First-trimester metabolomic prediction of stillbirth.

Background: Stillbirth remains a major problem in both developing and developed countries. Omics evaluation of stillbirth has been highlighted as a top research priority. Objective: To identify new putative first-trimester biomarkers in maternal serum for stillbirth prediction using metabolomics-based approach. Methods: Targeted, nuclear magnetic resonance (NMR) and mass spectrometry (MS), and untargeted liquid chromatography-MS (LC-MS) metabolomic analyses were performed on first-trimester maternal serum obtained from 60 cases that subsequently had a stillbirth and 120 matched controls. Metabolites by themselves or in combination with clinical factors were used to develop logistic regression models for stillbirth prediction. Prediction of stillbirths overall, early (<28 weeks and <32 weeks), those related to growth restriction/placental disorder, and unexplained stillbirths were evaluated. Results: Targeted metabolites including glycine, acetic acid, L-carnitine, creatine, lysoPCaC18:1, PCaeC34:3, and PCaeC44:4 predicted stillbirth overall with an area under the curve [AUC, 95% confidence interval (CI)] = 0.707 (0.628-0.785). When combined with clinical predictors the AUC value increased to 0.740 (0.667-0.812). First-trimester targeted metabolites also significantly predicted early, unexplained, and placental-related stillbirths. Untargeted LC-MS features combined with other clinical predictors achieved an AUC (95%CI) = 0.860 (0.793-0.927) for the prediction of stillbirths overall. We found novel preliminary evidence that, verruculotoxin, a toxin produced by common household molds, might be linked to stillbirth. Conclusions: We have identified novel biomarkers for stillbirth using metabolomics and demonstrated the feasibility of first-trimester prediction.

Using a multifaceted quality improvement initiative to reverse the rising trend of cesarean births.

PURPOSE: National efforts exist to safely reduce the rate of cesarean delivery, a major source of increased morbidity and healthcare costs. This is a report of a quality improvement study targeting reduction of primary cesarean deliveries. MATERIALS AND METHODS: From March 2014 to March 2016, interventions included a nested case-control review of local risk factors, provider and patient education, multidisciplinary reviews based on published guidelines with feedback, provider report cards, commitment to labor duration guidelines, and a focus on natural labor. Primary outcomes were the total primary singleton vertex and the nulliparous term singleton vertex (NTSV) cesarean delivery rates. Secondary outcome measures were postpartum hemorrhage, chorioamnionitis, perineal laceration, operative delivery, neonatal intensive care unit (NICU) admission, stillbirth, and neonatal mortality. Statistical process control charts identified significant temporal trends. RESULTS: Control chart analysis demonstrated that the institutional cesarean delivery rate was due to culture and not "outlier" obstetricians. The primary singleton vertex cesarean rate decreased from 23.4% to 14.1% and the NTSV rate decreased from 34.5% to 19.2% (both p < .0001). There was a decrease in NICU admission but no significant changes in postpartum hemorrhage, chorioamnionitis, stillbirth, or neonatal mortality. CONCLUSIONS: Structured quality improvement initiatives may decrease primary cesarean deliveries without increasing maternal or perinatal morbidity.

Vasa previa: clinical presentations, outcomes, and implications for management.

OBJECTIVE: To review experience with diagnosis, clinical associations, and outcomes of vasa previa in a single institution. METHODS: This was a retrospective review of all identified vasa previa cases from January 1 1990, to June 30, 2010. RESULTS: Sixty cases of vasa previa were identified (53 singletons, seven twins); 56 cases were diagnosed before delivery. An abnormal cord insertion or abnormal placental location was present in 55 cases. Missed diagnoses were attributed to technical and observer factors. Preterm bleeding was encountered in 25 (42%) case group participants. Seven case group participants required an emergent delivery, with significant neonatal morbidity and mortality. Twin pregnancies had a significantly earlier median age at delivery of 32 weeks of gestation compared with 35 weeks of gestations in singletons (P=.01). The seven twin pregnancies had a 28.6% emergent preterm delivery rate, whereas singletons had a 4.1% rate (P=.07). In 14 case group participants, the membranous fetal vessel was located in the lower uterus and not directly over the cervix. The vessel location was not related to the risk of emergent delivery. CONCLUSION: Transvaginal ultrasound scans of at-risk patients can identify most cases of vasa previa. Preterm bleeding does not usually require immediate delivery. The rate of emergent preterm delivery was low in singleton pregnancies. Twins were delivered, on average, 3 weeks earlier than singletons. LEVEL OF EVIDENCE: III.

Asymptomatic uterine rupture of a cornual pregnancy in the third trimester: a case report.

BACKGROUND: Reports of cornual pregnancy persisting until fetal viability and of ultrasound diagnosis of asymptomatic uterine rupture are rare. CASE: A 24-year-old woman, gravida 6, para 5, presented for initial ultrasound evaluation at 28 5/7 weeks' gestation after registering late for prenatal care. Her history included 2 prior cesarean deliveries. Obstetric ultrasound evaluation revealed a clinically silent uterine rupture with a live fetus. The site of rupture was suspected to be the prior uterine scar. After completion of a course of antenatal corticosteroids, the patient underwent exploratory laparotomy, abdominal delivery of a live, male neonate, hysterectomy and appendectomy. The patient experienced an unremarkable postoperative course and was discharged on postoperative day 4. The infant was discharged on hospital day 83 with chronic lung disease, stage 1 retinopathy of prematurity, atrial septal defect and a right clubfoot; there were no additional findings at the 4-month follow-up. Pathologic examination demonstrated cornual implantation with subsequent uterine rupture. CONCLUSION: This case demonstrates the importance of maintaining a suspicion for ectopic pregnancy at advanced gestational ages and for uterine rupture even in the absence of symptoms. The case also illustrates that fetal survival can occur in cornual pregnancy.

