Prenatal Surgery for Open Fetal Spina Bifida in Patients with Obesity: A Review of Current Evidence and Future Directions.

Background: Obesity rates have significantly increased globally, affecting up to 40% of women of childbearing age in the United States. While prenatal repair of open fetal spina bifida has shown improved outcomes, most fetal surgery centers exclude patients with a body mass index (BMI) ≥ 35 kg/m2 based on criteria from the Management of Myelomeningocele Study (MOMS) trial. This exclusion raises concerns about healthcare equity and highlights a significant knowledge gap regarding the safety and efficacy of fetal spina bifida repair in patients with obesity. Objective: To review the current state of knowledge regarding open fetal surgery for fetal spina bifida in patients with obesity, focusing on safety, efficacy, and clinical considerations. Methods: A comprehensive literature search was conducted using the PubMed and EMBASE databases, covering articles from the inception of the databases to April 2024. Studies discussing fetal surgery for neural tube defects and documenting BMI measurements and their impact on surgical outcomes, published in peer-reviewed journals, and available in English were included. Quantitative data were extracted into an Excel sheet, and data synthesis was conducted using the R programming language (version 4.3.3). Results: Three retrospective studies examining outcomes of prenatal open spina bifida repair in a total of 43 patients with a BMI ≥ 35 kg/m2 were identified. These studies did not report significant adverse maternal or fetal outcomes compared to patients with lower BMIs. Our pooled analysis revealed a perinatal mortality rate of 6.1% (95% CI: 1.76-18.92%), with 28.0% (95% CI: 14.0-48.2%) experiencing the premature rupture of membranes and 82.0% (95% CI: 29.2-98.0%) delivering preterm (<37 weeks). Membrane separation was reported in 10.3% of cases (95% CI: 3.3-27.7%), the mean gestational age at birth was 34.3 weeks (95% CI: 32.3-36.3), and the average birth weight was 2651.5 g (95% CI: 2473.7-2829.4). Additionally, 40.1% (95% CI: 23.1-60.0%) required a ventriculoperitoneal shunt. Conclusion: While current evidence suggests that fetal spina bifida repair may be feasible in patients with obesity, significant limitations in the existing body of research were identified. These include small sample sizes, retrospective designs, and a lack of long-term follow-up data. There is an urgent need for large-scale, prospective, multicenter studies to definitively establish the safety and efficacy of fetal spina bifida repair in patients with obesity. Such research is crucial for developing evidence-based guidelines, improving clinical outcomes, and addressing healthcare disparities in this growing patient population with obesity.

Characteristics and Outcomes of Fetal Cardiac Rhabdomyoma With or Without mTOR Inhibitors, a Systematic Review and Meta-Analysis.

OBJECTIVES: To investigate the characteristics and outcomes of fetal cardiac rhabdomyoma with or without prenatal use of mammalian target of rapamycin inhibitor (mTORi). SEARCH STRATEGY: We systematically searched PubMed, Scopus, and Web of Science until June 2023. SELECTION CRITERIA: Studies reporting on pregnancies with fetal cardiac rhabdomyoma were included. DATA COLLECTION AND ANALYSIS: A meta-analysis of proportions was conducted only on studies that included three or more cases. RESULTS: A systematic review included 61 studies reporting on 400 fetuses with cardiac rhabdomyoma, of which 52 studies (389 fetuses) had expectant management and 9 studies (11 fetuses) were managed with mTORi. The meta-analysis included 26 studies reporting on 354 fetuses. Prenatally, 14% (95% CI 4-36) had pericardial effusion, 13% (95% CI 6-27) had arrhythmia, 16% (95% CI 7-31) had outflow tract obstruction, and 10% (95% CI 4-21) had hydrops. Fetal demise occurred in 12% (95% CI 5-30). Before delivery, tumor size reduction was noted in 13%, and after birth in 58%. Following birth, 8% (95% CI 3-14) had neonatal death and 9% (95% 4-17) required cardiac surgery. 60% (95% CI 41-79) of cases were diagnosed with tuberous sclerosis. Seizures were reported only in cases with a tuberous sclerosis diagnosis (41/71 infants). For the 9 studies reporting all together on 11 fetuses with tuberous sclerosis receiving prenatal mTORi, they showed improvement in the size of cardiac rhabdomyoma as well as outflow obstruction and none had fetal demise or neonatal death, and none required postnatal cardiac surgery. CONCLUSIONS: We report on the natural history of prenatal cardiac rhabdomyoma, including characteristics, progression, and survival. We report 11 fetuses with tuberous sclerosis and cardiac rhabdomyoma receiving prenatal mTORi, showing promising results.

