Mitral Valve Abnormalities Associated with Single-Ventricle Palliation, Cardiac Death or Transplant in Fetuses with Postnatally Confirmed Coarctation of the Aorta.

Predicting if a fetus with borderline left heart structures and coarctation of the aorta (CoA) will require single ventricle palliation (SVP) is challenging, partly due to the limitations of fetal echocardiography in defining valvar abnormalities. Fetal echocardiographic findings predictive of SVP, particularly in relation to the mitral valve (MV), are not well defined. We performed a retrospective review of fetuses with postnatally confirmed CoA from 2010 to 2020. Fetuses with complex congenital heart disease or unequivocal hypoplastic left heart syndrome were excluded. Data were compared between those who underwent biventricular repair (BVR) versus SVP, cardiac death or orthotopic heart transplant (OHT) to determine differences in fetal echocardiograms. Of 67 fetuses with 131 total echocardiograms, 62 (93%) underwent BVR and 5 (7%) experienced SVP, cardiac death or OHT. Fetuses with confirmed CoA who experienced SVP, cardiac death, or OHT, had fetal MV z-scores that were 2.03 lower, on average, than those who underwent BVR (z-score = - 3.98 vs. - 1.94, 95% CI - 2.93, - 1.13). The incidences of MV anomalies and left to right flow across the foramen ovale were higher in the SVP, cardiac death and OHT group. SVP, cardiac death or OHT in fetuses with confirmed CoA were associated with severe fetal MV hypoplasia, MV anomalies and left to right flow across the foramen ovale. These findings may help guide prenatal counseling about the likelihood of SVP, cardiac death or OHT in fetuses with CoA and borderline left heart structures.

Mitral valve abnormalities associated with single-ventricle palliation, cardiac death or transplant in fetuses with postnatally confirmed coarctation of the aorta.

Introduction: Predicting if a fetus with borderline left heart structures and coarctation of the aorta (CoA) will require single ventricle palliation (SVP) is challenging, partly due to the limitations of fetal echocardiography in defining valvar abnormalities. Fetal echocardiographic findings predictive of SVP, particularly in relation to the mitral valve (MV), are not well defined. Methods: We performed a retrospective review of fetuses with postnatally confirmed CoA from 2010 to 2020. Fetuses with complex congenital heart disease or unequivocal hypoplastic left heart syndrome were excluded. Data were compared between those who underwent biventricular repair (BVR) vs. SVP cardiac death or orthotopic heart transplant (OHT) to determine differences in fetal echocardiograms. Results: Of 67 fetuses with 131 total echocardiograms, 62 (93%) underwent BVR and 5 (7%) experienced SVP, cardiac death or OHT. Fetuses with confirmed CoA who experienced SVP cardiac death, or OHT, had fetal MV z-scores that were 2.06 lower, on average, than those who underwent BVR (z-score = -3.98 vs. -1.92, 95% CI: -2.96, -1.16). The incidences of MV anomalies and left to right flow across the foramen ovale were higher in the SVP cardiac death and OHT group. Conclusion: SVP, cardiac death or OHT in fetuses with confirmed CoA were associated with fetal MV hypoplasia, MV anomalies and left to right flow across the foramen ovale. These findings may help guide prenatal counseling about the likelihood of SVP, cardiac death or OHT in fetuses with CoA and borderline left heart structures.

Reducing perinatal complications and preterm delivery for patients undergoing in utero closure of fetal myelomeningocele: further modifications to the multidisciplinary surgical technique.

