The NICHD Fetal 3D Study: A Pregnancy Cohort Study of Fetal Body Composition and Volumes.

There's a paucity of robust normal fractional limb and organ volume standards from a large and diverse ethnic population. The Fetal 3D Study was designed to develop research and clinical applications for fetal soft tissue and organ volume assessment. The NICHD Fetal Growth Studies (2009-2013) collected 2D and 3D fetal volumes. In the Fetal 3D Study (2015-2019), sonographers performed longitudinal 2D and 3D measurements for specific fetal anatomical structures in research ultrasounds of singletons and dichorionic twins. The primary aim was to establish standards for fetal body composition and organ volumes, overall and by maternal race/ethnicity, and determine whether these standards vary for twins versus singletons. We describe the study design, methods, and details about reviewer training. Basic characteristics of this cohort, with their corresponding distributions of fetal 3D measurements by anatomical structure, are summarized. This investigation is responsive to critical data gaps in understanding serial changes in fetal subcutaneous fat, lean body mass, and organ volume in association with pregnancy complications. In the future, this cohort can answer critical questions regarding the potential influence of maternal characteristics, lifestyle factors, nutrition, and biomarker and chemical data on longitudinal measures of fetal subcutaneous fat, lean body mass, and organ volumes.

Multiethnic growth standards for fetal body composition and organ volumes derived from 3D ultrasonography.

BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable. STUDY DESIGN: The National Institute of Child Health and Human Development Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (fifth, 50th, 95th percentiles) were derived from 15 to 41 weeks' using linear mixed models for repeated measures with cubic splines. RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid-arm and thigh circumferences were more linear. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic, or environmental influences and pregnancy complications, in ways not identifiable using corresponding 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

Perinatal outcomes of fetoscopic selective laser photocoagulation for spontaneous twin-anemia polycythemia sequence.

OBJECTIVES: Antenatal management of monochorionic pregnancies complicated by twin anemia polycythemia sequence (TAPS) remains sub-optimally defined. Our objective was to evaluate the safety and efficacy of fetoscopic selective laser photocoagulation with respect to fetal and neonatal survival. METHODS: A case series is reported with patients referred to the Texas Children's Fetal Center for evaluation and management of suspected spontaneous TAPS without concomitant twin-to-twin syndrome from 2014 to 2023. All evaluations were performed by our team and patients with stage II-IV TAPS were offered expectant management, intrauterine transfusion, or laser therapy. Cases of post-laser TAPS were excluded from this study. Pregnancy and neonatal outcomes were obtained from electronic medical records. RESULTS: During a 10-year time period, 18 patients presented to our center for the management of TAPS. Thirteen patients had stage II-IV TAPS (13/18, 72%) and elected to proceed with laser photocoagulation. All procedures were completed, and "solomonization" was performed for 12/13. Normalization of middle cerebral artery Dopplers in both fetuses was noted after all cases. There was one intrauterine fetal death of the 26 viable fetuses after laser treatment, which was complicated by selective growth restriction. Most patients (12/13) were delivered by Cesarean section at a mean gestational age of 29 ± 3 weeks. Subsequently, there was one ex-donor neonatal death in an infant who had prenatal hydrops. Overall, 30-day postnatal survival was 24/26 fetuses (92.3%). CONCLUSIONS: In the setting of spontaneous TAPS, laser therapy is feasible and appears to be an effective approach with overall favorable perinatal outcomes.

Prenatal diagnosis and postnatal outcome of closed spinal dysraphism.

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

Outcomes of fetal lower urinary tract obstruction based on timing of oligohydramnios onset.

OBJECTIVE: Fetal Lower Urinary Tract Obstruction (LUTO) is associated with oligohydramnios and significant fetal morbidity, resulting in poor lung development and perinatal death. However, oligohydramnios may develop at different gestational periods, and the impact of timing on fetal outcomes remains unknown. Our objective was to characterize the impact onset of oligohydramnios had on prenatal outcomes. METHODS: This study is a retrospective cohort study of all patients with a prenatal diagnosis of LUTO at our tertiary referral center from 2014 to 2023. All patients underwent detailed ultrasonography and interdisciplinary counseling and were subsequently delivered at our institution. Data were obtained from electronic medical records and complete extraction was required for final inclusion. RESULTS: During the study time period, 93 patients met inclusion criteria of which 68 (73.1%) developed oligohydramnios during their pregnancy. 63 (93%) of these pregnancies resulted in livebirths with 28 (41.1%) perinatal deaths. Onset of oligohydramnios was earlier in pregnancies with perinatal death (23 vs. 28 weeks, p = 0.004) and associated with pulmonary hypoplasia. CONCLUSIONS: Our data show the impact of oligohydramnios timing in pregnancy on pulmonary hypoplasia and ultimately perinatal death. This allows for detailed patient counseling on the impact oligohydramnios may have on pregnancies by the gestational age of onset.

