Left ventricular strain, arch angulation, and velocity-time integral ratio improve performance of a clinical pathway for fetal diagnosis of neonatal coarctation of the aorta.

INTRODUCTION: Neonatal presentation of coarctation of the aorta (CoA) is a potentially life-threatening condition that is difficult to diagnose in fetal life. We therefore sought to validate and compare novel metrics that may add diagnostic value for fetal coarctation of the aorta, including the diastolic to systolic aortic isthmus VTI ratio (VTId:VTIs), ascending aorta to descending aorta angle (AAo-DAo), transverse aorta to descending aorta angle (TAo-DAo), and LV longitudinal strain (LVS). Then to evaluate whether these novel metrics improve specificity to identify fetuses at the highest risk for postnatal coarctation of the aorta (CoA) without compromising sensitivity. METHODS: Retrospective cohort study of fetuses followed a prospective clinical pathway and previously classified as mild, moderate, or high-risk for CoA based on standard fetal echo metrics. Novel metrics were retrospectively measured in a blinded manner. RESULTS: Among fetuses with prenatal concern for coarctation of the aorta, VTId:VTIs, AAo-DAo angle, TAo-DAo angle, and LVS were significantly different between surgical and non-surgical cases (p <0.01 for all variables). In the subgroup of moderate- and high-risk fetuses, the standard high-risk criteria (flow reversal at the foramen ovale or aortic arch) did not discriminate effectively between surgical and non-surgical cases. VTId:VTIs, AAo-Dao angle, Tao-DAo angle, and LVS all demonstrated greater discrimination than standard high-risk criteria, with specificity of 100% and PPV (positive predictive value) of 78-100%. CONCLUSIONS: The incorporation of novel metrics added diagnostic value to our clinical pathway for fetal CoA with higher specificity than the previous high-risk criteria. The incorporation of these metrics into the evaluation of fetuses at moderate- or high-risk for surgical CoA may improve prenatal counseling, allow for more consistent surgical planning, and ultimately optimize hospital resource allocation.

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.

Mammalian target of rapamycin inhibitors: A new-possible approach for in-utero medication therapy.

The mammalian/mechanistic target of rapamycin (mTOR) is a protein kinase that plays a crucial role in regulating cellular growth, metabolism, and survival. Although there is no absolute contraindication for the use of mTOR inhibitors during pregnancy, the specific fetal effects remain unknown. Available data from the past 2 decades have examined the use of mTOR inhibitors during pregnancy in patients with solid organ transplantation, showing no clear link to fetal complications or structural abnormalities. Recently, a handful of case reports and series have described transplacental therapy of mTOR inhibitors to control symptomatic and complicated pathologies in the fetus. The effect of these agents includes a significant reduction in lesion size in the fetus and a reduced need for mechanical ventilation in neonates. In this context, we delve into the potential of mTOR inhibitors as in-utero therapy for fetal abnormalities, with a primary focus on lymphatic malformation (LM) and cardiac rhabdomyoma (CR). While preliminary reports underscore the efficacy of mTOR inhibitors for the treatment of fetal CR and fetal brain lesions associated with tuberous sclerosis complex, chylothorax, and LMs, additional investigation and clinical trials are essential to comprehensively assess the safety and efficacy of these medications.

Development and validation of a novel fetal vesico-amniotic shunt, the vortex shunt.