UNLABELLED: OBJECT.: As more pediatric neurosurgeons become involved with fetal myelomeningocele closure efforts, examining refined techniques in the overall surgical approach that could maximize beneficial outcomes becomes critical. The authors compared outcomes for patients who had undergone a modified technique with those for patients who had undergone fetal repair as part of the earlier Management of Myelomeningocele Study (MOMS). METHODS: Demographic and outcomes data were collected for a series of 43 delivered patients who had undergone in utero myelomeningocele closure at the Fetal Center at Vanderbilt from March 2011 through January 2013 (the study cohort) and were compared with data for 78 patients who had undergone fetal repair as part of MOMS (the MOMS cohort). For the study cohort, no uterine trocar was used, and uterine entry, manipulation, and closure were modified to minimize separation of the amniotic membrane. Weekly ultrasound reports were obtained from primary maternal-fetal medicine providers and reviewed. A test for normality revealed that distribution for the study cohort was normal; therefore, parametric statistics were used for comparisons. RESULTS: The incidence of premature rupture of membranes (22% vs 46%, p = 0.011) and chorioamnion separation (0% vs 26%, p < 0.001) were lower for the study cohort than for the MOMS cohort. Incidence of oligohydramnios did not differ between the cohorts. The mean (± SD) gestational age of 34.4 (± 6.6) weeks for the study cohort was similar to that for the MOMS cohort (34.1 ± 3.1 weeks). However, the proportion of infants born at term (37 weeks or greater) was significantly higher for the study cohort (16 of 41; 39%) than for the MOMS cohort (16 of 78; 21%) (p = 0.030). Compared with 10 (13%) of 78 patients in the MOMS cohort, only 2 (4%) of 41 infants in the study cohort were delivered earlier than 30 weeks of gestation (p = 0.084, approaching significance). For the study cohort, 2 fetal deaths were attributed to the intervention, and both were believed to be associated with placental disruption; one of these mothers had previously unidentified thrombophilia. Mortality rates did not statistically differ between the cohorts. CONCLUSIONS: These early results suggest that careful attention to uterine entry, manipulation, and closure by the surgical team can result in a decreased rate of premature rupture of membranes and chorioamnion separation and can reduce early preterm delivery. Although these results are promising, their confirmation will require further study of a larger series of patients.

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: a validated genetic association study.

Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary hypertension. A consecutive modeling cohort of children (N=131) with congenital heart defects requiring surgery was prospectively evaluated to determine key factors associated with increased postoperative PAP, defined as a mean PAP>20 mmHg for at least 1h during the 48h following surgery measured by an indwelling pulmonary artery catheter. Multiple dimensionality reduction (MDR) was used to both internally validate observations and develop optimal two-variable through five-variable models that were tested prospectively in a validation cohort (N=41). Unconditional logistic regression analysis of the modeling cohort revealed that age (OR=0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08, p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were independent predictors of this complex phenotype. MDR predicted that the best two-variable model consisted of age and CPSI T1405N genotype (p<0.001). This two-variable model correctly predicted 73% of the outcomes from the validation cohort. A five-variable model that added race, gender and Down's syndrome was not significantly better than the two-variable model. In conclusion, the CPSI T1405N genotype appears to be an important new factor in predicting susceptibility to increased PAP following surgical repair of congenital cardiac defects in children.

Report of the Tennessee Task Force on Screening Newborn Infants for Critical Congenital Heart Disease.

A member of the Tennessee state legislature recently proposed a bill that would mandate all newborn infants to undergo pulse oximetry screening for the purpose of identifying those with critical structural heart disease before discharge home. The Tennessee Task Force on Screening Newborn Infants for Critical Congenital Heart Defects was convened on September 29, 2005. This group reviewed the current medical literature on this topic, as well as data obtained from the Tennessee Department of Health, and debated the merits and potential detriments of a statewide screening program. The estimated incidence of critical congenital heart disease is 170 in 100,000 live births, and of those, 60 in 100,000 infants have ductal-dependent left-sided obstructive lesions with the potential of presentation by shock or death if the diagnosis is missed. Of the latter group, the diagnosis is missed in approximately 9 in 100,000 by fetal ultrasound assessment and discharge examination and might be identified by a screening program. Identification of the missed diagnosis in these infants before discharge could spare many of them death or neurologic sequelae. Four major studies using pulse oximetry screening were analyzed, and when data were restricted to critical left-sided obstructive lesions, sensitivity values of 0% to 50% and false-positive rates of between 0.01% and 12% were found in asymptomatic populations. Because of this variability and other considerations, a meaningful cost/benefit analysis could not be performed. It was the consensus of the task force to provide a recommendation to the legislature that mandatory screening not be implemented at this time. In addition, we determined that a very large, prospective, perhaps multistate study is needed to define the sensitivity and false-positive rates of lower-limb pulse oximetry screening in the asymptomatic newborn population and that there needs to be continued partnering between the medical community, parents, and local, state, and national governments in decisions regarding mandated medical care.