Diverging Maternal and Cord Antibody Functions From SARS-CoV-2 Infection and Vaccination in Pregnancy.

Maternal immunity impacts the infant, but how is unclear. To understand the implications of the immune exposures of vaccination and infection in pregnancy for neonatal immunity, we evaluated antibody functions in paired peripheral maternal and cord blood. We compared those who in pregnancy received mRNA coronavirus disease 2019 (COVID-19) vaccine, were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the combination. We found that vaccination enriched a subset of neutralizing activities and Fc effector functions that was driven by IgG1 and was minimally impacted by antibody glycosylation in maternal blood. In paired cord blood, maternal vaccination also enhanced IgG1. However, Fc effector functions compared to neutralizing activities were preferentially transferred. Moreover, changes in IgG posttranslational glycosylation contributed more to cord than peripheral maternal blood antibody functional potency. These differences were enhanced with the combination of vaccination and infection as compared to either alone. Thus, Fc effector functions and antibody glycosylation highlight underexplored maternal opportunities to safeguard newborns.

Three-year outcomes of a randomized clinical trial of perioperative vaginal estrogen as adjunct to native tissue vaginal apical prolapse repair.

BACKGROUND: As the muscular and connective tissue components of the vagina are estrogen responsive, clinicians may recommend vaginal estrogen to optimize tissues preoperatively and as a possible means to reduce prolapse recurrence, but long-term effects of perioperative intravaginal estrogen on surgical prolapse management are uncertain. OBJECTIVE: This study aimed to compare the efficacy of perioperative vaginal estrogen vs placebo cream in reducing composite surgical treatment failure 36 months after native tissue transvaginal prolapse repair. STUDY DESIGN: This was an extended follow-up of a randomized superiority trial conducted at 3 tertiary US sites. Postmenopausal patients with bothersome anterior or apical vaginal prolapse were randomized 1:1 to 1-g conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally twice weekly for ≥5 weeks preoperatively and continued twice weekly for 12 months postoperatively. All participants underwent vaginal hysterectomy (if the uterus was present) and standardized uterosacral or sacrospinous ligament suspension at the surgeon's discretion. The primary report's outcome was time to failure by 12 months postoperatively, defined by a composite outcome of objective prolapse of the anterior or posterior walls beyond the hymen or the vaginal apex descending below one-third the total vaginal length, subjective bulge symptoms, and/or retreatment. After 12 months, participants could choose to use-or not use-vaginal estrogen for atrophy symptom bother. The secondary outcomes included Pelvic Organ Prolapse Quantification points, subjective prolapse symptom severity using the Patient Global Impression of Severity and the Patient Global Impression of Improvement, and prolapse-specific subscales of the 20-Item Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire-Short Form 7. Data were analyzed as intent to treat and "per protocol" (ie, ≥50% of expected cream use per medication diary). RESULTS: Of 206 postmenopausal patients, 199 were randomized, and 186 underwent surgery. Moreover, 164 postmenopausal patients (88.2%) provided 36-month data. The mean age was 65.0 years (standard deviation, 6.7). The characteristics were similar at baseline between the groups. Composite surgical failure rates were not significantly different between the estrogen group and the placebo group through 36 months, with model-estimated failure rates of 32.6% (95% confidence interval, 21.6%-42.0%) and 26.8% (95% confidence interval, 15.8%-36.3%), respectively (adjusted hazard ratio, 1.55; 95% confidence interval, 0.90-2.66; P=.11). The results were similar for the per-protocol analysis. Objective failures were more common than subjective failures, combined objective and subjective failures, or retreatment. Using the Patient Global Impression of Improvement, 75 of 80 estrogen participants (94%) and 72 of 76 placebo participants (95%) providing 36-month data reported that they were much or very much better 36 months after surgery (P>.99). These data included reports from 51 of 55 "surgical failures." Pelvic Organ Prolapse Quantification measurements, Patient Global Impression of Severity scores, and prolapse subscale scores of the 20-Item Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire-Short Form 7 all significantly improved for both the estrogen and placebo groups from baseline to 36 months postoperatively without differences between the groups. Of the 160 participants providing data on vaginal estrogen usage at 36 months postoperatively, 40 of 82 participants (49%) originally assigned to the estrogen group were using prescribed vaginal estrogen, and 47 of 78 participants (60%) assigned to the placebo group were using vaginal estrogen (P=.15). CONCLUSION: Adjunctive perioperative vaginal estrogen applied ≥5 weeks preoperatively and 12 months postoperatively did not improve surgical success rates 36 months after uterosacral or sacrospinous ligament suspension prolapse repair. Patient perception of improvement remained very high at 36 months.

