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Objective: To evaluate, in economic terms, active vaccination campaigns against hepatitis A in comparison with the use of nonspecific immune globulin for the prevention of the disease among daycare centre employees in Israel.Setting: Hypothetical analysis of the costs and benefits related to vaccination campaigns of workers currently employed in daycare centres in Israel.Methods: A cost-benefit analysis was performed, comparing mass and selective active vaccination strategies for the daycare centre working force. Direct and indirect costs of diagnosis, treatment and immunisation as well as productivity loss were considered. A Markov-based model was developed using data from previous epidemiological studies and literature.Results: The benefit-to-cost ratios of selective and mass active vaccination strategies were 1.50 [net present value (NPV) $US606 396] and 0.04 (NPV-$US2.36 million), respectively (2000 values).Conclusion: Under these study assumptions, the practice of administering hepatitis A active vaccine to serologically proven non-immune daycare centre workers has a cost-benefit justification, and should be widely considered in countries with a similar hepatitis A epidemiology to that in this study. [ABSTRACT FROM AUTHOR]

Objective: This study aims to estimate the frequency of unintended upper uterine wall extensions during cesarean delivery (CD) and identify associated risk factors and adverse outcomes., Methods: A multicenter retrospective cohort study was conducted, including patients who underwent CD between 2005 and 2021. Demographic factors, obstetric history, CD indications, delivery and surgical characteristics, adverse maternal and neonatal outcomes were compared between those with unintended upper uterine wall extensions during CD and those without extensions. Crude and adjusted estimates (odds ratios [ORs] and 95% confidence intervals [CIs]) were used., Results: Among 30,517 patients meeting inclusion criteria, 117 (0.4%) had an unintended upper uterine wall extension. In univariate analysis, upper uterine wall extensions were associated with higher rates of intrapartum CD, second-stage CD, unplanned or emergency CD, CD following failed vacuum delivery or trial of labor after CD, chorioamnionitis, prolonged labor, increased vaginal exams, lower fetal head station, and higher birthweight. During surgery, higher rates of general anesthesia, significant intraperitoneal adhesion, fetal malpresentation, and fetal extraction by the leg were observed. Multivariable analysis identified fetal extraction not by head (adjusted OR [aOR] 9.17, 95% CI 5.35-15.73), vertex fetal presentation (aOR 3.65, 95% CI 1.81-7.35), second-stage CD (aOR 3.07, 95% CI 1.24-7.59), and TOLAC (aOR 2.04, 95% CI 1.08-3.84) as significant risk factors for unintended upper uterine wall extensions. Additionally, upper uterine wall extensions were associated with higher rates of maternal and neonatal complications, including longer operating times, excessive bleeding, postpartum hemorrhage, intraperitoneal drainage, blood product transfusion, puerperal fever, paralytic ileus, Apgar score <7 at 1 and 5 minutes, and fetal intracranial hemorrhage., Conclusion: Our study identifies risk factors for unintended upper uterine wall extensions during CD. While these extensions are infrequent, their occurrence is associated with increased maternal and neonatal morbidity., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To compare rates of adverse pregnancy outcomes in term pregnancies complicated by polyhydramnios between women who had induction of labor (IOB) versus women who had expectant management., Methods: This multicenter retrospective study included term pregnancies complicated by isolated polyhydramnios. Patients who underwent IOB were compared with those who had expectant management. The primary outcome was defined as a composite adverse maternal outcome, and secondary outcomes were various maternal and neonatal adverse outcomes. Univariate analyses were followed by multivariate logistic regression., Results: A total of 865 pregnancies with term isolated polyhydramnios were included: 169 patients underwent IOB (19.5%), while 696 had expectant management and developed spontaneous onset of labor (80.5%). Women who underwent IOB had significantly higher rates of composite adverse maternal outcome (23.1% vs 9.8%, P < 0.01), prolonged hospital stay, perineal tear grade 3/4, intrapartum cesarean, postpartum hemorrhage, blood products transfusion, and neonatal asphyxia compared with expectant management. While the perinatal fetal death rate was similar between the groups (0.6% vs 0.6%, P = 0.98), the timing of the loss was different. Four women in the expectant management group had a stillbirth, while in the induction group one case of intrapartum fetal death occurred due to uterine rupture. Multivariate analyses revealed that IOB was associated with a higher rate of composite adverse maternal outcome (adjusted odds ratio, 2.22 [95% CI, 1.28-3.83]; P < 0.01)., Conclusion: IOB in women with term isolated polyhydramnios is associated with higher rates of adverse maternal outcomes in comparison to expectant management. Further research is needed to determine the optimal approach for the management of isolated