Fetal bladder morphology as a predictor of outcome in fetal lower urinary tract obstruction.

OBJECTIVE: We evaluate survival of fetuses with severe Lower Urinary Tract Obstruction (LUTO) based on bladder morphology. We hypothesize that fetuses with a "floppy" appearing bladder on initial prenatal ultrasound will have worse infant outcomes than fetuses with full/rounded bladders. METHOD: We retrospectively reviewed all cases of LUTO evaluated in our fetal center between January 2013 and December 2021. Ultrasonographic assessment, renal biochemistry, and bladder refilling contributed to a "favorable" or "unfavorable" evaluation. Bladder morphology on initial ultrasound was classified as "floppy" or "full/rounded." Vesicoamniotic shunting was offered for favorably evaluated fetuses. Baseline demographics, ultrasound parameters, prenatal evaluations of fetal renal function, and infant outcomes were collected. Fetuses diagnosed with severe LUTO were included in analysis using descriptive statistics. The primary outcome measured was survival at 6 months of life. RESULTS: 104 LUTO patients were evaluated; 24 were included in analysis. Infant survival rate at 6 months was 60% for rounded bladders and 0% for floppy bladders (p = 0.003). Bladder refill adequacy was lower in fetuses with floppy bladders compared with rounded bladders (p value < 0.00001). CONCLUSION: We propose that bladder morphology in fetuses with severe LUTO may be a prognostication factor for predicting infant outcomes and provides a valuable, noninvasive assessment tool.

Suture Characteristics after Exposure to Amniotic Fluid from an in vitro Model of Fetal Surgery.

INTRODUCTION: Suture tensile properties have only been tested in extrauterine environments. Amniotic fluid (AF) is a complex milieu of enzymes and inflammatory factors. This study tested the mechanical properties of sutures with a variety of inherent properties, after exposure to AF from patients with conditions prompting fetal intervention. METHODS: AF was obtained from 3 patients with twin-twin transfusion syndrome (TTTS), and 3 patients with neural tube defects. Six types of 2-0 sutures were placed on 1.2 N of tension to mimic placement in vivo, and incubated in AF at 37°C (98.6°F). These included ethylene terephthalate (Ethibond), glycomer 631 (V-Loc), poliglecaprone 25 (Monocryl), poly-4-hydroxybutyrate (Monomax), polydioxanone (PDS), and polyglactin 910 (Vicryl). Failure load, stress, strain, and initial modulus were tested after 24 h of incubation and after 4 weeks, and compared with control (unincubated) sutures using t tests, Kruskal-Wallis tests, and stress-strain curves. RESULTS: Poliglecaprone 25 and polyglactin 910 dissolve more quickly in AF compared to outside the uterus, disintegrating at 4 weeks. Ethylene terephthalate and PDS experienced little change across 4 weeks of incubation. Glycomer 631 and poly-4-hydroxybutyrate exhibited interesting behavior in AF: glycomer 631 became more deformable at 24 h but later regained toughness by 4 weeks, while poly-4-hydroxybutyrate became tougher and in some cases stronger with time in AF. As a class, braided sutures act more like rigid materials, and monofilaments act like deformable plastics. CONCLUSION: These findings along with other suture characteristics such as ease of handling and availability may inform fetal intervention teams as they optimize procedures in a relatively new surgical field.

Fetal Anemia: Determinants and Perinatal Outcomes according to the Method of Intrauterine Blood Transfusion.