Ultrasound prediction of fetal macrosomia in pregnancies complicated by diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of ultrasound in identifying fetuses with macrosomia in pregnancies complicated by gestational or pregestational diabetes. METHODS: Medline, Embase and Cochrane databases were searched. Inclusion criteria were singleton pregnancies complicated by diabetes undergoing third-trimester ultrasound evaluation. The index test was represented by ultrasound estimation of fetal macrosomia (estimated fetal weight EFW or abdominal circumference AC >90th or 95th percentile). Subgroup analyses were also performed. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver-operating characteristics model. RESULTS: Twenty studies were included in the systematic review including 8,530 pregnancies complicated by diabetes. Ultrasound showed an overall moderate accuracy in identifying fetuses with macrosomia with a sensitivity of 71.2 % (95 % CI 63.1-78.2), a specificity of 88.6 % (95 % CI 83.9-92.0). The interval between ultrasound and birth of two weeks showed the highest sensitivity and specificity (71.6 %, 95 % CI 47.9-87.3 and 91.7, 95 % CI 86.2-95.5). EFW sensitivity and specificity were 76.6 % (95 % CI 70.1-82.3) and 82.9 % (95 % CI 80.9-84.8), while AC 84.8 % (95 % CI 78.2-90.0) and 73.7 % (95 % CI 71.0-76.4). CONCLUSIONS: Ultrasound demonstrates an overall good diagnostic accuracy in detecting fetal macrosomia in pregnancies with diabetes.

Intravenous immunoglobulin for the treatment of severe maternal alloimmunization: individual patient data meta-analysis.

OBJECTIVE: This study aimed to investigate the outcomes associated with the administration of maternal intravenous immunoglobulin in high-risk red blood cell-alloimmunized pregnancies. DATA SOURCES: Medline, Embase, and Cochrane Library were systematically searched until June 2023. STUDY ELIGIBILITY CRITERIA: This review included studies reporting on pregnancies with severe red blood cell alloimmunization, defined as either a previous fetal or neonatal death or the need for intrauterine transfusion before 24 weeks of gestation in the previous pregnancy as a result of hemolytic disease of the fetus and newborn. METHODS: Cases were pregnancies that received intravenous immunoglobulin, whereas controls did not. Individual patient data meta-analysis was performed using the Bayesian framework. RESULTS: Individual patient data analysis included 8 studies consisting of 97 cases and 97 controls. Intravenous immunoglobulin was associated with prolonged delta gestational age at the first intrauterine transfusion (gestational age of current pregnancy - gestational age at previous pregnancy) (mean difference, 3.19 weeks; 95% credible interval, 1.28-5.05), prolonged gestational age at the first intrauterine transfusion (mean difference, 1.32 weeks; 95% credible interval, 0.08-2.50), reduced risk of fetal hydrops at the time of first intrauterine transfusion (incidence rate ratio, 0.19; 95% credible interval, 0.07-0.45), reduced risk of fetal demise (incidence rate ratio, 0.23; 95% credible interval, 0.10-0.47), higher chances of live birth at ≥28 weeks (incidence rate ratio, 1.88; 95% credible interval, 1.31-2.69;), higher chances of live birth at ≥32 weeks (incidence rate ratio, 1.93; 95% credible interval, 1.32-2.83), and higher chances of survival at birth (incidence rate ratio, 1.82; 95% credible interval, 1.30-2.61). There was no substantial difference in the number of intrauterine transfusions, hemoglobin level at birth, bilirubin level at birth, or survival at hospital discharge for live births. CONCLUSION: Intravenous immunoglobulin treatment in pregnancies at risk of severe early hemolytic disease of the fetus and newborn seems to have a clinically relevant beneficial effect on the course and severity of the disease.

Right ventricular outflow tract obstruction in twin-to-twin transfusion syndrome undergoing laser surgery: A systematic review and meta-analysis.

INTRODUCTION: We aimed to investigate the incidence, prenatal factors and outcomes of twin-to-twin transfusion (TTTS) with right ventricular outflow tract obstruction (RVOTO). MATERIAL AND METHODS: A systematic search was conducted to identify relevant studies published until February 2023 in English using the databases PubMed, Scopus and Web of Science. Studies reporting on pregnancies with TTTS and RVOTO were included. The random-effect model pooled the mean differences or odds ratios (OR) and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 17 studies encompassing 4332 TTTS pregnancies, of which 225 cases had RVOTO, were included. Incidence of RVOTO at time of TTTS diagnosis was 6%. In all, 134/197 (68%) had functional pulmonary stenosis and 62/197 (32%) had functional pulmonary atresia. Of these, 27% resolved following laser and 55% persisted after birth. Of those persisting, 27% required cardiac valve procedures. Prenatal associations were TTTS stage III (53% vs 39% in no-RVOTO), stage IV TTTS (28% in RVOTO vs 12% in no-RVOTO) and ductus venosus reversed a-wave (60% in RVOTO vs 19% in no-RVOTO). Gestational age at laser and gestational age at delivery were comparable between groups. Survival outcomes were also comparable between groups, including fetal demise of 26%, neonatal death of 12% and 6-month survival of 82% in RVOTO group. Findings were similar when subgroup analysis was done for studies including head-to-head analysis. CONCLUSIONS: RVOT occurs in about 6% of the recipient twins with TTTS, especially in stages III and IV and those with reversed ductus venosus a-wave. The findings from this systematic review support the need for a thorough cardiac assessment of pregnancies complicated by TTTS, both before and after laser, to maximize perinatal outcome, and the importance of early diagnosis of TTTS and timely management.

Perinatal outcomes following fetoscopic laser surgery for early twin-to-twin transfusion syndrome: Systematic review and meta-analysis.

