North American Fetal Therapy Network: Maternal Outcomes in Fetal Aqueductal Stenosis.

INTRODUCTION: Fetal aqueductal stenosis (AS) affects approximately 1:1,000 pregnancies. Obstruction of cerebral spinal fluid (CSF) circulation occurs at the aqueduct of Sylvius, leading to progressive hydrocephalus, often necessitating cesarean section (CS) with a classical uterine incision. The purpose of this study is to describe maternal outcomes associated with fetal aqueductal stenosis. METHODS: This study is conducted through the North American Fetal Therapy Network (NAFTNet). Subjects were recruited at the diagnosis of severe CNS ventriculomegaly and were followed longitudinally. Maternal events around the delivery of fetuses with AS were recorded and analyzed. RESULTS: Thirty-seven subjects with fetal AS confirmed by neonatal neuroimaging were analyzed. The average gestation at delivery was 36.7 weeks. Overall, 86% were delivered by cesarean section (CS), and 62% of these were elective. Sixty-two percent were delivered electively by cesarean section (CS). Eighty-six percent were delivered by cesarean section. Ninety one percent of CSs were performed through a Pfannenstiel abdominal incision. A classical uterine incision was required in 13% of cesarean deliveries. The peripartum complication rate was 27%. CONCLUSION: Women carrying a fetus with AS were at risk for preterm birth, cesarean delivery, a classical uterine incision, and peripartum complications. These data highlight the maternal morbidity associated with fetal AS, and the potential benefit of in-utero therapy not only for neonatal but also maternal outcomes.

Monochorionic Twin Complications and Fetoscopic Interventions.

Monochorionic twins are at risk for complications due to the presence of placental vascular anastomoses, including twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, and twin reversed arterial perfusion sequence. While ultrasound is the primary modality to screen for the development of these complications, MRI plays an important role in assessing monochorionic twin pregnancies for the development of other complications, such as neurologic injury. In this article, the authors review the ultrasound imaging findings associated with monochorionic twin complications, management options, and the role for MRI in these pregnancies.

Amniocentesis in pregnancies at or beyond 24 weeks: an international multicenter study.

BACKGROUND: Amniocentesis for genetic diagnosis is most commonly done between 15 and 22 weeks of gestation but can be performed at later gestational ages. The safety and genetic diagnostic accuracy of amniocentesis have been well-established through numerous large-scale multicenter studies for procedures before 24 weeks, but comprehensive data on late amniocentesis remain sparse. OBJECTIVE: To evaluate the indications, diagnostic yield, safety, and maternal and fetal outcomes associated with amniocentesis performed at or beyond 24 weeks of gestation. STUDY DESIGN: We conducted an international multicenter retrospective cohort study examining pregnant individuals who underwent amniocentesis for prenatal diagnostic testing at gestational ages between 24w0d and 36w6d. The study, spanning from 2011 to 2022, involved 9 referral centers. We included singleton or twin pregnancies with documented outcomes, excluding cases where other invasive procedures were performed during pregnancy or if amniocentesis was conducted for obstetric indications. We analyzed indications for late amniocentesis, types of genetic tests performed, their results, and the diagnostic yield, along with pregnancy outcomes and postprocedure complications. RESULTS: Of the 752 pregnant individuals included in our study, late amniocentesis was primarily performed for the prenatal diagnosis of structural anomalies (91.6%), followed by suspected fetal infection (2.3%) and high-risk findings from cell-free DNA screening (1.9%). The median gestational age at the time of the procedure was 28w5d, and 98.3% of pregnant individuals received results of genetic testing before birth or pregnancy termination. The diagnostic yield was 22.9%, and a diagnosis was made 2.4 times more often for fetuses with anomalies in multiple organ systems (36.4%) compared to those with anomalies in a single organ system (15.3%). Additionally, the diagnostic yield varied depending on the specific organ system involved, with the highest yield for musculoskeletal anomalies (36.7%) and hydrops fetalis (36.4%) when a single organ system or entity was affected. The most prevalent genetic diagnoses were aneuploidies (46.8%), followed by copy number variants (26.3%) and monogenic disorders (22.2%). The median gestational age at delivery was 38w3d, with an average of 59 days between the procedure and delivery date. The overall complication rate within 2 weeks postprocedure was 1.2%. We found no significant difference in the rate of preterm delivery between pregnant individuals undergoing amniocentesis between 24 and 28 weeks and those between 28 and 32 weeks, reinforcing the procedure's safety across these gestational periods. CONCLUSION: Late amniocentesis, at or after 24 weeks of gestation, especially for pregnancies complicated by multiple congenital anomalies, has a high diagnostic yield and a low complication rate, underscoring its clinical utility. It provides pregnant individuals and their providers with a comprehensive diagnostic evaluation and results before delivery, enabling informed counseling and optimized perinatal and neonatal care planning.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.

