliveries than in singleton deliveries with a mean rate in twin deliveries of 1.89 cm/h (95th percentile, 0.51 cm/h) and a mean rate of 2.48 cm/h (95th percentile, 0.73 cm/h) in singleton deliveries (P<.001). In addition, epidural use further slowed labor progression in twin deliveries. The second stage of labor was also markedly longer in twin deliveries, both in nulliparous and multiparous women (95th percentile, 3.04 vs 2.83 hours, P=.002). CONCLUSION: Twin labors are characterized by a slower progression of the active phase and second stage of labor compared with singleton labors in nulliparous and multiparous parturients. Epidural analgesia further slows labor progression in twin labors. Implementation of these findings in clinical management might lower cesarean delivery rates among cases with protracted labor in twin gestations.

Urinary bladder injury during cesarean delivery: risk factors and the role of retrograde bladder filling.

INTRODUCTION AND HYPOTHESIS: Urinary bladder injury during cesarean delivery is an uncommon complication with substantial maternal morbidity. The aim of this study was to identify possible risk factors for bladder injury during cesarean delivery and to describe the role of retrograde bladder filling in the assessment of bladder wall integrity. METHODS: A retrospective cohort study at a large tertiary referral center. Women who underwent cesarean delivery between 2003 and 2017 were included. Women diagnosed with urinary bladder injury were compared to women who did not have such injuries. Data retrieved included demographic characteristics, general medical history, obstetric history and intra-partum and intra-operative data. Information regarding use of retrograde bladder filling intra-operatively was retrieved as well. RESULTS: During the study period, 21,177 cesarean deliveries were performed of which 68 (0.3%) cases of urinary bladder injury were identified. Two-thirds of injuries were located at the urinary bladder dome with the remaining third located at the posterior bladder wall. Most injuries were formed during uterine incision extension (60.0%) followed by peritoneal entry (22.0%). Following uni- and multivariate analyses, three parameters remained independent risk factors for bladder injury: urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of the uterine incision extension. In 15.4% of cases in which retrograde bladder filling was utilized following bladder repair, leakage of fluid was evident. CONCLUSION: Urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of uterine incision extension are independent risk factors for urinary bladder injury during cesarean delivery.

Prediction model for obstetric anal sphincter injury using machine learning.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) is a complication with substantial maternal morbidity. The aim of this study was to develop a machine learning model that would allow a personalized prediction algorithm for OASI, based on maternal and fetal variables collected at admission to labor. MATERIALS AND METHODS: We performed a retrospective cohort study at a tertiary university hospital. Included were term deliveries (live, singleton, vertex). A comparison was made between women diagnosed with OASI and those without such injury. For formation of a machine learning-based model, a gradient boosting machine learning algorithm was implemented. Evaluation of the performance model was achieved using the area under the receiver-operating characteristic curve (AUC). RESULTS: Our cohort comprised 98,463 deliveries, of which 323 (0.3%) were diagnosed with OASI. Applying a machine learning model to data recorded during admission to labor allowed for individualized risk assessment with an AUC of 0.756 (95% CI 0.732-0.780). According to this model, a lower number of previous births, fewer pregnancies, decreased maternal weight and advanced gestational week elevated the risk for OASI. With regard to parity, women with one previous delivery had approximately 1/3 of the risk for OASI compared to nulliparous women (OR = 0.3 (0.23-0.39), p < 0.001), and women with two previous deliveries had 1/3 of the risk compared to women with one previous delivery (OR = 0.35 (0.21-0.60), p < 0.001). CONCLUSION: Our machine learning-based model stratified births to high or low risk for OASI, making it an applicable tool for personalized decision-making upon admission to labor.

Obstetric anal sphincter injury following previous vaginal delivery.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery. The aim of this study was to identify risk factors for OASI in women with a previous vaginal delivery. We further attempted to detect specific risk factors for severe OASI in this subgroup. METHODS: We conducted a retrospective cohort study between 2003 and 2019. The study group included women who had a singleton, live, vertex, vaginal delivery at term and who also had at least one previous vaginal delivery. The control group included women with at least one previous vaginal delivery without OASI. General medical history, obstetric history, and ante-, intra- and post-partum data were collected and compared between groups. RESULTS: Following implementation of the inclusion criteria, 79,176 women were included. Allocation to study groups was according to OASI occurrence: 135 patients (0.2%) had a third- or fourth-degree perineal tear, while 79,041 patients (99.8%) had no such injury. Multivariate analysis revealed that one previous vaginal delivery, birthweight ≥ 3900 g (90th percentile), vacuum-assisted vaginal delivery and episiotomy were associated with increased risk of OASI. Comparison of more severe OASI (3C and 4th-degree) cases to the control group showed similar results with the addition of prolonged second stage and younger age to risk factors associated with severe OASI while episiotomy was no longer significant. CONCLUSION: In women with a previous vaginal delivery, one vs. two or more previous vaginal deliveries, increased birthweight, vacuum-assisted vaginal delivery and episiotomy are risk factors for OASI.