INTRODUCTION: Fetal anemia from hemolytic disease treated by intrauterine transfusion (IUT) can be performed by intraperitoneal, intracardiac, and intravascular transfusion (IVT). Objective of our study was to compare different transfusion techniques. METHODS: Retrospective review of IUT secondary to red cell alloimmunization was conducted at eight international centers from 2012 to 2020. Severe anemia suspected if middle cerebral artery peaks systolic velocity ≥1.5 multiples of the median. Demographic, delivery, and postnatal variables were analyzed. RESULTS: Total of 344 procedures, 325 IVT and 19 other techniques (non-IVT) included. No difference in demographics, history of stillbirth (20.5 vs. 15.8%, p = 0.7), prior pregnancy IUT (25.6 vs. 31.6%, p = 0.5) or neonatal transfusion (36.1 vs. 43.8%, p = 0.5). At first IUT, non-IVT had higher hydrops (42.1% vs. 20.4%, p = 0.03), lower starting hematocrit (13.3% [±6] vs. 17.7% [±8.2], p = 0.04), and trend toward lower gestational age (24.6 [20.1-27] vs. 26.4 [23.2-29.6] weeks, p = 0.08). No difference in birthweight, neonatal phototherapy, exchange, or simple transfusion was observed. CONCLUSION: This is one of the largest studies comparing techniques to treat fetal anemia. IVT was most performed, other techniques were more likely performed in hydrops, and lower starting hematocrit was seen. Neither technique affected outcomes. This study may suggest that physician's experience may be the strongest contributor of outcomes.

Systematic classification and comparison of maternal and obstetrical complications following 2 different methods of fetal surgery for the repair of open neural tube defects.

BACKGROUND: In utero repair of open neural tube defects using an open hysterotomy approach (hereafter referred to as "open") has been shown to reduce the need for ventriculoperitoneal shunting and to improve motor outcomes for affected infants. Laparotomy-assisted fetoscopic repair (hereafter referred to as "hybrid") is an alternative approach that may confer similar neurologic benefits while reducing the incidence of hysterotomy-related complications. OBJECTIVE: This study aimed to analyze procedure-related maternal and fetal complications of in utero repair using the Clavien-Dindo classification, and to compare the outcomes of the hybrid and open approaches. STUDY DESIGN: This was a retrospective cohort study conducted in a single center between September 2011 and July 2021. All patients who met the Management of Myelomeningocele Study criteria and who underwent either hybrid or open fetal surgery were included. Maternal complications were classified using a unique adaptation of the Clavien-Dindo scoring system, allowing the development of a comprehensive complication index score specific to fetal surgery. Primary fetal outcome was defined as gestational age at delivery and summarized according to the World Health Organization definitions of preterm delivery. RESULTS: There were 146 fetuses with open neural tube defects who were eligible for, and underwent, in utero repair during the study period. Of these, 102 underwent hybrid fetoscopic repair and 44 underwent open hysterotomy repair. Gestational age at the time of surgery was higher in the hybrid group than in the open group (25.1 vs 24.8 weeks; P=.004). Maternal body mass index was lower in the hybrid than in the open group (25.4 vs 27.1 kg/m2; P=.02). The duration of hybrid fetoscopic surgery was significantly longer in the hybrid than in the open group (250 vs 164 minutes; P<.001). There was a significantly lower Clavien-Dindo Grade III complication rate (4.9% vs 43.2%; P<.001) and a significantly lower overall comprehensive maternal complication index (8.7 vs 22.6; P=.021) in the hybrid group than in the open group. Gestational age at delivery was significantly higher in the hybrid group than in the open group (38.1 vs 35.8 weeks; P<.001), and this finding persisted when gestational age at delivery was analyzed using the World Health Organization definitions of preterm delivery. CONCLUSION: Use of our adaptation of the standardized Clavien-Dindo classification to assess the maternal complications associated with in utero open neural tube defect repair provides a new method for objectively assessing different fetal surgical approaches. It also provides a much-needed standardized tool to allow objective comparisons between methods, which can be used when counseling patients. The hybrid open neural tube defect repair was associated with lower rates of maternal adverse events , and later gestational age at delivery compared with the open approach.

Laser therapy versus expectant management for selective fetal growth restriction in monochorionic twins: A systematic review.

Selective fetal growth restriction (sFGR) complicates 10%-26% of monochorionic twins. Treatment options include cord coagulation, expectant management, and fetoscopic laser photocoagulation. This review compared laser to expectant management for situations when cord coagulation is not an option. The MEDLINE, EMBASE, and Cochrane databases were queried for studies that compared laser to expectant management for sFGR. GRADE was used to assess quality prior to meta-analysis. A random-effects model was used to generate relative risks. Six studies were included, encompassing 299 pregnancies. One study was randomized and the remainder were retrospective cohorts. Laser is associated with more fetal deaths of the FGR twin compared to expectant management (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.43-4.37, p = 0.001, I2 = 48%). Neonatal deaths and gestational age at delivery did not differ. Laser was associated with decreased abnormal neuroimaging in the AGA twin (RR 0.25, 95% CI 0.07-0.97, p = 0.05). Neurodevelopmental outcomes did not differ, although these data are limited. Laser causes more fetal deaths of the FGR twin without altering gestational age at delivery or rates of neonatal death. The literature is heterogeneous and the level of bias is high. Randomized trials that address laser for type II sFGR are needed and should include long-term neurological outcomes.