Enlarged cavum septum pellucidum and small thymus as markers for 22q11.2 deletion syndrome.

BACKGROUND: Enlarged cavum septum pellucidum (CSP) and hypoplastic thymus are proposed extra-cardiac fetal markers for 22q11.2 deletion syndrome. We sought to determine if they were part of the fetal phenotype of our cohort of fetuses with 22q11.2 deletion syndrome. METHODS: Case-control study of fetuses evaluated from 2016 to 2022. The study group included fetuses with laboratory confirmation of 22q11.2 deletion syndrome. The control group included pregnancies with conotruncal cardiac anomalies with normal microarray as well as structurally normal fetuses with normal microarray. The CSP and thymus were routinely measured during anatomical ultrasound in all patients at their initial visit at 27.1 ± 4.7 weeks. The CSP and thymus measurements were classified as abnormal if they were >95% or <5% for gestational age, respectively. The groups were compared using analysis of variance or Kruskal-Wallis for continuous variables and Fisher's exact test for categorical variables. Logistic regression was performed, and a Receiver Operating Characteristic (ROC) curve was constructed. RESULTS: We identified 47 fetuses with 22q11.2 deletion syndrome and compared them to 47 fetuses with conotruncal anomalies and normal microarray and 47 structurally normal fetuses with normal microarray. 51% (24/47) of fetuses with 22q11.2 deletion syndrome had an enlarged CSP compared to 6% (3/47) of fetuses with a conotruncal anomaly and normal microarray and none of the structurally normal fetuses (p < 0.001). Of the fetuses with 22q11.2 deletion syndrome, 83% (39/47) had a hypoplastic or absent thymus compared to 9% (4/47) of the fetuses with a conotruncal anomaly and normal microarray and none of the structurally normal fetuses (p < 0.001). 87% (41/47) of the fetuses with 22q11.2 deletion syndrome had conotruncal cardiac anomalies. Logistic regression revealed that both enlarged CSP and hypoplastic/absent thymus were associated with 22q11.2 deletion syndrome. The area under the ROC curve for the two markers was 0.94. CONCLUSION: An enlarged CSP and hypoplastic/absent thymus appear to be part of the fetal phenotype of 22q11.2 deletion syndrome. These markers are associated with conotruncal anomalies in the setting of 22q11.2 deletion syndrome but not in normal controls or fetuses with conotruncal defects and normal microarrays.

Prenatal Diagnosis of Fetal Aqueductal Stenosis: A Multicenter Prospective Observational Study through the North American Fetal Therapy Network.

