Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia.

Dysregulation of human trophoblast invasion and differentiation can result in preeclampsia (PE), a hypertensive disorder of pregnancy with significant morbidity and mortality for mother and offspring. miRNA microarray analysis of RNA from human cytotrophoblasts (CytT), before and after differentiation to syncytiotrophoblast (SynT) in primary culture, revealed that members of miR-515 family-including miR-515-5p, miR-519e-5p, miR-519c-3p, and miR-518f, belonging to the primate- and placenta-specific chromosome 19 miRNA cluster (C19MC)-were significantly down-regulated upon human SynT differentiation. The proto-oncogene, c-MYC, which declines during SynT differentiation, interacted with E-boxes upstream of pri-miR-515-1 and pri-miR-515-2, encoding these mRNAs, to enhance their expression. Predicted targets of miR-515-5p, known to be critical for human SynT differentiation, including hCYP19A1/aromatase P450, glial cells missing 1 (GCM1), frizzled 5 (FZD5), WNT2, Sp1, and estrogen receptor-α (ERα) mRNA, were markedly up-regulated during SynT differentiation. Notably, overexpression of miR-515-5p in cultured primary human trophoblasts impaired SynT differentiation and specifically decreased expression of hCYP19A1, GCM1, and Fzd5, which were validated as its direct targets. Interestingly, miR-515-5p levels were significantly increased in PE placentas, whereas mRNA and protein levels of targets, hCYP19A1, GCM1, and FZD5, were significantly decreased, compared with placentas of normotensive women. Thus, miR-515-5p may serve a key role in human trophoblast differentiation; its aberrant up-regulation may contribute to the pathogenesis of PE.

Association of influenza vaccination on decreased stillbirth rate.

OBJECTIVE: We have previously shown a decrease in the overall stillbirth rate at our institution in women receiving the seasonal influenza vaccine during pregnancy. The goal of this study was to ascertain factors associated with this decrease. STUDY DESIGN: This was a retrospective cohort study examining the stillbirth rate, etiology, autopsy findings, and placental pathology in pregnant women receiving the seasonal trivalent inactive influenza vaccine during five influenza seasons between 2003 and 2008. All stillbirths at our institution are investigated by a committee and an etiology is assigned. Autopsy is offered to all patients and placental evaluation is performed routinely. RESULTS: During the study period, 8,690 pregnant women received the seasonal influenza vaccine antepartum and delivered at our institution. Thirty of these births were complicated by stillbirth as compared with 436 stillbirths in the 76,153 women not vaccinated (0.35 vs. 0.57%, p = 0.006). No association was identified between assigned causes of stillbirth when comparing vaccinated and nonvaccinated women. CONCLUSION: No specific etiology commonly associated with stillbirth was identified to have been affected by maternal antepartum influenza vaccination.

Closed Incision Negative Pressure Therapy in Morbidly Obese Women Undergoing Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of incisional negative pressure wound therapy in the prevention of postoperative wound morbidity in women with class III obesity undergoing cesarean delivery. METHODS: In an open label randomized controlled trial, women admitted for delivery with class III obesity (body mass index 40 or higher) measured within 2 weeks of admission for delivery were offered participation in the study. They were consented either in the outpatient maternal-fetal medicine specialty clinic, during admission to labor and delivery and before a decision to perform cesarean delivery, or in the preoperative area of the hospital before scheduled cesarean delivery. Exclusion criteria included anticoagulation therapy, human immunodeficiency virus infection, and silver or acrylic allergy. Those who ultimately underwent cesarean delivery were randomized to standard surgical dressing or incisional negative pressure wound therapy dressing. The primary outcome was wound morbidity. Preplanned secondary outcomes included characteristics of composite wound morbidity, and hospital, emergency room, and clinic utilization. The sample size estimate required randomization of 440 women to detect a 50% decrease in composite outcome. RESULTS: Between January 1, 2015, and July 31, 2016, 850 women were screened and 677 women with class III obesity were enrolled. Of these, 441 underwent cesarean delivery and were subsequently randomized (219 to standard dressing and 222 to incisional negative pressure wound therapy). The primary outcome, overall composite wound morbidity rate, was 18%. This was not different between the two cohorts (incisional negative pressure wound therapy 17% vs standard dressing 19%, relative risk 0.9 [95% CI 0.5-1.4]). CONCLUSION: Prophylactic incisional negative pressure wound therapy use did not reduce postoperative wound morbidity when compared with a standard surgical dressing in women with class III obesity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02289157.

