Use of Web-Based Surveys to Collect Long-Term Pediatric Outcomes in Patients With Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Photocoagulation: Observational Study.

Background: In the United States, patients with monochorionic diamniotic twins who undergo in utero fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) may travel great distances for care. After delivery, many parents cannot return to study sites for formal pediatric evaluation due to geographic location and cost. Objective: The aim of this study was to collect long-term pediatric outcomes in patients who underwent FLP for TTTS. Methods: We assessed the feasibility of using a web-based survey designed in REDCap (Research Electronic Data Capture; Vanderbilt University) to collect parent-reported outcomes in children treated for TTTS at a single center during 2011-2019. Patients with ≥1 neonatal survivor were invited via email to complete 5 possible questionnaires: the child status questionnaire (CSQ); fetal center questionnaire (FCQ); Ages & Stages Questionnaires, Third Edition (ASQ-3); Modified Checklist for Autism in Toddlers, Revised With Follow-Up (M-CHAT-R/F); and thank you questionnaire (TYQ). The R programming language (R Foundation for Statistical Computing) was used to automate survey distribution, scoring, and creation of customized reports. The survey was performed in 2019 and repeated after 12 months in the same study population in 2020. Results: A total of 389 patients in 26 different states and 2 international locations had an email address on file and received an invitation in 2019 to complete the survey (median pediatric age 48.9, IQR 1.0-93.6 months). Among surveyed mothers in 2019, the overall response rate was 37.3% (145/389), and the questionnaire completion rate was 98% (145/148), 87.8% (130/148), 71.1% (81/100), 86.4% (19/22), and 74.3% (110/148) for the CSQ, FCQ, ASQ-3, M-CHAT-R/F, and TYQ, respectively. In 2020, the overall response rate was 57.8% (56/97), and the questionnaire completion rate was 96.4% (54/56), 91.1% (51/56), 86.1% (31/36), 91.7% (11/12), and 80.4% (45/56) for the CSQ, FCQ, ASQ-3, M-CHAT-R/F, and TYQ, respectively. Conclusions: This is the first study to use both REDCap and computer automation to aid in the dissemination, collection, and reporting of surveys to collect long-term pediatric outcomes in the field of fetal medicine.

Quantifying placenta accreta spectrum severity and its associated blood loss: a novel transvaginal ultrasound scoring system.

BACKGROUND: Hemorrhage associated with placenta accreta spectrum (PAS) is a leading cause of maternal morbidity and mortality. Estimating blood loss in these individuals is a critical component of comprehensive preoperative planning. OBJECTIVE: A semiquantitative score based on transvaginal ultrasound was developed and tested to predict PAS, estimate its severity, and blood loss in individuals with clinical and ultrasound evidence suggesting PAS. STUDY DESIGN: A secondary analysis was conducted of prospectively collected data from a quaternary center of patients with suspected accreta on 2D ultrasound and clinical suspicion. A predetermined scoring system was applied based on three components: (1) uterine wall (score 0: no loss of hypo-translucent uterine wall with overlying placenta in the lower uterine segment; 1: loss of hypo-translucent <3-cm defect; 2: 3-6-cm defect; and 3: >6-cm defect); (2) arterial vascularity at the uterine wall defect (score 0: no vessels observed; 1: 1-2 vessels over the defect; 2: 3-5 vessels; and 3: >5 vessels); and (3) cervical involvement (score 0: normal cervical length without previa; 1: previa with normal cervical length; 2: short cervix with previa, minimal vascularity and small lacunae; 3: short cervix with previa, increased vascularity and large lacunae). Each patient's three domain scores determined a cumulative, final score of 0-9. Patients were managed at the discretion of a multi-disciplinary team and patient's preference among the following options: cesarean delivery with placenta removal, cesarean delivery with placenta in-situ (conservative) with or without delayed hysterectomy, or cesarean hysterectomy. The frequency of different degrees of placental invasion per pathology examination per score unit was registered. Multiple linear regression analysis was performed for association of blood loss according to score adjusted by risk factors for PAS. RESULTS: A total of 73 patients were evaluated. All 11 patients who had a score of 0 had cesarean delivery with placenta removal without evidence of intraoperative PAS, thus resulting in a 100% negative predictive value. The remaining 62 had scores between 1 and 9. Among patients with scores 0-3 (n=20), only one had intraoperative PAS, yielding a negative predictive value of 97%. Higher scores were associated with severe PAS forms (r=0.301, P=.02). Based on the associations between PAS scores, clinical correlation, and blood loss, we divided patients into four categories: Category 0: PAS score 0; Category 1: scores 1-3; Category 2: scores 4-6; and Category 3: scores 7-9. The median blood loss in Category 0=635±352 mL, Category 1=634±599 mL, Category 2=1549±1284 mL, and Category 3=1895±2106 mL (P<.001). On multivariable analysis, Category 2 (ß=0.97, P<.01) and Category 3 (ß=1.26, P<.003) were associated with significantly greater blood loss than Category 0, irrespective of type of surgery. CONCLUSION: The transvaginal ultrasound score separates groups at low risk (Category 0) and at higher risk of PAS (Categories 1-3). Categories 1-3 may provide important clinical information to estimate the risk of severe forms of PAS and of blood loss during surgery. VIDEO ABSTRACT.

