The effect of cervical pessary on increasing gestational age at delivery in twin pregnancies with asymptomatic short cervix: a systematic review and meta-analysis of randomized controlled trials.

Objective: The incidence of preterm delivery is much higher in twin pregnancies than in singletons and even higher if a short cervical length is detected in the second trimester. Studies are contradictory regarding the efficacy of a cervical pessary to decrease preterm birth in twin pregnancies and short cervical length. To conduct a systematic review and meta-analysis investigating the efficacy of cervical pessary in prolonging gestation, preventing preterm birth, and reducing adverse neonatal outcomes in twin pregnancies with an asymptomatic short cervix. Data sources: PubMed, Scopus, Web of Science, and ClinicalTrials.org were searched for randomized controlled trials from inception to June 2023. Study eligibility criteria: In this study, randomized controlled trials comparing the cervical pessary to expectant management in the pregnant population with twin gestations and asymptomatic short cervix were included. Methods: The Cochrane risk-of-bias-2 tool for randomized controlled trials was used for the evaluation of the risk of bias in included studies. A meta-analysis was performed by calculating risk ratio and mean difference with their 95% confidence interval using the random effects model or fixed effect model on the basis of heterogeneity and accounting for potential covariates among the included randomized controlled trials. Results: A total of 6 randomized controlled trials were included in the analysis. Cervical pessary did not significantly increase the gestational age at delivery in twin pregnancies with asymptomatic patients (mean difference, 0.36 weeks [-0.27 to 0.99]; P=.270; I2=72.0%). Moreover, the cervical pessary use did not result in a reduction of spontaneous or all-preterm birth before 37 weeks of gestation (risk ratio, 0.88 [0.77-1.00]; P=.061; I2=0.0%). There was no statistically significant difference in the composite neonatal adverse outcomes (risk ratio, 1.001 [0.86-1.16]; P=.981; I2=20.9%), including early respiratory morbidity, intraventricular hemorrhage, necrotizing enterocolitis, and confirmed sepsis. Conclusion: The use of cervical pessary in twin pregnancies with asymptomatic short cervix does not seem to be effective in increasing the gestational age at delivery, preventing preterm birth, or reducing adverse neonatal outcomes. This indicates that alternative interventions should be sought for the management of this patient population.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

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.

Divergent growth of the transient brain compartments in fetuses with nonsyndromic isolated clefts involving the primary and secondary palate.

Cleft lip/palate is a common orofacial malformation that often leads to speech/language difficulties as well as developmental delays in affected children, despite surgical repair. Our understanding of brain development in these children is limited. This study aimed to analyze prenatal brain development in fetuses with cleft lip/palate and controls. We examined in utero MRIs of 30 controls and 42 cleft lip/palate fetal cases and measured regional brain volumes. Cleft lip/palate was categorized into groups A (cleft lip or alveolus) and B (any combination of clefts involving the primary and secondary palates). Using a repeated-measures regression model with relative brain hemisphere volumes (%), and after adjusting for multiple comparisons, we did not identify significant differences in regional brain growth between group A and controls. Group B clefts had significantly slower weekly cerebellar growth compared with controls. We also observed divergent brain growth in transient brain structures (cortical plate, subplate, ganglionic eminence) within group B clefts, depending on severity (unilateral or bilateral) and defect location (hemisphere ipsilateral or contralateral to the defect). Further research is needed to explore the association between regional fetal brain growth and cleft lip/palate severity, with the potential to inform early neurodevelopmental biomarkers and personalized diagnostics.

Mammalian target of rapamycin inhibitors: A new-possible approach for in-utero medication therapy.

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.

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.

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.

