Expansion of the prenatal phenotype of Baraitser-Winter syndrome: Presentation of two cases of multiple congenital anomaly syndrome.

Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a variable multiple congenital anomaly condition, typically presenting postnatally with neurocognitive delays, distinctive facial features, cortical brain malformations, and in some, a variety of additional congenital malformations. However, only a few cases have reported the prenatal presentation of this syndrome. Here, we report two cases of BWCFF and their associated prenatal findings. One case presented with non-immune hydrops fetalis and a horseshoe kidney and was found to have a de novo heterozygous variant in ACTB (c.158A>G). The second case presented with gastroschisis, bilateral cleft lip and palate, and oligohydramnios, and was found to harbor a different de novo variant in ACTB (c.826G>A). Limited reports exist describing prenatally identified anomalies that include fetal growth restriction, increased nuchal fold, bilateral hydronephrosis, rocker bottom foot, talipes, cystic hygroma, omphalocele, and hydrops fetalis. In addition, only three of these cases have included detailed prenatal imaging findings. The two prenatal cases presented here demonstrate an expansion of the prenatal phenotype of BWCFF to include gastroschisis, lymphatic involvement, and oligohydramnios, which should each warrant consideration of this diagnosis in the setting of additional anomalies.

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.

Is there an increased risk of genetic abnormalities in fetuses with congenital heart disease in the setting of growth restriction?

OBJECTIVE: To determine if the presence of fetal growth restriction (FGR) is associated with an increased risk of genetic abnormalities in the setting of congenital heart disease (CHD). METHODS: This was a retrospective cohort study involving pregnancies that met the following criteria: (i) prenatal diagnosis of CHD, (ii) singleton live-birth, and (iii) genetic testing was performed either pre- or postnatally. Genetic results were reviewed by a clinical geneticist for updated variant classification. Fetal growth was stratified as appropriate for gestational age (AGA) or FGR. RESULTS: Of the total of 445 fetuses that met the study criteria, 325 (73.0%) were AGA and 120 (27.0%) were FGR. Genetic abnormalities were detected in 131 (29.4%) pregnancies. There was a higher rate of genetic abnormalities (36.7% vs. 26.8%, p = 0.04), which was driven by aneuploidies (20.8% vs. 8.9%, p = 0.0006) in the FGR population. Early onset growth restriction was associated with a higher rate of genetic abnormalities (44.5% vs. 25.9%, p = 0.03). The rate of genetic abnormalities was significantly higher in the shunt category as compared to remainder of the cardiac anomalies (62.5% in shunt lesions vs. 24.7%, p < 0.00001). The rates of FGR (40.9% vs. 21.4%, p < 0.0001) and genetic abnormalities (52% vs. 20.4%, p < 0.0001) were significantly higher in the presence of extra-cardiac anomalies (ECA). CONCLUSION: The presence of FGR in fetal CHD population was associated with underlying genetic abnormalities, specifically aneuploidies. Patients should be appropriately counseled regarding the higher likelihood of a genetic condition in the presence of FGR, early onset FGR, shunt lesions and ECA.

Prenatal cardiac findings and 22q11.2 deletion syndrome: Fetal detection and evaluation.

Clinical features of 22q11.2 microdeletion syndrome (22q11.2DS) are highly variable between affected individuals and frequently include a subset of conotruncal and aortic arch anomalies. Many are diagnosed with 22q11.2DS when they present as a fetus, newborn or infant with characteristic cardiac findings and subsequently undergo genetic testing. The presence of an aortic arch anomaly with characteristic intracardiac anomalies increases the likelihood that the patient has 22q11.2 DS, but those with an aortic arch anomaly and normal intracardiac anatomy are also at risk. It is particularly important to identify the fetus at risk for 22q11.2DS in order to prepare the expectant parents and plan postnatal care for optimal outcomes. Fetal anatomy scans now readily identify aortic arch anomalies (aberrant right subclavian artery, right sided aortic arch or double aortic arch) in the three-vessel tracheal view. Given the association of 22q11.2DS with aortic arch anomalies with and without intracardiac defects, this review highlights the importance of recognizing the fetus at risk for 22q11.2 deletion syndrome with an aortic arch anomaly and details current methods for genetic testing. To assist in the prenatal diagnosis of 22q11.2DS, this review summarizes the seminal features of 22q11.2DS, its prenatal presentation and current methods for genetic testing.

Case report of fetus with Lowe syndrome: Expanding the prenatal phenotype.

