Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn.

BACKGROUND: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels. METHODS: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%). RESULTS: Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity. CONCLUSIONS: Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.).

Society for Maternal-Fetal Medicine Consult Series #72: Twin-twin transfusion syndrome and twin anemia-polycythemia sequence.

Thirty percent of spontaneously occurring twins are monozygotic, of which two-thirds are monochorionic, possessing a single placenta. A common placental mass with shared intertwin placental circulation is key to the development and management of complications unique to monochorionic gestations. In this Consult, we review general considerations and a contemporary approach to twin-twin transfusion syndrome and twin anemia-polycythemia sequence, providing management recommendations based on the available evidence. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend routine first-trimester sonographic determination of chorionicity and amnionicity (GRADE 1B); (2) we recommend that ultrasound surveillance for twin-twin transfusion syndrome begin at 16 weeks of gestation for all monochorionic-diamniotic twin pregnancies and continue at least every 2 weeks until delivery, with more frequent monitoring indicated with clinical concern (GRADE 1C); (3) we recommend that routine sonographic surveillance for twin-twin transfusion syndrome minimally include assessment of amniotic fluid volumes on both sides of the intertwin membrane and evaluation for the presence or absence of urine-filled fetal bladders, and ideally incorporate Doppler study of the umbilical arteries (GRADE 1C); (4) we recommend fetoscopic laser surgery as the standard treatment for stage II through stage IV twin-twin transfusion syndrome presenting between 16 and 26 weeks of gestation (GRADE 1A); (5) we recommend expectant management with at least weekly fetal surveillance for asymptomatic patients continuing pregnancies complicated by stage I twin-twin transfusion syndrome, and consideration for fetoscopic laser surgery for stage I twin-twin transfusion syndrome presentations between 16 and 26 weeks of gestation complicated by additional factors such as maternal polyhydramnios-associated symptomatology (GRADE 1B); (6) we recommend an individualized approach to laser surgery for early- and late-presenting twin-twin transfusion syndrome (GRADE 1C); (7) we recommend that all patients with twin-twin transfusion syndrome qualifying for laser therapy be referred to a fetal intervention center for further evaluation, consultation, and care (Best Practice); (8) after laser therapy, we suggest weekly surveillance for 6 weeks followed by resumption of every-other-week surveillance thereafter, unless concern exists for post-laser twin-twin transfusion syndrome, post-laser twin anemia-polycythemia sequence, or fetal growth restriction (GRADE 2C); (9) following the resolution of twin-twin transfusion syndrome after fetoscopic laser surgery, and without other indications for earlier delivery, we recommend delivery of dual-surviving monochorionic-diamniotic twins at 34 to 36 weeks of gestation (GRADE 1C); (10) in twin-twin transfusion syndrome pregnancies complicated by posttreatment single fetal demise, we recommend full-term delivery (39 weeks) of the surviving co-twin to avoid complications of prematurity unless indications for earlier delivery exist (GRADE 1C); (11) we recommend that fetoscopic laser surgery not influence the mode of delivery (Best Practice); (12) we recommend that prenatal diagnosis of twin anemia-polycythemia sequence minimally require either middle cerebral artery Doppler peak systolic velocity values >1.5 and <1.0 multiples of the median in donor and recipient twins, respectively, or an intertwin Δ middle cerebral artery peak systolic velocity >0.5 multiples of the median (GRADE 1C); (13) we recommend that providers consider incorporating middle cerebral artery Doppler peak systolic velocity determinations into all monochorionic twin ultrasound surveillance beginning at 16 weeks of gestation (GRADE 1C); and (14) consultation with a specialized fetal care center is recommended when twin anemia-polycythemia sequence progresses to a more advanced disease stage (stage ≥II) before 32 weeks of gestation or when concern arises for coexisting complications such as twin-twin transfusion syndrome (Best Practice).

Lasix for the prevention of de novo postpartum hypertension: a randomized placebo-controlled trial (LAPP Trial).