INTRODUCTION: A critical component of an evidence-based reassessment of in-utero intervention for fetal aqueductal stenosis (fetal AS) is determining if the prenatal diagnosis can be accurately made at a gestational age amenable to in-utero intervention. METHODS: A multicenter, prospective, observational study was conducted through the North American Fetal Therapy Network (NAFTNet). Pregnancies complicated by severe central nervous system (CNS) ventriculomegaly (lateral ventricle diameter >15 mm) not secondary to a primary diagnosis (myelomeningocele, encephalocele, etc.) were recruited at diagnosis. Imaging and laboratory findings were recorded in an online REDCap database. After evaluation, investigators were asked to render their degree of confidence in the diagnosis of fetal AS. The prenatal diagnosis was compared to the postnatal diagnosis obtained through neonatal neuroimaging. Performance characteristics of ultrasound and magnetic resonance imaging (MRI) were calculated, as was the mean gestational age at diagnosis. RESULTS: Between April 2015 and October 2022, eleven NAFTNet centers contributed 64 subjects with severe fetal CNS ventriculomegaly. Of these, 56 had both prenatal and postnatal diagnoses recorded. Ultrasound revealed 32 fetal AS true positives, 4 false positives, 7 false negatives, and 13 true negatives, rendering a sensitivity of 0.82, a specificity of 0.76, a positive predictive value of 0.89, and a negative predictive value of 0.65. The mean gestational age at diagnosis by ultrasound was 25.5 weeks (std +/- 4.7 weeks). The proportion of agreement (true positive + true negative/n) was highest at 24 weeks gestation. For fetal MRI (n = 35), the sensitivity for fetal AS was 0.95, specificity was 0.69, positive predictive value was 0.84, and negative predictive value was 0.90. MRI was performed at 25 weeks on average. CONCLUSION: The prenatal diagnosis of fetal AS can be made with accuracy at a gestational age potentially amenable to in-utero intervention. Only 7% of subjects were incorrectly diagnosed prenatally with fetal AS by ultrasound and 11% by MRI. Diagnostic accuracy of fetal AS will likely improve with increased experience.

Predictors of Poor Outcomes in Monochorionic Diamniotic Twin Pregnancies Complicated by Selective Fetal Growth Restriction.

INTRODUCTION: The aim of the study was to identify predictors of poor outcomes in monochorionic diamniotic twin (MCDA) pregnancies with selective fetal growth restriction (sFGR), irrespective of the umbilical artery (UA) Doppler abnormalities. METHODS: Single-center retrospective analysis of MCDA twins diagnosed with sFGR that opted for expectant management between 2010 and 2021. The presence of any of the following variables in the growth-restricted fetus: low amniotic fluid volume (DVP ≤2 cm), lack of a cycling bladder, absent or reversed flow in the ductus venosus (DV) with atrial contraction, and elevated middle cerebral artery peak systolic velocity (MCA-PSV) defined as ≥1.50 multiples of the median was categorized as complicated. sFGR cases were classified as simple in the absence of the above-mentioned variables. RESULTS: Overall, 63.3% of cases qualified as simple, and 36.7% were complicated. Intertwin EFW discordance was higher in the complicated category (26 vs. 33%, p = 0.0002). The median gestational age at delivery was earlier (33 weeks vs. 30.5 weeks, p = 0.002), and the likelihood of survival was lower in the complicated category (p < 0.0001). The likelihood of two survivors to discharge was lower in type I complicated cases (70% in complicated type I vs. 97.1% in simple type I, p = 0.0003). On logistic regression analysis, an increase in the "complicated" score negatively correlated with two survivors to discharge (p < 0.0001). An ROC curve was created, and the AUC was 0.79. Increasing intertwin EFW discordance also decreased the probability of two survivors to discharge. CONCLUSION: The presence of oligohydramnios, lack of a cycling bladder, abnormal DV Doppler, and elevated MCA-PSV in the growth restricted fetus is associated with poor perinatal outcomes and a lower likelihood of having two survivors to discharge. The addition of intertwin EFW discordance to these variables helped improve the survival predictability.

The Delivery Room Resuscitation of Infants with Congenital Diaphragmatic Hernia Treated with Fetoscopic Endoluminal Tracheal Occlusion: Beyond the Balloon.