Complete Placenta Previa: Ultrasound Biometry and Surgical Outcomes.

Objective To evaluate the relationship between surgical outcomes and ultrasound measurement of placental extension beyond the cervical os in women with placenta previa. Study Design This is a retrospective cohort study of singleton pregnancies with placenta previa undergoing third-trimester ultrasound and delivering at our institution from 2002 through 2011. For study purposes, an investigator measured placental extension, defined as the placental distance from the internal os across the placenta continuing out to the lowest placental edge. If morbidly adherent placentation was suspected, women were excluded. Receiver operating characteristic (ROC) curves were developed for pertinent surgical outcomes, and multivariate analysis was performed to determine the placental extension with the best predictive discriminatory zone. Results In total, 157 women had placenta previa, ultrasound, and delivery data: 86 (55%) had a placental extension of <40 mm, and 71 (45%) had a placental extension of ≥40 mm. Women with placental extension of ≥40 mm had increased surgical time, blood loss > 2,000 mL, blood transfusion, and rate of peripartum hysterectomy. After multivariate analysis, only peripartum hysterectomy and surgical time > 90 minutes remained significant, p ≤ 0.05 and p ≤ 0.01, respectively. Conclusion In women with placenta previa, the placental extension ultrasound measurement of ≥40 mm is a predictor of adverse surgical outcomes.

Bleeding complications in pregnancies with low-lying placenta.

OBJECTIVE: To evaluate pregnancy outcomes with low-lying placenta according to the distance from placenta to cervical os. METHODS: Retrospective cohort study of singleton pregnancies with low-lying placenta (placenta edge within 20 mm of internal os on transvaginal sonography) delivered at our hospital from 2002 to 2012, excluding suspected placenta accreta and vasa previa. Vaginal delivery was offered in the absence of another indication for cesarean. Outcomes were stratified according to placenta-os distance ≤10 mm and 11-20 mm. RESULTS: Of 98 pregnancies with low-lying placenta, 41% had placenta-os distance ≤10 mm and 59% placenta-os distance 11-20 mm. Fifty-four percent had a trial of labor. Six (15%) with placenta-os ≤10 mm and 21 (36%) with placenta-os 11-20 mm delivered vaginally, p = 0.02. Bleeding necessitating cesarean occurred in 25%, and postpartum hemorrhage in 43%; neither complication associated with placenta-os distance. Third-trimester bleeding prior to delivery hospitalization was reported in 44% and associated with later bleeding requiring cesarean in 51% versus 4% of those without third-trimester bleeding, p < 0.001. CONCLUSION: Whereas low-lying placenta does not contraindicate labor, we found significant risk for bleeding complications, regardless of the planned mode of delivery. Placenta-os distance did not significantly affect outcomes in our series.

Intrapartum hemorrhage.

Intrapartum hemorrhage is a serious and sometimes life-threatening event. Several etiologies are known and include placental abruption, uterine atony, placenta accreta, and genital tract lacerations. Prompt recognition of blood loss, identification of the source of the hemorrhage, volume resuscitation, including red blood cells and blood products when required, will result in excellent maternal outcomes.

Placenta accreta, increta, and percreta.

Placenta accreta is an abnormal adherence of the placenta to the uterine wall that can lead to significant maternal morbidity and mortality. The incidence of placenta accreta has increased 13-fold since the early 1900s and directly correlates with the increasing cesarean delivery rate. The prenatal diagnosis of placenta accreta by ultrasound along with risk factors including placenta previa and prior cesarean delivery can aid in delivery planning and improved outcomes. Referral to a tertiary care center and the use of a multidisciplinary care team is recommended.