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Objective: In‐utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in‐utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in‐utero ONTD repair. Methods: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy‐assisted fetoscopic repair or open‐hysterotomy fetal surgery at a single tertiary center between September 2011 and July 2021. All patients met the MOMS eligibility criteria and had a normal karyotype. In a subset of the pregnancies (n = 77), CMA testing was also conducted. We reviewed the CMA results and divided the cohort into two groups according to whether clinically reportable copy‐number variants (CNV) were detected (reportable‐CNV group) or not (normal‐CMA group). Surgical characteristics, complications, and maternal and early neonatal outcomes were compared between the two groups. The primary outcomes were fetal or neonatal death, hydrocephalus, motor function at 12 months of age and walking status at 30 months of age. Standard parametric and non‐parametric statistical tests were employed as appropriate. Results: During the study period, 146 fetuses with ONTD were eligible for and underwent in‐utero repair. CMA results were available for 77 (52.7%) patients. Of those, 65 (84%) had a normal CMA and 12 (16%) had a reportable CNV, two of which were classified as pathogenic. The first case with a pathogenic CNV was diagnosed with a 749‐kb central 22q11.21 deletion spanning low‐copy‐repeat regions B–D of chromosome 22; the second case was diagnosed with a 1.3‐Mb interstitial deletion at 1q21.1q21.2. Maternal demographics, clinical characteristics, operative data and postoperative complications were similar between those with normal CMA results and those with reportable CNVs. There were no significant differences in gestational age at delivery or any obstetric and early neonatal outcome between the study groups. Motor function at birth and at 12 months of age, and walking status at 30 months of age, were similar between the two groups. Conclusions: Standard diagnostic testing with CMA should be offered when an ONTD is detected prenatally, as this approach has implications for counseling regarding prognosis and recurrence risk. Our results indicate that the presence of a clinically reportable CNV should not a priori affect eligibility for in‐utero repair, as overall pregnancy outcome is similar in these cases to that of cases with normal CMA. Nevertheless, significant CMA results will require a case‐by‐case multidisciplinary discussion to evaluate eligibility. To generalize the conclusion of this single‐center series, a larger, multicenter long‐term study should be considered. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This article, titled "EP05.12: Prenatal imaging and clinical outcomes in isolated congenital aqueductal stenosis: a single-centre retrospective cohort study," explores the prenatal imaging measures, clinical course, and outcomes associated with isolated congenital aqueductal stenosis (CAS). CAS is a known cause of obstructive hydrocephalus and can lead to poor neurodevelopmental outcomes. The study included 22 patients with isolated CAS who were imaged prenatally and had at least one year of clinical follow-up. The findings indicate that there is a progressive increase in ventricular sizes from initial imaging to delivery, with most children requiring cerebrospinal fluid (CSF) diversion procedures and experiencing neurodevelopmental impairment. [Extracted from the article]

Objective: To evaluate the efficacy of long‐term indomethacin therapy (LIT) in prolonging pregnancy and reducing spontaneous preterm birth (PTB) in patients undergoing fetoscopic laser surgery (FLS) for the management of twin‐to‐twin transfusion syndrome (TTTS). Design: Retrospective cohort study of prospectively collected data. Setting: Collaborative multicentre study. Population: Five hundred and fifty‐seven consecutive TTTS cases that underwent FLS. Methods: Long‐term indomethacin therapy was defined as indomethacin use for at least 48 hours. Log‐binomial regression was used to estimate the relative risk of PTB in the LIT group compared with a non‐LIT group. Cox regression was used to evaluate the association between LIT use and FLS‐to‐delivery survival. Main outcome measures: Gestational age (GA) at delivery. Results: Among the 411 pregnancies included, a total of 180 patients (43.8%) received LIT after FLS and 231 patients (56.2%) did not. Median GA at fetal intervention did not differ between groups (20.4 weeks). Median GA at delivery was significantly higher in the LIT group (33.6 weeks) compared with the non‐LIT group (31.1 weeks; P < 0.001). FLS‐to‐delivery interval was significantly longer in the LIT group (P < 0.001). The risks of PTB before 34, 32, 28 and 26 weeks of gestation were all significantly lower in the LIT group compared with the non‐LIT group (relative risks 0.69, 0.51, 0.37 and 0.18, respectively). The number needed to treat with LIT to prevent one PTB before 32 weeks of gestation was four, and to prevent one PTB before 34 weeks was five. Conclusion: Long‐term indomethacin after FLS for TTTS was found to be associated with prolongation of pregnancy and reduced risk for PTB. Long‐term indomethacin used after fetoscopic laser surgery for twin‐to‐twin transfusion syndrome is effective in prolonging pregnancy and reducing the risk for preterm birth; especially extreme preterm birth. Long‐term indomethacin used after fetoscopic laser surgery for twin‐to‐twin transfusion syndrome is effective in prolonging pregnancy and reducing the risk for preterm birth; especially extreme preterm birth. Linked article This article is commented on by Y Ville pp. 607 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471-0528.17015. [ABSTRACT FROM AUTHOR]

Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17-39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007-2022). Patients were classified as one of the following categories: poor responders-daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders-4-15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD ( p = 0.005), and nulliparity with the composite outcome ( p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes.