INTRODUCTION: Randomized controlled trials found that fetoscopic endoluminal tracheal occlusion (FETO) resulted in increased fetal lung volume and improved survival for infants with isolated, severe left-sided congenital diaphragmatic hernia (CDH). The delivery room resuscitation of these infants is particularly unique, and the specific delivery room events are largely unknown. The objective of this study was to compare the delivery room resuscitation of infants treated with FETO to standard of care (SOC) and describe lessons learned. METHODS: Retrospective single-center cohort study of infants treated with FETO compared to infants who met FETO criteria during the same period but who received SOC. RESULTS: FETO infants were more likely to be born prematurely with 8/12 infants born <35 weeks gestational age compared to 3/35 SOC infants. There were 5 infants who required emergent balloon removal (2 ex utero intrapartum treatment and 3 tracheoscopic removal on placental bypass with delayed cord clamping) and 7 with prenatal balloon removal. Surfactant was administered in 6/12 FETO (50%) infants compared to 2/35 (6%) in the SOC group. Extracorporeal membrane oxygenation use was lower at 25% and survival was higher at 92% compared to 60% and 71% in the SOC infants, respectively. CONCLUSION: The delivery room resuscitation of infants treated with FETO requires thoughtful preparation with an experienced multidisciplinary team. Given increased survival, FETO should be offered to infants with severe isolated left-sided CDH, but only in high-volume centers with the experience and capability of removing the balloon, emergently if needed. The neonatal clinical team must be skilled in managing the unique postnatal physiology inherent to FETO where effective interdisciplinary teamwork is essential. Empiric and immediate surfactant administration should be considered in all FETO infants to lavage thick airway secretions, particularly those delivered <48 h after balloon removal.

The Impact of Comprehensive Fetal Care on Mortality of Children With Congenital Diaphragmatic Hernia when Delivery is Co-located in a Pediatric Hospital.

BACKGROUND: We evaluated the impact of delivery at a comprehensive fetal care center co-located in a pediatric hospital on extracorporeal membrane oxygenation (ECMO) exposure and survivorship of children with CDH. METHODS: This retrospective study includes maternal-fetal dyads with a prenatal diagnosis of isolated CDH who received any prenatal care at a single fetal center between February 2006 and March 2021. The principal variables included: (1) delivery setting (children born in the pediatric hospital ["inborn"] vs. children who were delivered elsewhere ["outborn"]), (2) exposure to ECMO (yes vs. no), and (3) survival-at-discharge from birth hospitalization (yes vs. no). Multivariable logistic regression was used to evaluate the association between delivery setting and ECMO cannulation, and whether delivery setting moderates the association between exposure to ECMO and survival-at-discharge. RESULTS: Among 418 maternal-fetal dyads, 77.0% of children were inborn and 32.0% of children were exposed to ECMO during their index hospitalization. Inborn children had more severe prenatal prognostic indicators but had a 57% lower odds of extracorporeal than outborn children. In multivariable logistic regression, delivery setting moderated the association between exposure to ECMO and survival-at-discharge. Although there was no statistically significant difference in mortality between inborn and outborn children who were not exposed to ECMO, inborn children exposed to ECMO had a 6.86 (1.98, 23.74) increased odds of death and outborn children exposed to ECMO had a 17.71 (4.69, 66.87) increased odds of death when both were compared to non-cannulated outborn children. CONCLUSIONS: Comprehensive fetal care with delivery co-located in a pediatric hospital was associated with decreased exposure to ECMO and a survivorship advantage among children with CDH who required extracorporeal support. LEVEL OF EVIDENCE: Level III.

Prenatal Brain Maturation is Delayed in Neonates with Congenital Diaphragmatic Hernia.

OBJECTIVE: To assess brain development in fetuses with congenital diaphragmatic hernia (CDH) using a fetal Total Maturation Score (fTMS). STUDY DESIGN: This is a retrospective cohort study using data from a single-center clinical registry. Neonates with an antenatal diagnosis of CDH between 2014 and 2020 and prenatal brain magnetic resonance imaging (MRI) (n = 48) were included. We compared our study sample with historical healthy controls (n = 48). The relationship between fTMS and gestational age (GA), as well as the association between fTMS and key prenatal variables and placental pathologic findings, were evaluated. RESULTS: Compared with healthy controls, neonates with CDH had a significant delay in fTMS (P value <.001). Within the CDH cohort, there was no significant difference in fTMS based on CDH severity, intrathoracic liver position, right vs left CDH, sex, presence of abnormal echocardiogram findings, treatment with extracorporeal membrane oxygenation (ECMO), or in-hospital mortality. Placentas of neonates with CDH had a high proportion of fetal vascular malperfusion (56%) and chronic inflammation (67%), and relatively large placentas had a protective effect on prenatal brain maturation (P value = .025). CONCLUSIONS: Prenatal brain maturation in neonates with CDH is delayed. Placental pathology may influence fetal brain development. The etiology and clinical impact of prenatal brain immaturity in neonates with CDH warrant further investigation.