Fetal lower urinary tract obstruction (LUTO) is a severe malformation associated with an up to 80% mortality risk as well as significant renal and pulmonary morbidity in survivors. Fetal vesico-amniotic shunts (VAS) bypass the bladder obstruction, improve amniotic fluid volume and enhance in-utero pulmonary development. VAS has been shown to reduce respiratory morbidity and mortality in the neonatal period without proven benefit on long-term renal and bladder function. Clinically available shunts are associated with an up to 80% dislodgement rate, leading to repeat invasive procedures which increase fetal and maternal risks. We developed a novel "Vortex" shunt, which incorporates enhanced fixation to reduce dislodgement, a one-way valve to optimize in-utero bladder function, and enhanced sonographic echogenicity that optimizes the accurate deployment. Following the validation of these characteristics in initial benchtop experiments we have moved to feasibility studies in the fetal lamb model. We hope that the Vortex shunt may ultimately facilitate shunt deployment, reduce dislodgement risk, improve neonatal morbidity and mortality, and decrease the significant healthcare expenditures associated with long-term morbidity in LUTO survivors. In this manuscript, we review the natural history of LUTO, the risks and benefits of clinically available fetal shunts, and our development and early validation experiments.

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.

Abortion Bans and Resource Utilization for Congenital Heart Disease: A Decision Analysis.

OBJECTIVE: To investigate the implications of potential national abortion ban scenarios on the incidence of neonatal single-ventricle cardiac defects. METHODS: A decision tree model was developed to predict the incidence of neonatal single-ventricle cardiac defects and related outcomes in the United States under four theoretical national abortion bans: 1) abortion restrictions in existence immediately before the June 2022 Dobbs v Jackson Women's Health Organization Supreme Court decision, 2) 20 weeks of gestation, 3) 13 weeks of gestation, and 4) a complete abortion ban. The model included incidence of live births of neonates with single-ventricle cardiac defects, neonatal heart surgery (including heart transplant and extracorporeal membrane oxygenation [ECMO]), and neonatal death. Cohort size was based on national pregnancy incidence and different algorithm decision point probabilities were aggregated from the existing literature. Monte Carlo simulations were conducted with 10,000 iterations per model. RESULTS: In the scenario before the Dobbs decision, an estimated 6,369,000 annual pregnancies in the United States resulted in 1,006 annual cases of single-ventricle cardiac defects. Under a complete abortion ban, the model predicted a 53.7% increase in single-ventricle cardiac defects, or an additional 9 cases per 100,000 live births. This increase would result in an additional 531 neonatal heart surgeries, 16 heart transplants, 77 ECMO utilizations, and 102 neonatal deaths annually. More restrictive gestational age-based bans are predicted to confer increases in cases of neonatal single-ventricle cardiac defects and related adverse outcomes as well. CONCLUSION: Universal abortion bans are estimated to increase the incidence of neonatal single-ventricle cardiac defects, associated morbidity, and resource utilization. States considering limiting abortion should consider the implications on the resources required to care for increasing number of children that will be born with significant and complex medical needs, including those with congenital heart disease.

Development of a Urine Metabolomics Biomarker-Based Prediction Model for Preeclampsia during Early Pregnancy.

Preeclampsia (PE) is a condition that poses a significant risk of maternal mortality and multiple organ failure during pregnancy. Early prediction of PE can enable timely surveillance and interventions, such as low-dose aspirin administration. In this study, conducted at Stanford Health Care, we examined a cohort of 60 pregnant women and collected 478 urine samples between gestational weeks 8 and 20 for comprehensive metabolomic profiling. By employing liquid chromatography mass spectrometry (LCMS/MS), we identified the structures of seven out of 26 metabolomics biomarkers detected. Utilizing the XGBoost algorithm, we developed a predictive model based on these seven metabolomics biomarkers to identify individuals at risk of developing PE. The performance of the model was evaluated using 10-fold cross-validation, yielding an area under the receiver operating characteristic curve of 0.856. Our findings suggest that measuring urinary metabolomics biomarkers offers a noninvasive approach to assess the risk of PE prior to its onset.

Persistent Bacterial Vaginosis and Risk for Spontaneous Preterm Birth.