Venous thromboembolism during pregnancy. Clinical suspicion warrants evaluation.

OBJECTIVE: To determine the incidence, signs, symptoms and clinical outcomes of venous thromboembolism (VTE) during pregnancy. STUDY DESIGN: A retrospective review was conducted from 1997 to 2001 including women with a diagnosis or suspicion of VTE during pregnancy. Demographics and clinical characteristics of patients with a suspicion for VTE were reviewed. RESULTS: Of 70 patients assessed for evidence of a VTE, 25.7% (n = 18) had confirmatory diagnostic testing. There was no difference in the clinical signs or symptoms between groups with a pulmonary embolism (PE) compared to those without a PE. For those patients with negative diagnostic testing (n = 52), an alternative diagnosis was confirmed in 55.8%. Of the patients with positive diagnostic testing, 30% had a concurrent condition contributing to their pulmonary symptoms. CONCLUSION: Lack of definitive signs and symptoms of thromboembolic disease during pregnancy warrants complete evaluation of patients clinically suspected of having VTE.

Cesarean delivery rates at the threshold of viability.

OBJECTIVE: The purpose of this study was to assess whether the treatment of deliveries at the traditional threshold of viability has become more interventional since the publication of higher survival rates. STUDY DESIGN: State vital statistic data from 1995 to 2000 were reviewed to identify deliveries at 22 to 25 weeks of gestation with a birth weight of <1 kg. Demographic data and frequency of cesarean delivery, antepartum bleeding, breech presentation, fetal distress, and cord prolapse were recorded. The cesarean delivery rate and the neonatal mortality rate were calculated for each year. Linear regression for cesarean delivery rate versus year and for neonatal mortality rate versus year were performed at each gestational age. RESULTS: Of 2924 births that met the study criteria, 1005 births (34.4%) were by cesarean delivery. The cesarean delivery rate at 23 weeks rose from 15.9% in 1995 to 28.2% in 2000 (P =.023). Demographic/obstetric factors did not vary with year of delivery. The neonatal mortality rate remained unchanged. CONCLUSION: These data suggest an increasingly aggressive approach to deliveries at the threshold of viability, beginning at 23 weeks of gestation.

The ninety-fifth percentile for growth discordance predicts complications of twin pregnancy.

OBJECTIVE: Our purpose was to define twin growth discordance on the basis of perinatal outcome. STUDY DESIGN: Twins delivered at >23 weeks' gestation between 1995 and 2000 were identified by use of our computerized perinatal database. Birth weight (BW), chorionicity, and the following outcomes were recorded: cesarean delivery for nonreassuring fetal status (NRFS), umbilical artery (UA) pH, 5-minute Apgar score, neonatal intensive care unit (NICU) admission, and stillbirth. Discordance was calculated as 100 x(Larger BW - Smaller BW)/Larger BW. The distribution of discordance values for the study population was determined. Outcomes were compared for twins with and without discordance at thresholds defined by population percentile. RESULTS: The mean discordance for 346 twins was 11.4% +/- 10.5%. The 75th percentile was 16% discordance, the 90th was 23%, and the 95th was 31%. Discordance was independently associated with outcomes. The 95th percentile was the threshold most predictive of cesarean section NRFS, UA pH <7.1, 5-minute Apgar score <7, and NICU admission. CONCLUSION: Defining pathologic discordance as the 95th percentile, or >30% difference, enhances its predictive value.

Relationship between meconium staining and amniotic fluid volume in term pregnancies.

OBJECTIVE: Our purpose was to evaluate the relationship between meconium-stained amniotic fluid (MEC-AF) and amniotic fluid volume (AFV) and their impact on the risk of cesarean delivery for fetal indications in term pregnancies. METHODS: 1,655 live-born singleton gestations delivering at > or = 37 weeks within 7 days of sonographic assessment of the amniotic fluid index (AFI) were studied. AFI was categorized as: oligohydramnios (< or = 5.0 cm); decreased (5.1-8.0 cm); normal (8.1-18.0 cm); increased (18.1-23.9 cm), and polyhydramnios (> or = 24.0 cm). Frequencies of MEC-AF for each AFV category were stratified by gestational age (GA) and rates of cesarean delivery for fetal indications compared between patients with clear amniotic fluid and those with MEC-AF. Stepwise logistic regression analyses were performed for determinants of MEC-AF and the need for cesarean delivery for fetal indications. RESULTS: The frequency of MEC-AF at birth in term pregnancies was not related to AFV: oligohydramnios (16.7%); decreased (16.7%); normal (20.1%); increased (24.4%), and polyhydramnios (22.1%). The only factor associated with the occurrence of MEC-AF was increasing GA at delivery (p < 0.01). Both MEC-AF (p < 0.02) and decreasing neonatal ponderal index (p < 0.02) were independently associated with cesarean delivery for fetal distress. CONCLUSIONS: MEC-AF does not appear to be related to AFV in term pregnancies, and its presence increases the risk of cesarean delivery for fetal distress independent of AFV and neonatal ponderal index.