polyhydramnios at term., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To evaluate the quality of ChatGPT responses to common issues in obstetrics and assess its ability to provide reliable responses to pregnant individuals. The study aimed to examine the responses based on expert opinions using predetermined criteria, including "accuracy," "completeness," and "safety.", Methods: We curated 15 common and potentially clinically significant questions that pregnant women are asking. Two native English-speaking women were asked to reframe the questions in their own words, and we employed the ChatGPT language model to generate responses to the questions. To evaluate the accuracy, completeness, and safety of the ChatGPT's generated responses, we developed a questionnaire with a scale of 1 to 5 that obstetrics and gynecology experts from different countries were invited to rate accordingly. The ratings were analyzed to evaluate the average level of agreement and percentage of positive ratings (≥4) for each criterion., Results: Of the 42 experts invited, 20 responded to the questionnaire. The combined score for all responses yielded a mean rating of 4, with 75% of responses receiving a positive rating (≥4). While examining specific criteria, the ChatGPT responses were better for the accuracy criterion, with a mean rating of 4.2 and 80% of the questions received a positive rating. The responses scored less for the completeness criterion, with a mean rating of 3.8 and 46.7% of questions received a positive rating. For safety, the mean rating was 3.9 and 53.3% of questions received a positive rating. There was no response with an average negative rating below three., Conclusion: This study demonstrates promising results regarding potential use of ChatGPT's in providing accurate responses to obstetric clinical questions posed by pregnant women. However, it is crucial to exercise caution when addressing inquiries concerning the safety of the fetus or the mother., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To assess the effect of each additional delivery among grand multiparous (GMP) women on maternal and neonatal outcomes., Methods: A multi-center retrospective cohort study that examined maternal and neonatal outcomes of GMP women (parity 5-10, analyzed separately for each parity level) compared to a reference group of multiparous women (parity 2-4). The study population included grand multiparous women with singleton gestation who delivered in one of four university-affiliated obstetrical centers in a single geographic area, between 2003 and 2021. We excluded nulliparous, those with parity > 10 (due to small sample sizes), women with previous cesarean deliveries (CDs), multifetal gestations, and out-of-hospital deliveries. The primary outcome of this study was postpartum hemorrhage (PPH, estimated blood loss exceeding 1000 ml, and/or requiring blood product transfusion, and/or a hemoglobin drop > 3 g/Dl). Secondary outcomes included unplanned cesarean deliveries, preterm delivery, along with other adverse maternal and neonatal outcomes. Univariate analysis was followed by multivariable logistic regression., Results: During the study period, 251,786 deliveries of 120,793 patients met the inclusion and exclusion criteria. Of those, 173,113 (69%) were of parity 2-4 (reference group), 27,894 (11%) were of parity five, 19,146 (8%) were of parity six, 13,115 (5%) were of parity seven, 8903 (4%) were of parity eight, 5802 (2%) were of parity nine and 3813 (2%) were of parity ten. GMP women exhibited significantly higher rates of PPH starting from parity eight. The adjusted odds ratios (aOR) were 1.19 (95 % CI: 1.06-1.34) for parity 8, 1.17 (95 % CI: 1.01-1.36) for parity 9, and 1.39 (95 % CI: 1.18-1.65) for parity 10. Additionally, they showed elevated rates of several maternal and neonatal outcomes, including placental abruption, large-for-gestational age (LGA) neonates, neonatal hypoglycemia, and neonatal seizures. Conversely, they exhibited decreased risk for other adverse maternal outcomes, including preterm deliveries, unplanned cesarean deliveries (CDs), vacuum-assisted delivery, and third- or fourth-degree perineal tears and small-for-gestational age (SGA) neonates. The associations with neonatal hypoglycemia, and neonatal seizure were correlated with the number of deliveries in a dose-dependent manner, demonstrating that each additional delivery was associated with an additional, significant impact on obstetrical complications., Conclusion: Our study demonstrates that parity 8-10 is associated with a significantly increased risk of PPH. Parity level > 5 correlated with increased odds of placental abruption, LGA neonates, neonatal hypoglycemia, and neonatal seizures. However, GMP women also demonstrated a reduced likelihood of certain adverse maternal outcomes, including unplanned cesarean, preterm deliveries, vacuum-assisted deliveries, SGA neonates, and severe perineal tears. These findings highlight the importance of tailored obstetrical care for GMP women to mitigate the elevated risks associated with higher parity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Second-stage cesarean delivery (CD) is associated with subsequent preterm birth (PTB). It has been suggested that an increased risk of PTB after second-stage cesarean delivery