Obstetric anal sphincter injury in adolescent mothers.

BACKGROUND: Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery which has yet to receive ample attention in adolescents. The aim of this study was to describe risk for OASI in adolescent mothers compared to adults. We further attempted to compare risk factors for OASI between these two age groups. METHODS: We performed a retrospective cohort study between 2003 and 2019. Primiparous women who delivered vaginally, 21 years and younger were compared to women ages 26-35. Excluded were preterm, multifetal, non-vertex, cesarean deliveries as well as intrauterine fetal death. Rate of OASI as well as obstetric and labor characteristics of women with OASI, were compared between groups. Finally, risk factors were assessed for each group separately. Univariate and multivariate logistic regression model were performed. RESULTS: Final analysis was performed on 5113 nulliparous adolescents and 13,845 nulliparous in the 26-35 age group. Allocation to study groups was according to OASI - Sixty-seven adolescents (1.3%) had a 3rd or 4th degree perineal tear and were defined as the OASI group, while 5046 patients (98.7%) did not have such a tear. In the adult group, 199 out of 13,845 patients (1.4%) were diagnosed with OASI. Occurrence of OASI did not differ between groups (p = 0.510). Comparison of women with OASI in the adolescent group vs. adult group found differences with regard to operative vaginal delivery, (20.9% vs. 36.2%, respectively; p = 0.023) and meconium stained amniotic fluid (9.1% vs. 21.3%, respectively; p = 0.027). Following multivariate analysis the only parameter independently associated with OASI in the adolescent age group was head circumference ≥ 90th percentile with an adjusted odds ratio of 3.08 (CI 1.48-6.38, p = 0.003). In the adult group the similar analysis revealed operative vaginal delivery (OR = 2.44, CI 1.72-3.47, p < 0.001) and a birthweight≥90th percentile (OR = 2.23, CI 1.19-4.18, p = 0.012) to be independent risk factors for OASI. CONCLUSION: Adolescents have similar risk for OASI compared to adults but differ in risk factors leading to OASI. Head circumference ≥ 90th percentile was found to be associated with OASI in this age group.

Transporting an Artificial Intelligence Model to Predict Emergency Cesarean Delivery: Overcoming Challenges Posed by Interfacility Variation.

Research using artificial intelligence (AI) in medicine is expected to significantly influence the practice of medicine and the delivery of health care in the near future. However, for successful deployment, the results must be transported across health care facilities. We present a cross-facilities application of an AI model that predicts the need for an emergency caesarean during birth. The transported model showed benefit; however, there can be challenges associated with interfacility variation in reporting practices.

Real-time data analysis using a machine learning model significantly improves prediction of successful vaginal deliveries.