INTRODUCTION: Our objective was to investigate outcomes in twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery (FLS) at <18 weeks vs ≥18 weeks, and to conduct subgroup analysis of TTTS with FLS at <16 weeks vs 16-18 weeks. MATERIAL AND METHODS: PubMed, Scopus and Web of Science were searched systematically from inception until May 2023. Primary outcome was survival, and secondary outcomes included preterm premature rupture of membranes (PPROM), preterm birth and gestational age (GA) at delivery. RESULTS: Nine studies encompassing 1691 TTTS pregnancies were included. TTTS stage III was significantly more common in TTTS pregnancies treated with FLS at <18 weeks (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.24-6.54), and procedure duration was shorter at <18 weeks (MD -5.27 minutes, 95% CI -9.19 to -1.34). GA at delivery was significantly earlier in TTTS pregnancies treated with FLS at <18 weeks (MD -3.12 weeks, 95% CI -6.11 to -0.13). There were no significant differences in outcomes, including PPROM, PPROM at <7 days post-FLS, preterm birth at <28 and <32 weeks, delivery at <7 days post-FLS, and survival outcomes, including fetal demise, live birth and neonatal survival. Similarly, TTTS stage III was more common in TTTS with FLS at <16 weeks than at 16-18 weeks (OR 2.95, 95% CI 1.62-5.35), with no significant differences in the aforementioned outcomes. CONCLUSIONS: In early TTTS treated with FLS, outcomes were comparable between those treated at <18 weeks compared with ≥18 weeks except for GA at delivery, which was 3 weeks earlier. In the subset treated at <16 weeks vs 16-18 weeks, the procedure was feasible without an increased risk of very early preterm birth or perinatal mortality.

Contribution of obesity to racial and ethnic disparities in the risk of fetal myelomeningocele: a population-based study.

BACKGROUND: Prepregnancy obesity and racial-ethnic disparities has been shown to be associated with meningomyelocele. OBJECTIVE: This study aimed to investigate the association of maternal periconceptional factors, including race-ethnicity and prepregnancy body mass index, with the prevalence of isolated fetal myelomeningocele. METHODS: This was a population-based cross-sectional study using Centers for Disease Control and Prevention birth data from 2016 to 2021. Major structural anomalies or chromosomal abnormalities were excluded. Race-ethnicity was classified as non-Hispanic White (reference population), non-Hispanic Black, non-Hispanic Asian, Hispanic, and others. Maternal prepregnancy body mass index was classified as underweight (<18.5 kg/m2), normal (reference group; 18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and class I (30-34.9 kg/m2), class II (35-39.9 kg/m2), and class III obesity (≥40 kg/m2). A chi-square test of independence was performed to identify factors significantly associated with myelomeningocele. These factors were then stratified into 3 adjusted clusters/levels. The prevalence was calculated per 10,000 live births. The Cochran-Armitage test for trend was used to detect any significant increasing or decreasing trends. RESULTS: A total of 22,625,308 pregnancies with live birth, including 2866 pregnancies with isolated fetal myelomeningocele, were included in the analysis. The prevalence of isolated fetal myelomeningocele per 10,000 live births varied among different racial/ethnic groups, with the highest prevalence found among the non-Hispanic White (1.60 [1.52-1.67]) and lowest among the non-Hispanic Asian (0.50 [0.40-0.64]) population. The prevalence significantly increased with body mass index, with the highest prevalence found in the population with class III obesity (1.88 per 10,000 live births). Subgroup analysis of the associations between the significant variables (obesity, diabetes, hypertension, and education) and each ethnicity in cases with myelomeningocele showed significant variations in prevalence of these variables among different racial/ethnic groups. Following the model with the 3 levels of adjustment described in the Methods section, prepregnancy overweight and class I, II, and III obesity remained significantly associated with the odds of isolated fetal myelomeningocele. The adjusted odds ratios were 1.32 (95% confidence interval, 1.19-1.46; P<.001) for overweight, 1.55 (95% confidence interval, 1.38-1.75; P<.001) for class I obesity, 1.68 (95% confidence interval, 1.45-1.94; P<.001) for class II obesity, and 1.73 (95% confidence interval, 1.47-2.04; P<.001) for class III obesity. Similarly, following the 3-level adjustment model, the obesity-mediated effect of maternal race-ethnicity on the odds of myelomeningocele remained significant (non-Hispanic Black: adjusted odds ratio, 1.03; 95% confidence interval, 1.02-1.05; P<.001; non-Hispanic Asian: adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P<.001; Hispanic: adjusted odds ratio, 1.5; 95% confidence interval, 1.03-1.6; P<.001). The test for trend among different racial/ethnic groups did not show significant results across the past 6 years. However, the test for trend showed a significant increase in the prevalence of isolated myelomeningocele associated with class II and III obesity over the past 6 years. CONCLUSION: There has been a rising trend of fetal isolated myelomeningocele in pregnancies with maternal class II and III obesity over the past 6 years after adjusting for other covariates. Prepregnancy obesity, a modifiable risk factor, is a significant driver of racial/ethnic disparities in the overall risk for isolated fetal myelomeningocele.

Prevalence, trend, and associated risk factors for cleft lip with/without cleft palate: a national study on live births from 2016 to 2021.