Incidence and causes of perinatal death in prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to estimate the perinatal mortality associated with prenatally diagnosed vasa previa and to determine what proportion of those perinatal deaths are directly attributable to vasa previa. DATA SOURCES: The following databases have been searched from January 1, 1987, to January 1, 2023: PubMed, Scopus, Web of Science, and Embase. STUDY ELIGIBILITY CRITERIA: Our study included all studies (cohort studies and case series or reports) that had patients in which a prenatal diagnosis of vasa previa was made. Case series or reports were excluded from the meta-analysis. All cases in which prenatal diagnosis was not made were excluded from the study. METHODS: The programming language software R (version 4.2.2) was used to conduct the meta-analysis. The data were logit transformed and pooled using the fixed effects model. The between-study heterogeneity was reported by I2. The publication bias was evaluated using a funnel plot and the Peters regression test. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS: Overall, 113 studies with a cumulative sample size of 1297 pregnant individuals were included. This study included 25 cohort studies with 1167 pregnancies and 88 case series or reports with 130 pregnancies. Moreover, 13 perinatal deaths occurred among these pregnancies, consisting of 2 stillbirths and 11 neonatal deaths. Among the cohort studies, the overall perinatal mortality was 0.94% (95% confidence interval, 0.52-1.70; I2=0.0%). The pooled perinatal mortality attributed to vasa previa was 0.51% (95% confidence interval, 0.23-1.14; I2=0.0%). Stillbirth and neonatal death were reported in 0.20% (95% confidence interval, 0.05-0.80; I2=0.0%) and 0.77% (95% confidence interval, 0.40-1.48; I2=0.0%) of pregnancies, respectively. CONCLUSION: Perinatal death is uncommon after a prenatal diagnosis of vasa previa. Approximately half of the cases of perinatal mortality are not directly attributable to vasa previa. This information will help in guiding physicians in counseling and will provide reassurance to pregnant individuals with a prenatal diagnosis of vasa previa.

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.

Atypical fetal brain development in fetuses with non-syndromic isolated musculoskeletal birth defects (niMSBDs).

Non-syndromic, isolated musculoskeletal birth defects (niMSBDs) are among the leading causes of pediatric hospitalization. However, little is known about brain development in niMSBDs. Our study aimed to characterize prenatal brain development in fetuses with niMSBDs and identify altered brain regions compared to controls. We retrospectively analyzed in vivo structural T2-weighted MRIs of 99 fetuses (48 controls and 51 niMSBDs cases). For each group (19-31 and >31 gestational weeks (GW)), we conducted repeated-measures regression analysis with relative regional volume (% brain hemisphere) as a dependent variable (adjusted for age, side, and interactions). Between 19 and 31GW, fetuses with niMSBDs had a significantly (P < 0.001) smaller relative volume of the intermediate zone (-22.9 ± 3.2%) and cerebellum (-16.1 ± 3.5%,) and a larger relative volume of proliferative zones (38.3 ± 7.2%), the ganglionic eminence (34.8 ± 7.3%), and the ventricles (35.8 ± 8.0%). Between 32 and 37 GW, compared to the controls, niMSBDs showed significantly smaller volumes of central regions (-9.1 ± 2.1%) and larger volumes of the cortical plate. Our results suggest there is altered brain development in fetuses with niMSBDs compared to controls (13.1 ± 4.2%). Further basic and translational neuroscience research is needed to better visualize these differences and to characterize the altered development in fetuses with specific niMSBDs.

Vasa Previa.

Vasa previa refers to unprotected fetal vessels running through the membranes over the cervix. Until recently, this condition was associated with an exceedingly high perinatal mortality rate attributable to fetal exsanguination when the membranes ruptured. However, ultrasonography has made it possible to diagnose the condition prenatally, allowing cesarean delivery before labor or rupture of the membranes. Several recent studies have indicated excellent outcomes with prenatally diagnosed vasa previa. However, outcomes continue to be dismal when vasa previa is undiagnosed before labor. Risk factors for vasa previa include second-trimester placenta previa and low-lying placentas, velamentous cord insertion, placentas with accessory lobes, in vitro fertilization, and multifetal gestations. Recognition of individuals who are at risk and screening them will greatly decrease the mortality rate from this condition. Because of the relative rarity of vasa previa, there are no randomized controlled trials to guide management. Therefore, recommendations on the diagnosis and management of vasa previa are based largely on cohort studies and expert opinion. This Clinical Expert Series review addresses the epidemiology, pathophysiology, natural history, diagnosis and management of vasa previa, as well as innovative treatments for the condition.

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.

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.

Association of Killer Cell Immunoglobulin-like Receptor (KIR) Genes and their HLA Ligands with Susceptibility to Takayasu Arteritis in the Iranian Population.