BACKGROUND: Birthing people with de novo postpartum hypertensive disorders continue to be among the populations at highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit of oral loop diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension. OBJECTIVE: This study aimed to evaluate whether oral furosemide can reduce the risk for de novo postpartum hypertension among high-risk birthing people by reducing postdelivery blood pressure. STUDY DESIGN: From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for de novo postpartum hypertension at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high risk for the development of de novo postpartum hypertension based on a prespecified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a 5-day course of 20-mg oral furosemide daily or identical-appearing placebo starting within 8 hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was mean arterial pressure averaged over the 24 hours before discharge or the 24 hours before antihypertensive therapy initiation. The study was powered to detect a 5 mm Hg difference in average mean arterial pressure (standard deviation, 6.4 mm Hg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of de novo postpartum hypertension, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. RESULTS: The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between the groups. There was no significant difference in average mean arterial pressure in the 24 hours before discharge (or antihypertensive initiation) in the furosemide group (88.9±7.4 mm Hg) compared with the placebo group (86.8±7.1 mm Hg; absolute difference, 2.1 mm Hg; 95% confidence interval, -1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed de novo postpartum hypertension and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between the groups (P=.71 and P>.99, respectively). CONCLUSION: De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces average mean arterial pressure in the 24 hours before discharge from the delivery hospitalization (or antihypertensive medication initiation) compared with placebo.

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.

Health Care Disparities in the COVID-19 Pandemic in the United States: A Focus on Obstetrics.

The influence of social determinants of health on disease dynamics and outcomes has become increasingly clear, making them a prime target of investigation and mitigation efforts. The obstetric population is uniquely positioned to provide insight into the health inequities exacerbated by the coronavirus disease 2019 pandemic given their susceptibility to infectious disease morbidity and frequent interactions with the health care system, which provide opportunities for ascertainment of disease incidence and severity. This review summarizes the data on disparities identified in the US obstetric population during the coronavirus disease 2019 pandemic as they relate to race and ethnicity, built environment, insurance status, language, and immigration status.

Maternal Diabetes and Intrapartum Fetal Electrocardiogram.

OBJECTIVE: Fetal electrocardiogram (ECG) ST changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST changes by maternal diabetic status and stage of labor. METHODS: This was a secondary analysis of a multicentered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST changes by the stage of labor. ECG tracings were categorized into mutually exclusive groups (ST depression, ST elevation without ST depression, or no ST changes). We compared participants with DM, gestational diabetes mellitus (GDM), and no DM. RESULTS: Of the 5,436 eligible individuals in the first stage of labor (95 with pregestational DM and 370 with GDM), 4,427 progressed to the second stage. ST depression occurred more frequently in the first stage of labor in participants with pregestational DM (15%, adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.14-4.24) and with GDM (9.5%, aOR 1.51, 95% CI 1.02-2.25) as compared with participants without DM (5.7%). The frequency of ST elevation was similar in participants with pregestational DM (33%, aOR 0.79, 95% CI 0.48-1.30) and GDM (33.2%, aOR 0.91, 95% CI 0.71-1.17) as compared with those without DM (34.2%). In the second stage, ST depression did not occur in participants with pregestational DM (0%) and occurred more frequently in participants with GDM (3.5%, aOR 2.01, 95% CI 1.02-3.98) as compared with those without DM (2.0%). ST elevation occurred more frequently in participants with pregestational DM (30%, aOR 1.81, 95% CI 1.02-3.22) but not with GDM (19.0%, aOR 1.06, 95% CI 0.77-1.47) as compared with those without DM (17.8%). CONCLUSION: ST changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor. CLINICALTRIALS: gov number, NCT01131260. PRECIS: ST changes in fetal ECG, a marker of fetal cardiac hypoxia, occur more frequently in fetuses of diabetic parturients. KEY POINTS: · Fetal hypertrophic cardiomyopathy (HCM) and cardiac dysfunction occur frequently among fetuses of diabetic patients.. · Fetal ECG changes such as ST elevation and depression reflect cardiac hypoxia.. · Fetuses of diabetic patients demonstrate a higher prevalence of fetal ECG tracings with ST changes..

Intrapartum Fetal Electrocardiogram in Small- and Large-for-Gestational Age Fetuses.

