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Complete atrioventricular block (CAVB) is a complication of maternal antibody positivity and treatment of fetal disease is controversial in terms of efficacy and safety. We hypothesized that dexamethasone treatment for fetal anti-Ro/SSA antibody-mediated cardiac disease leads to better pregnancy outcomes than expectant management.A retrospective multi-center cohort study of anti-Ro/SSA antibody positive pregnancies with fetal conduction disease reported by participating North American Fetal Therapy Network (NAFTNet) centers between January 2010 and December 2018. The primary outcomes included: fetal death, oligohydramnios, growth restriction, preterm delivery, and new maternal comorbidities. Secondary outcomes included: pacemaker prior to 28 days, transplantation, and neonatal death in maternal/fetal dyads treated with dexamethasone versus not.In 127 anti-Ro/SSA positive pregnancies, 98 were treated with dexamethasone and 29 were not. Of those treated, 61/96 (63.5%) met the primary outcome including 45/91 (49.4%) premature deliveries; 20 mothers developed comorbidities during treatment (fetal death 5, 10 growth restriction, 14 oligohydramnios, two new/worsening gestational diabetes). In the untreated group, 15/25 (60%) met the primary outcome including 11/22 (50%) premature deliveries and four mothers developing comorbidities during their pregnancy (fetal death 3, one growth restriction, one new onset maternal hypertension). Regarding secondary outcomes, 37/96 (43%) treated fetuses required a pacemaker or died by 28 days, while untreated 13/25 (52%) required pacemaker placement, died prior to 28 days or required listing for transplantation. Excluding terminations, survival without transplant was 17 (68%) in untreated and 85 (89%) in treated patients (While the use of dexamethasone in anti-Ro/SSA positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was an unexpected similarly high rate in untreated positive pregnancies. This suggests that the maternal disease itself is influencing pregnancy complications independent of dexamethasone. Our data, which show that treatment decreases neonatal morbidity and overall mortality without increasing overall pregnancy complications, warrant further study.

The prenatal detection of D-Transposition of the great arteries (D-TGA) and tetralogy of Fallot (TOF) has been reported to be less than 50% to as high as 77% when adding the outflow tracts to the four-chamber screening protocol. Because many examiners still struggle with the outflow tract examination, this study evaluated whether changes in the size and shape of the heart in the 4CV as well as the ventricles occurred in fetuses with D-TGA and TOF could be used to screen for these malformations.Forty-four fetuses with the pre-and post-natal diagnosis of D-TGA and 44 with TOF were evaluated between 19 and 36 weeks of gestation in which the 4CV was imaged. Measurements of the end-diastolic width, length, area, and global sphericity index were measured for the four-chamber view and the right and left ventricles. Using z-score computed values, logistic regression was performed between the 88 study and 200 control fetuses using the hierarchical forward selection protocol.Logistic regression identified 10 variables that correctly classified 83/88 of fetuses with TOF and TGA, for a sensitivity of 94%. Six of 200 normal controls were incorrectly classified for a false-positive rate of 3%. The area under the receiver operator classification curve was 98.1%. The true positive rate for D-TGA was 93.2%, with a false-negative rate to 6.8%. The true positive rate for TOF was 95.5%, with a false negative rate of 4.5%.Measurements of the 4CV and of the RV and LV may help identify fetuses at risk for D-TGA or TOF.

Twin-twin transfusion syndrome (TTTS) is a rare but serious cause of fetal cardiomyopathy with poorly understood pathophysiology and challenging prognostication. This study sought a nonbiased, comprehensive assessment of amniotic fluid (AF) microRNAs from TTTS pregnancies and associations of these miRNAs with clinical characteristics. For the discovery cohort, AF from ten fetuses with severe TTTS cardiomyopathy were selected and compared to ten normal singleton AF. Array panels assessing 384 microRNAs were performed on the discovery cohort and controls. Using a stringent q < 0.0025, arrays identified 32 miRNAs with differential expression. Top three microRNAs were miR-99b, miR-370 and miR-375. Forty distinct TTTS subjects were selected for a validation cohort. RT-PCR targeted six differentially-expressed microRNAs in the discovery and validation cohorts. Expression differences by array were confirmed by RT-PCR with high fidelity. The ability of these miRNAs to predict clinical differences, such as cardiac findings and later demise, was evaluated on TTTS subjects. Down-regulation of miRNA-127-3p, miRNA-375-3p and miRNA-886 were associated with demise. Our results indicate AF microRNAs have potential as a diagnostic and prognostic biomarker in TTTS. The top microRNAs have previously demonstrated roles in angiogenesis, cardiomyocyte stress response and hypertrophy. Further studies of the mechanism of actions and potential targets is warranted.