OBJECTIVE: The aim of this study was to determine the association between persistent bacterial vaginosis (BV) in pregnancy and risk for spontaneous preterm birth (sPTB). STUDY DESIGN: Retrospective data from IBM MarketScan Commercial Database were analyzed. Women aged between 12 and 55 years with singleton gestations were included and linked to an outpatient medications database and medications prescribed during the pregnancy were analyzed. BV in pregnancy was determined based on both a diagnosis of BV and treatment with metronidazole and/or clindamycin, and persistent treatment of BV was defined as BV in more than one trimester or BV requiring more than one antibiotic prescription. Odds ratios were calculated comparing sPTB frequencies in those with BV, or persistent BV, to women without BV in pregnancy. Survival analysis using Kaplan-Meier curves for the gestational age at delivery was also performed. RESULTS: Among a cohort of 2,538,606 women, 216,611 had an associated International Classification of Diseases, 9th Revision or 10th Revision code for diagnosis of BV alone, and 63,817 had both a diagnosis of BV and were treated with metronidazole and/or clindamycin. Overall, the frequency of sPTB among women treated with BV was 7.5% compared with 5.7% for women without BV who did not receive antibiotics. Relative to those without BV in pregnancy, odds ratios for sPTB were highest in those treated for BV in both the first and second trimester (1.66 [95% confidence interval [CI]: 1.52, 1.81]) or those with three or more prescriptions in pregnancy (1.48 [95% CI: 1.35, 1.63]. CONCLUSION: Persistent BV may have a higher risk for sPTB than a single episode of BV in pregnancy. KEY POINTS: · Persistent BV beyond one trimester may increase the risk for sPTB.. · Persistent BV requiring more than one prescription may increase the risk for sPTB.. · Almost half of antibiotic prescriptions treating BV in pregnancy are filled after 20 weeks gestation..

Vaginal Progesterone Is Associated with Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: The frequency of intrahepatic cholestasis of pregnancy (ICP) peaks during the third trimester of pregnancy when plasma progesterone levels are the highest. Furthermore, twin pregnancies are characterized by higher progesterone levels than singletons and have a higher frequency of cholestasis. Therefore, we hypothesized that exogenous progestogens administered for reducing the risk of spontaneous preterm birth may increase the risk of cholestasis. Utilizing the large IBM MarketScan Commercial Claims and Encounters Database, we investigated the frequency of cholestasis in patients treated with vaginal progesterone or intramuscular 17α-hydroxyprogesterone caproate for the prevention of preterm birth. STUDY DESIGN: We identified 1,776,092 live-born singleton pregnancies between 2010 and 2014. We confirmed second and third trimester administration of progestogens by cross-referencing the dates of progesterone prescriptions with the dates of scheduled pregnancy events such as nuchal translucency scan, fetal anatomy scan, glucose challenge test, and Tdap vaccination. We excluded pregnancies with missing data regarding timing of scheduled pregnancy events or progesterone treatment prescribed only during the first trimester. Cholestasis of pregnancy was identified based on prescriptions for ursodeoxycholic acid. We used multivariable logistic regression to estimate adjusted (for maternal age) odds ratios for cholestasis in patients treated with vaginal progesterone, and in patients treated with 17α-hydroxyprogesterone caproate compared with those not treated with any type of progestogen (the reference group). RESULTS: The final cohort consisted of 870,599 pregnancies. Among patients treated with vaginal progesterone during the second and third trimester, the frequency of cholestasis was significantly higher than the reference group (0.75 vs. 0.23%, adjusted odds ratio [aOR]: 3.16, 95% confidence interval [CI]: 2.23-4.49). In contrast, there was no significant association between 17α-hydroxyprogesterone caproate and cholestasis (0.27%, aOR: 1.12, 95% CI: 0.58-2.16) CONCLUSION: Using a robust dataset, we observed that vaginal progesterone but not intramuscular 17α-hydroxyprogesterone caproate was associated with an increased risk for ICP. KEY POINTS: · Previous studies have been underpowered to detect potential association between progesterone and ICP.. · Vaginal progesterone was significantly associated with ICP.. · Intramuscular 17α-hydroxyprogesterone was not associated with ICP..

Fetal growth disorders in twin gestations.