BACKGROUND: The process of childbirth is one of the most crucial events in the future health and development of the offspring. The vulnerability of parturients and fetuses during the delivery process led to the development of intrapartum monitoring methods and to the emergence of alternative methods of delivery. However, current monitoring methods fail to accurately discriminate between cases in which intervention is unnecessary, partly contributing to the high rates of cesarean deliveries worldwide. Machine learning methods are applied in various medical fields to create personalized prediction models. These methods are used to analyze abundant, complex data with intricate associations to aid in decision making. Initial attempts to predict vaginal delivery vs cesarean deliveries using machine learning tools did not utilize the vast amount of data recorded during labor. The data recorded during labor represent the dynamic process of labor and therefore may be invaluable for dynamic prediction of vaginal delivery. OBJECTIVE: We aimed to create a personalized machine learning-based prediction model to predict successful vaginal deliveries using real-time data acquired during the first stage of labor. STUDY DESIGN: Electronic medical records of labor occurring during a 12-year period in a tertiary referral center were explored and labeled. Four different models were created using input from multiple maternal and fetal parameters. Initial risk assessments for vaginal delivery were calculated using data available at the time of admission to the delivery unit, followed by models incorporating cervical examination data and fetal heart rate data, and finally, a model that integrates additional data available during the first stage of labor was created. RESULTS: A total of 94,480 cases in which a trial of labor was attempted were identified. Based on approximately 180 million data points from the first stage of labor, machine learning models were developed to predict successful vaginal deliveries. A model using data available at the time of admission to the delivery unit yielded an area under the curve of 0.817 (95% confidence interval, 0.811-0.823). Models that used real-time data increased prediction accuracy. A model that includes real-time cervical examination data had an initial area under the curve of 0.819 (95% confidence interval, 0.813-0.825) at first examination, which increased to an area under the curve of 0.917 (95% confidence interval, 0.913-0.921) by the end of the first stage. Adding the real-time fetal heart monitor data provided an area under the curve of 0.824 (95% confidence interval, 0.818-0.830) at first examination, which increased to an area under the curve of 0.928 (95% confidence interval, 0.924-0.932) by the end of the first stage. Finally, adding additional real-time data increased the area under the curve initially to 0.833 (95% confidence interval, 0.827-0.838) at the first cervical examination and up to 0.932 (95% confidence interval, 0.928-0.935) by the end of the first stage. CONCLUSION: Real-time data acquired throughout the process of labor significantly increased the prediction accuracy for vaginal delivery using machine learning models. These models enable translation and quantification of the data gathered in the delivery unit into a clinical tool that yields a reliable personalized risk score and helps avoid unnecessary interventions.

Prediction of vaginal birth after cesarean deliveries using machine learning.

BACKGROUND: Efforts to reduce cesarean delivery rates to 12-15% have been undertaken worldwide. Special focus has been directed towards parturients who undergo a trial of labor after cesarean delivery to reduce the burden of repeated cesarean deliveries. Complication rates are lowest when a vaginal birth is achieved and highest when an unplanned cesarean delivery is performed, which emphasizes the need to assess, in advance, the likelihood of a successful vaginal birth after cesarean delivery. Vaginal birth after cesarean delivery calculators have been developed in different populations; however, some limitations to their implementation into clinical practice have been described. Machine-learning methods enable investigation of large-scale datasets with input combinations that traditional statistical analysis tools have difficulty processing. OBJECTIVE: The aim of this study was to evaluate the feasibility of using machine-learning methods to predict a successful vaginal birth after cesarean delivery. STUDY DESIGN: The electronic medical records of singleton, term labors during a 12-year period in a tertiary referral center were analyzed. With the use of gradient boosting, models that incorporated multiple maternal and fetal features were created to predict successful vaginal birth in parturients who undergo a trial of labor after cesarean delivery. One model was created to provide a personalized risk score for vaginal birth after cesarean delivery with the use of features that are available as early as the first antenatal visit; a second model was created that reassesses this score after features are added that are available only in proximity to delivery. RESULTS: A cohort of 9888 parturients with 1 previous cesarean delivery was identified, of which 75.6% of parturients (n=7473) attempted a trial of labor, with a success rate of 88%. A machine-learning-based model to predict when vaginal delivery would be successful was developed. When features that are available at the first antenatal visit are used, the model showed a receiver operating characteristic curve with area under the curve of 0.745 (95% confidence interval, 0.728-0.762) that increased to 0.793 (95% confidence interval, 0.778-0.808) when features that are available in proximity to the delivery process were added. Additionally, for the later model, a risk stratification tool was built to allocate parturients into low-, medium-, and high-risk groups for failed trial of labor after cesarean delivery. The low- and medium-risk groups (42.4% and 25.6% of parturients, respectively) showed a success rate of 97.3% and 90.9%, respectively. The high-risk group (32.1%) had a vaginal delivery success rate of 73.3%. Application of the model to a cohort of parturients who elected a repeat cesarean delivery (n=2145) demonstrated that 31% of these parturients would have been allocated to the low- and medium-risk groups had a trial of labor been attempted. CONCLUSION: Trial of labor after cesarean delivery is safe for most parturients. Success rates are high, even in a population with high rates of trial of labor after cesarean delivery. Application of a machine-learning algorithm to assign a personalized risk score for a successful vaginal birth after cesarean delivery may help in decision-making and contribute to a reduction in cesarean delivery rates. Parturient allocation to risk groups may help delivery process management.

Grandmultiparity, maternal age, and the risk for uterine rupture-A multicenter cohort study.

