The factors associated with mode of delivery in fetuses with congenital heart defects.

Objective: It is not evident whether the mode of delivery (MOD) should be modified in pregnancies complicated by fetal congenital heart defects (CHDs). The question as to whether MOD of CHD infants has a significant impact on neonatal outcome remains elusive. The aim of this study was to evaluate factors associated with MOD and its impact on immediate neonatal outcomes in a cohort of late preterm or term fetuses with CHDs born in a tertiary center.Methods: This retrospective study comprised of singleton pregnancies with known fetal CHDs who delivered after 34 0/7 weeks of gestation over a 7-year period. Fetuses with chromosomal abnormality or stillbirths were excluded. Obstetric risk factors were classified as maternal medical, maternal surgical or fetal comorbidities. MOD was classified as elective cesarean delivery (CD) or attempted vaginal delivery (VD). The latter was further categorized as successful VD or intrapartum CD. The study population was stratified into four categories based on the severity of cardiac abnormalities diagnosed by fetal echocardiography. Immediate neonatal outcomes included Apgar scores and umbilical cord artery pH.Results: Of a total of 222 patients, 79.8% underwent attempted VD and 20.2% had elective CD. Of the attempted VD group, 80.2% had successful VD and 19.8% had intrapartum CD. The frequencies of maternal medical, maternal surgical and fetal comorbidities were higher in the elective CD group than in the attempted VD group and also were higher in the intrapartum CD group than in the successful VD group (p < .05 for all). Multivariate logistic regression models revealed that maternal surgical or fetal comorbidities increased the chance of elective CD and maternal medical or fetal comorbidities decreased the chance of successful VD. The severity of CHDs was not an independent factor that affected MOD. Elective or intrapartum CD did not improve immediate neonatal outcomes.Conclusion: Our results demonstrated that preexisting obstetric comorbidities were significant variables that affected the MOD in fetuses with CHD. Vaginal delivery should be attempted unless obstetric and medical contraindications accompany index pregnancy.

Novel mutations highlight the key role of the ankyrin repeat domain in TRPV4-mediated neuropathy.

OBJECTIVE: To characterize 2 novel TRPV4 mutations in 2 unrelated families exhibiting the Charcot-Marie-Tooth disease type 2C (CMT2C) phenotype. METHODS: Direct CMT gene testing was performed on 2 unrelated families with CMT2C. A 4-fold symmetric tetramer model of human TRPV4 was generated to map the locations of novel TRPV4 mutations in these families relative to previously identified disease-causing mutations (neuropathy, skeletal dysplasia, and osteoarthropathy). Effects of the mutations on TRPV4 expression, localization, and channel activity were determined by immunocytochemical, immunoblotting, Ca(2+) imaging, and cytotoxicity assays. RESULTS: Previous studies suggest that neuropathy-causing mutations occur primarily at arginine residues on the convex face of the TRPV4 ankyrin repeat domain (ARD). Further highlighting the key role of this domain in TRPV4-mediated hereditary neuropathy, we report 2 novel heterozygous missense mutations in the TRPV4-ARD convex face (p.Arg237Gly and p.Arg237Leu). Generation of a model of the TRPV4 homotetramer revealed that while ARD residues mutated in neuropathy (including Arg237) are likely accessible for intermolecular interactions, skeletal dysplasia-causing TRPV4 mutations occur at sites suggesting disruption of intramolecular and/or intersubunit interactions. Like previously described neuropathy-causing mutations, the p.Arg237Gly and p.Arg237Leu substitutions do not alter TRPV4 subcellular localization in transfected cells but cause elevations of cytosolic Ca(2+) levels and marked cytotoxicity. CONCLUSIONS: These findings expand the number of ARD residues mutated in TRPV4-mediated neuropathy, providing further evidence of the central importance of this domain to TRPV4 function in peripheral nerve.