Adaptive evolution of the vertebrate skeletal muscle sodium channel

Tetrodotoxin (TTX) is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Nav). The skeletal muscle Nav (Nav1.4) channels in most pufferfish species and certain North American garter snakes are resistant to TTX, whereas in most mammals they are TTX-sensitive. It still remains unclear as to whether the difference in this sensitivity among the various vertebrate species can be associated with adaptive evolution. In this study, we investigated the adaptive evolution of the vertebrate Nav1.4 channels. By means of the CODEML program of the PAML 4.3 package, the lineages of both garter snakes and pufferfishes were denoted to be under positive selection. The positively selected sites identified in the p-loop regions indicated their involvement in Nav1.4 channel sensitivity to TTX. Most of these sites were located in the intracellular regions of the Nav1.4 channel, thereby implying the possible association of these regions with the regulation of voltage-sensor movement

Postpartum anticoagulation in women with mechanical heart valves

Roxanna A Irani,1,* Ann Santa-Ines,2,* Robert W Elder,2 Heather S Lipkind,1 Michael J Paidas,1 Katherine H Campbell1 1Department of Obstetrics, Gynecology and Reproductive Sciences, Section of Maternal-Fetal Medicine, Yale University School of Medicine, New Haven, CT, USA; 2Department of Pediatrics, Section of Pediatric Cardiology, Adult Congenital Heart Program, Yale University School of Medicine, New Haven, CT, USA *These authors contributed equally to this work Background: Women with mechanical heart valves (MHV) requiring anticoagulation (AC) are at high risk for hemorrhagic complications. Despite guidelines to manage antenatal and peripartum AC, there are few evidence-based recommendations to guide the initiation of postpartum AC. We reviewed our institutional experience of pregnant women with MHV to lay the groundwork for recommendations of immediate postpartum AC therapy.Study design: This descriptive retrospective cohort used ICD-9 and -10 codes to identify pregnant women with MHV on AC at the Yale-New Haven Hospital from 2007 to 2018. All identified patients were confirmed by chart review. Delivery hospitalization and the immediate postpartum AC management were reviewed. Maternal complications recorded were postpartum hemorrhage, transfusion, wound hematoma, intra-abdominal bleeding, stroke, valve thrombosis, and death. Further, immediate neonatal outcomes were detailed.Results: Forty-two pregnant women with nonnative heart valves were identified during the study period. From those pregnant women, nine had an MHV and were anticoagulated throughout gestation. Of 19 total pregnancies, 14 met the inclusion criteria. The median gestational age of the delivered pregnancies was early term (37w2d). Nine deliveries were via cesarean (64%). The median time to restart AC after birth was 6 hours. After six deliveries (43%), AC was initiated ≤6 hours postpartum. Hemorrhagic complications occurred in six cases (43%), including wound and intra-abdominal hematomas. Four cases (29%) required blood transfusion. No maternal strokes, thrombotic events, or deaths were recorded. Five (38.5%) neonates required admission to the neonatal intensive care unit.Conclusion: MHV in pregnancy was rare but was associated with significant maternal morbidity, particularly postpartum hemorrhagic complications. We noted significant variability in the timing of restarting postpartum AC and in the selected agents. Pooled institutional data and an interdisciplinary approach are recommended to minimize competing risks and sequelae of valve thrombosis and obstetrical hemorrhage and, thereby, to optimize maternal outcomes and develop evidence-based guidelines for postpartum AC management. Keywords: pregnancy, anticoagulation, postpartum hemorrhage, mechanical heart valve&nbsp

Descriptive Epidemiology of Chronic Hypertension, Gestational Hypertension, and Preeclampsia in New York State, 1995–2004

We examined social, demographic, and behavioral predictors of specific forms of hypertensive disorders in pregnancy in New York State. Administrative data on 2.3 million births over the period 1995–2004 were available for New York State, USA, with linkage to birth certificate data for New York City (964,071 births). ICD-9 hospital discharge diagnosis codes were used to assign hypertensive disorders hierarchically as chronic hypertension, chronic hypertension with superimposed preeclampsia, preeclampsia (eclampsia/severe or mild), or gestational hypertension. Sociodemographic and behavioral predictors of these outcomes were examined separately for upstate New York and New York City by calculating adjusted odds ratios. The most commonly diagnosed conditions were preeclampsia (2.57 % of upstate New York births, 3.68 % of New York City births) and gestational hypertension (2.46 % of upstate births, 1.42 % of New York City births). Chronic hypertension was much rarer. Relative to non-Hispanic Whites, Hispanics in New York City and Black women in all regions had markedly increased risks for all hypertensive disorders, whereas Asian women were at consistently decreased risk. Pregnancy-associated conditions decreased markedly with parity and modestly among smokers. A strong positive association was found between pre-pregnancy weight and risk of hypertensive disorders, with slightly weaker associations among Blacks and stronger associations among Asians. While patterns of chronic and pregnancy-induced hypertensive disorders differed, the predictors of gestational hypertension and both mild and severe preeclampsia were similar to one another. The increased risk for Black and some Hispanic women warrants clinical consideration, and the markedly increased risk with greater pre-pregnancy weight suggests an opportunity for primary prevention among all ethnic groups

Neonatal outcomes after preterm birth by mothers’ health insurance status at birth: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Publicly insured women usually have a different demographic background to privately insured women, which is related to poor neonatal outcomes after birth. Given the difference in nature and risk of preterm versus term births, it would be important to compare adverse neonatal outcomes after preterm birth between these groups of women after eliminating the demographic differences between the groups.</p> <p>Methods</p> <p>The study population included 3085 publicly insured and 3380 privately insured, singleton, preterm deliveries (32–36 weeks gestation) from Western Australia during 1998–2008. From the study population, 1016 publicly insured women were matched with 1016 privately insured women according to the propensity score of maternal demographic characteristics and pre-existing medical conditions. Neonatal outcomes were compared in the propensity score matched cohorts using conditional log-binomial regression, adjusted for antenatal risk factors. Outcomes included Apgar scores less than 7 at five minutes after birth, time until establishment of unassisted breathing (>1 minute), neonatal resuscitation (endotracheal intubation or external cardiac massage) and admission to a neonatal special care unit.</p> <p>Results</p> <p>Compared with infants of privately insured women, infants of publicly insured women were more likely to receive a low Apgar score (ARR = 2.63, 95% CI = 1.06-6.52) and take longer to establish unassisted breathing (ARR = 1.61, 95% CI = 1.25-2.07), yet, they were less likely to be admitted to a special care unit (ARR = 0.84, 95% CI = 0.80-0.87). No significant differences were evident in neonatal resuscitation between the groups (ARR = 1.20, 95% CI = 0.54-2.67).</p> <p>Conclusions</p> <p>The underlying reasons for the lower rate of special care admissions in infants of publicly insured women compared with privately insured women despite the higher rate of low Apgar scores is yet to be determined. Future research is warranted in order to clarify the meaning of our findings for future obstetric care and whether more equitable use of paediatric services should be recommended.</p