PURPOSE OF REVIEW: Twin gestations account for approximately 3% of all births. Although there appear to be physiologic differences in the third trimester growth of twins compared with singleton gestations, reasons for this remain unclear. As growth-restricted fetuses and neonates are at increased risk for adverse outcomes, there is a clinical need to optimize our ability to delineate normally from pathologically grown twins. RECENT FINDINGS: Recent studies have addressed current limitations in the way growth restriction is diagnosed in twin gestations. Twin-specific fetal and neonatal growth charts have been shown to decrease the number of cases inappropriately labeled as growth restricted compared with singleton nomograms. In addition, individual growth assessment (IGA) is a promising method of diagnosing pathological growth using each fetus's growth potential rather than a comparison of the estimated fetal weight with population nomograms. SUMMARY: There is a recent focus on improving our understanding of physiologic and pathologic twin growth. The increased use of twin-specific growth curves is likely to result in a decrease in the incidence of FGR diagnosis among twin gestations and could improve the outcomes of twins currently misclassified as FGR. Future research will hopefully clarify the reasons behind differences seen in twin versus singleton third trimester twin growth.

Epidural-related maternal fever: incidence, pathophysiology, outcomes, and management.

Epidural-related maternal fever affects 15% to 25% of patients who receive a labor epidural. Two meta-analyses demonstrated that epidural-related maternal fever is a clinical phenomenon, which is unlikely to be caused by selection bias. All commonly used neuraxial techniques, local anesthetics with or without opioids, and maintenance regimens are associated with epidural-related maternal fever, however, the impact of each component is unknown. Two major theories surrounding epidural-related maternal fever development have been proposed. First, labor epidural analgesia may lead to the development of hyperthermia through a sterile (noninfectious) inflammatory process. This process may involve reduced activation of caspase-1 (a protease involved in cell apoptosis and activation of proinflammatory pathways) secondary to bupivacaine, which impairs the release of the antipyrogenic cytokine, interleukin-1-receptor antagonist, from circulating leucocytes. Detailed mechanistic processes of epidural-related maternal fever remain to be determined. Second, thermoregulatory mechanisms secondary to neuraxial blockade have been proposed, which may also contribute to epidural-related maternal fever development. Currently, there is no prophylactic strategy that can safely prevent epidural-related maternal fever from occurring nor can it easily be distinguished clinically from other causes of intrapartum fever, such as chorioamnionitis. Because intrapartum fever (of any etiology) is associated with adverse outcomes for both the mother and baby, it is important that all parturients who develop intrapartum fever are investigated and treated appropriately, irrespective of labor epidural utilization. Institution of treatment with appropriate antimicrobial therapy is recommended if an infectious cause of fever is suspected. There is currently insufficient evidence to warrant a change in recommendations regarding provision of labor epidural analgesia and the benefits of good quality labor analgesia must continue to be reiterated to expectant mothers.

Data-driven longitudinal characterization of neonatal health and morbidity.

Although prematurity is the single largest cause of death in children under 5 years of age, the current definition of prematurity, based on gestational age, lacks the precision needed for guiding care decisions. Here, we propose a longitudinal risk assessment for adverse neonatal outcomes in newborns based on a deep learning model that uses electronic health records (EHRs) to predict a wide range of outcomes over a period starting shortly before conception and ending months after birth. By linking the EHRs of the Lucile Packard Children's Hospital and the Stanford Healthcare Adult Hospital, we developed a cohort of 22,104 mother-newborn dyads delivered between 2014 and 2018. Maternal and newborn EHRs were extracted and used to train a multi-input multitask deep learning model, featuring a long short-term memory neural network, to predict 24 different neonatal outcomes. An additional cohort of 10,250 mother-newborn dyads delivered at the same Stanford Hospitals from 2019 to September 2020 was used to validate the model. Areas under the receiver operating characteristic curve at delivery exceeded 0.9 for 10 of the 24 neonatal outcomes considered and were between 0.8 and 0.9 for 7 additional outcomes. Moreover, comprehensive association analysis identified multiple known associations between various maternal and neonatal features and specific neonatal outcomes. This study used linked EHRs from more than 30,000 mother-newborn dyads and would serve as a resource for the investigation and prediction of neonatal outcomes. An interactive website is available for independent investigators to leverage this unique dataset: https://maternal-child-health-associations.shinyapps.io/shiny_app/.