Objective: To evaluate the prenatal diagnosis of closed dysraphism (CD) and its correlation with postnatal findings and neonatal adverse outcomes., Methods: A retrospective cohort study including pregnancies diagsnosed with fetal CD by prenatal ultrasound (US) and magnetic resonance imaging (MRI) at a single tertiary center between September 2011 and July 2021., Results: CD was diagnosed prenatally and confirmed postnatally in 12 fetuses. The mean gestational age of prenatal imaging was 24.2 weeks, in 17% the head circumference was ≤fifth percentile and in 25% the cerebellar diameter was ≤fifth percentile. US findings included banana sign in 17%, and lemon sign in 33%. On MRI, posterior fossa anomalies were seen in 33% of cases, with hindbrain herniation below the foramen magnum in two cases. Mean clivus-supraocciput angle (CSA) was 74°. Additional anomalies outside the CNS were observed in 50%. Abnormal foot position was demonstrated prenatally in 17%. Neurogenic bladder was present in 90% of patients after birth., Conclusion: Arnold Chiari II malformation and impaired motor function can be present on prenatal imaging of fetuses with CD and may be associated with a specific type of CD. Prenatal distinction of CD can be challenging. Associated extra CNS anomalies are frequent and the rate of neurogenic urinary tract dysfunction is high., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies., Objective: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique., Study Design: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated., Results: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa., Conclusion: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The mammalian/mechanistic target of rapamycin (mTOR) is a protein kinase that plays a crucial role in regulating cellular growth, metabolism, and survival. Although there is no absolute contraindication for the use of mTOR inhibitors during pregnancy, the specific fetal effects remain unknown. Available data from the past 2 decades have examined the use of mTOR inhibitors during pregnancy in patients with solid organ transplantation, showing no clear link to fetal complications or structural abnormalities. Recently, a handful of case reports and series have described transplacental therapy of mTOR inhibitors to control symptomatic and complicated pathologies in the fetus. The effect of these agents includes a significant reduction in lesion size in the fetus and a reduced need for mechanical ventilation in neonates. In this context, we delve into the potential of mTOR inhibitors as in-utero therapy for fetal abnormalities, with a primary focus on lymphatic malformation (LM) and cardiac rhabdomyoma (CR). While preliminary reports underscore the efficacy of mTOR inhibitors for the treatment of fetal CR and fetal brain lesions associated with tuberous sclerosis complex, chylothorax, and LMs, additional investigation and clinical trials are essential to comprehensively assess the safety and efficacy of these medications., (© 2024 John Wiley & Sons Ltd.)

Objective: The primary aim of this study is to utilize a neural network model to predict adverse neonatal outcomes in pregnancies complicated by gestational diabetes (GDM)., Design: Our model, based on XGBoost, was implemented using Python 3.6 with the Keras framework built on TensorFlow by Google. We sourced data from medical records of GDM-diagnosed individuals who delivered at our tertiary medical center between 2012 and 2016. The model included simple pregnancy parameters, maternal age, body mass index (BMI), parity, gravity, results of oral glucose tests, treatment modality, and glycemic control. The composite neonatal adverse outcomes defined as one of the following: large or small for gestational age, shoulder dystocia, fetal umbilical pH less than 7.2, neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), hyperbilirubinemia, or polycythemia. For the machine training phase, 70% of the cohort was randomly chosen. Each sample in this set consisted of baseline parameters and the composite outcome. The remaining samples were then employed to assess the accuracy of our model., Results: The study encompassed a total of 452 participants. The composite adverse outcome occurred in 29% of cases. Our model exhibited prediction accuracies of 82% at the time of GDM diagnosis and 91% at delivery. The factors most contributing to the prediction model were maternal age, pre-pregnancy BMI, and the results of the single 3-h 100 g oral glucose tolerance test., Conclusion: Our advanced neural network algorithm has significant potential in predicting adverse neonatal outcomes in GDM-diagnosed individuals.