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 circulation occurs at the aqueduct of Sylvius, leading to progressive hydrocephalus and macrocephaly, which often necessitates cesarean section (CS). The purpose of this study was to describe maternal outcomes associated with fetal AS. METHODS: This study is conducted through the North American Fetal Therapy Network (NAFTNet). Subjects with a prenatal diagnosis of severe fetal central nervous system ventriculomegaly were recruited and 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 gestational age at delivery was 36.7 weeks. Overall, 86% were delivered by CS, and 62% of these were elective. 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 outcomes but also for maternal outcomes.

Prenatal diagnostic and intervention considerations in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect with significant morbidity and mortality. The prenatal management of a pregnancy with a fetus affected with CDH is complex and requires a multi-disciplinary team approach. An improved understanding of prenatal diagnosis and management is essential to developing strategies to optimize outcomes for these patients. In this review, we explore the current knowledge on diagnosis, severity stratification, prognostic prediction, and indications for fetal intervention in the fetus with CDH.

Morphometric Analysis of Spina Bifida after Fetal Repair Shows New Subtypes with Associated Outcomes.

Importance: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies, which have not been correlated to clinical characteristics and outcomes. Objective: To characterize spina bifida lesion types and correlate them with preoperative presentation and postoperative outcomes. Design: Secondary analysis of images and videos obtained during fetoscopic spina bifida repair surgery from 2020-2023. Setting: Fetal surgery was performed at a quaternary care center. Participants: A prospective cohort of patients referred for fetal spina bifida underwent fetoscopic repair under an FDA-approved protocol. Of 60 lesions repaired, 57 had available images and were included in the analysis. Interventions or Exposures: We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. Main Outcomes and Measures: The reproducibility of the lesion classification was assessed via Kappa interrater agreement. Preoperative characteristics analyzed include ventricle size, tonsillar herniation level, lower extremities movement, and lesion dimensions. Outcomes included surgical time, need for patch for skin closure, gestational age at delivery, preterm premature rupture of membranes (PPROM), and neonatal cerebrospinal fluid (CSF) diversion. Results: We distinguished five lesion types that differ across a range of sac sizes, nerve root stretching, and placode exposure, with 93% agreement between examiners (p<0.001). Fetal characteristics at preoperative evaluation differed significantly by lesion type, including lesion volume (p<0.001), largest ventricle size (p=0.008), tonsillar herniation (p=0.005), and head circumference (p=0.03). Lesion level, talipes, and lower extremities movement did not differ by type. Surgical and perinatal outcomes differed by lesion type, including need for patch skin closure (p<0.001), gestational age at delivery (p=0.01), and NICU length of stay (p<0.001). PPROM, CSF leakage at birth, and CSF diversion in the NICU did not differ between lesion groups. Linear regression associated severity of ventriculomegaly with lesion type, but not with tonsillar herniation level. Conclusions and Relevance: There is a distinct phenotypic spectrum in open spina bifida with differential baseline presentation and outcomes. Severity of ventriculomegaly is associated with lesion type, rather than tonsillar herniation level. Our findings expand the classification of spina bifida to reveal a spectrum that warrants further study.

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.

Abnormal Shape and Size of the Cardiac Ventricles Are Associated with a Higher Risk of Neonatal Death in Fetuses with Isolated Left Congenital Diaphragmatic Hernia.

INTRODUCTION: The objective of this study was to evaluate the association between fetal cardiac deformation analysis (CDA) and cardiac function with severe adverse perinatal outcomes in fetuses with isolated left congenital diaphragmatic hernia (CDH). METHODS: CDA in each ventricle (contractility, size, and shape), evaluated by speckle tracking and novel FetalHQ software, and markers of cardiac function (E/A ratios, pulmonary and aortic peak systolic velocities, and sigmoid annular valve diameters), were evaluated in fetuses with isolated left CDH. Two evaluations were performed: at referral (CDA and function) and within 3 weeks of delivery (CDA). Severe adverse neonatal outcomes were considered neonatal death (ND) or survival with CDH-associated pulmonary hypertension (CDH-PH). Differences and associations between CDA, cardiac function, and severe adverse outcomes were estimated. RESULTS: Fifty fetuses were included, and seventeen (34%) had severe adverse neonatal outcomes (11 ND and 6 survivors with CDH-PH). At first evaluation, the prevalence of a small left ventricle was 34% (17/50) with a higher prevalence among neonates presenting severe adverse outcomes (58.8 [10/17] vs. 21.2% [7/33]; p = 0.01; OR, 5.03 [1.4-19.1; p = 0.01]) and among those presenting with neonatal mortality (8/11 [72.7] vs. 9/39 [23.0%]; p = 0.03; OR, 8.9 [1.9-40.7; p = 0.005]). No differences in cardiac function or strain were noted between fetuses with or without severe adverse outcomes. Within 3 weeks of delivery, the prevalence of small left ventricle was higher (19/34; 55.8%) with a more globular shape (reduced transverse/longitudinal ratio). A globular right ventricle was significantly associated with ND or survival with CDH-PH (OR, 14.2 [1.5-138.3]; p = 0.02). CONCLUSION: Fetuses with isolated CDH at risk of perinatal death or survival with CDH-PH had a higher prevalence of a small left ventricle and abnormal shape of the right ventricle.

Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%).

Does Prediction of Neonatal Mortality by the Observed/Expected Lung-To-Head Ratio Change during Pregnancy in Fetuses with Left Congenital Diaphragmatic Hernia?

INTRODUCTION: The aim of this study was to evaluate prediction of neonatal mortality in fetuses with isolated left congenital diaphragmatic hernia (CDH) when the observed/expected lung-to-head ratio (O/E LHR) was estimated at two different gestational time points during pregnancy. METHODS: Forty-four (44) fetuses with isolated left CDH were included. O/E LHR was estimated at the time of referral (first scan) and before delivery (last scan). The main outcome was neonatal death due to respiratory complications. RESULTS: There were 10/44 (22.7%) perinatal deaths. The areas under (AU) the ROC curves were: first scan, 0.76, best O/E LHR cut-off 35.5% with 76% sensitivity and 70% specificity; last scan, AU-ROC 0.79, best O/E LHR cut-off 35.2%, with 79.0% sensitivity and 80% specificity. Considering an O/E LHR cut-off ≤35% to define high-risk fetuses at any examination, prediction for perinatal mortality showed: 80% sensitivity, 73.5% specificity, 47.1% positive and 92.6% negative predictive values, and 3.02 (95% CI 1.59-5.73) positive and 0.27 (95% CI 0.08-0.96) negative likelihood ratios. Prediction was similar in the two evaluations as 16/21 (76.2%) of fetuses considered at risk had an O/E LHR ≤35% in the two examinations; in the remaining 5 cases, two were identified only in the first and three only in the last scan. CONCLUSION: The O/E LHR is a good predictor of perinatal death in fetuses with left isolated CDH. Approximately 80% of fetuses at risk of perinatal death can be identified with an O/E LHR ≤35%, and 90% of them will have similar O/E LHR values at the first and at the last ultrasound examinations prior to delivery. In general, 88.6% of all CDH fetuses have a similar severity classification based on the O/E LHR at the first diagnostic ultrasound or at the ultrasound examination prior to delivery.

Quincke versus Diamond-Tip Needles for Entry in Placental Laser Surgery for Twin-to-Twin Transfusion Syndrome.

INTRODUCTION: Chorioamniotic membrane separation (CAS), preterm prelabor rupture of membranes (PPROM), and preterm delivery (PTD) remain as major complications of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS). We sought to examine whether use of Quincke-tip needles for initial entry during FLP reduces the risk of these complications. METHODS: This is a secondary analysis of prospectively collected data from patients that had FLP for TTTS at a single tertiary care center (2011-2021). We excluded patients for whom direct trocar entry was used. Patients for whom a Quincke-tip needle was used were compared to those for whom a diamond-tip needle was used during Seldinger entry. Demographics, ultrasound findings and operative characteristics were compared between groups. Postoperative outcomes and complications (including CAS, PPROM, and PTD) were also compared. Multivariate logistic regression models were fit to assess independent risk factors for complications. RESULTS: 386 patients met inclusion criteria; Quincke-tip needles were used in 81 (21.0%) cases, while diamond-tip needles were used in 305 (79.0%). Rates of CAS (11.1 vs. 9.5%, p = 0.67) and PPROM (44.4 vs. 41.0%, p = 0.57) were similar between groups. Patients in the Quincke-tip group delivered 1.5 weeks earlier than those in the diamond-tip group (30.5 vs. 32.0 weeks, p = 0.01). However, these patients were more likely to be delivered for maternal (35.9 vs. 19.0%) and fetal (23.1 vs. 15.3%) indications (p < 0.01). In multivariate analysis, needle type was not identified as an independent risk factor for PPROM. However, Quincke-tip needle use was associated with PTD less than 32 weeks (aOR 1.74, 95% CI: 1.02-2.97, p = 0.043). CONCLUSION: Membrane complications following FLP were not associated with the needle type used for entry. Earlier delivery in the Quincke-tip group was likely attributable to higher rates of delivery for maternal and fetal indications, and not membrane complications. The needle chosen for entry is likely best determined by operator preference.