Impact of maternal infection on outcomes in extremely preterm infants.

BACKGROUND: Infants born less than 29 weeks, or extremely preterm (EPT), experience increased morbidity and mortality. We hypothesized that exposure to maternal infection might contribute to neurodevelopmental impairment (NDI) or death at 2 years of age. METHODS: We conducted a retrospective cohort study of EPT infants from January 2010 to December 2020. Maternal data extracted included maternal infections, classified as extrauterine or intrauterine. Placental pathologic and infant data were extracted. The primary outcome was NDI or death at 2 years of age. RESULTS: 548 EPT infants were born to 496 pregnant people: 379 (69%) were not exposed to any documented maternal infection prenatally, 124 (23%) to extrauterine infection, and 45 (8%) to intrauterine infection. Neither diagnosis of maternal extrauterine nor intrauterine infection was associated with NDI or death at 2 years of age (p > 0.05). Acute histologic chorioamnionitis was associated with NDI or death at 2 years of age (p = 0.033). CONCLUSIONS: Maternal infection was not associated with NDI or death at 2 years of age in EPT infants. However, acute histologic chorioamnionitis was associated with this outcome. Further work should investigate the differential influence of infection and immune response with this pathology as relates to outcomes in EPT infants. IMPACT: Maternal infection was not associated with neurodevelopmental impairment (NDI) or death at 2 years of age in extremely preterm (EPT) infants. This is reassuring support that mechanisms at the maternal-fetal interface largely protect the EPT infant. However, pathologic findings of acute histologic chorioamnionitis were associated with NDI and death at 2 years of age. Further work should investigate the differential influence of infection and immune response with acute histologic chorioamnionitis on pathology as relates to outcomes in EPT infants.

Somatic and autonomic nerve density and distribution within the clitoris: an immunohistochemical study in adult female cadavers.

INTRODUCTION AND HYPOTHESIS: Knowledge of clitoral neuroanatomy is critical to vulvar surgery. We sought to characterize the density and distribution of autonomic and somatic nerves supplying the clitoris. METHODS: Pelvic tissue harvested from female cadavers was sectioned axially at three anatomic levels: the proximal aspect of the clitoral body (CB), the distal CB, and the glans. The CB, glans, and the surrounding connective tissue (dorsal, lateral, and ventral) were outlined microscopically. An area containing large nerve bundles dorsal to the CB, referred to as the dorsal nerve subregion, was analyzed separately. Double-immunofluorescent staining for beta III tubulin (ßIIIT), a global axonal marker, and myelin basic protein (MBP), a myelinated nerve marker, was performed. Threshold-based automatic image-segmentation distinguished stained areas. Autonomic and somatic density were calculated as percentage of tissue stained with ßIIIT alone, and ßIIIT and MBP respectively. Comparisons were made using nonparametric Friedman tests. RESULTS: Seven cadavers, aged 22-81, were examined. Somatic (mean 4.42%, SD ± 1.97) and autonomic (2.14% ± 2.42) nerve density was highest in the dorsal nerve subregion and dorsal region at the distal CB level. Compared with the CB, somatic density was higher in proximal (0.05% ± 0.03 vs 1.27% ± 0.69, p = 0.03) and distal (0.29% ± 0.25 vs 1.09% ± 0.41, p = 0.05) dorsal regions. Somatic density was greater in the glans than in the surrounding lateral (0.78% ± 0.47 vs 0.43% ± 0.23, p = 0.03) and ventral (0.78% ± 0.47 vs 0.52% ± 0.2, p = 0.03) regions. Autonomic density was greater than somatic in all areas, except for the dorsal nerve subregion. CONCLUSIONS: Somatic and autonomic nerve density were greatest in a well-defined region dorsal to the CB. Surgical preservation of this region is critical for maintaining nerve supply to the clitoris.

Traffic-related air pollution is associated with spontaneous extremely preterm birth and other adverse perinatal outcomes.