Update on Management and Outcomes of Congenital Diaphragmatic Hernia.

Infants with congenital diaphragmatic hernia (CDH) benefit from comprehensive multidisciplinary teams that have experience in caring for the unique and complex issues associated with CDH. Despite prenatal referral to specialized high-volume centers, advanced ventilation strategies and pulmonary hypertension management, and extracorporeal membrane oxygenation, mortality and morbidity remain high. These infants have unique and complex issues that begin in fetal and infant life, but persist through adulthood. Here we will review the literature and share our clinical care pathway for neonatal care and follow up. While many advances have occurred in the past few decades, our work is just beginning to continue to improve the mortality, but also importantly the morbidity of CDH.

Amnioreduction vs expectant management in pregnancies with moderate to severe polyhydramnios.

BACKGROUND: The rate of polyhydramnios is higher in pregnancies complicated by congenital anomalies. These pregnancies have higher rates of peripartum complications. Amnioreduction is offered to relieve maternal symptoms such as dyspnea, abdominal and respiratory discomfort, and other issues like satiety. OBJECTIVE: This study aimed to report the rates of amnioreduction and its associated complications in pregnancies with moderate to severe polyhydramnios secondary to fetal anomalies. We also sought to determine if amnioreduction provided additional benefits, including prolongation of pregnancy and a decrease in the rates of peripartum morbidities associated with moderate to severe polyhydramnios. STUDY DESIGN: This was a retrospective review of anomalous singleton pregnancies with moderate to severe polyhydramnios that were evaluated and delivered at a single center between 2013 and 2021. Peripartum outcomes were compared between pregnancies that underwent amnioreduction and those that were expectantly managed. Mann-Whitney U tests were used to compare continuous variables and Fisher's exact tests were used for categorical variables. A multiple regression model was created to understand the effects of amnioreduction on gestational age at delivery. RESULTS: A total of 218 singleton pregnancies met the inclusion criteria of moderate to severe polyhydramnios in the study period. Of those, 110 patients (50.5%) underwent amnioreduction and 108 patients (49.5%) opted for expectant management. A total of 147 procedures were performed at a median gestational age of 32.5 weeks and a median of 1900 mL of amniotic fluid was removed per procedure. Complications occurred in 10.9% (n=16) of procedures, including preterm delivery within 48 hours in 5.4% cases (n=8). The median amniotic fluid index was higher in the amnioreduction group than in the expectant group (38.9 cm vs 35.5 cm; P<.0001). Patients who underwent amnioreduction had an earlier median gestational age at delivery (36.3 weeks vs 37.0 weeks; P=.048), however, the rates of spontaneous preterm delivery were similar. A higher percentage of women in the amnioreduction group had vaginal delivery (49.4% vs 30.5%; P=.01) and lower rates of uterine atony (2.4% vs 13.7%; P=.006). In the multiple linear regression analysis, the gestational age at delivery positively correlated with gestational age at amnioreduction after controlling for amniotic fluid volume (P<.0001; 95% confidence interval, 0.34-0.71). In addition, the patients in the amnioreduction group were twice as likely to have a vaginal delivery (P=.02). CONCLUSION: Amnioreduction in the setting of moderate-severe polyhydramnios has a reasonably low rate of complications but does not provide any benefits in terms of prolonging the pregnancy. The procedure may increase the likelihood of vaginal delivery and lower the rates of uterine atony.

Impaired Maternal-Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease.