Background: The administration of antenatal corticosteroids (ACS) is standard practice for management of threatened preterm birth. Its benefit, especially in small for gestational age (SGA) late preterm, is unclear., Objectives: To evaluate the impact of ACS on perinatal outcome of late preterm SGA neonates., Methods: We conducted a retrospective cohort study of all women carrying a singleton gestation who had late preterm delivery (34-36 gestational weeks) of SGA neonates at a single tertiary university-affiliated medical center (July 2012-December 2017). Exclusion criteria included termination of pregnancy, intrauterine fetal death, and birth weight ≥ 10th percentile. Outcomes were compared between ACS and non-ACS treatment prior to delivery. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, and transient tachypnea., Results: Overall, 228 women met inclusion criteria; 102 (44.7%) received ACS and 126 did not (55.3%). Median birth weight among the non-ACS group was significantly higher (1896.0 vs. 1755.5 grams P < 0.001). Rates of NICU and jaundice requiring phototherapy were higher among the ACS group (53.92% vs. 31.74%, P = 0.01; 12.74% vs. 5.55%, P = 0.05, respectively). Composite neonatal outcome was significantly higher among the ACS group (53.92% vs. 32.53%, odds ratio [OR] 2.42, 95% confidence interval [95%CI] 1.41-4.15, P = 0.01). After adjustment for potential confounders, this association remained significant (OR 2.15, 95%CI 1.23-3.78, P = 0.007)., Conclusions: ACS given during pregnancy did not improve respiratory outcome for SGA late preterm neonates. ACS may be associated with a worse outcome.

To investigate the outcomes of asymptomatic stage I twin-to-twin transfusion syndrome (stage I TTTS) among patients treated with fetoscopic laser photocoagulation (FLP) versus expectant management. Databases such as PubMed, Web of Science and Scopus were systematically searched from inception up to March 1st, 2022. The primary outcome was at least one fetal survival at birth and secondary outcomes included gestational age at delivery, preterm premature rupture of membranes < 32 weeks, preterm birth < 32 weeks, and single and dual fetal survival. Five studies were included in the meta-analysis. There was no significant difference in terms of at least one survival (odds ratio (OR) = 1.40, 95%CI= (0.26, 7.43), P = 0.70), single survival (OR = 0.87, 95%CI= (0.51, 1.48), P = 0.60) and dual survival (OR = 1.63, 95%CI= (0.74, 3.62), P = 0.23) among FLP and expectant groups. Gestational age at delivery (mean difference = 1.19, 95%CI= (-0.25, 2.63), P = 0.10), the risk of PTB<32 weeks (OR = 0.88, 95%CI= (0.50, 1.54), P = 0.65), and pPROM<32 weeks (OR = 1.80, 95% CI= (0.41, 7.98), P = 0.44) were also comparable between the groups. Routine FLP of the placental anastomoses before 26 weeks of gestation is unlikely to be beneficial among asymptomatic stable stage I TTTS patients without cervical shortening as the procedure does not offer a survival advantage compared with expectant management., (© 2023 John Wiley & Sons Ltd.)

Background: In utero repair of open neural tube defects using an open hysterotomy approach (hereafter referred to as "open") has been shown to reduce the need for ventriculoperitoneal shunting and to improve motor outcomes for affected infants. Laparotomy-assisted fetoscopic repair (hereafter referred to as "hybrid") is an alternative approach that may confer similar neurologic benefits while reducing the incidence of hysterotomy-related complications., Objective: This study aimed to analyze procedure-related maternal and fetal complications of in utero repair using the Clavien-Dindo classification, and to compare the outcomes of the hybrid and open approaches., Study Design: This was a retrospective cohort study conducted in a single center between September 2011 and July 2021. All patients who met the Management of Myelomeningocele Study criteria and who underwent either hybrid or open fetal surgery were included. Maternal complications were classified using a unique adaptation of the Clavien-Dindo scoring system, allowing the development of a comprehensive complication index score specific to fetal surgery. Primary fetal outcome was defined as gestational age at delivery and summarized according to the World Health Organization definitions of preterm delivery., Results: There were 146 fetuses with open neural tube defects who were eligible for, and underwent, in utero repair during the study period. Of these, 102 underwent hybrid fetoscopic repair and 44 underwent open hysterotomy repair. Gestational age at the time of surgery was higher in the hybrid group than in the open group (25.1 vs 24.8 weeks; P=.004). Maternal body mass index was lower in the hybrid than in the open group (25.4 vs 27.1 kg/m 2 ; P=.02). The duration of hybrid fetoscopic surgery was significantly longer in the hybrid than in the open group (250 vs 164 minutes; P<.001). There was a significantly lower Clavien-Dindo Grade III complication rate (4.9% vs 43.2%; P<.001) and a significantly lower overall comprehensive maternal complication index (8.7 vs 22.6; P=.021) in the hybrid group than in the open group. Gestational age at delivery was significantly higher in the hybrid group than in the open group (38.1 vs 35.8 weeks; P<.001), and this finding persisted when gestational age at delivery was analyzed using the World Health Organization definitions of preterm delivery., Conclusion: Use of our adaptation of the standardized Clavien-Dindo classification to assess the maternal complications associated with in utero open neural tube defect repair provides a new method for objectively assessing different fetal surgical approaches. It also provides a much-needed standardized tool to allow objective comparisons between methods, which can be used when counseling patients. The hybrid open neural tube defect repair was associated with lower rates of maternal adverse events , and later gestational age at delivery compared with the open approach., (Copyright © 2022. Published by Elsevier Inc.)