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis.

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n = 671 undergoing Solomon and n = 993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: -1.167; 95% credible interval [CrI]: -2.01, -0.33; p = 0.021; I2 : 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p = 0.012; I2 : 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: -0.43, 1.49; p = 0.131; I2 : 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption.

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

Impact of Transfer of Maternal Care for Fetal Anomalies on Maternal Depression and Anxiety Screening: A Prospective Cohort at a Tertiary Care Center.

INTRODUCTION: Perinatal depression and anxiety are major causes of maternal morbidity, and are more common in high-risk pregnancies compared to low-risk pregnancies. This study used validated screening tools to assess the prevalence of depression and anxiety symptoms in pregnant patients who transferred their obstetric care to a specialized fetal center for fetal anomaly. METHODS: This is a prospective cohort of patients with a fetal anomaly prompting transfer of obstetric care to Texas Children's Hospital Fetal Center between January 2021 and February 2022. The primary outcome was a self-assessed Edinburgh Postnatal Depression Scale score of 13 or higher, either antepartum or postpartum ("ever-positive EPDS"). Secondary outcomes included self-assessed Perinatal Anxiety Screening Scale (PASS) scores of 21 or higher ("ever-positive PASS"), obstetric outcomes, and neonatal outcomes. A frequentist analysis was performed. RESULTS: Of 149 women who transferred to Texas Children's Hospital during the study period, 94 enrolled in this study. Twenty-six percent of women had an ever-positive EPDS; 20% of patients had an ever-positive PASS. Patients were more likely to have an ever-positive EPDS if they were single (46% compared to 20%, p = 0.025). Women who had an ever-positive EPDS were more likely to be referred to psychiatry (46% compared to 14%, p = 0.004) and psychotherapy (29% compared to 1%, p < 0.001). Surprisingly, patients were more likely to have an ever-positive PASS if they reported good social support (p = 0.03). Antepartum EPDS and PASS scores had no relationship with postpartum EPDS scores. CONCLUSION: Women who transfer care to a tertiary setting have positive EPDS scores at double the rate of the general population, but tend to experience this either antepartum or postpartum (not both). Fetal centers should be prepared to screen for mental health symptoms before and after delivery and provide appropriate referral or treatment.

Characterization of Suboptimal Responses to Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia.

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

Single fetal demise following fetoscopic ablation for twin-to-twin transfusion syndrome-cohort study, systematic review, and meta-analysis.