Background Infants with congenital heart disease (CHD) are at risk for white matter injury (WMI) before neonatal heart surgery. Better knowledge of the causes of preoperative WMI may provide insights into interventions that improve neurodevelopmental outcomes in these patients. Methods and Results A prospective single-center study of preoperative WMI in neonates with CHD recorded data on primary cardiac diagnosis, maternal-fetal environment (MFE), delivery type, subject anthropometrics, and preoperative care. Total maturation score and WMI were assessed, and stepwise logistic regression modeling selected risk factors for WMI. Among subjects with severe CHD (n=183) who received a preoperative brain magnetic resonance imaging, WMI occurred in 40 (21.9%) patients. WMI prevalence (21.4%-22.1%) and mean volumes (119.7-160.4 mm3) were similar across CHD diagnoses. Stepwise logistic regression selected impaired MFE (odds ratio [OR], 2.85 [95% CI, 1.29-6.30]), male sex (OR, 2.27 [95% CI, 1.03-5.36]), and older age at surgery/magnetic resonance imaging (OR, 1.20 per day [95% CI, 1.03-1.41]) as risk factors for preoperative WMI and higher total maturation score values (OR, 0.65 per unit increase [95% CI, 0.43-0.95]) as protective. A quarter (24.6%; n=45) of subjects had ≥1 components of impaired MFE (gestational diabetes [n=12; 6.6%], gestational hypertension [n=11; 6.0%], preeclampsia [n=2; 1.1%], tobacco use [n=9; 4.9%], hypothyroidism [n=6; 3.3%], and other [n=16; 8.7%]). In a subset of 138 subjects, an exploratory analysis of additional MFE-related factors disclosed other potential risk factors for WMI. Conclusions This study is the first to identify impaired MFE as an important risk factor for preoperative WMI. Vulnerability to preoperative WMI was shared across CHD diagnoses.

Predictors of dual demise within the first week after selective cord occlusion via radiofrequency ablation for complex monochorionic pregnancies.

BACKGROUND: Selective cord occlusion is an option in complicated monochorionic multiple gestations with the goal of reducing the pregnancy by one fetus and to optimize the outcomes for the remaining fetus(es). OBJECTIVE: This study aimed to determine the rate and associated risk factors of dual demise in complex monochorionic pregnancies after selective cord occlusion via radiofrequency ablation. STUDY DESIGN: This was a single-center analysis of a prospective registry cohort of complex monochorionic pregnancies managed with selective cord occlusion via radiofrequency ablation between 2014 and 2021. A total of 167 pregnancies met the inclusion criteria and were evaluated on the basis of the intended outcome of dual demise vs singleton survival. Risk factors were compared between the 2 groups. The Mann-Whitney U test was used for continuous variables and the Fisher exact test was used for categorical variables. RESULTS: The incidence of postprocedure dual demise within the first week after performing radiofrequency ablation was 10.8% (18/167). The risk was higher in pregnancies undergoing radiofrequency ablation for discordant anomaly, and this subcategory constituted 38.9% of pregnancies in the dual demise subgroup (P=.02). Lower intertwin estimated fetal weight discordance (P=.01) was associated with dual demise. Perioperative variables including gestational age at procedure, placental cord insertion distance, operative time, and radiofrequency ablation time were similar in those with and without dual demise. CONCLUSION: Our results show that selective cord occlusion via radiofrequency ablation is a safe and reasonable option in complicated monochorionic pregnancies, with low rates of dual demise within the first week after the procedure.

Risks of Single Fetal Demise after Laser for Twin-Twin Transfusion Syndrome.

INTRODUCTION: The aim of the study was to determine if markers of donor placental insufficiency and recipient cardiac dysfunction increase the risk for single fetal demise (SFD) after laser for twin-twin transfusion syndrome (TTTS). METHODS: Single-center retrospective review of patients who had laser for TTTS. Risk factors for donor and recipient demise within 1 week were compared in pregnancies with SFD and pregnancies with dual survival using χ2 or Fisher's exact test. Multivariate logistic regression was then performed. RESULTS: Of 398 procedures, 305 (76.6%) had dual survival, 36 (9.0%) had donor demise, 28 (7.0%) had recipient demise, and 9 (2.3%) had dual demise. The remaining 20 (5.0%) patients had complicated courses with pregnancy loss or further intervention. In the 64 pregnancies with SFD, 29 (81%) in the donor group and 20 (71%) in the recipient group occurred in the first postoperative week. For the donor demise group, estimated fetal weight (EFW) <10%, EFW <3%, EFW <1%, EFW discordance >25%, and EFW discordance >30% did not increase the risk for donor demise except in cases that also had umbilical artery absent or reversed end diastolic flow (AREDF). Donor AREDF was the only independent risk factor for early donor demise. For the recipient demise group, recipient abnormal venous Dopplers were associated with increased risk while EFW discordance >25% was associated with decreased risk of recipient loss. DISCUSSION/CONCLUSION: In our cohort, donor growth restriction did not increase the risk of early donor demise after laser unless there was also donor AREDF. Donor AREDF was an independent risk factor for donor demise likely due to the severity of placental insufficiency. Abnormal recipient venous Doppler indices increased the risk of early recipient loss while a large intertwin discordance decreased the risk. This may be explained by profound overload in cases with recipient abnormal venous Doppler velocimetry and a lower risk of substantial fluid shifts from a relatively smaller donor territory when there is a large discordance.