INTRODUCTION: Uterine rupture is a critical complication causing fetal and maternal morbidity and mortality. Data are conflicting regarding whether grandmultiparity (parity ≥ 6) is a risk factor. This multicenter cohort study aimed to determine whether grandmultiparity (parity ≥ 6) poses a risk for uterine rupture in women with no previous cesarean delivery. MATERIAL AND METHODS: A multicenter retrospective study of deliveries that occurred between the years 2003 and 2015 in three tertiary medical centers. Deliveries of grandmultiparous women were compared with those of multiparous women (parity 2-5). Women with previous cesarean deliveries were excluded. Multivariable regression modeling was applied to control for possible confounders. RESULTS: A total of 388 784 deliveries of multiparous women with unscarred uteri were recorded during the study period, including 53 965 deliveries of grandmultiparous women and 334 819 deliveries of multiparous women. Grandmultiparous women were significantly older (33.9 ± 5 vs 27.3 ± 5 years; P < 0.0001). Fourteen cases of uterine rupture were recorded in the grandmultiparae group (1 per 3855 labors) vs 41 in the multiparae group (1 per 8166 labors) (odds ratio [OR] 2.07, 95% confidence interval [95% CI] 1.13-3.81; P = 0.030). However, in a multivariable model controlling for maternal age, the association between grandmultiparity and uterine rupture lost its significance (adjusted OR 1.26, 95% CI 0.66-2.41; P = 0.491), and maternal age emerged as an independent predictor of uterine rupture (adjusted OR 1.08, 95% CI 1.04-1.13; P < 0.0001). Additionally, the risk for uterine rupture was elevated in a linear fashion, concomitant with age. CONCLUSIONS: Maternal age is a risk factor for uterine rupture. Grandmultiparity does not increase the risk beyond that associated with maternal age.

Cervical dilation at the time of epidural catheter insertion is not associated with the degree of prolongation of the first or second stages of labor, or the rate of instrumental vaginal delivery.

INTRODUCTION: Epidural analgesia (EA) is an established option for efficient intrapartum analgesia. Meta-analyses have shown that EA differentially affects the first stage of labor but prolongs the second. The question of EA timing remains open. We aimed to investigate whether EA prolongs delivery in total and whether the EA administration timing vis-à-vis cervical dilation at catheter insertion is associated with a modulation of its effects on the duration of the first and second stages, as well as the rate of instrumental vaginal delivery in primiparas and multiparas. MATERIAL AND METHODS: A retrospective electronic medical records-based study of 18 870 singleton term deliveries occurring in our institution from 2003 to 2015. Cervical dilation was determined within a half-hour of EA administration. We examined whether cervical dilation at EA administration correlated with the duration of the first and/or second stage, with the rate of prolonged second stage, and with the rate of interventional delivery. The study group was stratified to 10 subgroups defined by 1-cm intervals of cervical dilation at EA administration. Logistic regression modeling was applied to analyze the association between EA timing and rate of instrumental delivery while controlling for possible confounders. RESULTS: In primiparas, receiving EA correlated with longer medians of active first stage (+51 minutes; P < .001) and second stage (+55 minutes; P < .001). In multiparas, median increases in active first stage (+43 minutes; P < .001) and second stage (+8 minutes; P < .001) were noted. The timing of EA, vis-à-vis cervical dilation (1-10 cm) was not associated with a substantial modulation of these effects. Logistic regression showed that cervical dilation at EA was not associated with a higher instrumental vaginal delivery rate. CONCLUSIONS: Epidural analgesia prolonged the first and second stages of labor vs no epidural. Having EA was associated with a higher instrumental delivery rate but not with higher rates of maternal or neonatal complications, in primi- and multiparas. Importantly, the timing of EA, vis-à-vis cervical dilation, was not associated with substantial changes in the duration of labor stages or the instrumental delivery rate. Thus, EA may be offered early in the first stage of labor.

Unplanned Cesarean Delivery in the Second Stage of Labor Holds Higher Odds of Complications than in the First Stage, while Similar in Primiparas and Multiparas.