Takayasu arteritis (TA) is a chronic inflammatory disorder characterized by vascular damage and fibrosis in the intima that commonly occurs in the aorta. In many damaged sites in TA patients, natural killer (NK) cells have been shown to be hyperactivated and produce inflammatory cytokines and toxic components. Killer cell immunoglobulin-like receptors (KIRs) are found on NK cells and interact with human leukocyte antigen (HLA) class I ligands to activate or suppress NK cells. The present study assessed the possible role of KIR and their HLA ligand genes in susceptibility to TA in Iranian patients. This case-control study included 50 TA patients and 50 healthy subjects. DNA was extracted from whole peripheral blood samples, and polymerase chain reaction with sequence-specific primers (PCR-SSP) was performed to recognize the presence or absence of polymorphism in 17 KIR genes and 5 HLA class I ligands in each participant. Among the KIR and HLA genes, a significant decrease was detected in the frequency of 2DS4 (full allele) in TA patients (38%) compared with healthy controls (82%) (OR=0.13, 95% CI=0.05-0.34). However, none of the KIR and HLA genotypes or the interactions between these genes were associated with susceptibility to TA. The KIR2DS4 gene might be involved in the regulation of activation as well as the production of cytotoxic mediators of NK cells in patients with TA.

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.

The effect of smoking on response to methotrexate in rheumatoid arthritis patients: A systematic review and meta-analysis.

OBJECTIVES: In the current study, we aimed to investigate the effect of smoking on inadequate response to methotrexate (MTX-IR) in rheumatoid arthritis (RA) patients. METHODS: We searched PubMed, Embase, and Web of Science until 6 June 2022. Observational or interventional studies investigating MTX-IR in RA patients based on smoking status were included. Two independent reviewers assessed the risk of bias and the certainty of the evidence using the Risk of Bias in Nonrandomized Studies-of Interventions and Grades of Recommendation, Assessment, Development, and Evaluation tools, respectively. RESULTS: We included 23 studies in the systematic review and 13 in the meta-analysis. Of the 13 included studies, 6 had a moderate risk, 3 had a serious risk, and 4 had a critical risk of bias. The overall random-effect meta-analysis suggested that smokers were 58% more likely to be MTX-IR when compared with nonsmokers [odds ratio (OR) 1.58, 95% confidence interval 1.21-2.06; P = .001; I2 = 69.3%]. The common-effect meta-analysis of the adjusted ORs demonstrated an overall OR of 2.69 (1.88-3.83; P < .001; I2 = 27.1%). CONCLUSIONS: The current study showed that smoking is a significant predictor of MTX-IR, especially in disease-modifying antirheumatic drug-naïve early RA patients, as most of the included studies in the meta-analysis consisted of this population.

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.

Cardiopulmonary predictors of mortality in patients with COVID-19: What are the findings?

BACKGROUND: Since 2019, coronavirus disease 2019 (COVID-19) has been the leading cause of mortality worldwide. AIMS: To determine independent predictors of mortality in COVID-19, and identify any associations between pulmonary disease severity and cardiac involvement. METHODS: Clinical, laboratory, electrocardiography and computed tomography (CT) imaging data were collected from 389 consecutive patients with COVID-19. Patients were divided into alive and deceased groups. Independent predictors of mortality were identified. Kaplan-Meier analysis was performed, based on patients having a troponin concentration>99th percentile (cardiac injury) and a CT severity score ≥18. RESULTS: The mortality rate was 29.3%. Cardiac injury (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.14-4.18; P=0.018), CT score ≥18 (OR 2.24, 95% CI 1.15-4.34; P=0.017), localized ST depression (OR 3.77, 95% CI 1.33-10.67; P=0.012), hemiblocks (OR 3.09, 95% CI 1.47-6.48; P=0.003) and history of leukaemia/lymphoma (OR 3.76, 95% CI 1.37-10.29; P=0.010) were identified as independent predictors of mortality. Additionally, patients with cardiac injury and CT score ≥ 18 were identified to have a significantly shorter survival time (mean 14.21 days, 95% CI 10.45-17.98 days) than all other subgroups. There were no associations between CT severity score and electrocardiogram or cardiac injury in our results. CONCLUSIONS: Our findings suggest that using CT imaging and electrocardiogram characteristics together can provide a better means of predicting mortality in patients with COVID-19. We identified cardiac injury, CT score ≥18, presence of left or right hemiblocks on initial electrocardiogram, localized ST depression and history of haematological malignancies as independent predictors of mortality in patients with COVID-19.