Impact of Obesity on Pregnancies Undergoing Laser Therapy for Twin-Twin Transfusion Syndrome.

INTRODUCTION: We sought to determine if maternal obesity, defined by body mass index (BMI) 30-34.9 or BMI ≥35, negatively impacts the technical aspects and pregnancy outcomes in women treated with selective laser photocoagulation of placental communicating vessels for twin-twin transfusion syndrome (TTTS). METHODS: Retrospective review of women undergoing laser for TTTS from January 2010 to December 2021. Outcomes were stratified based on maternal BMI <30, 30-34.9, and ≥35. Data obtained included maternal age, parity, ethnicity, gestational age at laser, placental location, Quintero stage, CHOP cardiovascular score, operative and anesthesia times, procedure-to-delivery interval, gestational age at delivery, survival to birth, survival to discharge, and the presence of residual anastomoses. Statistical analysis included the χ2 or Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables with p < 0.05 being significant. RESULTS: A total of 434 women underwent laser for TTTS during the study period. Of those, 274 (63%) had a BMI of <30, 92 (21.2%) had a BMI between 30 and 34.9, and 68 (15.7%) had a BMI ≥ 35. There were no differences in maternal age, parity or ethnicity, Quintero stage, CHOP cardiovascular score, placental location, operative time, laser-to-delivery interval, gestational age at delivery, survival outcomes, or the presence of residual anastomoses between the three groups. Patients with a BMI of 30-34.9 were operated on at a slightly later gestational age, and those with a BMI > 35 had longer operative and anesthesia times. There were no technical failures as a result of BMI ≥ 30 or 35. CONCLUSION: Using appropriate technical adjustments, outcomes for obese women undergoing laser for TTTS are similar to nonobese women, although patients with BMI ≥35 have longer operative and anesthesia times.

The Genomics of Congenital Diaphragmatic Hernia: A 10-Year Retrospective Review.

OBJECTIVE: To evaluate genetic testing use in infants with congenital diaphragmatic hernia (CDH) over the past decade to better inform future practices and individualize prognostication and management. STUDY DESIGN: A retrospective cohort study was performed of all infants with CDH enrolled in the Pulmonary Hypoplasia Program at Children's Hospital of Philadelphia, born between January 2011 and February 2021. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed. RESULTS: The charts of 411 infants were analyzed. Overall, 22% (n = 89) were complex/syndromic and 78% (n = 322) were isolated/nonsyndromic. Mortality was significantly higher in complex/syndromic infants (P < .001) and in infants with diagnostic genetic testing (P < .001). Microarray was diagnostic in 9% (n = 34/399) and exome sequencing was diagnostic in 38% (n = 15/39). Genetic testing was diagnostic in 57% (n = 51/89) of complex/syndromic infants, but in only 2% of isolated/nonsyndromic infants (n = 8/322). Overall, genetic testing was diagnostic in 14% (n = 56). CONCLUSIONS: The high diagnostic rate in this cohort highlights the utility of comprehensive genetic testing in infants with CDH. However, 43% of complex/syndromic and 98% of isolated/nonsyndromic infants do not have a genetic etiology identified. This finding underscores the need for additional genetic and genomic studies (eg, whole genome, RNA sequencing) to identify novel genes and mutational mechanisms (single genes, regulatory elements, complex traits) that will allow for improved diagnostic rates and ultimately individualized management of infants with CDH.

Magnetic resonance neuroimaging after laser for twin-twin transfusion syndrome with single fetal demise.