Prepregnancy body mass index and gestational diabetes mellitus across Asian and Pacific Islander subgroups in California.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends early screening for gestational diabetes mellitus among pregnant Asian people with a prepregnancy body mass index ≥23.0 kg/m2, in contrast with the recommended screening at a body mass index ≥25 kg/m2 for other races and ethnicities. However, there is significant heterogeneity within Asian and Pacific Islander populations, and gestational diabetes mellitus and its association with body mass index among Asian and Pacific Islander subgroups may not be uniform across all groups. OBJECTIVE: This study aimed to analyze the association between body mass index and gestational diabetes mellitus among Asian and Pacific Islander subgroups in California, specifically gestational diabetes mellitus rates among those with a body mass index above vs below 23 kg/m2, which is the cutoff point for the designation of being overweight among Asians populations. STUDY DESIGN: Using a linked delivery hospitalization discharge and vital records database, we identified patients who gave birth in California between 2007 and 2017 and who self-reported to be 1 of 13 Asian and Pacific Islander subgroups, which was collected from birth and fetal death certificates. In each subgroup, we evaluated the association between body mass index and gestational diabetes mellitus using multivariable logistic regression models adjusted for age, education, parity, payment method, the trimester in which prenatal care was initiated, and nativity. We fit body mass index nonlinearly with splines and categorized body mass index as being above or below 23 kg/m2. Predicted probabilities of gestational diabetes mellitus with 95% confidence intervals were calculated across body mass index values using the nonlinear regression models. RESULTS: The overall prevalence of gestational diabetes mellitus was 14.3% (83,400/584,032), ranging between 8.4% and 17.1% across subgroups. The highest prevalence was among Indian (17.1%), Filipino (16.7%), and Vietnamese (15.5%) subgroups. In these subgroups, gestational diabetes mellitus was diagnosed in 10% to 13% of those with a body mass index <23.0 kg/m2 and in 22% of those with a body mass index ≥23 kg/m2. Gestational diabetes mellitus was least common among Korean (8.4%), Japanese (9.0%), and Samoan (9.8%) subgroups with a gestational diabetes mellitus rate of 5% to 7% among those with a body mass index <23.0 kg/m2 and in 10% to 15% among those with a body mass index ≥23 kg/m2. Although Samoan patients had the highest rate of obesity, defined as body mass index ≥30 kg/m2 (57.4%), they had the third lowest prevalence of gestational diabetes mellitus. Conversely, Vietnamese patients had the second lowest rate of obesity (2.4%) but the highest rate of gestational diabetes mellitus at a body mass index of ≥23 kg/m2 (22.3%). CONCLUSION: Gestational diabetes mellitus and its association with body mass index varied among Asian subgroups but increased as body mass index increased. Subgroups with the lowest prevalence of obesity trended toward a higher prevalence of gestational diabetes mellitus and those with a higher prevalence of obesity trended toward a lower prevalence of gestational diabetes mellitus.