Background: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure., Methods: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records., Results and Discussion: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Frier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To compare perinatal outcomes in pregnancies with fetal growth restriction (FGR) undergoing induction of labor by extra-amniotic balloon (EAB) versus prostaglandin E 2 (PGE 2 )., Methods: A retrospective cohort study of women with singleton pregnancies and FGR, undergoing induction at term via EAB, PGE 2 , or both, at a single medical center (2014-2017). Primary outcome was rate of cesarean deliveries (CDs). Secondary outcomes included composite maternal and neonatal outcomes., Results: Overall, 266 women met the inclusion criteria. Among them, 131 (49.2%) underwent induction by PGE 2 , 116 (43.6%) by EAB, and 19 (7.14%) by both methods. No differences were noted in baseline characteristics. Rate of CD (17.24% vs. 6.11% vs. 10.53%, P = 0.022) and maternal composite outcome (18.97% vs. 6.11% vs. 10.53%, P < 0.01) were higher among women who underwent induction by EAB compared with PGE 2 or both. No difference was noted between groups in neonatal outcomes. In a multivariable logistic regression, rates of cesarean delivery and composite maternal outcome were no longer higher in the EAB group (adjusted odds ratio [aOR] 1.68, 95% confidence interval [CI] 0.68-4.16, P = 0.260; and aOR 1.94, 95% CI 0.84-4.45, P = 0.120, respectively)., Conclusion: EAB and PGE 2 have comparable maternal and neonatal outcomes when used for induction of labor due to FGR., (© 2022 International Federation of Gynecology and Obstetrics.)

Background: Induction of labor is performed in up to 25% of pregnant women. When the cervix is unfavorable, cervical ripening may be safely and effectively performed using slow-release vaginal inserts of prostaglandin E2. However, the risk factors, management, and outcome of patients who fail to respond remain unclear., Objective: To evaluate the outcomes of women who fail to respond to cervical ripening with prostaglandins., Methods: A retrospective cohort analysis (2013-2019) was conducted. Women with a singleton gestation who underwent induction of labor due to post-date pregnancy using a slow-release prostaglandin E2 vaginal insert for cervical ripening were included. Data on clinical and outcome factors were derived from the medical files, and findings were compared between patients who achieved ripening within 24 h of treatment onset and those who did not. The primary outcome measure was the vaginal delivery rate following the ripening process. Secondary outcome measures were adverse composite maternal and neonatal outcomes. A model combining maternal characteristics and response rates to ripening was constructed., Results: The final cohort included 1285 women: 1202 responded to cervical ripening (93.54%) and 83 (6.46%) did not. Compared to non-responders, responders had higher rates of vaginal delivery (96.51% vs. 66.27%, P  < 0.001); lower rates of adverse maternal composite outcome (12.81% vs. 24.10%, P  = 0.031) and adverse neonatal composite respiratory outcome (1.33% vs. 6.02%, P  = 0.009). Responders were younger than non-responders (mean 30.03 years vs 31.73 years, P  = 0.005) and had a lower nulliparity rate (50.99% vs 76.92%, P  < 0.001). On multivariate analysis, failure to achieve cervical ripening was an independent risk factor for intrapartum cesarean delivery due to prolonged labor (aOR 11.90, 95% CI 6.13-23.25)., Conclusion: Women who achieve cervical ripening with prostaglandin E2 vaginal inserts are younger and more often multiparous than women who fail to respond. Good response to the cervical ripening process is associated with lower rates of intrapartum cesarean delivery and of adverse outcomes., Competing Interests: 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., (© 2023 The Authors.)