Oculocerebrorenal syndrome (Lowe syndrome) is a rare X-linked disorder affecting 1/500,000 males that most frequently affects the eyes, central nervous system, and kidneys. Phenotypic presentation includes congenital cataracts, developmental delay, intellectual disability, and Fanconi-type renal dysfunction. Lowe Syndrome is caused by hemizygous loss of function variants in the OCRL gene. While individuals may live into the third and fourth decade of life, some will die in the first few years of either renal failure or infection. While early diagnosis is important, few cases have documented the prenatal phenotype of this condition, which has included bilateral cataracts and variable neurological abnormalities. We report a case of a family with an extensive history of congenital cataracts, immune compromise, and neonatal death in male members. The fetus was found to have a unilateral cataract, mild ventriculomegaly, vertebral anomalies, and an underlying diagnosis of Lowe Syndrome with a mutation in OCRL at c.2582-1G>C (IVS23-1G>C).

Fetus with multiple congenital anomaly syndrome caused by novel variant in ATP1A2.

We report a 32-year-old G3P1 at 35 weeks 3 days with a dichorionic, diamniotic twin gestation who presented for evaluation secondary to ventriculomegaly (VM) in one twin. Fetal ultrasound and MRI demonstrated microcephaly, severe VM, compression of the corpus callosum, scalp and nuchal thickening, elongated ears, bilateral talipes, right-sided congenital diaphragmatic hernia (CDH), and loss of normal cerebral architecture, indicative of a prior insult in the affected twin. The co-twin was grossly normal. The family pursued a palliative care pathway for the affected twin and was delivered at 37 weeks and 6 days. The affected twin passed away within the first hour of life due to respiratory compromise. Postmortem trio exome sequencing identified a homozygous likely pathogenic variant in ATP1A2 (c.2439+1G>A). Although this variant is novel, it is predicted to affect the donor split site in intron 17, resulting in a frameshift and complete loss-of-function of the gene. Biallelic loss of function variants in this gene have been reported in seven individuals with multiple anomalies similar to those in the affected twin. However, only one other individual with a possible CDH has been previously reported. Our case suggests that CDH be included in the phenotypic spectrum of this disorder and reports the first frameshift mutation causing this autosomal recessive multiple congenital anomaly syndrome.

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.

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.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

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.

Prenatal Diagnosis of Skeletal Dysplasias: What Can CT Do for You?

Skeletal dysplasias (SDs) are a heterogeneous group of heritable disorders that affect development of bone and cartilage. Because each SD is individually rare and because of the heterogeneity within and among disorders, prenatal diagnosis of a specific SD remains challenging. Molecular genetic diagnosis involves invasive testing, which some patients are not amenable to. Further, genetic analysis is time consuming, and results may not become available in time to make pregnancy management decisions. Low-dose fetal CT can aid in the prenatal evaluation of SDs. The main downside is the low but true risk of fetal radiation exposure. As such, fetal CT should only be performed when there is concern for a severe skeletal dysplasia and the diagnosis is in question after a detailed ultrasound or if molecular genetic testing is unavailable and when prenatal diagnosis may affect management or counseling. Fetal CT should be obtained after consultation with geneticists, maternal-fetal medicine specialists, and fetal radiologists, and sometimes orthopedic surgeons or neonatologists. The purpose of this study was to review the technique of and indications for fetal CT, as well as discuss fetal radiation risk. Illustrative cases will demonstrate when and how CT may be helpful in the diagnosis of SDs.

Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions.

Diagnosis of a chromosome 22q11.2 microdeletion and its associated deletion syndrome (22q11.2DS) is optimally made early. We reviewed the available literature to provide contemporary guidance and recommendations related to the prenatal period. Indications for prenatal diagnostic testing include a parent or child with the 22q11.2 microdeletion or suggestive prenatal screening results. Definitive diagnosis by genetic testing of chorionic villi or amniocytes using a chromosomal microarray will detect clinically relevant microdeletions. Screening options include noninvasive prenatal screening (NIPS) and imaging. The potential benefits and limitations of each screening method should be clearly conveyed. NIPS, a genetic option available from 10 weeks gestational age, has a 70-83% detection rate and a 40-50% PPV for most associated 22q11.2 microdeletions. Prenatal imaging, usually by ultrasound, can detect several physical features associated with 22q11.2DS. Findings vary, related to detection methods, gestational age, and relative specificity. Conotruncal cardiac anomalies are more strongly associated than skeletal, urinary tract, or other congenital anomalies such as thymic hypoplasia or cavum septi pellucidi dilatation. Among others, intrauterine growth restriction and polyhydramnios are additional associated, prenatally detectable signs. Preconception genetic counselling should be offered to males and females with 22q11.2DS, as there is a 50% risk of transmission in each pregnancy. A previous history of a de novo 22q11.2 microdeletion conveys a low risk of recurrence. Prenatal genetic counselling includes an offer of screening or diagnostic testing and discussion of results. The goal is to facilitate optimal perinatal care.

