Alison Wortman

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.

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

Significance Preeclampsia, a hypertensive disorder of pregnancy and leading cause of maternal and neonatal morbidity and mortality, is associated with defective placental implantation and vascularization. Herein, we characterized regulation and function of miR-515-5p, which belongs to the primate- and placenta-specific chromosome 19 miRNA cluster, one of the largest miRNA clusters in humans. We observed that miR-515-5p was markedly downregulated during human syncytiotrophoblast differentiation and upregulated in placentas from preeclamptic women. miR-515-5p overexpression inhibited syncytiotrophoblast differentiation. Important miR-515-5p targets were identified, including hCYP19A1/aromatase, transcription factor glial cells missing 1 and WNT receptor, frizzled 5, which share critical roles in trophoblast differentiation. Thus, miR-515-5p may serve a key role in human trophoblast differentiation and provide a marker and therapeutic target for 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.

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.

Effect of body mass index on maternal morbidity following peripartum hysterectomy

The objective of this study was to estimate the impact of maternal body mass index (BMI) on maternal morbidity following unscheduled peripartum hysterectomy. A retrospective cohort study of consecutive peripartum hysterectomies at our institution from 1988 through 2012; scheduled hysterectomies were excluded. Medical records were reviewed and maternal, foetal and surgical data collected for each subject. Maternal BMI was categorized by the National Institute of Health classifications for overweight and obese. Statistical analyses included evaluation for trend. A total of 360 774 women delivered at Parkland Hospital during the study period with 665 (1.8 per 1000 deliveries) unscheduled peripartum hysterectomies performed. BMI was available for 635 women. Gestational diabetes, chronic hypertension and pregnancy‐related hypertension were significantly higher in all three obesity categories, P = < 0.01. Post‐partum complications, such as venous thrombosis and composite surgical morbidity did not differ among BMI groups. Estimated blood loss and units transfused did not differ across the BMI categories, P = 0.42 and P = 0.38, respectively. Increasing BMI was associated with longer surgical times and more wound infections, P = 0.01. These complications should be considered when approaching a peripartum hysterectomy in patients with obesity.