Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women.

Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.

Anomalous Pulmonary Venous Return: Insights Into Prenatal Detection.

OBJECTIVES: To review all cases of total anomalous pulmonary venous return (TAPVR) or partial anomalous pulmonary venous return (PAPVR) identified prenatally or postnatally at a single institution and to identify factors that may lead to a correct or missed diagnosis in both high- and low-risk fetuses on screening examinations. METHODS: Fetal images from 16 cases of prenatally or postnatally diagnosed T/PAPVR were retrospectively reviewed to analyze factors that influenced interpretations and diagnoses. RESULTS: Sixteen diagnoses of T/PAPVR were made, with a final number of 10 confirmed cases, 1 of which was PAPVR. Ten fetuses with a presumptive diagnosis of T/PAPVR before delivery were at an average gestational age of 24.7 weeks, with 5 cases diagnosed postnatally. None of the diagnoses of isolated TAPVR were made during a screening examination. Twelve of the pregnancies were complicated by complex cardiac defects, including 6 with heterotaxy syndromes. Of the 5 abnormal cases identified in the postpartum period, 3 had isolated TAPVR. In the 3 patients with isolated defects, prenatal echocardiography was not performed; the anatomy scan interpretations were confounded by multiple factors. In retrospect, there was no obvious sonographic evidence of TAPVR in these patients; however, color flow Doppler imaging of the pulmonary veins was not performed on any of them. CONCLUSIONS: Although fetal echocardiography has improved the overall detection of TAPVR or PAPVR, this abnormality continues to elude prenatal diagnosis during screening in both low- and high-risk patients. We hypothesize that the use of color flow Doppler imaging in the 4-chamber view may assist in diagnosing TAPVR in screening low-risk patients, especially in those with difficult scans.

Postnatal systemic blood flow in neonates with abnormal fetal umbilical artery Doppler.

Objective. Abnormal umbilical artery Doppler (UAD) studies are associated with poor neonatal outcomes. We sought to determine if postnatal measures of systemic blood flow (SBF), as measured by functional echocardiography (fECHO), could identify which fetuses with abnormal UAD were at the highest risk of adverse outcomes. Study Design. This is a retrospective review of fetuses with abnormal UAD who received fECHO in the first 72 hours of life. Measures of SBF (right ventricular output (RVO) and superior vena cava (SVC) flow) were performed and compared with prenatal variables and postnatal outcomes. Result. 63 subjects had abnormal UAD, 20 of which also had fECHO. Six subjects had abnormal flow. Gestational age at delivery was similar between the two groups. Those with abnormal SBF had fewer days of abnormal UAD prior to delivery and developed RDS (P < 0.001). Conclusion. Postnatal measures of SBF were associated with poor postnatal outcomes in fetuses with abnormal UAD. Future studies incorporating antenatal measures of SBF may help obstetricians determine which pregnancies complicated by UAD are likely to have postnatal morbidity.

Correlation between spontaneous preterm birth and mid-trimester maternal serum estriol.

OBJECTIVE: Elevated third trimester salivary estriol levels have been associated with preterm birth. We evaluated whether maternal estriol concentrations from second trimester serum correlated with preterm delivery. METHODS: A retrospective cohort study of 7767 patients evaluated with second trimester aneuploidy screening. Unconjugated serum estriol was measured by immunoassay, expressed as multiples of the median (MoM) for gestational age and evaluated for association with preterm (<37 week) birth. RESULTS: Elevated maternal serum estriol was significantly associated with preterm birth (1.15 MoM versus 1.03 MoM for delivery at term, OR 1.69 CI 1.41 to 2.02). 9.95% of spontaneously laboring patients <34 weeks had estriol MoM > 2, as opposed to 6.23% of >34 week deliveries (p = 0.031). There was a direct correlation between level of estriol concentrations and gestational age at time of delivery. CONCLUSIONS: Elevated second trimester maternal serum unconjugated estriol is independently associated with a higher rate of spontaneous preterm birth.

Bakri balloon effectiveness for postpartum hemorrhage: a "real world experience".

INTRODUCTION: The Bakri balloon has been advocated for management of obstetric hemorrhage, based on several small studies (2-16 patients) where it was over 90% effective. OBJECTIVE: To estimate the effectiveness of the Bakri balloon for treating postpartum hemorrhage (PPH) in clinical practice at academic institutions. METHODS: This is a retrospective cohort study evaluating efficacy of Bakri balloon use in 35 women with PPH, performed as a chart review. Charts were reviewed to determine if balloon placement was deemed a "success" or "failure", as well as to abstract relevant demographic and clinical factors. Failure was defined as need for another form of hemorrhage control. RESULTS: Success rate was 67.57%. Bakri failure was associated with Cesarean section (67% versus 16%, p = 0.031) and predelivery Pitocin (67% versus 28%, p = 0.003) and had more ICU admissions (58% versus 4%, p = 0.0003), transfusions (5.4 red blood cell units versus 1.6, p = 0.007) and hospital days (5.65 versus 3.75, p = 0.011). Reasons for failure were continued bleeding or balloon extrusion. CONCLUSION: Our results suggest that the Bakri balloon is useful for treating PPH but not as effective as previously published. When balloon use is effective, however, the maternal morbidity is significantly decreased.

Abnormal second-trimester serum analytes are more predictive of preterm preeclampsia.

OBJECTIVE: We sought to determine the association of abnormal second-trimester serum analytes with early preterm preeclampsia. STUDY DESIGN: We conducted a retrospective study of 7767 subjects undergoing second-trimester serum aneuploidy screening. Values of maternal serum α-fetoprotein (AFP), ß-human chorionic gonadotropin (hCG), and inhibin (INH) were calculated as multiples of the median (MoM) and evaluated by gestational age at delivery and occurrence of preeclampsia. RESULTS: Of 459 (6.5%) cases of preeclampsia, 65 (14%) delivered <34 weeks and 394 (86%) delivered >34 weeks. Elevated AFP, hCG, and INH >2 MoM were associated with preeclampsia, and the odds ratio was higher for the development of preeclampsia <34 weeks than >34 weeks (odds ratio, 8.04 vs 2.91 for AFP, 3.6 vs 2 for hCG, and 4.17 vs 3.08 for INH, P < .001 for all). The higher the MoM for each analyte the greater the likelihood of preeclampsia. CONCLUSION: Elevated AFP, hCG, and INH levels >2 MoM are associated with developing early preeclampsia, and the more elevated they are, the higher the likelihood.