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.

International Society for Prenatal Diagnosis 2022 DEBATE: There should be formal accreditation and ongoing quality assurance/review for units offering fetal therapy that includes public reporting of outcomes.

The field of fetal therapy has so far escaped from formal accreditation and quality control. Despite that, current published evidence shows that outcomes of interventions in younger fetal therapy centers are similar to what is achieved in more experienced centers and outcomes of interventions have improved over time. The question however remains what is not being published and what should be the standard of care, given the lack of level 1 evidence from randomized controlled trials for many interventions. Formal collaborative networks such as NAFTnet and others allow for anonymized benchmarking of center outcomes, without publicly shaming (and financially punishing) underperforming centers. Large registries also allow for tracking of rare complications and may result in improved patient outcomes over time. Core outcome sets, which could serve as a basis for outcome reporting, are available for some conditions, but certainly not for all, resulting in communication difficulties between centers. Formal accreditation, quality control, and outcome reporting are hard to implement, expensive, and may result in decreasing access to care by pushing smaller centers out of the market. Despite the existing difficulties, international societies have committed to quality improvement, and fetal therapy programs are strongly recommended to participate in voluntary outcome tracking.

Tethered cord release in patients after open fetal myelomeningocele closure: intraoperative neuromonitoring data and patient outcomes.

PURPOSE: The purpose of the study was to better understand the clinical course and impact of tethered cord release surgery on patients who have previously undergone open spinal dysraphism closure in utero. METHODS: This is a single-center retrospective observational study on patients undergoing tethered cord release after having previously had open fetal myelomeningocele (MMC) closure. All patients underwent tethered cord release surgery with a single neurosurgeon. A detailed analysis of the patients' preoperative presentation, intraoperative neuromonitoring (IONM) data, and postoperative course was performed. RESULTS: From 2009 to 2021, 51 patients who had previously undergone fetal MMC closure had tethered cord release surgery performed. On both preoperative and postoperative manual motor testing, patients were found to have on average 2 levels better than would be expected from the determined anatomic level from fetal imaging. The electrophysiologic functional level was found on average to be 2.5 levels better than the anatomical fetal level. Postoperative motor levels when tested on average at 4 months were largely unchanged when compared to preoperative levels. Unlike the motor signals, 46 (90%) of patients had unreliable or undetectable lower extremity somatosensory evoked potentials (SSEPs) prior to the tethered cord release. CONCLUSION: Tethered cord surgery can be safely performed in patients after open fetal MMC closure without clinical decline in manual motor testing. Patients often have functional nerve roots below the anatomic level. Sensory function appears to be more severely affected in patients leading to a consistent motor-sensory imbalance.

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.

Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial.

PURPOSE: Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days. METHODS: A consortium of 9 North American Fetal Therapy Network (NAFTNet) centers was formed, and the RAFT protocol was refined in collaboration with the NAFTNet Scientific Committee. Enrollment in the trial began in April 2020. Participants may elect to receive amnioinfusions or to join the nonintervention observational expectant management group. Eligible pregnant women must be at least 18 years of age with a fetal diagnosis of isolated early-pregnancy renal anhydramnios. FINDINGS: In addition to the primary study objective stated above, secondary objectives include (1) to assess maternal safety and feasibility of the serial amnioinfusion intervention (2) to perform an exploratory study of the natural history of untreated early pregnancy renal anhydramnios (3) to examine correlations between prenatal imaging and lung specific factors in amniotic fluid as predictive of the efficacy of serial percutaneous amnioinfusions and (4) to determine short- and long-term outcomes and quality of life in surviving neonates and families enrolled in RAFT IMPLICATIONS: The RAFT trial is the first clinical trial to investigate the efficacy, safety, and feasibility of amnioinfusions to treat the survival-limiting pulmonary hypoplasia associated with anhydramnios. Although the intervention offers an opportunity to treat a condition known to be almost universally fatal in affected neonates, the potential burdens associated with end-stage kidney disease from birth must be acknowledged. CLINICALTRIALS: gov identifier: NCT03101891.