could be linked to a higher chance of cervical injury due to the extension of the uterine incision. Previous studies have shown that reverse breech extraction is associated with lower rates of uterine incision extensions compared to the "push" method. We aimed to investigate the association between the method of fetal extraction during second-stage CD and the rate of spontaneous PTB (sPTB), as well as other maternal and neonatal outcomes during the subsequent pregnancy., Methods: This was a multicenter retrospective cohort study. The study population included women in their first subsequent singleton delivery following a second-stage CD between 2004 and 2021. The main exposure of interest was the method of fetal extraction in the index CD ("push" method vs. reverse breech extraction). The primary outcome of this study was sPTB <37 weeks in the subsequent pregnancy. Secondary outcomes were overall PTB, trial of labor, and other adverse maternal and neonatal outcomes. Univariate analysis was followed by multiple logistic regression modeling., Results: During the study period, 2969 index CD during second stage were performed, of those 583 met the inclusion criteria, of whom 234 (40.1%) had fetal extraction using the reverse breech extraction method, while 349 (59.9%) had the "push" method for extraction. In univariate analysis, women in those two groups had statistically similar rates of sPTB (3.7% vs. 3.0%; odds ratio [OR] 1.25, 95% CI: 0.49-3.19) and overall PTB (<37, <34 and <32 weeks), as well as other maternal, neonatal, and trial of labor outcomes. This was confirmed by multivariate analyses with an adjusted OR of 1.27 (95% CI: 0.43-3.71) for sPTB., Conclusion: Among women with a previous second-stage CD, no significant difference was observed in PTB rates in the subsequent pregnancies following the "push" method compared to the reverse breech extraction method., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To evaluate obstetric and perinatal outcomes among small for gestational age (SGA) infants born to patients diagnosed with Gestational diabetes mellitus (GDM)., Materials and Methods: A multicenter retrospective cohort study between 2005 and 2021. The perinatal outcomes of SGA infants born to patients with singleton pregnancy and GDM were compared to SGA infants born to patients without GDM. The primary outcome was a composite adverse neonatal outcome. Infants with known structural/genetic abnormalities or infections were excluded. A univariate analysis was conducted followed by a multivariate analysis (adjusted odds ratio [95% confidence interval])., Results: During the study period, 11,662 patients with SGA infants met the inclusion and exclusion criteria. Of these, 417 (3.6%) SGA infants were born to patients with GDM, while 11,245 (96.4%) were born to patients without GDM. Overall, the composite adverse neonatal outcome was worse in the GDM group (53.7% vs 17.4%, p < 0.01). Specifically, adverse neonatal outcomes such as a 5 min Apgar score < 7, meconium aspiration, seizures, and hypoglycemia were independently associated with GDM among SGA infants. In addition, patients with GDM and SGA infants had higher rates of overall and spontaneous preterm birth, unplanned cesarean, and postpartum hemorrhage. In a multivariate logistic regression assessing the association between GDM and neonatal outcomes, GDM was found to be independently associated with the composite adverse neonatal outcome (aOR 4.26 [3.43-5.3]), 5 min Apgar score < 7 (aOR 2 [1.16-3.47]), meconium aspiration (aOR 4.62 [1.76-12.13]), seizures (aOR 2.85 [1.51-5.37]) and hypoglycemia (aOR 16.16 [12.79-20.41])., Conclusions: Our study demonstrates that GDM is an independent risk factor for adverse neonatal outcomes among SGA infants. This finding underscores the imperative for tailored monitoring and management strategies in those pregnancies., (© 2024. The Author(s).)

This study aims to investigate whether trial of labor after cesarean delivery (TOLAC) in women with antepartum fetal death, is associated with an elevated risk of maternal morbidity. A retrospective multicenter. TOLAC of singleton pregnancies following a single low-segment incision were included. Maternal adverse outcomes were compared between women with antepartum fetal death and women with a viable fetus. Controls were matched with cases in a 1:4 ratio based on their previous vaginal births and induction of labor rates. Univariate analysis was followed by multiple logistic regression modeling. During the study period, 181 women experienced antepartum fetal death and were matched with 724 women with viable fetuses. Univariate analysis revealed that women with antepartum fetal death had significantly lower rates of TOLAC failure (4.4% vs. 25.1%, p < 0.01), but similar rates of composite adverse maternal outcomes (6.1% vs. 8.0%, p = 0.38) and uterine rupture (0.6% vs. 0.3%, p = 0.56). Multivariable analyses controlling for confounders showed that an antepartum fetal death vs. live birth isn't associated with the composite adverse maternal outcomes (aOR 0.96, 95% CI 0.21-4.44, p = 0.95). TOLAC in women with antepartum fetal death is not associated with an increased risk of adverse maternal outcomes while showing high rates of successful vaginal birth after cesarean (VBAC)., (© 2024. The Author(s).)

