Association of Circulating Extracellular Matrix Components with Central Hemodynamics and Arterial Distensibility of Peripheral Arteries.

BACKGROUND: In addition to neuronal and endothelial regulators of vascular tone, the passive mechanical properties of arteries, determined by the molecular structure of extracellular matrices, are the principle modulators of vascular distensibility. Specifically, the association between collagen type IV (Col IV), a constituent of basement membrane, and arterial compliance remains unclear. METHODS: In 31 healthy adult men, radial applanation tonometry and pulse wave analysis were used to assess aortic augmentation index (AIx), aortic-to-radial pulse pressure amplification (PPAmpl), and time to reflection wave. RESULTS: Plasma Col IV and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) concentrations were correlated with AIx (r = 0.51, p = 0.021 and r = -0.45, p = 0.042, respectively) after adjustment for age and heart rate (HR). Greater matrix metalloproteinase-9 (MMP-9) and TIMP-1 levels were associated with high PPAmpl (r = 0.45 and r = 0.64, respectively) and hence with compliant arteries. Multiple regression analyses revealed that 99% of the variation in PPAmpl was attributable to age, HR, Col IV, TIMP-1, and Col × TIMP-1 interaction (p < 0.001). No relations between tonometric variables and levels of MMP-1, -2, and -3; TIMP-2 and -4; fibronectin; glycosaminoglycans; and hydroxyproline were found. CONCLUSION: High circulating Col IV level indexes were associated with stiffer peripheral arteries whereas increased MMP-9 and TIMP-1 concentrations were associated with more compliant ones.

Assessing the multidisciplinary team approaches to placenta accreta spectrum across five institutions within the University of California fetal Consortium (UCfC).

PURPOSE: To describe the multidisciplinary approaches to placenta accreta spectrum (PAS) across five tertiary care centers that comprise the University of California fetal Consortium (UCfC) and to identify potential best practices. MATERIALS AND METHODS: Retrospective review of all cases of pathologically confirmed invasive placenta delivered from 2009 to 2014 at UCfC. Differences in intraoperative management and outcomes based on prenatal suspicion were compared. Interventions assessed included ureteral stent use, intravascular balloon use, anesthetic type, gynecologic oncology (Gyn Onc) involvement, and cell saver use. Intervention variation by institution was also assessed. Analyses were adjusted for final pathologic diagnosis. Chi-square, Fisher's exact, Student's t-test, and Mann-Whitney's U-test were used as appropriate. Binary logistic regression and multivariable linear regression were used to adjust for confounders. RESULTS: One hundred and fifty-one cases of pathologically confirmed invasive placenta were identified, of which 82% (123) were suspected prenatally. There was no correlation between the degree of invasion on prenatal imaging and use of each intervention. Ureteral stents were placed in 33% (41) of cases and did not reduce GU injury. Intravascular balloons were placed in 29% (36) of cases and were associated with shorter OR time (161 versus 236 min, p < .01) and lower estimated blood loss (EBL) (1800 versus 2500 ml, p < .01). General endotracheal anesthesia (GETA) was used in 70% (86). EBL did not differ between GETA and regional anesthesia. Gyn Onc was involved in 58% (71) of cases and EBL adjusted for final pathology was reduced with their involvement (2200 versus 2250 ml, p = .02) while OR time and intraoperative complications did not differ. Cell saver was used in 20% (24) and was associated with longer OR time (296 versus 200 min, p < .01). Use of cell saver was not associated with a difference in EBL or number of units of packed red cells transfused. All analyses were adjusted for pathologic severity of invasion. CONCLUSIONS: Intravascular interventions such as uterine artery balloons and the inclusion of Gynecologic Oncologists as part of a multidisciplinary approach to treating PAS reduce EBL. Additionally, the placement of intravascular balloons may reduce OR time. No significant differences were seen in outcomes when comparing the use of ureteral stents, general anesthesia, or institutions. A team of experienced operators with a standard approach may be more significant than specific practices.

Maternal and neonatal outcomes among scheduled versus unscheduled deliveries in women with prenatally diagnosed, pathologically proven placenta accreta.

OBJECTIVE: To evaluate maternal and neonatal outcomes among scheduled versus unscheduled deliveries in cases of prenatally diagnosed, pathologically proven placenta accreta. STUDY DESIGN: Retrospective cohort of placenta accreta cases delivered in five University of California hospitals. RESULTS: Of 151 cases of histopathologically proven placenta accreta, 82% were prenatally diagnosed. Sixty-seven percent of women underwent scheduled deliveries and 33% were unscheduled. There were no differences in demographics between groups except a higher rate of antepartum bleeding in the unscheduled delivery group (81 versus 53%; p = .003). Scheduled deliveries were associated with a later gestational age at delivery (34.6 versus 32.6 weeks; p = .001), lower blood loss (2.0 versus 2.5 l; p = .04), higher birth weight (2488 versus 2010 g; p < .001), shorter postpartum length of stay (4 versus 5 d; p = .03) and neonatal length of stay (12 versus 20 d; p = .005). CONCLUSION: Despite a prenatal diagnosis of placenta accreta, 1/3 of these cases require unscheduled delivery, portending poorer maternal and neonatal outcomes.

Association between the Degree of Twin Birthweight Discordance and Perinatal Outcomes.