BACKGROUNDS: Cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial anomaly, including non-syndromic cleft lip with or without cleft palate and cleft palate only. Failure in the fusion of median and lateral nasal processes, the maxillary prominence, and soft tissues around the oral cavity can cause CL/P. Previously, the prevalence has been estimated to be 1 among every 1000 births in 2014 among American neonates and no other reports have been available since. Thus, this study aimed to calculate the prevalence and trend of isolated CL/P among American live births from 2016 to 2021 with its associated risk factors. METHODS AND MATERIALS: In this cross-sectional population-based retrospective study, we used live birth data provided by the National Center for Health Statistics (NCHS) from the Center for Disease Control and Prevention (CDC). We calculated the prevalence per 10,000 live births of isolated (non-syndromic) CL/P from 2016 to 2021. To examine risk factors for developing isolated CL/P, we used logistic regression modelling. RESULTS: The total prevalence per 10,000 births from 2016 to 2021 was 4.88 (4.79-4.97), for both sexes, and 5.96 (5.82-6.10) for males, and 3.75 (3.64-3.87) for females. The prevalence did not show any consistent linear decreasing or increasing pattern. We found significant association between increased odds of developing isolated CL/P among cases with 20 to 24 year-old mothers (OR = 1.07, 1.01-1.13, p = 0.013), mothers who smoked 11 to 20 cigarettes per day (OR = 1.46, 1.33-1.60, p <  0.001), mothers with extreme obesity (OR = 1.32, 1.21-1.43, p <  0.001), mothers with grade II obesity (OR = 1.32, 1.23-1.42, p <  0.001), mothers with pre-pregnancy hypertension (OR = 1.17, 1.04-1.31, p = 0.009), mothers with pre-pregnancy diabetes mellitus (OR = 1.96, 1.71-2.25, p <  0.001), and mothers who used assisted reproductive technology (OR = 1.40, 1.18-1.66, p <  0.001). CONCLUSIONS: Our findings suggest a minuscule increase, albeit insignificant, in the trend of CL/P prevalence from 2016 to 2021. Developing CL/P had greater odds among mothers with pre-pregnancy diabetes, smoking, obesity, and pre-pregnancy hypertension mothers along with mothers who used assisted reproductive technology. Isolated CL/P had the highest prevalence in non-Hispanic Whites, American Indian or Alaskan Native and Native Hawaiian and Other Pacific Islanders.

Prenatal Risk Factors and Outcomes of Pseudoamniotic Band Sequence following Fetoscopic Laser Surgery: Systematic Review, and Meta-Analysis.

BACKGROUND: Pseudoamniotic band sequence (PABS) is a rare iatrogenic consequence of invasive fetal interventions, most commonly fetoscopic laser surgery (FLS) in monochorionic multiple pregnancies complicated by twin-to-twin transfusion syndrome (TTTS). OBJECTIVES: The aim of this study was to investigate prenatal risk factors and perinatal outcomes for pregnancies involving PABS after FLS for TTTS and compare outcomes between those undergoing fetoscopic band release versus not. METHOD: We conducted a systematic search of PubMed, Scopus, and Web of Science on studies reporting PABS following FLS for TTTS. A meta-analysis of pooled proportions was conducted. RESULTS: There were 16 studies covering 47 pregnancies complicated by PABS following FLS, mostly case series and case reports. The incidence of PABS was 2%, with the recipient twin affected in 94% of the cases. Pregnancies complicated by PABS were associated with inter-twin septostomy in 32% and chorioamniotic separation (CAS) in 90%. The mean gestational age (GA) at FLS and delivery were 17.7 and 30.9 weeks, respectively. Preterm premature rupture of membranes (PPROM) happened in 62% of pregnancies. The risk of preterm birth (PTB) <34 weeks, <32 weeks, and <28 weeks were 94%, 67%, and 31%, respectively. There were 41% fetal demises and 64% live births among the affected fetuses. Results of fetoscopic band release versus not were comparable, including GA at delivery, PPROM, and PTB at 32 weeks. It was noted that the likelihood of PTB by 28 weeks (67% vs. 23%) and fetal death (50% vs. 39%) were higher in the band release group. It was similar between groups in terms of postnatal amputation. CONCLUSIONS: PABS causes amputations or fetal death in more than one-third of cases. Pregnancies with an inter-twin septostomy, CAS, advanced TTTS staging, and early GA are more likely to experience PABS. In addition, more than a third of FLS-treated TTTS resulted in PTB and PPROM. PABS cases with prenatal band release showed higher rates of PTB and fetal death, but the data were from small, heterogeneous studies.

Diagnostic performance of 32 vs 36 weeks ultrasound in predicting late-onset fetal growth restriction and small-for-gestational-age neonates: a systematic review and meta-analysis.