Objective:  In the era of group B Streptococcus (GBS) screening and intrapartum antibiotic prophylaxis (IAP), GBS colonization has been associated with a lower risk of chorioamnionitis, possibly due to a protective effect of IAP. We sought to confirm this finding and assess whether this association varies by gestational week at delivery., Study Design:  We performed a retrospective cohort study of term (37.0-42.6 weeks), singleton parturients with known GBS status who delivered from 2005 to 2021 at two academic medical centers in Israel. We excluded patients who underwent planned cesarean, out of hospital birth, or had a fetal demise. Patients received GBS screening and IAP for GBS positivity as routine clinical care. The primary outcome was a diagnosis of clinical chorioamnionitis as determined by the International Classification of Diseases 10th Revision code, compared between GBS-positive and -negative groups, and assessed by gestational week at delivery., Results:  Of 292,126 deliveries, 155,255 met inclusion criteria. In total, 30.1% were GBS positive and 69.9% were negative. GBS-positive patients were 21% less likely to be diagnosed with clinical chorioamnionitis than GBS-negative patients, even after controlling for confounders (1.5 vs. 2.2%, adjusted odds ratio: 0.79, 95% confidence interval: 0.68-0.92). When assessed by gestational week at delivery, there was a significantly greater difference in rates of clinical chorioamnionitis between GBS-positive versus GBS-negative groups with advancing gestational age: 1.5-fold difference at 38 to 40 weeks, but a twofold difference at 42 weeks. The risk of clinical chorioamnionitis remained stable in the GBS-positive group, but increased significantly in the GBS-negative group at 41- and 42-week gestation (2.0 vs. 2.9%, p  < 0.01 at 41 weeks; up to 3.9% at 42 weeks, p  < 0.01)., Conclusion:  In a large multicenter cohort with universal GBS screening and IAP, GBS positivity was associated with a lower risk of chorioamnionitis, driven by an increasing rate of chorioamnionitis among GBS-negative patients after 40 weeks., Key Points: · GBS positivity and IAP may be associated with lower risk of chorioamnionitis.. · GBS-positive patients were less likely to be diagnosed with chorioamnionitis.. · This difference increased with advancing gestational age after 40 weeks.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Trial of labor after cesarean after 2 cesarean deliveries is linked to a lower success rate of vaginal delivery and higher rates of adverse obstetrical outcomes than trial of labor after cesarean after 1 previous cesarean delivery., Objective: This study aimed to investigate the factors associated with failed trial of labor after cesarean among women with 2 previous cesarean deliveries., Study Design: This was a multicenter retrospective cohort study, which included all women with singleton pregnancies attempting trial of labor after cesarean after 2 previous cesarean deliveries between 2003 and 2021. This study compared labor, maternal, and neonatal characteristics between women with failed trial of labor after cesarean and those with successful trial of labor after cesarean. Univariate analysis was initially performed, followed by multivariable analysis (adjusted odds ratios with 95% confidence intervals)., Results: The study included a total of 1181 women attempting trial of labor after cesarean after 2 previous cesarean deliveries. Among these cases, vaginal birth after cesarean was achieved in 973 women (82.4%). Women with failed trial of labor after cesarean had higher rates of maternal and neonatal morbidities. Several factors were found to be associated with failed trial of labor after cesarean, including longer interpregnancy and interdelivery intervals, lower gravidity and parity, lower rates of previous successful vaginal delivery, smoking, earlier gestational age at delivery (38.3±2.1 vs 39.5±1.3 weeks), late preterm delivery (34-37 weeks of gestation), lower cervical dilation on admission, no use of epidural, and smaller neonatal birthweight. Our multivariable model revealed that late preterm delivery (adjusted odds ratio, 3.79; 95% confidence interval, 1.37-10.47) and cervical dilation on admission for labor <3 cm (adjusted odds ratio, 2.58; 95% confidence interval, 1.47-4.54) were associated with higher odds of failed trial of labor after cesarean., Conclusion: In the investigated population of women with 2 previous cesarean deliveries undergoing trial of labor after cesarean, admission at the late preterm period with a cervical dilation of <3 cm, which reflects the latent phase, may elevate the risk of failed trial of labor after cesarean and a repeated intrapartum cesarean delivery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: An increased risk for preterm birth has been observed among individuals with a previous second stage cesarean delivery when compared with those with a previous vaginal delivery. One mechanism that may contribute to the increased risk for preterm birth following a second stage cesarean delivery is the increased risk for cervical injury because of extension of the uterine incision (hysterotomy) into the cervix. The contribution of hysterotomy extension to the rate of preterm birth in a subsequent pregnancy has not been investigated and may shed light on the mechanism underlying the observed relationship between the mode of delivery and subsequent preterm birth., Objective: We aimed to quantify the association between unintended hysterotomy extension and preterm birth in a subsequent delivery., Study Design: We performed a retrospective cohort study using