Objective: To assess outcomes in twin-twin transfusion syndrome (TTTS) according to middle cerebral artery pulsatility index (MCA-PI) prior to fetoscopic laser photocoagulation (FLPC) surgery., Methods: A retrospective cohort analysis of monochorionic-twin pregnancies complicated by TTTS who underwent FLPC at two fetal centers (2012-2021). The cohort was stratified according to abnormal MCA-PI of the donor twin, defined as below fifth centile for gestational age., Results: Abnormal MCA-PI of the donor twin was detected in 46 (17.7%) cases compared to 213 (83.3%) controls with no such abnormality. The abnormal PI group presented with higher rates of sFGR (56.5% vs. 36.8% in controls, p = 0.014) and lower donor survival rates within 48 h after FLPC (73.9 vs. 86.8%, p = 0.029). Donor twin survival rates at the time of delivery and 30 days after birth were lower in the abnormal MCA-PI. Multivariate logistic regression analysis controlling for sFGR and MCA-PI

Introduction: The aim of the study was to characterize the changes in fetal lung volume following fetoscopic endoluminal tracheal occlusion (FETO) that are associated with infant survival and need for extracorporeal membrane oxygenation (ECMO) in congenital diaphragmatic hernia (CDH)., Methods: Fetuses with CDH who underwent FETO at a single institution were included. CDH cases were reclassified by MRI metrics [observed-to-expected total lung volume (O/E TLV) and percent liver herniation]. The percent changes of MRI metrics after FETO were calculated. ROC-derived cutoffs of these changes were derived to predict infant survival to discharge. Regression analyses were done to determine the association between these cutoffs with infant survival and ECMO need, adjusted for site of CDH, gestational age at delivery, fetal sex, and CDH severity., Results: Thirty CDH cases were included. ROC analysis demonstrated that post-FETO increases in O/E TLV had an area under the curve of 0.74 (p = 0.035) for the prediction of survival to hospital discharge; a cutoff of less than 10% was selected. Fetuses with a &lt;10% post-FETO increase in O/E TLV had lower survival to hospital discharge [44.8% vs. 91.7%; p = 0.018] and higher ECMO use [61.1% vs. 16.7%; p = 0.026] compared to those with an O/E TLV increase ≥10%. Similar results were observed when the analyses were restricted to left-sided CDH cases. A post-FETO &lt;10% increase in O/E TLV was independently associated with lower survival at hospital discharge (aOR: 0.073, 95% CI: 0.008-0.689; p = 0.022) and at 12 months of age (aOR: 0.091, 95% CI: 0.01-0.825; p = 0.036) as well as with higher ECMO use (aOR: 7.88, 95% CI: 1.31-47.04; p = 0.024)., Conclusion: Fetuses with less than 10% increase in O/E TLV following the FETO procedure are at increased risk for requiring ECMO and for death in the postnatal period when adjusted for gestational age at delivery, CDH severity, and other confounders., (© 2023 S. Karger AG, Basel.)

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n = 671 undergoing Solomon and n = 993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: -1.167; 95% credible interval [CrI]: -2.01, -0.33; p = 0.021; I 2 : 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p = 0.012; I 2 : 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: -0.43, 1.49; p = 0.131; I 2 : 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption., (© 2022 John Wiley & Sons Ltd.)