OBJECTIVE: This study aimed to evaluate whether intrapartum fetal electrocardiogram (ECG) tracings with ST-elevation or depression occur more frequently in each stage of labor in small-for-gestational age (SGA) or large-for-gestational age (LGA), as compared with appropriate-for-gestational age (AGA) fetuses. STUDY DESIGN: We conducted a secondary analysis of a large, multicenter trial in which laboring patients underwent fetal ECG waveform-analysis. We excluded participants with diabetes mellitus and major fetal anomalies. Birth weight was categorized as SGA (<10th percentile), LGA (>90th percentile), or AGA (10-90th percentile) by using a gender and race/ethnicity specific nomogram. In adjusted analyses, the frequency of ECG tracings with ST-depression or ST-elevation without depression was compared according to birthweight categories and labor stage. RESULTS: Our study included 4,971 laboring patients in the first stage and 4,074 in the second stage. During the first stage of labor, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (6.7 vs. 5.5%; adjusted odds ratio [aOR]: 1.41, 95% confidence interval [CI]: 0.93-2.13), or in ST-elevation without depression (35.8 vs. 34.1%; aOR: 1.17, 95% CI: 0.94-1.46). During the second stage, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (1.6 vs. 2.0%; aOR: 0.69, 95% CI: 0.27-1.73), or in ST-elevation without depression (16.2 vs. 18.1%; aOR: 0.90, 95% CI: 0.67-1.22). During the first stage of labor, there were no differences in the frequency of ST-depression in LGA fetuses compared with AGA fetuses (6.3 vs. 5.5%; aOR: 0.97, 95% CI: 0.60-1.57), or in ST-elevation without depression (33.1 vs. 34.1%; aOR: 0.80, 95% CI: 0.62-1.03); during the second stage of labor, the frequency of ST-depression in LGA compared with AGA fetuses (2.5 vs. 2.0%, aOR: 1.36, 95% CI: 0.61-3.03), and in ST-elevation without depression (15.5 vs. 18.1%; aOR: 0.83, 95% CI: 0.58-1.18) were similar as well. CONCLUSION: The frequency of intrapartum fetal ECG tracings with ST-events is similar among SGA, AGA, and LGA fetuses. KEY POINTS: · SGA and LGA neonates are at increased risk of cardiac dysfunction.. · Fetal ECG has been used to evaluate fetal response to hypoxia.. · Fetal ST-elevation and ST-depression occur during hypoxia.. · Frequency of intrapartum ST-events is similar among SGA, AGA and LGA fetuses..

Telehealth for High-Risk Pregnancies in the Setting of the COVID-19 Pandemic.

As New York City became an international epicenter of the novel coronavirus disease 2019 (COVID-19) pandemic, telehealth was rapidly integrated into prenatal care at Columbia University Irving Medical Center, an academic hospital system in Manhattan. Goals of implementation were to consolidate in-person prenatal screening, surveillance, and examinations into fewer in-person visits while maintaining patient access to ongoing antenatal care and subspecialty consultations via telehealth virtual visits. The rationale for this change was to minimize patient travel and thus risk for COVID-19 exposure. Because a large portion of obstetric patients had underlying medical or fetal conditions placing them at increased risk for adverse outcomes, prenatal care telehealth regimens were tailored for increased surveillance and/or counseling. Based on the incorporation of telehealth into prenatal care for high-risk patients, specific recommendations are made for the following conditions, clinical scenarios, and services: (1) hypertensive disorders of pregnancy including preeclampsia, gestational hypertension, and chronic hypertension; (2) pregestational and gestational diabetes mellitus; (3) maternal cardiovascular disease; (4) maternal neurologic conditions; (5) history of preterm birth and poor obstetrical history including prior stillbirth; (6) fetal conditions such as intrauterine growth restriction, congenital anomalies, and multiple gestations including monochorionic placentation; (7) genetic counseling; (8) mental health services; (9) obstetric anesthesia consultations; and (10) postpartum care. While telehealth virtual visits do not fully replace in-person encounters during prenatal care, they do offer a means of reducing potential patient and provider exposure to COVID-19 while providing consolidated in-person testing and services. KEY POINTS: · Telehealth for prenatal care is feasible.. · Telehealth may reduce coronavirus exposure during prenatal care.. · Telehealth should be tailored for high risk prenatal patients..

Telehealth Uptake into Prenatal Care and Provider Attitudes during the COVID-19 Pandemic in New York City: A Quantitative and Qualitative Analysis.