OBJECTIVE: Fetal growth restriction is an independent risk factor for fetal death and adverse neonatal outcomes. The main aim of this study was to investigate the diagnostic performance of 32 vs 36 weeks ultrasound of fetal biometry in detecting late-onset fetal growth restriction and predicting small-for-gestational-age neonates. DATA SOURCES: A systematic search was performed to identify relevant studies published until June 2022, using the databases PubMed, Web of Science, and Scopus. STUDY ELIGIBILITY CRITERIA: Cohort studies in low-risk or unselected singleton pregnancies with screening ultrasound performed at ≥32 weeks of gestation were used. METHODS: The estimated fetal weight and abdominal circumference were assessed as index tests for the prediction of small for gestational age (birthweight of <10th percentile) and detecting fetal growth restriction (estimated fetal weight of <10th percentile and/or abdominal circumference of <10th percentile). The quality of the included studies was independently assessed by 2 reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. For the meta-analysis, hierarchical summary area under the receiver operating characteristic curves were constructed, and quantitative data synthesis was performed using random-effects models. RESULTS: The analysis included 25 studies encompassing 73,981 low-risk pregnancies undergoing third-trimester ultrasound assessment for growth, of which 5380 neonates (7.3%) were small for gestational age at birth. The pooled sensitivities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in predicting small for gestational age were 36% (95% confidence interval, 27%-46%) and 37% (95% confidence interval, 19%-60%), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%-56%) and 50% (95% confidence interval, 25%-74%), respectively, at 36 weeks ultrasound. The pooled specificities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in detecting small for gestational age were 93% (95% confidence interval, 91%-95%) and 95% (95% confidence interval, 85%-98%), respectively, at 32 weeks ultrasound and 93% (95% confidence interval, 91%-95%) and 97% (95% confidence interval, 85%-98%), respectively, at 36 weeks ultrasound. The observed diagnostic odds ratios for an estimated fetal weight of <10th percentile and an abdominal circumference of <10th percentile in detecting small for gestational age were 8.8 (95% confidence interval, 5.4-14.4) and 11.6 (95% confidence interval, 6.2-21.6), respectively, at 32 weeks ultrasound and 13.3 (95% confidence interval, 10.4-16.9) and 36.0 (95% confidence interval, 4.9-260.0), respectively, at 36 weeks ultrasound. The pooled sensitivity, specificity, and diagnostic odds ratio in predicting fetal growth restriction were 71% (95% confidence interval, 52%-85%), 90% (95% confidence interval, 79%-95%), and 25.8 (95% confidence interval, 14.5-45.8), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%-55%), 94% (95% confidence interval, 93%-96%), and 16.9 (95% confidence interval, 10.8-26.6), respectively, at 36 weeks ultrasound. Abdominal circumference of <10th percentile seemed to have comparable sensitivity to estimated fetal weight of <10th percentile in predicting small-for-gestational-age neonates. CONCLUSION: An ultrasound assessment of the fetal biometry at 36 weeks of gestation seemed to have better predictive accuracy for small-for-gestational-age neonates than an ultrasound assessment at 32 weeks of gestation. However, an opposite trend was noted when the outcome was fetal growth restriction. Fetal abdominal circumference had a similar predictive accuracy to that of estimated fetal weight in detecting small-for-gestational-age neonates.

Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: a systematic review and meta-analysis.

OBJECTIVE: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management. METHODS: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. RESULTS: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I2=86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I2=82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I2=96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I2=56.3%). CONCLUSION: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

Transplacental non-steroidal anti-inflammatory drugs versus expectant management in fetal Ebstein anomaly with circular shunt: Systematic review and meta-analysis.

Ebstein anomaly (EA) is a rare congenital cardiac malformation associated with high perinatal mortality. In this systematic review and meta-analysis, we aimed to investigate the outcomes of pregnancies affected by EA or tricuspid valve dysplasia (TVD) with circular shunt, focusing on two prenatal management approaches: (1) expectant management (EM) and (2) transplacental non-steroidal anti-inflammatory drugs (NSAID) therapy. We searched PubMed, Scopus, and Web of Science systematically from its inception until June 2023. The random-effect model was used to pool the data. Heterogeneity was assessed using the I2 value. Twenty-one studies with a total of 610 fetuses with EA/TVD with circular shunt were included in the synthesis, of which 17 studies (583 fetuses) were on EM and 4 studies (27 fetuses) used transplacental NSAID therapy. The NSAID group had higher rates of moderate to severe tricuspid regurgitation, hydrops, and pericardial effusion on prenatal ultrasound compared with the EM group. However, ductal constriction was achieved in 81% of NSAID cases, mitigating the disease pathophysiology, although 65% of them experienced oligohydramnios. Notably, the NSAID group showed significantly higher rates of live birth (86%) and survival to hospital discharge (89%) compared with the EM group (67% and 43%, respectively). Despite these promising results, it's important to acknowledge that the number of cases treated with NSAIDs was small, with limited safety data. Therefore, caution is advised in interpreting these findings, and patients considering NSAID therapy should be informed about these limitations. Future multicenter studies are necessary to further explore the safety and effectiveness of NSAID therapy in this particular population.

Selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome, natural history, and risk factors for fetal death: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the natural history of selective intrauterine growth restriction in monochorionic twin pregnancies based on the Gratacós classification, including progression of, improvement in, or stability of umbilical artery Dopplers and progression to twin-to-twin transfusion syndrome or twin anemia polycythemia syndrome. We also aimed to investigate risk factors for smaller twin demise. DATA SOURCES: A systematic search was performed to identify relevant studies published in English up to June 2022 using the databases PubMed, Scopus, and Web of Science STUDY ELIGIBILITY: We used retrospective and prospective studies published in English that reported on selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome. STUDY APPRAISAL AND SYNTHESIS METHODS: Articles that investigated selective intrauterine growth restriction progression and outcomes by umbilical artery Doppler end-diastolic flow (Gratacós classification) were included. Type I included selective intrauterine growth restriction cases with positive end-diastolic flow, type II included those cases with persistently absent end-diastolic flow, and type III included cases with intermittent absent or reversed end-diastolic flow. Pregnancies in which a diagnosis of twin-to-twin transfusion syndrome or twin anemia polycythemia sequence was made before the diagnosis of selective intrauterine growth restriction were not included in the analysis. A random effects model was used to pool the odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 17 studies encompassing 2748 monochorionic pregnancies complicated by selective intrauterine growth restriction were included in the analysis. The incidence of stable, deteriorating, or improving umbilical artery Dopplers in type I cases was 68% (95% confidence interval, 26-89), 23% (95% confidence interval, 7-40), and 9% (95% confidence interval, 0.0-100), respectively. In type II cases, the incidence was 40% (95% confidence interval, 18-81), 50% (95% confidence interval, 23-82), and 10% (95% confidence interval, 4-37), respectively, and in type III cases, the incidence was 55% (95% confidence interval, 2-99), 23% (95% confidence interval, 9-43), and 22% (95% confidence interval, 6-54), respectively. The risk for progression to twin-to-twin transfusion syndrome was comparable between type I (7%) and type III (9%) cases and occurred in 4% (95% confidence interval, 0-67) of type II cases with no significant subgroup differences. Progression to twin anemia polycythemia syndrome was highest in type I cases (12%) and comparable between type II (2%) and III (1%) cases with no significant subgroup differences. Risk factors for smaller twin demise were earlier gestational age at diagnosis (mean difference, -2.69 weeks; 95% confidence interval, -4.94 to -0.45; I2, 45%), larger intertwin weight discordance (mean difference, 34%; 95% confidence interval, 1.35-5.38; I2, 28%), deterioration of umbilical artery Dopplers for each of type II and III cases (odds ratio, 3.05; 95% confidence interval, 1.36-6.84; I2, 24%; and odds ratio, 4.5; 95% confidence interval, 2.31-8.77; I2, 0.0%, respectively), and absent or reversed ductus venosus a-wave for each of type II and III cases (odds ratio, 3.35; 95% confidence interval, 2.28-4.93; I2, 0.0%; and odds ratio, 2.36; 95% confidence interval, 1.08-5.13; I2, 0.0%, respectively). Progression to twin-to-twin transfusion syndrome was not significantly associated with smaller twin demise for each of type II and III selective intrauterine growth restriction cases. CONCLUSION: These findings improve our understanding of the natural history of the types of selective intrauterine growth restriction and of the predictors of smaller twin demise in type II and III selective intrauterine growth restriction cases. The current data provide vital counseling points and support the need for modifications of the current selective intrauterine growth restriction classification system to include the variations in umbilical artery and ductus venosus Dopplers to better identify a cohort that might benefit from fetal intervention for which future multicenter prospective randomized trials are needed.

Fetal cardiac intervention in hypoplastic left heart syndrome with intact or restrictive atrial septum, systematic review, and meta-analysis.

To investigate outcomes of fetuses with hypoplastic left heart syndrome (HLHS) with an intact or restrictive atrial septum (I/RAS) managed expectantly or with fetal atrial septal intervention (FASI PubMed, Scopus, and Web of Science were searched systematically from inception until April 2023. Outcomes were classified by those who had FASI and those who had expectant management (EM). To estimate the overall proportion of each endpoint, a meta-analysis of proportions was employed using a random-effects model. Heterogeneity was assessed using the I2 value. Thirty-two studies reporting on 746 fetuses with HLHS and I/RAS met our inclusion criteria. Eleven studies (123 fetuses) were in the FASI group and 21 studies (623 fetuses) were in the EM group. Among the 123 FASI cases, 107 (87%) were reported to be technically successful. The mean gestational age (GA) at diagnosis was comparable between the groups (26.2 weeks FASI vs. 24.4 weeks EM group). The mean GA at FASI was 30.4 weeks (95% CI 28.5, 32.5). The mean GA at delivery was also comparable (37.7 weeks FASI vs. 38.1 weeks EM group). Neonatal outcomes, including live birth, neonatal death, and survival to hospital discharge pooled proportions, were also comparable between groups (live birth: 92% (95% CI 64, 99) FASI versus 93% (95% CI 79, 98) in EM, neonatal death: 32% (95% CI 11, 65) FASI versus 30% (95% CI 21, 41) EM, survival to hospital discharge: 37% (95% CI 25, 52) FASI versus 52% (95% CI 42, 61) EM). Age at neonatal death was higher in the FASI group (mean: 17 days FASI vs. 7.2 days EM group). There was a lower rate of postnatal atrial restrictive septum in the FASI group 38% (95% CI 17, 63) compared to the EM group 88% (95% CI 57, 98). Our review shows variations across centers in the selection criteria and techniques used for FASI. Although survival including livebirth, neonatal death, and survival to hospital discharge did not differ between groups, the procedure may translate into a less restrictive septum at birth. Future multicenter studies are needed to better identify the subset of cases that might have improved outcomes, use standardized definitions, unified techniques, utilize core outcome set, and assess long-term benefits.

Connecting the dots: Carrier screening and the Genetic Information Nondiscrimination Act in the United States.