Background: Ample evidence supports fetoscopic laser photocoagulation of placental anastomoses as a first-line treatment for twin-to-twin transfusion syndrome, but little is known about the outcomes following procedures conducted in the early second trimester., Objective: This study aimed to evaluate perinatal outcomes following early fetoscopic laser placental photocoagulation performed for twin-to-twin transfusion syndrome at 16 weeks' gestation., Study Design: This retrospective review included monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome necessitating fetoscopic laser photocoagulation at a single tertiary center from 2012 to 2021. The 2 cohorts were defined as cases undergoing laser surgery at 16+0/7 to 16+6/7 weeks' gestation (early laser group) and those undergoing laser surgery ≥17 weeks' gestation (standard laser group), respectively. Primary outcomes included rates of immediate chorioamniotic membrane separation, preterm premature rupture of membranes, and clinical chorioamnionitis. Secondary outcomes included twin survival rates at birth and 30 days of life. Outcomes were compared between cohorts with a P value of <.05 denoting statistical significance., Results: A total of 343 cases were included (35 early laser participants and 308 standard laser participants). The early laser group typically had higher Quintero staging at the time of the procedure. Following intervention, the early laser group had significantly higher rates of chorioamniotic separation than the standard laser group (34.3% vs 1.3% of cases; P<.001) and higher rates of preterm prelabor rupture of membranes (45.7% vs 25.0%; P=.009) and chorioamnionitis (11.4% vs 1.3%; P=.005). Even after adjustment for higher Quintero staging in the early laser group, twin survival was not significantly different between study groups., Conclusion: Early laser surgery for twin-to-twin transfusion syndrome performed at 16 weeks' gestation is associated with significantly higher rates of chorioamniotic separation, preterm rupture of membranes, and chorioamnionitis. However, twin survival does not seem to be negatively impacted following early laser surgery., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To compare the outcomes of dichorionic triamniotic (DCTA) triplets with that of monochorionic diamniotic (MCDA) twin gestations undergoing fetoscopic laser surgery (FLS) for treatment of twin-to-twin transfusion syndrome (TTTS)., Methods: Retrospective cohort study of prospectively collected data of consecutive DCTA triplet and MCDA twin pregnancies with TTTS that underwent FLS at two fetal treatment centers between 2012 and 2020. Preoperative, operative and, postoperative variables were collected. Perinatal outcomes were investigated. Primary outcome was survival to birth and to neonatal period. Secondary outcomes were gestational age (GA) at birth and procedure-to-delivery interval. Literature review was conducted in which PubMed, Web of Science, and Scopus were searched from inception to September, 2020., Results: Twenty four sets of DCTA triplets were compared to MCDA twins during the study period. There were no significant differences in survival (no survivor, single, or double survivors) to birth and to the neonatal period of the MC twin pairs of the DCTA triplets vs MCDA twins. Median GA at delivery was approximately three weeks earlier in DCTA triplets compared to MCDA twins (28.4 weeks vs 31.4 weeks, p  = .035, respectively). Rates of preterm birth (PTB) less than 32 and less than 28 weeks were significantly higher in DCTA triplets compared to twins (<32 weeks: 70.8% vs 51.1%, p  = .037, respectively, and <28 weeks: 37.5% vs 20.8%, p  = .033, respectively)., Conclusion: Perinatal survival including fetal and neonatal are comparable between DCTA triplets and MCDA twins. However, this might have resulted from the small sample size of the DCTA triplets. GA at delivery is earlier in triplets, which could be due to the nature of triplet gestation rather than to the laser procedure itself.

Objectives: To evaluate the survival of twin-to-twin transfusion syndrome (TTTS) and concomitant twin anemia polycythemia sequence (TAPS) compared to TTTS without TAPS at the time of fetoscopic laser photocoagulation (FLP)., Methods: TTTS pregnancies undergoing FLP were divided to three groups including (i) traditional TAPS definition of middle cerebral artery (MCA) peak systolic velocity (PSV) < 1 multiple of the median (MoM) in recipient and > 1.5 MoM in the donor fetus, (ii) delta MCA-PSV > 0.5 MoM and (iii) delta MCA-PSV > 1.0 MoM., Results: A total of 353 monochorionic twins underwent FLP for TTTS. Based on the traditional definition, 335 (94.9 %) had TTTS only and 18 (5.1 %) had TTTS + TAPS. There were 245 (69.4 %) TTTS only and 108 (30.6 %) TTTS + TAPS considering delta MCA-PSV > 0.5 MoM and 339 (96 %) TTTS only and 14 (4 %) TTTS + TAPS considering delta MCA-PSV > 1.0 MoM. No significant differences in survival were noted at birth or 30-days after delivery between TTTS and TTTS with TAPS patients using the traditional definition, delta > 0.5 MoM or delta > 1.0 MoM., Conclusion: The rate of neonatal survival at birth or at 30-days of life following FLP for TTTS only and TTTS with TAPS were not different based on any of the clinically used TAPS definitions., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: The appropriate medical treatment for gestational diabetes mellitus (GDM) is controversial and recommendations vary between different organizations., Objective: To compare the safety and efficacy of glyburide and insulin as treatments for GDM., Methods: Retrospective analysis of all pregnant women diagnosed with GDM and treated with either glyburide or insulin. Demographic features, clinical characteristics, maternal and neonatal outcomes were compared according to type of pharmacological treatment., Results: Included in the study were 323 women, of whom 269 (83.28%) were treated with glyburide and 54 (16.72%) with insulin. There were no significant differences between the groups, apart from a higher one-hour oral glucose tolerance test (OGTT) value (191.80 mg/dl in the glyburide group, 204.33 in the insulin group, p = .01). Optimal glucose control was achieved in 130 women in the glyburide group (48.32%) and 15 in the insulin group (27.77%), p = .007. This difference remained significant after adjustment for age, BMI, and fasting glucose during OGTT (aOR = 2.22). Mean gestational weight gain was lower in the glyburide group vs. insulin group (10.01 vs. 11.99 kg, p  = .048). Apart from higher maternal hypoglycemia rate (12.64% in glyburide group vs. 1.85% in insulin group, p  = .016), there were no other differences in maternal and neonatal outcomes between the groups. Glyburide failure rate was 13.38%, and associated with higher fasting OGTT value (100.70 mg/dl in glyburide failure group vs. 94.67 mg/dl in the glyburide treatment until delivery group, p  = .041)., Conclusions: Glyburide is at least as safe and effective as insulin except for higher rates of maternal hypoglycemia. Considering its advantages compared to insulin (ease of use and storage, increased patient responsiveness, and lower cost), it may be considered as first line treatment in GDM, especially when fasting OGTT value is not high.