BACKGROUND: Twin birthweight discordance is associated with adverse outcomes. OBJECTIVE: To determine what degree of twin birthweight discordance is associated with adverse outcomes. STUDY DESIGN: This is a retrospective cohort study of twins with vertex twin A delivered vaginally at 36 to 40 weeks (U.S. Vital Statistics Natality birth certificate registry data 2012-2014). The primary outcome was a composite of neonatal morbidity: 5-minute Apgar < 7, neonatal intensive care unit admission, neonatal mechanical ventilation > 6 hours, neonatal seizure, and/or neonatal transport to a higher level of care. Effect estimates were expressed as incidence rate and adjusted odds ratio (aOR) controlling for confounding using multivariate clustered analysis for between-pair effects, and multilevel random effect generalized estimating equation regressions to account for within-pair effects. We adjusted for sex discordance, breech delivery of the second twin, maternal race/ethnicity, nulliparity, age, marital status, obesity, and socioeconomic status. RESULTS: In comparison to birthweight discordance of ≤20%, aORs with 95% confidence intervals (CIs) by weight discordance of the primary outcome among 27,276 twin deliveries were as follows: 20.01 to 25% (aOR: 1.46 [95% CI: 1.29-1.65]); 25.01 to 30% (aOR: 1.96 [95% CI: 1.68-2.29]); and 30.01 to 60% (aOR: 2.97 [95% CI: 2.52-3.50]). CONCLUSION: Twin birthweight discordance >20% was associated with increased odds of adverse neonatal outcome.

Acceptability and feasibility of serial HIV antibody testing during pregnancy/postpartum and male partner testing in Tororo, Uganda.

Our objective was to determine whether serial HIV testing during pregnancy and the postpartum period as well as male partner testing are acceptable and feasible in Tororo, Uganda. This was a prospective study of pregnant women at the Tororo District Hospital (TDH) Antenatal Clinic. Patients presenting for routine antenatal care were asked to participate in a serial HIV testing integrated into standard antenatal and postpartum/child immunization visits, and to invite their male partners for HIV testing. Serial testing was defined as ≥2 tests during pregnancy and ≥2 tests within 24 weeks postpartum. Of the 214 enrolled women, 80 (37%) completed serial testing, 176 (82%) had ≥2 tests, and 147 (69%) had ≥3 tests during the study period. One hundred eighty-two women (85%) accepted male partner testing, but only 19 men (10%) participated. One woman seroconverted during the study, for a cumulative HIV incidence of 0.5% (1/214). In multivariable logistic regression analysis, longer distance between home and clinic (aOR 0.87 [95% CI 0.79-0.97]) and not knowing household income (aOR 0.30 [95% CI 0.11-0.84]) were predictive of not completing serial testing. Higher level of education was associated with completing serial testing (linear trend p value = 0.05). In conclusion, partial serial HIV testing was highly acceptable and feasible, but completion of serial testing and male partner testing had poor uptake.

The cost-effectiveness of repeat HIV testing during pregnancy in a resource-limited setting.

OBJECTIVE: To estimate the cost-effectiveness of HIV screening strategies for the prevention of perinatal transmission in Uganda, a resource-limited country with high HIV prevalence and incidence. STUDY DESIGN: We designed a decision analytic model from a health care system perspective to assess the vertical transmission rates and cost-effectiveness of 4 different HIV screening strategies in pregnancy: (1) rapid HIV antibody (Ab) test at initial visit (current standard of care), (2) strategy 1 + HIV RNA at initial visit (adds detection of acute HIV), (3) strategy 1 + repeat HIV Ab at delivery (adds detection of incident HIV), and (4) strategy 3 + HIV RNA at delivery (adds detection of acute HIV at delivery). Model estimates were derived from the literature and local sources, and life years saved were discounted at a rate of 3% per year. Based on World Health Organization guidelines, we defined our cost-effectiveness threshold as ≤3 times the gross domestic product per capita, which for Uganda was US$3300 in 2008. RESULTS: Using base case estimates of 10% HIV prevalence among women entering prenatal care and 3% incidence during pregnancy, strategy 3 was incrementally the cost-effective option that led to the greatest total life years. CONCLUSIONS: Repeat rapid HIV Ab testing at the time of labor is a cost-effective strategy even in a resource-limited setting such as Uganda.

Is preeclampsia associated with an increased risk of cesarean delivery if labor is induced?

OBJECTIVE: To determine whether preeclampsia is associated with an increased risk of cesarean delivery if labor is induced. METHODS: This retrospective cohort study of 3505 women >or=24 weeks gestation with singleton pregnancies undergoing labor induction compares cesarean delivery rates between preeclamptics and non-preeclamptics. Multivariable logistic regression analysis was used to control for potential confounders including unfavorable cervix (Bishop score

Pharmacokinetics of single-dose levonorgestrel in adolescents.

PURPOSE: The purpose of this study is to compare the pharmacokinetics of levonorgestrel, a drug used for emergency contraception between female adolescents and adults. METHODS: Twenty-two female subjects, aged 13-16 years, received a single 0.75-mg dose of the drug. Serial blood samples were collected for 72 h and used to measure plasma levonorgestrel concentrations. Previously published data from 16 adults, aged 18-45 years, served as comparison. RESULTS: There was a statistically significant higher total plasma clearance divided by the bioavailability (CL/F) of levonorgestrel in adolescents compared to adults, resulting in lower maximum and average total plasma concentrations. There was a trend for a larger volume of distribution divided by bioavailability (V/F), but there was no significant difference in the half-life of levonorgestrel in adolescents relative to adults (p=.098). CONCLUSION: The differences between adolescents and adults are unlikely to be clinically significant because specific changes in total concentrations suggest that unbound concentrations are probably not affected. Furthermore, empirically high doses of levonorgestrel are given for emergency contraception.