Based on fourteen case reports from various centres from 1992–2015 and three original studies in 2006–2011, 122 fetuses were subjected to analysis. In these reports, transplacental digoxin treatment was administered to different cardiac anomalies such as SVT, Ebstein’s anomaly, critical AS , absent pulmonary valve syndrome, complete heart block, in foetuses with aneurysm/diverticulum of LV, in tricuspid atresia or dysplasia, rhabdomyoma, pulmonary atresia, HLHS with fibroelastosis, in TTTS and in extracardiac anomalies such as atriovenous malformation or sacrococcygeal teratoma. There was no statistical difference to suggest (Chi-square test) that digoxin was more efficient to control fetal arrhythmias than fetal congestive heart failure in nonarrhythmic patients. Conclusions: Foetal cardiac insufficiency may appear due to different reasons (in normal heart anatomy or in heart defects, in normal sinus rhythm or due to foetal arrhythmias: tachycardias or severe bradycardia) and may be a cause of intrauterine demise. So far, we do not have strong evidence that digoxin treatment may prevent foetal death or prematurity. More research is needed to ascertain if the prolonging of pregnancy resulted from digoxin treatment or if improvement in foetal circulatory insufficiency was influenced by spontaneous regression of foetal cardiac symptoms.

The objective of this study is to perform a longitudinal evaluation of blood flow patterns in the ductus arteriosus (DA) during the perioperative period in fetal myelomeningocele (MMC) surgical patients.Serial fetal echocardiograms were reviewed in 10 MMC cases where mothers received indomethacin and intravenous and inhaled anesthesia. One-way analysis of variance was utilized to evaluate for differences in peak systolic velocity, end-diastolic velocity (EDV), time-averaged mean velocity (TAMV), and Pulsatility Index (PI) throughout the monitoring period. Regression analysis was performed to evaluate the relationship between PI and maternal hemodynamics and medications.The DA TAMV and EDV increased between baseline and inhaled anesthesia and decreased between inhaled anesthesia and postoperative day 2. PI decreased to a nadir during inhaled anesthesia and then increased through postoperative day 2. Three distinct ductal flow patterns, characterizing degree of ductal constriction, were observed. Two fetuses exhibited a severely constricted ductal flow pattern with concurrent moderate tricuspid insufficiency and right ventricular dysfunction during inhaled anesthesia.Abnormal DA flow patterns culminating in significant DA constriction occurred during fetal MMC repair. Limiting maternal exposure to indomethacin, supplemental oxygen, and inhaled anesthesia may reduce the incidence and severity of DA constriction and perhaps reduce fetal cardiac dysfunction during open fetal surgery.

DISEASE AFTER OPTIMAL IN UTERO MANAGEMENT MAUREEN LEE, JAMES HUHTA, JENNY LESHKO, ANDREA KEMP, BARBARA PARILLA, BETTINA CUNEO, University of Illinois at Chicago, Chicago, Illinois, University of South Florida, St. Petersburg, Florida, University of South Florida, Pediatrics, St. Petersburg, Florida, University of Illinois at Chicago, Park Ridge, Illinois, Society for Maternal-Fetal Medicine, Oak Lawn, Illinois OBJECTIVE: The optimal time for delivery of the fetus with isoimmune 2° or 3° AV block (AVB) is at term and without heart failure. We evaluated the indications for delivery after basing our in utero management on fetal heart rate (FHR) and degree of heart failure, based on a cardiovascular profile score (CVPS). STUDY DESIGN: We retrospectively reviewed medical records, echocardiograms and ultrasounds of fetuses with AVB from 2 perinatal-cardiology centers over 12 years. Weekly, from diagnosis to delivery, we monitored FHR, the CVPS (a 10-point score assessing cardiothoracic area, venous and arterial Doppler flow patterns, hydrops, and valvular insufficiency), the presence of endocardiofibroelastosis (EFE), fetal growth, and after 30 weeks, biophysical profile. Dexamethasone was given to the mother at diagnosis; we added terbutaline if CVPS 8 or FHR 55 bpm; and digoxin if CVPS was 7. Fetuses were divided into group 1 if they delivered at term and group 2 if they delivered at 36 weeks. Groups differences were tested using Fisher Exact’s test. RESULTS: All fetuses (group 1: n 13 with 3° AV block; group 2: n 8; 2 with 2° and 6 with 3° AV block) were born alive. Indications for early delivery were abnormal BPP(2), ventricular dysfunction alone(3) or with abnormal BPP(1) and oligohydramnios (1) or IUGR (1). Both group 2 fetuses with 2° AVB were delivered because of abnormal BPP. More group 2 fetuses required terbutaline (62.5% vs. 37.5%) for low FHR, had EFE (63% vs. 6 %, p .014), had lower pre-delivery CVPS (p .028), and were diagnosed earlier (p .03). CONCLUSION: The CVPS, fetal HR and the presence of EFE, but not the degree of AVB, correlated with the need for early delivery. Ventricular dysfunction is an indication for one third of premature deliveries. The CVPS is useful in monitoring the in utero management of isoimmune AVB.