BACKGROUND: Although there is growing awareness of the relationship between air pollution and preterm birth, limited data exist regarding the relationship with spontaneous preterm birth and severe neonatal outcomes. OBJECTIVE: This study aimed to examine the association between traffic-associated air pollution exposure in pregnancy and adverse perinatal outcomes including extremes of preterm birth, neonatal intensive care unit admissions, low birthweight, neonatal respiratory diagnosis, neonatal respiratory support, and neonatal sepsis evaluation. STUDY DESIGN: This was a retrospective cohort study of singleton pregnancies of patients residing in a metropolitan area in the southern United States. Using monitors strategically located across the region, average nitrogen dioxide concentrations were obtained from the Environmental Protection Agency Air Quality System database. For patients living within 10 miles of a monitoring station, average exposure to nitrogen dioxide was estimated for individual patients' pregnancy by trimester. Logistic regression models were used to assess the effect of pollutant exposure on gestational age at birth, indicated vs spontaneous delivery, and neonatal outcomes while adjusting for maternal age, self-reported race, parity, season of conception, diabetes mellitus, body mass index, registered Health Equity Index, and nitrogen dioxide monitor region. Adjusted odds ratios and 95% confidence intervals were calculated for an interquartile increase in average nitrogen dioxide exposure. RESULTS: Between January 1, 2013 and December 31, 2021, 93,164 patients delivered a singleton infant. Of these, 62,189 had measured nitrogen dioxide exposure during the pregnancy from a nearby monitoring station. Higher average nitrogen dioxide exposure throughout pregnancy was significantly associated with preterm birth (adjusted odds ratio, 1.94; 95% confidence interval, 1.77-2.12) and an increase in neonatal intensive care unit admissions, low birthweight infants, neonatal respiratory diagnosis, neonatal respiratory support, and neonatal sepsis evaluation. This relationship persisted for nulliparous patients and spontaneous preterm birth, and had a greater association with earlier preterm birth. CONCLUSION: In a metropolitan area, increased exposure to the air pollutant nitrogen dioxide in pregnancy was associated with spontaneous preterm birth and had a greater association with extremely preterm birth. A greater association with neonatal intensive care unit admissions, low-birthweight infants, neonatal respiratory diagnosis, neonatal respiratory support, and neonatal sepsis evaluation was found even in term infants.

Transfusion and hematologic indices in cases of stillbirth due to placental abruption.

BACKGROUND: Stillbirth because of placental abruption is often associated with maternal hemorrhage and coagulopathy. OBJECTIVE: This study aimed to describe blood product requirements, hematologic indices, and the overall clinical picture of patients experiencing abruption demise. STUDY DESIGN: This retrospective cohort included patients with abruption demise at an urban hospital from 2010 to 2020. Outcome data from patients who delivered stillborn infants ≥500 g or with gestational age of ≥24 weeks were included. Abruption was a clinical diagnosis made by a multidisciplinary stillbirth review committee. The overall number and type of blood products given were analyzed. Patients with a stillbirth who required blood transfusion were compared with those that did not. In addition, the hematologic indices of these 2 populations were analyzed and compared with one another. Finally, the overall clinical characteristics of the 2 populations were analyzed. The analysis of data included chi-square, t test, and logistic and negative binomial regression models. RESULTS: Of 128,252 deliveries, 615 patients (0.48%) experienced a stillbirth, with 76 cases (12%) caused by abruption. Of note, 42 patients (55.2%) required blood transfusion; all received either packed red blood cells or whole blood with a median 3.5 units (2.0-5.5) received. The total units ranged from 1 to 59, with 12 of 42 patients (29%) requiring ≥10 units. Maternal age, gestational age, and mode of delivery were not different, with most (61/76 [80%]) delivering vaginally. Hematocrit level on arrival (odds ratio, 0.80; 95% confidence interval, 0.68-0.91; P=.002) and vaginal bleeding on arrival (odds ratio, 3.73; 95% confidence interval, 1.15-13.40; P=.033) were associated with blood transfusion, as was a diagnosis of preeclampsia (odds ratio, 8.40; 95% confidence interval, 2.49-33.41; P=.001). Those that required a blood transfusion often presented with lower hematologic indices and were more likely to develop disseminated intravascular coagulation (28% vs 0%; P<.001). CONCLUSION: Most patients experiencing stillbirth because of abruption required blood transfusion, with almost 1 in 3 of those patients consuming ≥10 units of blood products. Hematocrit level on arrival, vaginal bleeding, and preeclampsia were all predictors of the need for blood transfusion. Those requiring blood transfusion were more likely to develop disseminated intravascular coagulation. Blood transfusion should be prioritized when abruption demise is suspected.

Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse.

BACKGROUND: Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder, and vulvovaginal atrophy symptoms. Past evidence suggests that postmenopausal women with symptomatic prolapse gain benefit from the preoperative application of intravaginal estrogen, but it is unknown whether they would experience improvement in other pelvic floor symptoms when treated with intravaginal estrogen. OBJECTIVE: This study aimed to determine the effects of intravaginal estrogen (compared with placebo) on stress and urgency urinary incontinence, urinary frequency, sexual function and dyspareunia, and vaginal atrophy symptoms and signs in postmenopausal women with symptomatic prolapse. STUDY DESIGN: This was a planned ancillary analysis of a randomized, double-blind trial, "Investigation to Minimize Prolapse Recurrence Of the Vagina using Estrogen," which included participants with ≥stage 2 apical and/or anterior prolapse scheduled for transvaginal native tissue apical repair at 3 US sites. The intervention was 1 g conjugated estrogen intravaginal cream (0.625 mg/g) or identical placebo (1:1), inserted nightly for 2 weeks and then twice weekly for ≥5 weeks total before surgery and continued twice weekly for 1 year postoperatively. For this analysis, question responses were compared from participants' baseline and preoperative visits: lower urinary tract symptoms (Urogenital Distress Inventory-6 Questionnaire); sexual health questions, including dyspareunia (Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised); and atrophy-related symptoms (dryness, soreness, dyspareunia, discharge, and itching; each scored 1-4, 4 being quite a bit bothersome). Masked examiners assessed vaginal color, dryness, and petechiae (each scored 1-3, total range 3-9, with 9 being the most estrogenized appearing). Data were analyzed by intent to treat and "per protocol" (ie, those adherent with ≥50% of expected intravaginal cream use, per objective tube before and after weights). RESULTS: Of 199 participants randomized (mean age of 65 years) and contributing baseline data, 191 had preoperative data. The characteristics were similar between groups. Total Urogenital Distress Inventory-6 Questionnaire scores showed minimal change during this median time of 7 weeks between baseline and preoperative visits, but for those with at least moderately bothersome baseline stress urinary incontinence (32 in the estrogen group and 21 in the placebo group), 16 (50%) in the estrogen group and 9 (43%) in the placebo group showed improvement (P=.78). In addition, 43% of participants in the estrogen group and 31% of participants in the placebo group showed improvement in urgency urinary incontinence (P=.41), and 41% of participants in the estrogen group and 26% of participants in the placebo group showed improvement in urinary frequency (P=.18). There was minimal change in the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised scores among sexually active women; dyspareunia rates did not differ between intravaginal estrogen and placebo at the preoperative assessment: 42% and 48%, respectively (P=.49). The maximum score for most bothersome atrophy symptom (among those with baseline symptoms and adherent to study cream) improved slightly more with intravaginal estrogen (adjusted mean difference, -0.33 points; 95% confidence interval, -0.98 to 0.31), but this was not statistically significant (P=.19). However, on examination, among adherent participants, objective signs of atrophy were more improved with intravaginal estrogen treatment (+1.54 vs +0.69; mean difference, 0.85; 95% confidence interval, 0.05-1.65; P=.01). CONCLUSION: Despite objective changes in the vaginal epithelium consistent with increased estrogenization among drug-adherent participants, the results were inconclusive regarding whether 7 weeks of preoperative intravaginal estrogen cream in postmenopausal women with symptomatic pelvic organ prolapse was associated with improved urinary function, sexual function, dyspareunia symptoms, and other symptoms commonly attributed to atrophy. Additional study is needed.

A comparison of criteria for defining metabolic acidemia in live-born neonates and its effect on predicting serious adverse neonatal outcomes.