Fasting Compared With Fed and Oral Intake Before the 1-Hour Oral Glucose Tolerance Test: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of fasting compared with eating before the 1-hour oral glucose tolerance test (OGTT) on gestational diabetes mellitus (GDM) screening results. METHODS: In a single-center, prospective randomized trial, participants were randomized to: 1) fasting for 6 or more hours or 2) oral intake ("fed") within 2 hours of the 50-g, 1-hour OGTT. The 1-hour OGTT was administered after 24 weeks of gestation. A positive screen result was defined as a serum glucose level of 140 mg/dL or higher. Protocol adherence was assessed by a survey administered immediately after the OGTT. We planned to enroll 100 participants in each group to detect an absolute difference of 20 percentage points or more on the 1-hour OGTT screen-positive rate using Fisher exact test, assuming an estimated screen-positive rate of 45% in the fasting and 25% in the fed group and 10% attrition, with a two-sided α=0.05, power=0.8. The primary outcome was the 1-hour OGTT screen-positive rate. Secondary outcomes included mean 1-hour OGTT glucose values, GDM diagnosis, maternal and neonatal outcomes, and patient perceptions regarding the 1-hour OGTT. RESULTS: From November 2020 through April 2021, 200 participants were randomized. One hundred ninety-five completed the 1-hour OGTT (97 fasting, 98 fed). Participant surveys confirmed 97.9% (n=95) adherence to the fasting and 91.8% (n=90) adherence to the fed groups. The screen-positive rate was significantly higher in the fasting than the fed group (32.0% vs 13.3%, respectively, P=.002), as was the mean glucose value (127.7 mg/dL vs 113.3 mg/dL, P=.002). The incidence of GDM in the fasting group was 12.4% (n=12) and in the fed group was 5.1% (n=5) (P=.08). There were no significant differences in maternal or neonatal outcomes. CONCLUSION: Fasting for 6 or more hours doubled the incidence of a positive 1-hour OGTT result when compared with eating within 2 hours of the test. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04547023.

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.

Impact of a Potential 20-Week Abortion Ban on Likelihood of Completing Required Views in Second-Trimester Fetal Anatomy Ultrasound.

OBJECTIVE: The aim of this study was to quantify the likelihood of assessing all mandated fetal views during the second-trimester anatomy ultrasound prior to the proposed federal 20-week abortion ban. STUDY DESIGN: Retrospective cohort study of a random sample of 1,983 patients undergoing anatomy ultrasound in 2017 at a tertiary referral center. The difference in proportion of incomplete anatomic surveys prior compared with after 20-week gestation was analyzed using X 2 and adjusted logistic regression; difference in mean days elapsed from anomaly diagnosis to termination tested using t-tests and survival analysis. RESULTS: Incomplete views were more likely with initial ultrasound before 20 weeks (adjusted relative risk: 1.70; 95% confidence interval: 1.50-1.94); 43.5% versus 26.1% were incomplete before and after 20 weeks, respectively. Fetal structural anomalies were identified in 6.4% (n = 127/1,983) scans, with 38.0% (n = 49) identified at follow-up after initial scan was incomplete. 22.8% (n = 29) with an anomaly terminated. CONCLUSIONS: A complete assessment of fetal views during an anatomy ultrasound prior to 20-week gestation is often not technically feasible. Legislation limiting abortion to this gestational age would greatly impact patient's ability to make informed choices about their pregnancies. KEY POINTS: · It is often not technically possible to complete anatomy ultrasound prior to 20-week gestation.. · Often, anomalies are missed during early, incomplete anatomy ultrasounds.. · After the diagnosis of a structural anomaly, one in five chose to terminate the pregnancy..

A data-driven health index for neonatal morbidities.

Whereas prematurity is a major cause of neonatal mortality, morbidity, and lifelong impairment, the degree of prematurity is usually defined by the gestational age (GA) at delivery rather than by neonatal morbidity. Here we propose a multi-task deep neural network model that simultaneously predicts twelve neonatal morbidities, as the basis for a new data-driven approach to define prematurity. Maternal demographics, medical history, obstetrical complications, and prenatal fetal findings were obtained from linked birth certificates and maternal/infant hospitalization records for 11,594,786 livebirths in California from 1991 to 2012. Overall, our model outperformed traditional models to assess prematurity which are based on GA and/or birthweight (area under the precision-recall curve was 0.326 for our model, 0.229 for GA, and 0.156 for small for GA). These findings highlight the potential of using machine learning techniques to predict multiple prematurity phenotypes and inform clinical decisions to prevent, diagnose and treat neonatal morbidities.