Introduction: This study sought to investigate the correlation between histologically proven chorioamnionitis and placental bacteriologic infection in preterm births., Methods: Women who gave birth before 34 + 0 weeks' gestation at a tertiary medical center between the years 2018-2019 were identified by a database review. Data was collected on clinical characteristics and findings on placental histology, cultures, and polymerase chain reaction. The correlation between histologically confirmed chorioamnionitis and bacteriologic infection was evaluated., Results: Of 183 placentas included in the study, 88 (48.1%) were histologically positive for chorioamnionitis and 95 (51.9%) were negative. Baseline characteristics were similar in the patients with and without chorioamnionitis. Concordance rates between the histology and microbiology results in the two groups were 51.1% and 64.2%, respectively. Similar types of bacterial microorganisms were isolated in both groups, though at different rates. On chi-square analysis of association, a positive microbiological study had a sensitivity of 51.1%, specificity of 64.2%, and positive predictive value of 56.9% for predicting histologically confirmed chorioamnionitis. Histologically confirmed chorioamnionitis was associated with higher antepartum white blood cell count (14.2 ± 4.6 vs 12.3 ± 3.3 K/μL; p = 0.01), higher rate of clinically suspected chorioamnionitis (10.2% vs 1.1%, p = 0.02), and higher rate of neonatal adverse composite outcome (36.4% vs. 22.1%, p = 0.009)., Discussion: The correlation between histologic and bacteriologic placental findings in the setting of early premature delivery is not high, nor is the clinical yield of placental bacteriology. The discordant results might be explained by early stage of bacterial infection, hard-to-cultivate bacterial species, noninfectious conditions, or contamination of the placental surfaces during passage through the vaginal tract., (Copyright © 2022. Published by Elsevier Ltd.)

This retrospective study was conducted to determine if infants born prematurely despite prophylactic maternal progesterone treatment during pregnancy may still benefit from its adjunct properties and have decreased neonatal complications. 248 women treated with vaginal/intramuscular progesterone during pregnancy and 2519 controls who gave birth to a preterm newborn (24 + 0-36 + 6 gestational weeks) at a tertiary medical centre in 2012-2019. The primary outcome measure was neonatal infectious composite outcome. Secondary outcome measures were other maternal and neonatal complications. Compared to controls, the study group was characterised by lower gestational age at birth (35.0 ± 2.66 vs. 36.0 ± 2.23 weeks, p  < .001), lower birth weight (2294 vs. 2485 g, p  < .001), higher rates of neonatal infectious composite outcome (27.82 vs. 21.36%, p  = 0.024), NICU admission, periventricular leukomalacia, and mechanical ventilation. The higher neonatal infectious composite outcome is likely associated with the lower gestational age at birth in this high-risk group and not the progesterone treatment per se.IMPACT STATEMENT What is already known on this subject? Several randomised controlled trials have shown that progesterone administration in pregnancy significantly reduced the rate and complications of preterm birth. A recent study reported that vaginal administration of progesterone during pregnancy was more effective than intramuscular administration in decreasing vaginal group B Streptococcus (GBS) colonisation. This finding raises the question of whether progesterone treatment may have additional benefits besides preventing preterm birth and may reduce neonatal complication rate in preterm infants. What do the results of this study add? This is the first study examining the impact of gestational progesterone exposure on outcomes of preterm infants. The primary objective was a composite measure of infectious neonatal outcomes. Newborns who had progesterone exposure on average had lower gestational age, lower birth weight and higher neonatal infectious composite outcome. The significant difference is explained by lower gestational age. What are the implications of these findings for clinical practice and/or further research? Progesterone is widely used to prevent preterm birth, and may have important additive effects even when prematurity is not avoided. Although the findings did not support our initial hypothesis, they warrant further examination with larger cohorts.

