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Objective Cord gas values and Apgar scores, currently used as markers for newborn wellbeing and postpartum complications, provide rough estimates, and their use remains elusive. Circulating cell-free DNA (cfDNA) may better represent newborn status at birth and the effect of parturition on the fetus. This pilot study investigates the association between cord blood (CB) cfDNA and neonatal outcomes. Study Design In a prospective cohort study, cfDNA concentration was measured in immediately following delivery collected CB sera of newborns using our rapid fluorescent assay. Results During the study period, blood samples from umbilical cords of 100 newborns were collected. Vaginal delivery was associated with a higher median CB cfDNA than cesarean delivery (277 [95% confidence interval [CI] 199–377] vs. 100 [95% CI 43–265] ng/mL, p < 0.01). cfDNA levels were significantly associated with gestational age at delivery (rho = 0.308, p = 0.002) and CB base deficit (BD, r = 0.252, p = 0.017). According to maternal and fetal complications, CB cfDNA was elevated in fetuses with category II of heart rate tracing (p < 0.05), with maternal positive vaginal culture (p < 0.01), and with premature rupture of membranes (PROM, p < 0.001). Logistic regression models of CB cfDNA fourth quartiles demostrate a double odds ratio for elevated BD (>3mmol/L) and for worse heart rate tracing category. Conclusion Serum CB cfDNA concentration reflects the newborn's status and hazards with an excellent association with CB BD, fetal heart rate category, and maternal risk factors for infection (positive vaginal culture and PROM). This preliminary observation suggests that cfDNA can serve as a point of care biomarker for newborn status at the time of delivery. Key Points CB cfDNA levels correlated with newborn's BD. CB cfDNA levels reflect parturition stress and inflammation. cfDNA serve as a diagnostic and prediction tool for the identification of newborns at risk for morbidity. [ABSTRACT FROM AUTHOR]

Disseminated Intravascular Coagulation (DIC) is a life-threatening condition. Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is one of the obstetrical syndromes mostly associated with DIC and thus, high rates of fatal complications. There is a lack of information regarding epidemiologic and clinical characteristics of women who developed HELLP syndrome with and without DIC. Additionally, until now, there is no adapted and widely accepted way to diagnose DIC among pregnant women presenting with HELLP syndrome, despite the evident maternal mortality linked to the disease. Objectives: (1) Address the gaps in knowledge regarding the prevalence, epidemiologic and clinical characteristics of women with HELLP syndrome who develop DIC; and (2) determine the risk factors for the development of DIC among women with HELLP syndrome. This was a population-based retrospective cohort study, including all women who delivered at the Soroka University Medical Center between the years 2001–2017. The study population was divided into three groups: (1) comparison group (n = 207,266 deliveries); (2) HELLP syndrome without DIC (n = 320); (3) HELLP syndrome with DIC (n = 21). The diagnosis of DIC was based on the ICD-9 code as recorded in the obstetrical database of the Soroka University Medical Center. The coding is based on the diagnosis made by the attending physician during hospitalization. (1) The rate of HELLP syndrome in the study population was 0.16% (341/207,607), of them 6.16% (21/341) had DIC; (2) among patients with HELLP syndrome, those with DIC had a higher median gravidity and parity; (3) a higher rate of severe maternal morbidity including blood product transfusion, placental abruption, eclampsia, acute renal failure and maternal death was observed in those who had HELLP syndrome and DIC compared to those with HELLP syndrome without DIC and the comparison group (p-value <.001 for comparison among the three groups); (4) among women with HELLP syndrome, those with DIC had a longer median PT difference, higher serum creatinine and lower AST as well as ALT median concentrations than those without DIC; (5) patients with HELLP syndrome and DIC had a higher rate of stillbirth and postpartum death than patients in the other groups (p-value <.001 for comparison among the three groups); and (6) placental abruption was an independent risk factor for the development of DIC in women with HELLP syndrome (p-value <.001). (1) Among women with HELLP syndrome, those who developed DIC had a higher rate of maternal and neonatal morbidity and mortality than those without DIC; and (2) placental abruption, but not abnormal liver function, was an independent risk factor for the development of DIC in women with HELLP syndrome. [ABSTRACT FROM AUTHOR]