electronic perinatal data collected from 2 university-affiliated obstetrical centers. The study included patients with a primary cesarean delivery of a term, singleton live birth and a subsequent singleton birth in the same catchment (2005-2021). The primary outcome was subsequent preterm birth <37 weeks' gestation; secondary outcomes included subsequent preterm birth at <34, <32, and <28 weeks' gestation. We assessed crude and adjusted associations between unintended hysterotomy extensions and subsequent preterm birth with log binomial regression models using rate ratios and 95% confidence intervals. Adjusted models included several characteristics of the primary cesarean delivery such as maternal age, length of active labor, indication for cesarean delivery, chorioamnionitis, and maternal comorbidity., Results: A total 4797 patients met the study inclusion criteria. The overall rate of unintended hysterotomy extension in the primary cesarean delivery was 6.0% and the total rate of preterm birth in the subsequent pregnancy was 4.8%. Patients with an unintended hysterotomy extension were more likely to have a longer duration of active labor, chorioamnionitis, failed vacuum delivery attempt, second stage cesarean delivery, and persistent occiput posterior position of the fetal head in the primary cesarean delivery and higher rates of smoking in the subsequent pregnancy. Multivariable analyses that controlled for several confounders showed that a history of hysterotomy extension was not associated with a higher risk for preterm birth <37 weeks' gestation (adjusted rate ratio, 1.55; 95% confidence interval, 0.98-2.47), but it was associated with preterm birth <34 weeks' gestation (adjusted rate ratio, 2.49; 95% confidence interval, 1.06-5.42)., Conclusion: Patients with a uterine incision extension have a 2.5 times higher rate of preterm birth <34 weeks' gestation when compared with patients who did not have this injury. This association was not observed for preterm birth <37 weeks' gestation. Future research should aim to replicate our analyses with incorporation of additional data to minimize the potential for residual confounding., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: With the increasing popularity of elective induction after 39 + 0 weeks, the question of whether induction of labor (IOL) is safe in women with isolated polyhydramnios has become more relevant. We aimed to evaluate the pregnancy outcomes associated with IOL among women with and without isolated polyhydramnios. Methods: This was a multicenter retrospective cohort that included women who underwent induction of labor at term. The study compared women who underwent IOL due to isolated polyhydramnios to low-risk women who underwent elective IOL due to gestational age only. The main outcome measure was a composite adverse maternal outcome, while the secondary outcomes included maternal and neonatal adverse pregnancy outcomes. Results: During the study period, 1004 women underwent IOL at term and met inclusion and exclusion criteria; 162 had isolated polyhydramnios, and 842 had a normal amount of amniotic fluid. Women who had isolated polyhydramnios had higher rates of the composite adverse maternal outcome (28.7% vs. 20.4%, p = 0.02), prolonged hospital stay, perineal tear grade 3/4, postpartum hemorrhage, and neonatal hypoglycemia. Multivariate analyses revealed that among women with IOL, polyhydramnios was significantly associated with adverse composite maternal outcome [aOR 1.98 (1.27-3.10), p < 0.01]. Conclusions: IOL in women with isolated polyhydramnios at term was associated with worse perinatal outcomes compared to low-risk women who underwent elective IOL. Our findings suggest that the management of women with polyhydramnios cannot be extrapolated from studies of low-risk populations and that clinical decision-making should take into account the individual patient's risk factors and preferences.

Background: Second-stage cesarean delivery is associated with subsequent preterm delivery. Failed vacuum-assisted delivery is a subgroup of second-stage cesarean delivery in which the fetal head is engaged deeper in the pelvis and, thus, is associated with an increased risk of short-term maternal complications., Objective: This study aimed to investigate the maternal and neonatal outcomes of women at their subsequent delivery after a second-stage cesarean delivery with failed vacuum-assisted extraction vs after a second-stage cesarean delivery without a trial of vacuum-assisted extraction., Study Design: This was a multicenter retrospective cohort study. The study population included all women in their subsequent pregnancy after a second-stage cesarean delivery who delivered in all university-affiliated obstetrical centers (n=4) in a single geographic area between 2003 and 2021. Maternal and neonatal outcomes of women who had second-stage cesarean delivery after a failed vacuum-assisted delivery were compared with women who had second-stage cesarean delivery without a trial of vacuum-assisted delivery. The primary outcome of this study was preterm delivery at <37 weeks of gestation. The secondary outcomes were vaginal birth rate and other adverse maternal and neonatal outcomes. Univariate analysis was followed by multiple logistic regression modeling., Results: During the study period, 1313 women met the inclusion criteria, of whom 215 (16.4%) had a history of failed vacuum-assisted delivery at the previous delivery and 1098 (83.6%) did not. In univariate analysis, women with previously failed vacuum-assisted delivery had similar preterm delivery rates (<37, <34, <32, and <28 weeks of