OBJECTIVE: To highlight the possibility of genetic discrimination in the United States with respect to carrier screening under limitations of the Genetic Information Nondiscrimination Act (GINA) and to encourage providers to educate patients about this possibility during pretest counseling. METHODS: Review of current professional guidelines and practice resources regarding the necessary components of pretest counseling for carrier screening in the context of GINA's limitations and the potential impact of carrier screening results on life, long-term care and disability insurance. RESULTS: Current practice resources advise that patients in the United States should be informed that their employer or health insurance company generally cannot use their genetic information during the underwriting process. However, these resources do not elaborate on GINA's limitations or explain why there may be adverse consequences to patients regarding these limitations. Studies have demonstrated significant gaps in provider knowledge of GINA, especially for those without formal genetic training. CONCLUSION: Enhanced education and provision of GINA educational resources for providers and patients will help ensure that patients have the opportunity to prioritize their insurance needs prior to undergoing carrier screening.

Diagnostic yield with exome sequencing in prenatal severe bilateral ventriculomegaly: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to determine the incremental diagnostic yield of prenatal exome sequencing after negative chromosomal microarray analysis results in prenatally diagnosed bilateral severe ventriculomegaly or hydrocephalus; another objective was to categorize the associated genes and variants. DATA SOURCES: A systematic search was performed to identify relevant studies published until June 2022 using 4 databases (Cochrane Library, Web of Science, Scopus, and MEDLINE). STUDY ELIGIBILITY CRITERIA: Studies in English reporting on the diagnostic yield of exome sequencing following negative chromosomal microarray analysis results in cases of prenatally diagnosed bilateral severe ventriculomegaly were included. METHODS: Authors of cohort studies were contacted for individual participant data, and 2 studies provided their extended cohort data. The incremental diagnostic yield of exome sequencing was assessed for pathogenic/likely pathogenic findings in cases of: (1) all severe ventriculomegaly; (2) isolated severe ventriculomegaly (as the only cranial anomaly); (3) severe ventriculomegaly with other cranial anomalies; and (4) nonisolated severe ventriculomegaly (with extracranial anomalies). To be able to identify all reported genetic associations, the systematic review portion was not limited to any minimal severe ventriculomegaly case numbers; however, for the synthetic meta-analysis, we included studies with ≥3 severe ventriculomegaly cases. Meta-analysis of proportions was done using a random-effects model. Quality assessment of the included studies was performed using the modified STARD (Standards for Reporting of Diagnostic Accuracy Studies) criteria. RESULTS: A total of 28 studies had 1988 prenatal exome sequencing analyses performed following negative chromosomal microarray analysis results for various prenatal phenotypes; this included 138 cases with prenatal bilateral severe ventriculomegaly. We categorized 59 genetic variants in 47 genes associated with prenatal severe ventriculomegaly along with their full phenotypic description. There were 13 studies reporting on ≥3 severe ventriculomegaly cases, encompassing 117 severe ventriculomegaly cases that were included in the synthetic analysis. Of all the included cases, 45% (95% confidence interval, 30-60) had positive pathogenic/likely pathogenic exome sequencing results. The highest yield was for nonisolated cases (presence of extracranial anomalies; 54%; 95% confidence interval, 38-69), followed by severe ventriculomegaly with other cranial anomalies (38%; 95% confidence interval, 22-57) and isolated severe ventriculomegaly (35%; 95% confidence interval, 18-58). CONCLUSION: There is an apparent incremental diagnostic yield of prenatal exome sequencing following negative chromosomal microarray analysis results in bilateral severe ventriculomegaly. Although the greatest yield was found in cases of nonisolated severe ventriculomegaly, consideration should also be given to performing exome sequencing in cases of isolated severe ventriculomegaly as the only brain anomaly identified on prenatal imaging.

Prenatal predictors of need for cerebrospinal fluid diversion in infants following prenatal repair of open spina bifida; systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate prenatal predictors of the need for cerebrospinal fluid diversion in infants following prenatal repair of open spina bifida. DATA SOURCES: A systematic search was performed to identify relevant studies published from inception until June 2022 in the English language using the databases PubMed, Scopus, and Web of Science. STUDY ELIGIBILITY CRITERIA: We included retrospective and prospective cohort studies and randomized controlled trials reporting on prenatal repair of open spina bifida. METHODS: The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 9 studies including 948 pregnancies undergoing prenatal repair of open spina bifida were included in the final analysis. Prenatal factors that were significantly associated with the need for postnatal cerebrospinal fluid diversion were gestational age at surgery ≥25 weeks (odds ratio, 4.2; 95% confidence interval, 1.8-9.9; I2=54%; P=.001), myeloschisis (odds ratio, 2.2; 95% confidence interval, 1.1-4.1; I2=0.0%; P=.02), preoperative lateral ventricle width ≥15 mm (odds ratio, 4.5; 95% confidence interval, 2.9-6.9; I2=0.0%; P<.0001), predelivery lateral ventricle width (mm) (mean difference, 8.3; 95% confidence interval, 6.4-10.2; I2=0.0%; P<.0001), and preoperative lesion level at T12-L2 (odds ratio, 2.5; 95% confidence interval, 1.03-6.3; I2=68%; P=.04). Factors that significantly reduced the need for postnatal shunt placement were gestational age at surgery <25 weeks (odds ratio, 0.3; 95% confidence interval, 0.15-0.6; I2=67%; P=.001) and preoperative lateral ventricle width <15 mm (odds ratio, 0.3; 95% confidence interval, 0.2-0.4; I2=0.0%; P<.0001). CONCLUSION: This study demonstrated that among fetuses that underwent surgical repair of open spina bifida, having gestational age at surgery of ≥25 weeks, preoperative lateral ventricle width of ≥15 mm, myeloschisis lesion type, and preoperative lesion level above L3 was predictive of the need for cerebrospinal fluid diversion during the first year of life.