BACKGROUND: Metabolic acidemia is a known risk factor for serious adverse neonatal outcomes in both preterm and term infants. OBJECTIVE: This study aimed to evaluate the clinical significance of delivery umbilical cord gas measurements with regard to serious adverse neonatal outcomes, and to determine if distinct thresholds for defining metabolic acidemia differ in their ability to predict such adverse neonatal complications. STUDY DESIGN: This is a retrospective cohort study of singleton live-born deliveries between January 2011 and December 2019. Stratification according to gestational age at birth (≥35 and <35 weeks of gestation) was performed, and comparisons of maternal characteristics, obstetrical complications, intrapartum events, and adverse neonatal outcomes were made between neonates with metabolic acidemia and those without. Metabolic acidemia (based on delivery umbilical cord gas analyses) was defined using both American College of Obstetricians and Gynecologists and Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria. The primary outcome of interest was hypoxic-ischemic encephalopathy requiring whole-body hypothermia. RESULTS: A total of 91,694 neonates born at ≥35 weeks of gestation met the inclusion criteria. By American College of Obstetricians and Gynecologists criteria, 2659 (2.9%) infants had metabolic acidemia. Neonates with metabolic acidemia were at markedly increased risk for neonatal intensive care unit admission, seizures, need for respiratory support, sepsis, and neonatal death. Metabolic acidemia by American College of Obstetricians and Gynecologists criteria was associated with an almost 100-fold increased risk of hypoxic-ischemic encephalopathy requiring whole-body hypothermia (relative risk, 92.69; 95% confidence interval, 64.42-133.35) in neonates born at ≥35 weeks of gestation. Diabetes mellitus, hypertensive disorders of pregnancy, postterm deliveries, prolonged second stages, chorioamnionitis, operative vaginal deliveries, placental abruption and cesarean deliveries were associated with metabolic acidemia in neonates born ≥ 35 weeks of gestation. The highest relative risk was in those diagnosed with placental abruption (relative risk, 9.07; 95% confidence interval, 7.25-11.36). The neonatal cohort born <35 weeks of gestation had similar findings. When comparing those infants born ≥ 35 weeks of gestation with metabolic acidemia by American College of Obstetricians and Gynecologists criteria vs Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria, the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria identified more neonates at risk for serious adverse neonatal outcomes. In particular, 4.9% more neonates were diagnosed with metabolic acidemia, and 16 more term neonates were identified as requiring whole-body hypothermia. Mean 1-minute and 5-minute Apgar scores were similar and reassuring among neonates born at ≥35 weeks of gestation with and without metabolic acidemia as defined by both American College of Obstetricians and Gynecologists and Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria (8 vs 8 and 9 vs 9, respectively; P<.001). Sensitivity and specificity were 86.7% and 92.2%, respectively, with the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria, and 74.2% and 97.2% with the American College of Obstetricians and Gynecologists criteria. CONCLUSION: Infants with metabolic acidemia identified on cord gas collection at delivery are at considerably greater risk of serious adverse neonatal outcomes, including an almost 100-fold increased risk of hypoxic-ischemic encephalopathy requiring whole-body hypothermia. Use of the more sensitive Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria for defining metabolic acidemia identifies more neonates born at ≥35 weeks of gestation at risk for adverse neonatal outcomes, including hypoxic-ischemic encephalopathy requiring whole-body hypothermia.

Somatic and autonomic nerve density of the urethra, periurethral tissue, and anterior vaginal wall: an immunohistochemical study in adult female cadavers.