BACKGROUND: Several studies have assessed preoperative and operative factors associated with fetal demise after laser for TTTS, yet these findings are not completely conclusive. OBJECTIVE: This study aimed to identify risk factors for single fetal demise (recipient and donor twins) after fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome. STUDY DESIGN: We searched PubMed, Scopus, and Web of Science systematically from the inception of the database to June 2020. We conducted a systemic review on studies investigating risk factors for fetal demise (donor and/or recipient) after fetoscopic laser photocoagulation in monochorionic pregnancies complicated with twin-to-twin transfusion syndrome. Initially, we investigated the cohort of women with twin-to-twin transfusion syndrome that underwent fetoscopic laser photocoagulation at our 2 high-volume fetal centers between 2012 and 2020 to identify risk factors for donor demise and recipient demise. Furthermore, we conducted a systematic review of the literature to better characterize these factors. Among studies that met the entry criteria, multiple preoperative and operative factors were tabulated. The random-effect model was used to pool the standardized mean differences or odds ratios and corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 514 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were included in the final analysis. Following the logistic regression, factors that remained significant for donor demise were selective fetal growth restriction (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P=.001) and umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.06; 95% confidence interval, 1.2-3.4; P=.004). A significant factor associated with recipient demise was absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 1.74; 95% confidence interval, 1.07-3.13; P=.04). Data from 23 studies and our current cohort were included. A total of 4892 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were analyzed for risk factors for donor demise, and 4594 pregnancies with twin-to-twin transfusion syndrome were analyzed for recipient demise. Among studies, the overall incidence rates ranged from 10.9% to 35.8% for donor demise and 7.3% to 24.5% for recipient demise. Significant risk factors for donor demise were intertwin estimated fetal weight discordance of >25% (odds ratio, 1.86; 95% confidence interval, 1.44-2.4; I2, 0.0%), selective fetal growth restriction (odds ratio, 1.78; 95% confidence interval, 1.4-2.27; I2, 0.0%), twin-to-twin transfusion syndrome stage III (odds ratio, 2.18; 95% confidence interval, 1.53-3.12; I2, 0.0%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.31; 95% confidence interval, 1.9-2.8; I2, 23.7%), absent or reversed a-wave in the ductus venosus of the donor (odds ratio, 1.83; 95% confidence interval, 1.45-2.3; I2, 0.0%), and presence of arterioarterial anastomoses (odds ratio, 2.81; 95% confidence interval, 1.35-5.85; I2, 90.7%). Sequential selective coagulation was protective against donor demise (odds ratio, 0.31; 95% confidence interval, 0.16-0.58; I2, 0.0%). Significant risk factors for recipient demise were twin-to-twin transfusion syndrome stage IV (odds ratio, 2.18; 95% confidence interval, 1.01-4.6; I2, 16.5%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the recipient (odds ratio, 2.68; 95% confidence interval, 1.91-3.74; I2, 0.0%), absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 2.37; 95% confidence interval, 1.55-3.64; I2, 60.2%), and middle cerebral artery peak systolic velocity of >1.5 multiple of the median (odds ratio, 3.06; 95% confidence interval, 1.36-6.88; I2, 0.0%). CONCLUSION: Abnormal blood flow patterns represented by abnormal Doppler studies and low fetal weight were associated with single fetal demise in women with twin-to-twin transfusion syndrome undergoing laser therapy. Although sequential selective coagulation was protective against donor demise, the presence of arterioarterial anastomoses was considerably associated with donor demise. This meta-analysis extensively investigated the association of a wide range of preoperative and operative factors with fetal demise. These findings may be important inpatient counseling, in further understanding the disease, and perhaps in improving surgical techniques.

Fetal reduction of triplet pregnancies to twins vs singletons: a meta-analysis of survival and pregnancy outcome.

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

Selective reduction in complicated monochorionic pregnancies: a systematic review and meta-analysis of different techniques.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the perinatal outcomes of complicated monochorionic pregnancies after selective reduction by radiofrequency ablation, bipolar cord coagulation, and interstitial laser. DATA SOURCES: We searched PubMed, Scopus, and Web of Science, from the inception of the database up to April 26, 2021. STUDY ELIGIBILITY CRITERIA: Studies comparing at least 2 selective reduction techniques among complicated monochorionic pregnancies and presenting data on perinatal outcomes, including gestational age at procedure, gestational age at delivery, procedure to delivery interval, preterm premature rupture of membranes, preterm birth, survival rate, and birthweight, were eligible. METHODS: The random-effects model was used to pool the mean differences or odds ratios and corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 10 studies with 734 cases of fetal reduction met the inclusion criteria, of which 9 studies with 674 fetuses were eligible for quantitative synthesis. In 8 studies that compared radiofrequency ablation with bipolar cord coagulation, radiofrequency ablation was associated with increased procedure to delivery interval (days) (mean difference, 13.42; 95% confidence interval, 1.90-24.94; P=.02; I2=0.0%), decreased preterm birth (odds ratio, 0.50; 95% confidence interval, 0.29-0.85; P=.01; I2=3.0%), and decreased preterm premature rupture of membranes (odds ratio, 0.45; 95% confidence interval, 0.27-0.73; P=.001; I2=0.0%). Radiofrequency ablation and bipolar cord coagulation had comparable survival rates (odds ratio, 0.85; 95% confidence interval, 0.54-1.35; P=.49; I2=0.0%). In 3 studies that compared radiofrequency ablation with interstitial laser, there was no significant difference in gestational age at delivery (P=.07) or survival (P=.15). In 3 studies that compared bipolar cord coagulation with interstitial laser, bipolar cord coagulation was associated with a higher survival rate (odds ratio, 3.21; 95% confidence interval, 1.13-9.10; P=.03; I2=0.0%), but the gestational age at delivery was comparable between groups (P=.16). CONCLUSION: This study demonstrated that radiofrequency ablation has a greater procedure to delivery interval and decreased preterm premature rupture of membranes and preterm birth than bipolar cord coagulation. Although there was no difference in gestational age at delivery for either bipolar cord coagulation, radiofrequency ablation, or interstitial laser, survival was higher with bipolar cord coagulation than with interstitial laser.