Prepregnancy Roux-en-Y gastric bypass vs sleeve gastrectomy: a systematic review, pairwise, and network meta-analysis of obstetrical and neonatal outcomes.

OBJECTIVE: This study aimed to systematically investigate a wide range of obstetrical and neonatal outcomes with respect to 2 types of prepregnancy bariatric surgery, Roux-en-Y gastric bypass and sleeve gastrectomy, through: (1) providing a meta-analysis of the effect of bariatric surgery (Roux-en-Y gastric bypass vs no surgery and, separately, sleeve gastrectomy vs no surgery) on adverse obstetrical and neonatal outcomes, and (2) comparing the relative benefit of Roux-en-Y gastric bypass vs sleeve gastrectomy using both conventional and network meta-analysis. DATA SOURCES: We searched PubMed, Scopus, and Embase systematically from inception up to April 30, 2021. ELIGIBILITY CRITERIA: Studies reporting on pregnancies' obstetrical and neonatal outcomes with respect to 2 types of prepregnancy bariatric surgery-Roux-en-Y gastric bypass and sleeve gastrectomy-were included. The included studies either indirectly compared between the procedure and controls or directly compared between the 2 procedures. METHODS: We performed a systematic review followed by pairwise and network meta-analysis in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In the pairwise analysis, multiple obstetrical and neonatal outcomes were tabulated and compared between 3 groups: (1) Roux-en-Y gastric bypass vs controls, (2) sleeve gastrectomy vs controls, and (3) Roux-en-Y gastric bypass vs sleeve gastrectomy. Primary outcomes included small for gestational age, large for gestational age, gestational hypertension/preeclampsia, and gestational diabetes mellitus. Secondary outcomes included preterm birth, anemia, cesarean delivery, and biochemical profile. The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. The Newcastle-Ottawa scale was used to assess individual study quality. To resolve inconclusive findings and to rank current treatments, network meta-analysis was conducted for the primary outcomes. Quality of evidence was assessed with the Confidence in Network Meta-Analysis approach and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) tool within the summary of findings table. RESULTS: A total of 20 studies were included, reporting on 40,108 pregnancies, of which 5194 underwent Roux-en-Y gastric bypass, 405 underwent sleeve gastrectomy, and 34,509 were controls. Compared with controls, Roux-en-Y gastric bypass increased the risk of small for gestational age infants (odds ratio, 2.56; 95% confidence interval, 1.77-3.70; I2, 29.1%; P<.00001), decreased the risk of large for gestational age infants (odds ratio, 0.25; 95% confidence interval, 0.18-0.35; I2, 0%; P<.00001), decreased gestational hypertension/preeclampsia (odds ratio, 0.54; 95% confidence interval, 0.30-0.97; I2, 26.8%; P=.04), decreased gestational diabetes mellitus (odds ratio, 0.43; 95% confidence interval, 0.23-0.81; I2, 32%; P=.008), increased maternal anemia (odds ratio, 2.70; 95% confidence interval, 1.53-4.79; I2, 40.5%; P<.001), increased neonatal intensive care unit admission (odds ratio, 1.36; 95% confidence interval, 1.04-1.77; I2, 0%; P=.02), and decreased mean gestational weight gain (mean difference, -3.37 kg; 95% confidence interval, -5.62 to -1.11; I2, 65.3%; P=.003). Only 3 studies compared sleeve gastrectomy with controls, and found no significant differences in primary outcomes or in mean gestational weight gain. The network meta-analysis showed that Roux-en-Y gastric bypass (malabsorptive procedure) resulted in greater decrease of large for gestational age, gestational hypertension/preeclampsia, and gestational diabetes mellitus, and a greater increase in small for gestational age infants when compared with sleeve gastrectomy (restrictive procedure). However, the small number of studies, small number of sleeve gastrectomy patients, limited outcomes, and data heterogeneity resulted in low-to-moderate network GRADE of evidence. CONCLUSION: This network meta-analysis showed that Roux-en-Y gastric bypass, compared with sleeve gastrectomy, resulted in greater decrease in large for gestational age, gestational hypertension/preeclampsia, and gestational diabetes mellitus, but in greater increase in small for gestational age infants. Certainty of evidence in the network meta-analysis was of a low-to-moderate GRADE. Evidence is still lacking for periconception biochemical profile, congenital malformations, and reproductive health outcomes for both interventions; thus, future well-designed prospective studies are needed to further characterize these outcomes.

Impact of middle cerebral artery pulsatility index on donor survival in twin-twin transfusion syndrome.

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

Fetoscopic laser surgery for twin-to-twin transfusion syndrome in DCTA triplets compared to MCDA twins: collaborative study and literature review.

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.