INTRODUCTION AND HYPOTHESIS: Retropubic procedures may disrupt nerves supplying the pelvic viscera; however, knowledge of pelvic neuroanatomy is limited. We sought to characterize somatic and autonomic nerve density within the urethra, periurethral tissue, and anterior vagina. METHODS: Axial sections were obtained from pelvic tissue harvested from female cadavers ≤24 h from death at three anatomical levels: the midurethra, proximal urethra, and upper trigone. Periurethral/perivesical tissue was divided into medial and lateral sections, and the anterior vagina into middle, medial, and lateral sections. Double immunofluorescent staining for beta III tubulin (ßIIIT), a global axonal marker, and myelin basic protein (MBP), a myelinated nerve marker, was performed. Threshold-based automatic image segmentation distinguished stained areas. Autonomic and somatic density were calculated as percentage of tissue stained with ßIIIT alone, and with ßIIIT and MBP respectively. Statistical comparisons were made using nonparametric Friedman tests. RESULTS: Six cadavers, aged 22-73, were examined. Overall, autonomic nerve density was highest at the midurethral level in the lateral and middle anterior vagina. Somatic density was highest in the external urethral sphincter (midurethra mean 0.15%, SD ±0.11; proximal urethra 0.19%, SD ±0.19). Comparison of annotated sections revealed significant differences in autonomic density among the lateral, medial, and middle vagina at the midurethra level (0.71%, SD ±0.48 vs 0.60%, SD ±0.48 vs 0.70%, SD ±0.63, p=0.03). Autonomic density was greater than somatic density in all sections. CONCLUSIONS: Autonomic and somatic nerves are diffusely distributed throughout the periurethral tissue and anterior vagina, with few significant differences in nerve density among sections analyzed. Minimizing tissue disruption near urethral skeletal muscle critical for urinary continence may prevent adverse postoperative urinary symptoms.

Neuraxial Anesthesia during the COVID-19 Pandemic: Report from a Large Academic Medical Center.

OBJECTIVE: Three primary neuraxial techniques reduce labor pain: epidural, dural puncture epidural (DPE), and combined spinal-epidural (CSE). This study aims to determine whether neuraxial analgesia techniques changed after the onset of the coronavirus disease 2019 (COVID-19) pandemic. Given that a dural puncture confirms neuraxial placement, we hypothesized that DPE was more frequent in women with concerns for COVID-19. STUDY DESIGN: A single-center retrospective cohort study comparing neuraxial analgesia techniques for labor and delivery pain management before and after the onset of the COVID-19 pandemic and in patients with and without SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at a maternity hospital in Dallas, Texas, with a large delivery service. Statistical analyses included the Chi-square test for categorical and Kruskal-Wallis test for nonparametric ordinal comparisons. The Cochran-Mantel-Haenszel test was used to assess the association between neuraxial technique and accidental dural puncture or postdural puncture headache. RESULTS: Of 10,971 patients who received neuraxial analgesia for labor, 5,528 were delivered in 2019 and 5,443 in 2020. Epidural analgesia was the most common neuraxial technique for labor pain in 2019 and 2020. There was no difference in the frequency of neuraxial analgesia techniques or the rates of accidental dural puncture or postdural puncture headaches comparing all deliveries in 2019 to 2020. Despite a significant increase in DPEs relative to epidurals in the SARS-CoV-2-positive group compared with the SARS-CoV-2-negative group in 2020, there was no significant difference in postdural puncture headaches or accidental dural punctures. CONCLUSION: The advantages of a DPE, specifically the ability to confirm epidural placement using a small gauge spinal needle, likely led to an increase in the placement of this neuraxial in SARS-CoV-2-positive patients. There was no effect on the frequency of postdural puncture headaches or accidental dural punctures within the same period. KEY POINTS: · Epidural analgesia was the most common neuraxial technique for labor pain management.. · Dural puncture epidural placements increased in SARS-CoV-2-positive patients.. · Rates of postdural puncture headaches and accidental dural puncture after neuraxial placement did not change..

Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair: A Randomized Clinical Trial.

Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897.

Single-Stage Surgical Management of Atrioventricular Septal Defects with Coarctation of the Aorta.

Surgical options for coarctation of aorta (CoA) with atrioventricular septal defect (AVSD) include single-stage repair vs. staged approach with neonatal CoA repair and delayed AVSD repair. The durability of left atrioventricular valve (LAVV) function after neonatal repair is questioned, and the optimal approach remains controversial. Eighteen CoA-AVSD patients who underwent single-stage repair 2005-2015 by a single surgeon were retrospectively analyzed. Fifteen patients had complete and three had partial AVSD. Birth weight was 3.19 kg (2.17-4.08). Age at surgery was 16 days (6-127). One- and ten-year survival were 80% and 69%. Freedom from reintervention was 60% and 40% at one and ten-year respectively. Reinterventions included relief of left ventricular outflow tract obstruction (LVOTO) (n = 4), repair of cleft LAVV (n = 3), and LAVV and aortic valve replacement (n = 1). Freedom from LAVV reintervention was 85.6% and 66% at 1 and 10 years respectively. There were four deaths: two post-operative and two following hospital discharge. Mortality was due to sepsis in three patients, and heart failure related to LVOTO and LAVV insufficiency in one. At 68-month (0.6-144) follow-up the majority had mild or less LAVV regurgitation, and all had normal LV dimension and systolic function. There was no recurrent arch obstruction. Single-stage surgical repair of CoA-AVSD is feasible and reasonable. Survival and freedom from reintervention in our cohort approximate those outcomes of two-stage repair with durable left AV valve function and no recurrent arch obstruction. These patients are frequently syndromic and demonstrate mortality risk from non-cardiac causes. Consideration of a single-staged approach is warranted for appropriate patients with CoA-AVSD.