BACKGROUND: Neurologic injury in the surviving twin is a risk after single fetal demise in a monochorionic pregnancy. OBJECTIVE: This study aimed to describe fetal magnetic resonance neuroimaging findings in pregnancies complicated by single fetal demise after laser photocoagulation for twin-twin transfusion syndrome. STUDY DESIGN: This was a single-center retrospective analysis of a cohort of prospectively collected patients in a monochorionic twin registry who had fetoscopic laser photocoagulation for twin-twin transfusion syndrome with single fetal demise at follow-up. Magnetic resonance neuroimaging was offered 3 to 4 weeks after the demise to assess for potential neurologic sequelae. Magnetic resonance images were interpreted by 2 board-certified neuroradiologists and classified as normal, mildly abnormal, or severely abnormal. The groups were compared on the basis of recipient vs donor demise using the Fisher exact test and Mann-Whitney U test. Multivariate logistic regression was performed to determine risk factors for abnormal magnetic resonance neuroimaging. RESULTS: In 378 laser photocoagulation procedures, 64 cases (16.9%) of single demise were identified (36 in the donor group and 28 in the recipient group). Of note, 6 patients had rupture of membranes with nonviable delivery (3 from each group). Moreover, 40 patients (69%) underwent magnetic resonance imaging. Of those patients, 12 (30%) had abnormal findings: 10 (83%) were associated with mild changes, and 2 (17%) were associated with severe findings. Abnormal magnetic resonance neuroimaging was seen in 3 of 22 patients (14%) after donor demise and 9 of 18 patients (50%) after recipient demise (P=.02). Logistic regression revealed that recipient vs donor demise was an independent risk factor for abnormal magnetic resonance imaging. In addition, 2 pregnancies with severe magnetic resonance imaging findings had complicated courses. CONCLUSION: Mildly abnormal magnetic resonance neuroimaging findings were common after laser photocoagulation for twin-twin transfusion syndrome complicated by single fetal demise and were more common in cases of recipient demise than donor demise. Severe magnetic resonance neuroimaging findings in this series were limited to patients with complicated peri- or postoperative courses.

Postnatal outcomes and risk factor analysis for patients with prenatally diagnosed oropharyngeal masses.

OBJECTIVES: To describe our experience treating prenatally diagnosed oropharyngeal masses in a novel, multidisciplinary collaboration. To identifying outcomes and risk factors associated with adverse postnatal outcomes. METHODS: This is a sixty-two patient case series at an academic referral center. Patients with prenatally diagnosed oropharyngeal masses were identified through a programmatic database and confirmed in the electronic health record. RESULTS: Sixty-two patient with prenatally diagnosed oropharyngeal mass were identified, with prenatal imaging at our institution confirming this diagnosis in fifty-seven patients, short term outcomes analysis conducted on forty-four patients, and long-term outcomes analysis conducted on seventeen patients. The most common pathology was lymphatic malformations (n = 27, 47.4%), followed by teratomas (n = 22, 38.6%). The median mass volume from all available patient imaging (n = 57) was 60.54 cm3 (range 1.73-742.5 cm3). Thirteen pregnancies were interrupted, six infants expired, and thirteen cases had an unknown fetal outcome. Confirmed mortality was 6/57 patients with imaging-confirmed oropharyngeal masses (10.5%). Fourteen (56%) of the surviving patients (n = 25) were delivered by Ex Utero Intrapartum Treatment (EXIT) procedure and the median NICU stay was thirty-six days (range: 3-215 days). There was no association between airway compression/deviation/displacement, stomach size, polyhydramnios, or mass size and mortality. Seventeen patients had more than one year of follow-up (mean 5.3 ± 2.4 years). These seventeen patients underwent general anesthesia a total of ninety-two times (mean 5.4 ± 4.3) and had a total of twenty-three mass-related surgeries. The great majority of patients required an artificial airway at birth, feeding support, and speech/swallow therapy. CONCLUSIONS: Oropharyngeal mass involvement of key anatomic structures-the neck, upper thorax, orbit, and ear, has a greater association with mortality than mass size. Regardless of the size and involved structures, oropharyngeal masses are associated with a high burden of intensive medical care and surgical care beginning at or before birth.