gestation), a successful trial of labor after cesarean delivery rates, uterine rupture, and hysterectomy. However, multivariable analyses controlling for confounders showed that a history of failed vacuum-assisted delivery is associated with a higher risk of preterm delivery at <37 weeks of gestation (adjusted odds ratio, 2.05; 95% confidence interval, 1.11-3.79; P=.02), but not with preterm delivery at <34 or <32 weeks of gestation., Conclusion: Among women with a previous second-stage cesarean delivery, previously failed vacuum-assisted delivery was associated with an increased risk of preterm delivery at <37 weeks of gestation in the subsequent birth., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between unintended uterine extension in cesarean delivery and uterine scar disruption (rupture or dehiscence) at the subsequent trial of labor after cesarean delivery (TOLAC)., Methods: This is a multicenter retrospective cohort study (2005-2021). Parturients with a singleton pregnancy who had unintended lower-segment uterine extension during the primary cesarean delivery (excluding T and J vertical extensions) were compared with patients who did not have an unintended uterine extension. We assessed the subsequent uterine scar disruption rate following the subsequent TOLAC and the rate of adverse maternal outcome., Results: During the study period, 7199 patients underwent a trial of labor and were eligible for the study, of whom 1245 (17.3%) had a previous unintended uterine extension and 5954 (82.7%) did not. In univariate analysis, previous unintended uterine extension during the primary cesarean delivery was not significantly associated with uterine scar rupture in the following subsequent TOLAC. Nevertheless, it was associated with uterine scar dehiscence, higher rates of TOLAC failure, and a composite adverse maternal outcome. In multivariate analyses, only the association between previous unintended uterine extension and higher rates of TOLAC failure was confirmed., Conclusion: A history of unintended lower-segment uterine extension is not associated with an increased risk for uterine scar disruption following subsequent TOLAC., (© 2023 International Federation of Gynecology and Obstetrics.)

Aim: To investigate whether women with twin gestation and one abnormal value on the diagnostic 3-hour oral glucose tolerance test (OGTT) are at an increased risk of adverse perinatal outcomes., Methods: This was a retrospective multicenter study of women with twin gestation, comparing four groups: (1) normal 50-g screening, (2) normal 100-g 3-hour OGTT, (3) one abnormal value on the 3-hour OGTT, and (4) GDM. Multivariable logistic regressions adjusted for maternal age, gravidity, parity, previous CDs, fertility treatments, smoking, obesity and chorionicity were used., Results: The study included 2,597 women with twin gestations, of which 79.7% had a normal screen, and 6.2% had one abnormal value on the OGTT. In adjusted analyses, women with one abnormal value were found to have higher rates of preterm delivery < 32 weeks, large for gestational age neonates, and composite neonatal morbidity of at least one fetus, however, similar maternal outcomes as those with a normal screen., Conclusion: Our study provides evidence that women with twin gestation and one abnormal value on the 3-hour OGTT are at an increased risk of unfavorable neonatal outcomes. This was confirmed by multivariable logistic regressions. Further research is needed to determine whether interventions such as nutritional counseling, blood glucose monitoring, and treatment with diet and medication would improve perinatal outcomes in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: While it is widely acknowledged that pregnancy losses can lead to negative outcomes for both mothers and fetuses, there is limited information available on the specific levels of risk associated with each additional pregnancy loss., Objective: This study aimed to investigate the effect of number of previous pregnancy losses among nulliparous women on maternal and neonatal adverse outcomes., Study Design: This was a multicenter retrospective cohort study. The study population included all nulliparous women with singleton pregnancies who delivered in all university-affiliated obstetrical centers in a single geographic area between 2003 and 2021. Maternal and neonatal outcomes of women who delivered at our medical centers and had varying numbers of previous pregnancy losses were compared with women who had no previous pregnancy loss. The primary outcome of this study was preterm delivery rate at <37 weeks of gestation. The secondary outcomes were adverse maternal and neonatal outcomes. Univariate analysis was performed using multiple logistic regression modeling., Results: During the study period, 97,904 nulliparous women met the inclusion and exclusion criteria. Of those women, 84,245 (86%) had no previous pregnancy losses (reference group), 10,724 (11%) had 1 previous pregnancy loss, 2150 (2.2%) had 2 previous pregnancy losses, 516 (0.5%) had 3 previous pregnancy losses, 160 (0.2%) had 4 previous pregnancy losses, and 99 (0.1%) had ≥5 previous pregnancy losses. Women who had previous pregnancy losses had significantly higher rates of preterm delivery, hypertensive disorders of pregnancy, diabetes mellitus (pregestational and gestational), unplanned cesarean delivery, perinatal death, neonatal intensive care unit admissions, and neonatal hypoglycemia. The risks of preterm delivery and most other adverse obstetrical outcomes correlated with the number of previous pregnancy losses. Multivariate analyses showed that each