Maternal-fetal medicine fellows' perception and comfort with obstetrical ultrasound and prenatal diagnosis.

BACKGROUND: Ultrasound training is a vital component of maternal-fetal medicine fellowships in the United States. Of the 18 months of core clinical training, the American Board of Obstetrics and Gynecology currently requires a minimum of 3 months to be dedicated to ultrasound to be eligible for board certification. However, the experience and degree of hands-on training differ among the fellowship programs and have not been reassessed for nearly a decade. OBJECTIVE: To assess regional heterogeneity in the ultrasound training experience during maternal-fetal medicine fellowship in the United States. STUDY DESIGN: A survey was distributed to postgraduate year (PGY)-6 maternal-fetal medicine fellows registered to attend an annual ultrasound training course before the conference (n=114). For programs with >1 fellow attending (n=39), only 1 of them completed the survey to represent the program. The questions included demographics of the program, ultrasound training structure, the fellows' self-perception of ultrasound capabilities, research, mentorship, and technical aspects of sonography. RESULTS: Seventy two postgraduate year 6 fellows with a wide geographic distribution as follows completed the survey (96% response rate): 10 (14%) from the West, 16 (22%) from the Midwest, 17 (24%) from the South, and 29 (40%) from the Northeast. Respondents undergoing training in the South were less likely to report feeling comfortable performing nuchal translucency and detailed anatomic surveys than those from other regions (nuchal translucency: P=.046; anatomy: P=.011). Most of the respondents reported feeling comfortable performing growth (78%) and umbilical artery Doppler (58%) and feeling uncomfortable with three-dimensional ultrasound, neurosonography, and fetal echocardiography. Respondents in the Northeast were more likely to report feeling comfortable performing chorionic villus sampling (P=.001). There was no difference among fellowship programs in the presence or absence of ultrasound curriculum, bedside teaching, ultrasound-focused research mentorship, or months of ultrasound training. CONCLUSION: Despite the standardization of ultrasound training structure across the United States, there remains regional heterogeneity in fellow self-reported comfort with specific ultrasound techniques and chorionic villus sampling at a midpoint in their fellowship training. The maternal-fetal medicine attending involvement at the bedside did not affect the fellow self-reported comfort with ultrasound surveys. This study highlights the need for further optimization of maternal-fetal medicine fellowship ultrasound training, especially in advanced sonography and diagnostic procedures.

Development and in-vitro characterization of a novel fetal vesicoamniotic shunt - The Vortex shunt.

OBJECTIVES: To develop and test a novel vesicoamniotic shunt (VAS) to treat fetal lower urinary tract obstruction (LUTO), decrease dislodgement and optimize shunt deployment in-vitro. METHODS: Vesicoamniotic shunt design objectives included: (1) robust and atraumatic fixation elements, (2) kink resistant conduit to adjust to fetal movement and growth, (3) one-way pressure valve to facilitate bladder cycling, and (4) echogenic deployment visualization aids. The force to dislodge the novel Vortex shunt was compared with existing commercially available shunts in a bench-top porcine bladder model. Sonographic echogenicity was evaluated with ultrasound-guided deployment, and the shunt valve pressure measured. RESULTS: A prototype novel Vortex shunt was developed using braided nitinol "umbrella-type" ends with a kink-resistant stem incorporating an internal one-way valve. The peak force required to dislodge the Vortex shunt was significantly higher than commercially available shunts (p < 0.01). Shunt deployment in the bench-top model was easily confirmed with ultrasound guidance and the brisk decompression of the inflated porcine bladder thereafter. In-vitro valve gauge pressure testing mirrored bladder pressures in human LUTO cases. CONCLUSION: In-vitro testing shows that the Vortex shunt may improve deployment, sonographic visualization, kink resistance, and dynamic size adjustment. Validation in preclinical animal models are warranted and currently underway.