OBJECTIVE: This study aimed to (1) determine to what degree prenatal care was able to be transitioned to telehealth at prenatal practices associated with two affiliated hospitals in New York City during the novel coronavirus disease 2019 (COVID-19) pandemic and (2) describe providers' experience with this transition. STUDY DESIGN: Trends in whether prenatal care visits were conducted in-person or via telehealth were analyzed by week for a 5-week period from March 9 to April 12 at Columbia University Irving Medical Center (CUIMC)-affiliated prenatal practices in New York City during the COVID-19 pandemic. Visits were analyzed for maternal-fetal medicine (MFM) and general obstetrical faculty practices, as well as a clinic system serving patients with public insurance. The proportion of visits that were telehealth was analyzed by visit type by week. A survey and semistructured interviews of providers were conducted evaluating resources and obstacles in the uptake of telehealth. RESULTS: During the study period, there were 4,248 visits, of which approximately one-third were performed by telehealth (n = 1,352, 31.8%). By the fifth week, 56.1% of generalist visits, 61.5% of MFM visits, and 41.5% of clinic visits were performed via telehealth. A total of 36 providers completed the survey and 11 were interviewed. Accessing technology and performing visits, documentation, and follow-up using the telehealth electronic medical record were all viewed favorably by providers. In transitioning to telehealth, operational challenges were more significant for health clinics than for MFM and generalist faculty practices with patients receiving public insurance experiencing greater difficulties and barriers to care. Additional resources on the patient and operational level were required to optimize attendance at in-person and video visits for clinic patients. CONCLUSION: Telehealth was rapidly implemented in the setting of the COVID-19 pandemic and was viewed favorably by providers. Limited barriers to care were observed for practices serving patients with commercial insurance. However, to optimize access for patients with Medicaid, additional patient-level and operational supports were required. KEY POINTS: · Telehealth uptake differed based on insurance.. · Medicaid patients may require increased assistance for telehealth.. · Quick adoption of telehealth is feasible..

A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis.

BACKGROUND: It is unclear whether using fetal electrocardiographic (ECG) ST-segment analysis as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring modifies intrapartum and neonatal outcomes. METHODS: We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were randomly assigned to "open" or "masked" monitoring with fetal ST-segment analysis. The masked system functioned as a normal fetal heart-rate monitor. The open system displayed additional information for use when uncertain fetal heart-rate patterns were detected. The primary outcome was a composite of intrapartum fetal death, neonatal death, an Apgar score of 3 or less at 5 minutes, neonatal seizure, an umbilical-artery blood pH of 7.05 or less with a base deficit of 12 mmol per liter or more, intubation for ventilation at delivery, or neonatal encephalopathy. RESULTS: A total of 11,108 patients underwent randomization; 5532 were assigned to the open group, and 5576 to the masked group. The primary outcome occurred in 52 fetuses or neonates of women in the open group (0.9%) and 40 fetuses or neonates of women in the masked group (0.7%) (relative risk, 1.31; 95% confidence interval, 0.87 to 1.98; P=0.20). Among the individual components of the primary outcome, only the frequency of a 5-minute Apgar score of 3 or less differed significantly between neonates of women in the open group and those in the masked group (0.3% vs. 0.1%, P=0.02). There were no significant between-group differences in the rate of cesarean delivery (16.9% and 16.2%, respectively; P=0.30) or any operative delivery (22.8% and 22.0%, respectively; P=0.31). Adverse events were rare and occurred with similar frequency in the two groups. CONCLUSIONS: Fetal ECG ST-segment analysis used as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring did not improve perinatal outcomes or decrease operative-delivery rates. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Neoventa Medical; ClinicalTrials.gov number, NCT01131260.).

North American Fetal Therapy Network: intervention vs expectant management for stage I twin-twin transfusion syndrome.