BACKGROUND: While endeavors to reduce cesarean delivery (CD) rates are given priority worldwide, it is important to evaluate if these efforts place parturients and neonates at risk. CD performed in the second stage of labor carries higher risks of maternal and fetal complications and is a more challenging surgical procedure than that performed in the first stage or before labor. In a population with a low CD rate, we sought to evaluate the rate of maternal and fetal complications associated with unplanned CD (UCD) performed in the second vs. the first stage of labor, in primiparas and multiparas, as well as the risk factors leading to and the complications associated with UCD in the second stage of labor in this low-CD rate setting. METHODS: This was a retrospective, electronic medical record-based study of 7,635 term and preterm singletons born via UCD in the period 2003-2015. Maternal and neonatal background and outcome parameters were compared between groups. Logistic regression modeling was applied to adjust for clinically and statistically significant risk factors. RESULTS: UCD was more likely to be performed in the second stage of labor in mothers delivering larger fetuses (head circumference and body weight ≥90 centile) and those with persistent occiput posterior (POP) presentation. UCD in the second stage was strongly associated with serious maternal complications (excessive hemorrhage and fever) compared to UCD performed in the first stage, in both primiparas and multiparas. CONCLUSIONS: UCD performed in the second stage of labor, while less frequent than first-stage UCD, is more likely with larger neonates and POP presentation, and is associated with a higher rate of maternal complications in primiparas and multiparas. Complication rates in our low-CD-rate population did not exceed those reported in the literature from high-CD-rate areas.

Sonographic large fetal head circumference and risk of cesarean delivery.

BACKGROUND: Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. OBJECTIVE: In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. STUDY DESIGN: This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. RESULTS: In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. CONCLUSION: Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management.

Higher Rates of Operative Delivery and Maternal and Neonatal Complications in Persistent Occiput Posterior Position with a Large Head Circumference: A Retrospective Cohort Study.

INTRODUCTION: We investigated whether large head circumference (HC) combined with persistent occiput posterior (OP) position is associated with higher rates of operative delivery and obstetric and neonatal complications than OP deliveries without large HC or in occiput anterior (OA) position. MATERIALS AND METHODS: Term singleton deliveries in our centers from January 2010 to December 2014, delivered in cephalic OA (n = 41,038) or OP position (n = 1,740), were assessed. We compared delivery modes, maternal and neonatal complications in OA versus OP deliveries, and HC ≥90th centile versus HC <90th centile in persistent OP position. RESULTS: Persistent OP position combined with HC ≥90th centile was associated with higher rates of vacuum extraction and unplanned cesarean delivery than HC <90th centile in OP position (20.1 vs. 17.2%, OR 1.53 [95% CI 0.99-2.36], and 23.4 vs. 9.2%, OR 3.326 [95% CI 2.17-5.11], respectively). Rates of prolonged second stage of labor and neonatal intensive care unit admission were also increased compared to those in either OA position with HC ≥90th centile or OP position with HC <90th centile. DISCUSSION: Large HC combined with OP position is associated with higher rates of operative delivery and prolonged second stage of labor compared to OP delivery with HC <90th centile. HC might be included with other measures to assess women in labor, as it is associated with fetal outcomes in OP deliveries.

[PROLONGED SECOND STAGE OF LABOR: CAUSES AND OUTCOMES].

INTRODUCTION: Professional bodies have published guidelines defining the length of the second stage of labor and when it is "prolonged", according to parity and epidural anesthesia administration. Recently these guidelines have been extended, aiming to reduce rates of unplanned cesarean deliveries. AIMS: To examine the risk factors and outcomes of a prolonged second stage of labor, in order to understand its causes and implications for mothers and neonates, including the delivery mode. METHODS: A retrospective study based on 26,476 electronic medical records of deliveries to primiparous mothers of a term singleton fetus, at Hadassah Medical Center, between 2003 and 2015. RESULTS: A prolonged second stage of labor was recorded in 3,225 (12.2%) of mothers (i.e. exceeding 2 hours without epidural anesthesia and 3 hours with it). Epidural anesthesia, persistent occiput posterior, and head circumference or birth weight above the 90th percentile, increased the risk of the prolonged second stage. The risk of unplanned cesarean delivery rose significantly before the 2- or 3-hour cut-off defining a prolonged second stage. Risks of maternal and neonatal complications included: grade III-IV perineal tear, maternal hemorrhage, 5-minute Apgar≤7, umbilical artery pH<7.1, neonatal intensive care admission were also increased. CONCLUSIONS: Epidural anesthesia and fetal parameters increased the risk of prolonged second stage; risks of maternal and fetal complications were also increased. The risk of interventional delivery increased significantly well before the defined cut-off. DISCUSSION: Prolongation of the second stage of labor is a common pathway of many obstetric outcomes. Obstetric management should be based on considerations of individual maternal and neonatal well-being, rather than administrative goals. While reducing cesarean rates is an important goal, attempts to achieve this by prolonging the second stage of labor exposes mothers and neonates to excess risk of cesarean and vacuum delivery as well as obstetric and neonatal complications.