Cardiac transplantation in adults with congenital heart disease: A single center case series.

BACKGROUND: Adult congenital heart disease (CHD) transplant recipients historically experienced worse survival early after transplantation. We aim to review updated trends in adult CHD transplantation. METHODS: We performed a single center case series of adult cardiac transplants from January 2013 through July 2020. Outcomes of patients with CHD were compared to non-CHD. The primary outcome was overall survival. Secondary outcomes included a variety of post-operative complications. RESULTS: 18/262 (7%) transplants were CHD recipients. CHD patients were younger with median age 41 (32-47) versus 58 (48-65) (P < .001). Fontan circulation for single ventricle physiology was present in 4/18 (22%) of CHD recipients, while 16/18 (89%) had systemic right ventricles. CHD recipients had higher rates of previous cardiovascular operations (94% vs. 51%, P < .001). 9/18 (50%) of CHD patients required reconstructive procedures at the time of transplant. Operative and cardiopulmonary bypass times were longer for the CHD cohort (7.5 h [6.6-8.5] vs. 5.6 h [4.6-7] P < .001) and (197 min [158-240] vs. 130 [105-167] P < .001), respectively. There were no differences in operative complications or survival between CHD and non-CHD recipients. CONCLUSIONS: These data highlight the added technical challenges of performing adult CHD transplants. However, similar outcomes can be achieved as for non-CHD recipients. SUMMARY: Modern advances in palliation of congenital heart defects (CHD) has led to increased survival into adulthood. Many of these patients require heart transplantation as adults. There are limited data on adult CHD transplantation. Historically, these patients have had worse perioperative outcomes with improved long-term survival. We retrospectively analyzed 262 heart transplants at a single center, 18 of which were for adult CHD. Here, we report our series of 18 CHD recipients. We detail the palliative history of all CHD patients and highlight the added technical challenges for each of the 18 patients at transplant. In our analysis, CHD patients had more prior cardiovascular surgeries as well as longer transplant operative and bypass times. Despite this, there were no differences in perioperative and long-term outcomes. We have added patient and institution specific data for transplanting patients with adult CHD. We hope that our experience will add to the growing body of literature on adult CHD transplantation.

Mitral Valve Surgery in the First Year of Life.

Data are limited on outcomes associated with mitral valve surgery in infants. Prior studies report high mortality and increased risk for late cardiac failure particularly for those with mitral stenosis. We sought to evaluate outcomes in patients with mitral stenosis (MS) or regurgitation (MR) who had mitral valvuloplasty or replacement in the first year of life. A retrospective analysis of all patients in a single institution who underwent mitral valvuloplasty or replacement in their first year of life from 2004 to 2016 (n = 25), excluding patients with single ventricle pathology or those undergoing surgery for atrioventricular canal defect, was carried out. Median age and weight at surgery were 76.5 days (range 2-329) and 4.5 kg (range 3.0-10.1), respectively. The primary mitral pathology was MR in 16 and MS in 9 patients. Median follow-up among living patients was 4 years (range 106 days-12.3 years). Overall survival was 96% at 30 days and 87.8% at 1, 5, and 10 years. There were three early deaths (12%), all within 6 weeks of surgery. There were no late deaths. Three patients required valve replacement, 1 of which had a primary mitral valve replacement and died within 30 days of surgery. Re-intervention-free survival (surgical and catheter based) was 83.8%, 73.3%, and 48.9% at 1, 5, and 10 years per Kaplan-Meier estimates. There was no difference in re-intervention-free survival between patients with MR versus MS. No risk factors for death or re-intervention were identified. Mitral valvuloplasty and replacement can be performed in infants under 1 year of age with acceptable survival and need for re-intervention.