Objective: This systematic review and meta-analysis aimed to compare the fetal survival rate and perinatal outcomes of triplet pregnancies after selective reduction to twin pregnancies vs singleton pregnancies., Data Sources: PubMed, Web of Science, Scopus, and Embase were systematically searched from the inception of the databases to January 16, 2022., Study Eligibility Criteria: Studies comparing the survival and perinatal outcomes between reduction to twin pregnancies and reduction to singleton pregnancies were included. The primary outcomes were fetal survival, defined as a live birth at >24 weeks of gestation. The secondary outcomes were gestational age at birth, preterm birth at <32 and <34 weeks of gestation, early pregnancy loss (<24 weeks of gestation), low birthweight, and rate of neonatal demise (up to 28 days after birth)., Methods: The random-effect model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. To provide a range of expected effects if a new study was conducted, 95% prediction intervals were calculated for outcomes presented in >3 studies., Results: Of note, 10 studies with 2543 triplet pregnancies undergoing fetal reduction, of which 2035 reduced to twin pregnancies and 508 reduced to singleton pregnancies, met the inclusion criteria. Reduction to twin pregnancies had a lower rate of fetal survival (odds ratio, 0.61; 95% confidence interval, 0.40-0.92; P=.02; 95% prediction interval, 0.36-1.03) and comparable rates of early pregnancy loss (odds ratio, 0.89; 95% confidence interval, 0.58-1.38; P=.61; 95% prediction interval, 0.54-1.48) and neonatal demise (odds ratio, 0.57; 95% confidence interval, 0.09-3.50; P=.55) than reduction to singleton pregnancies. Reduction to twin pregnancies had a significantly lower gestation age at birth (weeks) (mean difference, -2.20; 95% confidence interval, -2.80 to -1.61; P<.001; 95% prediction interval, -4.27 to -0.14) than reduction to singleton pregnancies. Furthermore, reduction to twin pregnancies was associated with lower birthweight and greater risk of preterm birth at <32 and <34 weeks of gestation., Conclusion: Triplet pregnancies reduced to twin pregnancies had a lower fetal survival rate of all remaining fetuses, lower gestational age at birth, higher risk of preterm birth, and lower birthweight than triplet pregnancies reduced to singleton pregnancies; reduction to twin pregnancies vs reduction to singleton pregnancies showed no substantial difference for the rates of early pregnancy loss and neonatal death., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To compare perinatal outcomes following induction of labor in dichorionic versus monochorionic twin pregnancies., Study Design: A retrospective cohort study analyzing all women with twin pregnancies who underwent induction of labor in a single university-affiliated tertiary medical center. The cohort included 290 women who were divided into 2 groups according to chorionicity: (1) dichorionic twin pregnancies (n = 203); (2) monochorionic twin pregnancies (n = 87). Induction of labor methods included oxytocin infusion, extra-amniotic balloon catheter and artificial amniotomy. Primary outcome was defined as mode of delivery. Secondary outcomes included maternal and neonatal adverse events., Results: Primary outcome did not differ between groups, with vaginal delivery rate of 92.1% in the dichorionic group and 94.2% in the monochorionic group. Women with dichorionic twins delivered later compared to monochorionic twins (38.00 weeks vs. 36.43 weeks, respectively, p < 0.001). While no differences were observed in Apgar scores or umbilical cord pH measurements, dichorionic twins were less frequently admitted to the neonatal intensive care unit compared to monochorionic twins (2.4% vs. 3.4%, p = 0.01 for 1st twin; and 6.9% vs. 10.3%, p = 0.089 for 2nd twin). Multivariate logistic regression adjusting outcomes to potential confounders, found gestational age at delivery to be the only variable significantly associated with neonatal intensive care unit admission rates (odds ratio 0.236, 95% confidence interval 0.152-0.366, p < 0.001)., Conclusion: Labor induction might be considered for both di- and monochorionic uncomplicated twin pregnancies with excellent vaginal delivery rates. The higher rates of neonatal adverse outcomes among monochorionic twins are presumably related to earlier gestation age at delivery., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Vulvovaginitis and labial adhesion are the most common gynecological morbidity among girls and adolescents. Even though pediatricians or family physicians should be capable of dealing with these "ailments", in Israel, these patients are referred to gynecologists because physicians from these two medical specialties are deterred to treat these populations. Treatment is based on softening and antibiotic creams applied locally. In the current relevant literature the present notion regarding these two pathologies is shifted toward follow-up and habit changes in terms of proper hygiene and clothing. In the present review the relevant current literature is examined and updated recommendations are suggested.