previous pregnancy loss was associated with an additional, significant, increased risk of preterm delivery of 14% at <37 weeks of gestation, 37% at <34 weeks of gestation, 45% at <32 weeks of gestation, and 77% at <28 weeks of gestation., Conclusion: A history of previous pregnancy losses increased the risk of preterm delivery and other perinatal outcomes in a dose-dependent manner. To minimize perinatal complications, obstetricians should be aware of the risks and complications in this unique population, consider close monitoring of the cervical length, and maintain high vigilance in case of complications with special attention to other potentially modifiable risks., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine whether mode of preterm delivery is associated with the risk of recurrent preterm delivery in subsequent pregnancy., Study Design: A multicenter retrospective study. Women with the first two consecutive singleton deliveries at two university-affiliated medical centers between August 2005-March 2021, with first delivery occurring spontaneously < 37 weeks of gestation were included. Excluded were women with multifetal pregnancies in either pregnancy and those with an indicated first preterm delivery. A univariate analysis was followed by a multivariate analysis., Results: A total of 1,019 women with spontaneous preterm first delivery were included. Of those, 141 (13.8 %) underwent cesarean delivery in their first preterm delivery, while 878 (86.2 %) had a vaginal delivery. Univariate analysis revealed that women who underwent cesarean delivery in their first delivery had, during the subsequent delivery: longer mean gestational age at delivery (37.8 ± 3.3 vs 36.8 ± 3.7 weeks; p < 0.01), but statistically similar rates of recurrent preterm delivery both < 37 weeks and < 34 weeks (23.4 % vs 27.2 % and 7.1 % vs 10.6 %; p = 0.34 and p = 0.20, respectively). Multivariate analysis revealed that mode of delivery- cesarean - in the preterm delivery was not associated with recurrent pre-term delivery (0.66 (0.41-1.04), p = 0.07)., Conclusion: Mode of delivery in first preterm delivery is not associated with higher or lower rates of recurrent preterm delivery., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Twin trial of labor after a cesarean section (TOLAC) is associated with a lower success rate of vaginal delivery than singleton TOLAC, and a higher rate of adverse outcomes in comparison to an elective repeat cesarean delivery. This study aims to investigate the factors associated with failed TOLAC, among women with twin gestation. Study design: A multicenter retrospective cohort study was undertaken. All women with twin pregnancies attempting a trial of labor after a previous cesarean in two university-affiliated obstetrical centers, between 2005 and 2021 were included. The study population included women with a twin gestation where twin A presented in the vertex position, a single previous low segment transverse section, and those who were eligible for a vaginal delivery. Labor, maternal, and neonatal characteristics were compared. A univariate analysis was undertaken, followed by multivariate analysis (aORs; [95% CI]). Results: A total of 160 women attempting a twin TOLAC were included. Vaginal birth after cesarean was achieved in 86.3% of these cases. Assisted reproductive technology (ART), the lack of oxytocin use for augmentation during labor, the lack of epidural analgesia, and preterm birth before 34, 32, and 28 gestational weeks were all found to be associated with failed TOLAC. In the multivariate analysis, cervical dilation on admission (aOR 0.6 [0.40−0.82], p < 0.01), no use of oxytocin (aOR 5.2 [1.36−19.73], p = 0.02), gestational age at delivery (aOR 0.8 [0.65−1.00], p = 0.047) and lack of epidural analgesia (aOR 4.5 [1.01−20.16], p = 0.049), were all found to be significantly associated with failed TOLAC. Conclusion: In the investigated population of women with twins undergoing TOLAC, the use of epidural analgesia, the use of oxytocin and increased cervical dilation to the delivery room are associated with a higher rate of vaginal delivery, and may reduce the risk of repeat cesarean delivery.

Omidubicel (nicotinamide-expanded cord blood) is a potential alternative source for allogeneic hematopoietic cell transplantation (HCT) when an HLA-identical donor is lacking. A phase I/II trial with standalone omidubicel HCT showed rapid and robust neutrophil and platelet engraftment. In this study, we evaluated the immune reconstitution (IR) of patients receiving omidubicel grafts during the first 6 months post-transplant, as IR is critical for favorable outcomes of the procedure. Data was collected from the omidubicel phase I-II international, multicenter trial. The primary endpoint was the probability of achieving adequate CD4+ T-cell IR (CD4IR: > 50 × 10 6 /L within 100 days). Secondary endpoints were the recovery of T-cells, natural killer (NK)-cells, B-cells, dendritic cells (DC), and monocytes as determined with multicolor flow cytometry. LOESS-regression curves and cumulative incidence plots were used for data description. Thirty-six omidubicel recipients (median 44; 13-63 years) were included, and IR data was available from 28 recipients. Of these patients, 90% achieved adequate CD4IR. Overall, IR was complete and consisted of T-cell, monocyte, DC, and notably fast NK- and B-cell reconstitution, compared to conventional grafts. Our data show that transplantation of adolescent and adult patients with omidubicel results in full and broad IR, which is comparable with IR after HCT with conventional graft sources., (© 2021. The Author(s).)

Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). The primary end point was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% confidence interval [CI], 10-14 days) for the omidubicel arm and 22 days (95% CI, 19-25 days) for the control arm (P < .001). The cumulative incidence of neutrophil engraftment was 96% for patients receiving omidubicel and 89% for patients receiving control transplants. The omidubicel arm had faster platelet recovery (55% vs 35% recovery by 42 days; P = .028), had a lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs 57%; P = .027), and spent more time out of hospital during the first 100 days after transplant (median, 61 vs 48 days; P = .005) than controls. Differences in GVHD and survival between the 2 arms were not statistically significant. Transplantation with omidubicel results in faster hematopoietic recovery and reduces early transplant-related complications compared with standard UCBT. The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT. The trial was registered at www.clinicaltrials.gov as #NCT02730299., (© 2021 by The American Society of Hematology.)

Umbilical cord blood (UCB) transplantation has a high early mortality rate primarily related to transplanted stem cell dose. To decrease early mortality and enhance engraftment, a portion of selected cord blood units (20% to 50%) was expanded with cytokines and the copper chelator tetraethylenepentamine (carlecortemcel-L) and transplanted with the unmanipulated fraction after myeloablative conditioning. The primary endpoint was 100-day survival, which was compared with a contemporaneous double-unit cord blood transplantation (DUCBT) group. We enrolled 101 patients at 25 sites; the DUCBT comparison (n = 295) was selected from international registries using study eligibility criteria. Baseline carlecortemcel-L study group unit nucleated cell (NC) and CD34 + were 3.06 × 10 7 cell dose/kg and 1.64 × 10 5 cell dose/kg. Median NC and CD34 + fold expansion were 400 and 77, with a mean total CD34 infused of 9.7 × 10 5 /kg. The 100-day survival was 84.2% for the carlecortemcel-L study group versus 74.6% for the DUCBT group (odds ratio, .50; 95% CI, .26 to .95; P = .035). Survival at day 180 was similar for the 2 groups; the major cause of death after day 100 was opportunistic infections. Faster median neutrophil (21 days versus 28 days; P < .0001), and platelet (54 days versus 105 days; P = .008) engraftment was seen in the carlecortemcel-L study group; acute and chronic graft-versus-host disease rates were similar. In this multinational comparative study, transplanting expanded CD34 + stem cells from a portion of a single UCB unit, with the remaining unmanipulated fraction improved 100-day survival compared with DUCBT control patients while facilitating myeloid and platelet engraftment. This trial was registered at www.clinicaltrials.gov as #NCT00469729., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment., Methods: In a phase I trial, 11 adults with hematologic malignancies received myeloablative bone marrow conditioning followed by transplantation with NiCord and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and compared with historical controls., Results: No adverse events were attributable to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in 8 patients, and NiCord engraftment remained stable in all patients, with a median follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P < 0.001) compared with that seen in historical controls. The 1-year overall and progression-free survival rates were 82% and 73%, respectively., Conclusion: UCB-derived hematopoietic stem and progenitor cells expanded in the presence of nicotinamide and transplanted with a T cell-containing fraction contain both short-term and long-term repopulating cells. The results justify further study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed, NiCord has the potential to broaden accessibility and reduce the toxicity of UCB transplantation., Trial Registration: Clinicaltrials.gov NCT01221857., Funding: Gamida Cell Ltd.

Strategies that increase homing to the bone marrow and engraftment efficacy of ex vivo expended CD34(+) cells are expected to enhance their clinical utility. Here we report that nicotinamide (NAM), a form of vitamin B-3, delayed differentiation and increased engraftment efficacy of cord blood-derived human CD34(+) cells cultured with cytokines. In the presence of NAM, the fraction of CD34(+)CD38(-) cells increased and the fraction of differentiated cells (CD14(+), CD11b(+), and CD11c(+)) decreased. CD34(+) cells cultured with NAM displayed increased migration toward stromal cell derived factor-1 and homed to the bone marrow with higher efficacy, thus contributing to their increased engraftment efficacy, which was maintained in competitive transplants with noncultured competitor cells. NAM is a known potent inhibitor of several classes of ribosylase enzymes that require NAD for their activity, as well as sirtuin (SIRT1), class III NAD(+)-dependent-histone-deacetylase. We demonstrated that EX-527, a specific inhibitor of SIRT1 catalytic activity, inhibited differentiation of CD34(+) cells similar to NAM, while specific inhibitors of NAD-ribosylase enzymes did not inhibit differentiation, suggesting that the NAM effect is SIRT1-specific. Our findings suggest a critical function of SIRT1 in the regulation of hematopoietic stem cell activity and imply the clinical utility of NAM for ex vivo expansion of functional CD34(+) cells., (Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)