Acid retention in chronic kidney disease is inversely related to GFR.

Greater H+ retention in animal models of chronic kidney disease (CKD) mediates faster glomerular filtration rate (GFR) decline and dietary H+ reduction slows eGFR decline in CKD patients with reduced eGFR and H+ retention due to the high acid (H+) diets of developed societies. We examined if H+ retention in CKD is inversely associated with estimated GFR (eGFR) using cross-sectional and longitudinal analysis of individuals with CKD stage 1 (>90 ml·min- 1·1.73 m-2), CKD stage 2 (60-89 ml/min per 1.73 m2), and CKD stage 3 (30-59 ml·min- 1·1.73 m-2) eGFR. H+ retention was assessed using the difference between observed and expected plasma total CO2 2 h after 0.5 meq/kg body wt oral NaHCO3. H+ retention was higher in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.02) at baseline and 5 yr, and was higher in CKD 2 vs. CKD 1 ( P < 0.01) at 10 yr. All groups had lower eGFR at subsequent time points ( P < 0.01) but H+ retention was not different among the three time points for CKD 1. By contrast, eGFR decrease was associated with higher H+ retention in CKD 2 at 5 yr ( P = 0.04) and 10 yr ( P < 0.01) and with higher H+ retention in CKD 3 at 5 yr ( P < 0.01). Yearly eGFR decline rate was faster in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.01). The data show that H+ retention is inversely associated with eGFR, with faster eGFR decline, and support the need for greater dietary H+ reduction therapy for CKD individuals with lower eGFR.

Acid retention with reduced glomerular filtration rate increases urine biomarkers of kidney and bone injury.

Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-ß-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues.

Antibiotic Exposure and Risk for Death or Bronchopulmonary Dysplasia in Very Low Birth Weight Infants.

We assessed the association between antibiotic exposure in the first 2 weeks of life and development of bronchopulmonary dysplasia in a cohort of very low birth weight infants. After controlling for the severity of illness, each additional day of antibiotic therapy was associated with both an increased risk for and severity of bronchopulmonary dysplasia.

Cigarette Smoking Attenuates Kidney Protection by Angiotensin-Converting Enzyme Inhibition in Nondiabetic Chronic Kidney Disease.

BACKGROUND: Cigarette smoking exacerbates the estimated glomerular filtration rate (eGFR) decline in nondiabetic chronic kidney disease (CKD) despite the kidney protection that is achieved by angiotensin converting enzyme inhibition (ACEI). Whether smoking cessation restores ACEI-related kidney protection is not known. METHODS: This 5-year, prospective, prevention trial recruited 108 smokers and 108 nonsmokers with stage-2 nondiabetic CKD with primary hypertension and urine albumin-to-creatinine ratio (Ualb) >200 mg/g. All smokers underwent smoking cessation intervention programs. Blood pressure was reduced in all participants toward achieving a goal of <130 mm Hg with regimens including ACEI. The primary outcome was eGFR change, and secondary outcomes included Ualb and urine levels of angiotensinogen (UATG), a surrogate for kidney angiotensin II (AII) levels, and isoprostane 8-isoprostaglandin F2α (U8-iso), an indicator of oxidative stress. RESULTS: One-year Ualb was lower than baseline in nonsmokers but not in either smoking group, supporting greater ACEI-related kidney protection in nonsmokers than smokers. Higher Ualb at 1 year in continued smokers was associated with higher UATG and higher U8-iso, consistent with smoking-induced AII and increased oxidative stress contributing to less ACEI-related kidney protection in smokers. Baseline eGFR was not different among groups (p = 0.92), but 5-year eGFR was higher in quitters than in continued smokers (62.0 ± 5.4 vs. 52.9 ± 5.6 mL/min/1.73 m2, p < 0.001); this value was lower in quitters than in nonsmokers (64.7 ± 5.6 mL/min/1.73 m2, p = 0.02). CONCLUSIONS: Smoking cessation compared with continued smoking ameliorates eGFR decline in nondiabetic CKD treated with ACEI, possibly by restoring kidney-protective effects of ACEI through reductions in kidney AII and oxidative stress.