BACKGROUND: Stage I twin-twin transfusion syndrome presents a management dilemma. Intervention may lead to procedure-related complications while expectant management risks deterioration. Insufficient data exist to inform decision-making. OBJECTIVE: The aim of this retrospective observational study was to describe the natural history of stage I twin-twin transfusion syndrome, to assess for predictors of disease behavior, and to compare pregnancy outcomes after intervention at stage I vs expectant management. STUDY DESIGN: Ten North American Fetal Therapy Network centers submitted well-documented cases of stage I twin-twin transfusion syndrome for analysis. Cases were retrospectively divided into 3 management strategies: those managed expectantly, those who underwent amnioreduction at stage I, and those who underwent laser therapy at stage I. Outcomes were categorized as no survivors, 1 survivor, 2 survivors, or at least 1 survivor to live birth, and good (twin live birth ≥30.0 weeks), mixed (single fetal demise or delivery between 26.0-29.9 weeks), and poor (double fetal demise or delivery <26.0 weeks) pregnancy outcomes. Outcomes were analyzed by initial management strategy. RESULTS: A total of 124 cases of stage I twin-twin transfusion syndrome were studied. In all, 49 (40%) cases were managed expectantly while 30 (24%) underwent amnioreduction and 45 (36%) underwent laser therapy at stage I. The overall fetal mortality rate was 20.2% (50 of 248 fetuses). Of those managed expectantly, 11 patients regressed (22%), 4 remained stage I (8%), 29 advanced in stage (60%), and 5 experienced spontaneous previable preterm birth (10%) during observation. The mean number of days from diagnosis of stage I to a change in status (progression, regression, loss, or delivery) was 11.1 (SD 14.3) days. Intervention by amniocentesis or laser therapy was associated with a lower risk of fetal loss (P = .01) than expectant management. The unadjusted odds of poor outcome were 0.33 (95% confidence interval, 0.09-01.20), for amnioreduction and 0.26 (95% confidence interval, 0.09-0.77) for laser therapy vs expectant management. Adjusting for nulliparity, recipient maximum vertical pocket, gestational age at diagnosis, and placenta location had negligible effect. Both amnioreduction and laser therapy at stage I decreased the likelihood of no survivors (odds ratio, 0.11; 95% confidence interval, 0.02-0.68 and odds ratio, 0.07; 95% confidence interval, 0.01-0.37, respectively). Only laser therapy, however, was protective against poor outcome in our data (odds ratio, 0.29; 95% confidence interval, 0.07-1.30 for amnioreduction vs odds ratio, 0.12, 95% confidence interval, 0.03-0.44 for laser), although the estimate for amnioreduction suggests a protective effect. CONCLUSION: Stage I twin-twin transfusion syndrome was associated with substantial fetal mortality. Spontaneous resolution was observed, although the majority of expectantly managed cases progressed. Progression was associated with a worse prognosis. Both amnioreduction and laser therapy decreased the chance of no survivors, and laser was particularly protective against poor outcome independent of multiple factors. Further studies are justified to corroborate these findings and to further define risk stratification and surveillance strategies for stage I disease.

New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome).

OBJECTIVE: To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. METHODS: Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. RESULTS: We identified a novel heterozygous de novo missense variant in ACTG2 c.770G>A (p.Arg257His) encoding x03B3;-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. ACTG2 immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. CONCLUSION: Our study demonstrates that de novo mutations in ACTG2 are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.

Propranolol Therapy for Congenital Chylothorax.

Congenital chylothorax is a rare and often severe anomaly without well-established medical therapies. Previously, propranolol use in patients with lymphatic malformations and secondary chylothorax was associated with improvement in clinical signs. We hypothesized that propranolol treatment would be beneficial for severe congenital chylothorax. We reviewed medical records of neonates born from 2015 to 2019 at our tertiary center with a prenatal diagnosis of congenital chylothorax for whom either prenatal or postnatal propranolol therapy was initiated. Inclusion was limited to fetuses diagnosed with severe congenital chylothorax without significant genetic, infectious, or cardiac anomalies, and who underwent prenatal interventions to mitigate consequences of the condition. Propranolol was administered orally to pregnant women at 20 mg 4 times daily and increased to a maximum dose of 40 mg 4 times daily, or to infants at 0.3 mg/kg/d and increased to 1 to 2 mg/kg/d. Primary outcomes were the time course of resolution of ultrasonographical, clinical, and/or radiologic signs of chylothorax after treatment with propranolol. Four neonates met the inclusion criteria. In 2 cases, prenatal initiation of propranolol led to resolution of the chylothoraxes before delivery (38 and 32 days after treatment) on a dose of 40 mg/day 4 times daily. Neonates had a normal postnatal course. Postnatal propranolol was initiated in 2 neonates with respiratory failure when chylothoraces were refractory to standard management. Stabilization and improvement of their pleural effusion was observed by imaging at 29 and 13 days after initiation of propranolol. There were no significant maternal or neonatal complications from prenatal or postnatal propranolol use. Propranolol may be efficacious in treating severe fetal congenital chylothorax.

Effectiveness of timing strategies for delivery of monochorionic diamniotic twins.