Fetoscopic Balloon Dilation and Stent Placement of Congenital High Airway Obstruction Syndrome Leading to Successful Cesarean Delivery.

INTRODUCTION: Without fetal or perinatal intervention, congenital high airway obstruction syndrome (CHAOS) is a fatal anomaly. The ex utero intrapartum treatment (EXIT) procedure has been used to secure the fetal airway and minimize neonatal hypoxia but is associated with increased maternal morbidity. CASE PRESENTATION: A 16-year-old woman (gravida 1, para 0) was referred to our hospital at 31 weeks gestation with fetal anomalies, including echogenic lungs, tracheobronchial dilation, and flattened diaphragms. At 32 weeks, fetoscopic evaluation identified laryngeal stenosis, which was subsequently treated with balloon dilation and stent placement. The patient developed symptomatic and regular preterm contractions at postoperative day 7 with persistent sonographic signs of CHAOS, which prompted a repeat fetoscopy with confirmation of a patent fetal airway followed by Cesarean delivery under neuraxial anesthesia. Attempts to intubate through the tracheal stent were limited and resulted in removal of the stent. A neonatal airway was successfully established with rigid bronchoscopy. Direct laryngoscopy and bronchoscopy confirmed laryngeal stenosis with a small tracheoesophageal fistula immediately inferior to the laryngeal stenosis and significant tracheomalacia. A tracheostomy was then immediately performed for anticipated long-term airway and pulmonary management. The procedures were well tolerated by both mom and baby. The baby demonstrated spontaneous healing of the tracheoesophageal fistula by day of life 7 with discharge home with ventilator support at 3 months of life. CONCLUSION: Use of repeated fetoscopy in order to relieve fetal upper airway obstruction offers the potential to minimize neonatal hypoxia, while concurrently decreasing maternal morbidity by avoiding an EXIT procedure. Use of the tracheal stent in CHAOS requires further investigation. The long-term reconstruction and respiratory support of children with CHAOS remain challenging.

Two-port, exteriorized uterus, fetoscopic meningomyelocele closure has fewer adverse neonatal outcomes than open hysterotomy closure.

BACKGROUND: In utero closure of meningomyelocele using an open hysterotomy approach is associated with preterm delivery and adverse neonatal outcomes. OBJECTIVE: This study compared the neonatal outcomes in in utero meningomyelocele closure using a 2-port, exteriorized uterus, fetoscopic approach vs the conventional open hysterotomy approach. STUDY DESIGN: This retrospective cohort study included all consecutive patients who underwent in utero meningomyelocele closure using open hysterotomy (n=44) or a 2-port, exteriorized uterus, fetoscopic approach (n=46) at a single institution between 2012 and 2020. The 2-port, exteriorized uterus, fetoscopic closure was composed of the following 3 layers: a bovine collagen patch, a myofascial layer, and a skin. The frequency of respiratory distress syndrome and a composite of other adverse neonatal outcomes, including retinopathy of prematurity, periventricular leukomalacia, and perinatal death, were compared between the study groups. Regression analyses were performed to determine any association between the fetoscopic closure and adverse neonatal outcomes, adjusted for several confounders, including gestational age of <37 weeks at delivery. RESULTS: The fetoscopic closure was associated with a lower rate of respiratory distress syndrome than the open hysterotomy closure (11.5% [5 of 45] vs 29.5% [13 of 44]; P=.037). The proportion of neonates with a composite of other adverse neonatal outcomes in the fetoscopic group was half of that observed patients in the open hysterotomy group; however, this difference did not reach statistical significance (4.3% [2 of 46] vs 9.1% [4 of 44]; P=.429). Here, regression analysis has demonstrated that fetoscopic meningomyelocele closure was associated with a lower risk of respiratory distress syndrome (adjusted odds ratio, 0.23; 95% confidence interval, 0.06-0.84; P=.026) than open hysterotomy closure. CONCLUSION: In utero meningomyelocele closure using a 2-port, exteriorized uterus, fetoscopic approach was associated with a lower risk of respiratory distress syndrome than the conventional open hysterotomy meningomyelocele closure.

Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium.

BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.