OBJECTIVE: The purpose of this study was to compare strategies for delivery timing of uncomplicated monochorionic diamniotic twin pregnancies. STUDY DESIGN: A decision tree compared 9 strategies that included scheduled delivery between 32 and 38 weeks' gestation, with or without confirmation of fetal lung maturity. Outcomes in the model included fetal death, infant death, respiratory distress syndrome, mental retardation, and cerebral palsy. RESULTS: A scheduled delivery at 38 weeks' gestation was the preferred strategy, which resulted in the highest quality adjusted life years under base-case assumptions. Decreased, but comparable, quality adjusted life years estimates resulted from scheduled deliveries at 36 and 37 weeks' gestation, with or without amniocentesis. Sensitivity analyses demonstrated that the optimal gestational age for delivery was always ≥36 weeks' gestation. CONCLUSION: This decision analysis suggests that, for women with uncomplicated monochorionic twins, delivery between 36 and 38 weeks' gestation is the preferred strategy for timing of delivery.

Cesarean hysterectomy requiring emergent thoracotomy: a case report of a complication of placenta percreta requiring a multidisciplinary effort.

BACKGROUND: Currently a leading indication for cesarean hysterectomy among multiparous women, placenta accreta is associated with significant maternal morbidity and mortality. CASE: A 34-year-old woman with a pregnancy complicated by placenta previa and previous cesarean deliveries was transferred to our institution following late diagnosis of placenta percreta. She underwent cesarean hysterectomy complicated by substantial hemorrhage. Massive blood product replacement precipitated severe hyperkaIemia and hypocalcemia with resultant asystole. Cardiac bypass with concomitant obligate anticoagulation was temporarily required while normalizing the patient's electrolytes. Numerous surgical and medical interventions were required to achieve hemostasis, and the patient survived to hospital discharge with moderate residual morbidity. CONCLUSION: Optimal management of placenta accreta requires a multidisciplinary approach within a tertiary center possessing extensive resources necessary for managing the most severe complications.

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.

Fetal omphalocele ratios predict outcomes in prenatally diagnosed omphalocele.

OBJECTIVE: The objective of the study was to evaluate whether ratios considering omphalocele diameter relative to fetal biometric measurements perform better than giant omphalocele designation at predicting inability to achieve neonatal primary surgical closure. STUDY DESIGN: Cases of fetal omphalocele that underwent evaluation between May 2003 and July 2010 were identified. Inclusion was restricted to live births with plan for postnatal repair. Omphalocele diameter upon antenatal ultrasound was compared with abdominal circumference, femur length, and head circumference, yielding the respective omphalocele (O)/abdominal circumference (AC), O/femur length (FL), and O/head circumference (HC) ratios. The absolute measurements were used to classify giant lesions. Omphalocele ratios and giant omphalocele designations were evaluated as predictors of inability to achieve primary repair. RESULTS: Among 25 included cases, staged or delayed closure occurred in 52%. With an optimal cutoff of 0.21 or greater, O/HC best predicted the primary outcome (sensitivity, 84.6%; specificity, 58.3%; odds ratio, 7.7). The O/HC of 0.21 or greater outperformed giant designations. CONCLUSION: The O/HC of 0.21 or greater best predicted staged or delayed omphalocele closure. Giant omphalocele designation, regardless of definition, poorly predicted outcome.

Beta-2 adrenoceptor genotype and progress in term and late preterm active labor.

OBJECTIVE: We sought to evaluate whether beta-2 adrenoceptor (ß2AR) genotype at a functional polymorphic site encoding for amino acid residue 16 influences rate of cervical dilatation in term and late preterm active labor. STUDY DESIGN: Subjects who underwent vaginal delivery at ≥34 weeks' gestational age from May 2006 through August 2007 were identified. Each subject had provided venous blood from which DNA was extracted for ß2AR genotyping. Digital cervical examinations with paired examination times were collected from intrapartum records. Rate of cervical dilatation in active labor was determined using linear regression. Rates were compared between genotype groups. RESULTS: Among 401 subjects with satisfactory genotype and intrapartum data, overall rate of active labor was 0.76±0.01 cm/h. When labor was compared by genotype, homozygous Arg/Arg16 subjects progressed at a slower rate (0.64±0.03 cm/h) than all other pooled genotypes (0.8±0.02 cm/h, P<.001). CONCLUSION: Homozygous ß2AR genotype encoding for Arg/Arg16 was associated with slower progress in active labor.