Nonovert disseminated intravascular coagulation (DIC) is a subclinical hemostatic dysfunction that has not yet reached the decompensation stage. The detection of pregnant patients at this stage may assist in the identification of those who will develop severe obstetrical hemorrhage, as it is one of the leading causes for preventable maternal mortality. Currently, nonovert DIC is diagnosed by a scoring system based on nonpregnant patients, originally generated by the International Society on Thrombosis and Hemostasis (ISTH), which does not address the physiologic changes of the hemostatic system during pregnancy. (1) To develop a pregnancy-specific nonovert DIC score, (2) to determine the diagnostic performance of this score in detecting women at risk for obstetrical hemorrhage requiring blood product transfusion, and (3) to compare it to the existing ISTH nonovert DIC score. This retrospective study has longitudinal and cross-sectional components and includes three steps: (1) characterization of the longitudinal changes in the components of modified ISTH nonovert DIC scores, including these parameters – fibrinogen, antithrombin III, protein C, prothrombin time (PT), platelets, thrombin-antithrombin (TAT) complex, and D-dimer – during gestation in a group of normal pregnancies (n = 50); (2) development of a pregnancy-specific nonovert DIC score in a cross-sectional design of high-risk (n = 152) and control (n = 50) pregnancies, based on the predictive performance of each analyte for the detection of women at risk for obstetrical hemorrhage requiring blood product transfusion and a logistic regression model; and (3) comparison between the diagnostic performance of the pregnancy-specific nonovert DIC score and the modified ISTH nonovert DIC score to detect, upon admission, women who are at increased risk for subsequent development of obstetrical hemorrhage requiring blood product transfusion. (1) The study cohort included 202 patients, of which 21 (10%) had obstetrical hemorrhage that required blood product transfusion and were considered to have nonovert DIC; (2) using the nonpregnant ISTH nonovert DIC score, 92% of the patients had a D-dimer concentration above the 0.5 mg/L threshold, and only 2% were identified to have a low fibrinogen concentration (<100 mg/dL); thus, this scoring system was unable to identify any of the patients with nonovert DIC based on the suggested cutoff of a score of ≥5; (3) the parameters included in the pregnancy-specific nonovert DIC score were selected based on their contribution to the performance of the model for the prediction of women at risk for obstetrical hemorrhage requiring blood product transfusion; as a result, we excluded the PT difference parameter from the score and the TAT complex concentration was added; and (4) a pregnancy-specific nonovert DIC score of ≥3 had a sensitivity of 71.4% and a specificity of 77.9% to identify patients at risk for obstetrical hemorrhage requiring blood product transfusion. We propose (1) a pregnancy-specific nonovert DIC score adjusted for the physiologic changes in the hemostatic system during gestation; and (2) that the pregnancy-specific nonovert DIC score can be a useful tool for the identification of patients at risk for obstetrical hemorrhage requiring blood product transfusion. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether previously established mRNA signatures are predictive of early preeclampsia when evaluated by maternal cellular transcriptome analysis in samples collected before clinical manifestation.Materials and Methods: We profiled gene expression at exon-level resolution in whole blood samples collected longitudinally from 49 women with normal pregnancy (controls) and 13 with early preeclampsia (delivery <34 weeks of gestation). After preprocessing and removal of gestational age-related trends in gene expression, data were converted into Z-scores based on the mean and standard deviation among controls for six gestational-age intervals. The average Z-scores of mRNAs in each previously established signature considered herein were compared between cases and controls at 9-11, 11-17, 17-22, 22-28, 28-32, and 32-34 weeks of gestation.Results: (1) Average expression of the 16-gene untargeted cellular mRNA signature was higher in women diagnosed with early preeclampsia at 32-34 weeks of gestation, yet more importantly, also prior to diagnosis at 28-32 weeks and 22-28 weeks of gestation, compared to controls (all, p < .05). (2) A combination of four genes from this signature, including a long non-protein coding RNA [H19 imprinted maternally expressed transcript (H19)], fibronectin 1 (FN1), tubulin beta-6 class V (TUBB6), and formyl peptide receptor 3 (FPR3) had a sensitivity of 0.85 (0.55-0.98) and a specificity of 0.92 (0.8-0.98) for prediction of early preeclampsia at 22-28 weeks of gestation. (3) H19, FN1, and TUBB6 were increased in women with early preeclampsia as early as 11-17 weeks of gestation (all, p < .05). (4) After diagnosis at 32-34 weeks, but also prior to diagnosis at 11-17 weeks, women destined to have early preeclampsia showed a coordinated increase in whole blood expression of several single-cell placental signatures, including the 20-gene signature of extravillous trophoblast (all, p < .05). (5) A combination of three mRNAs from the extravillous trophoblast signature (MMP11, SLC6A2, and IL18BP) predicted early preeclampsia at 11-17 weeks of gestation with a sensitivity of 0.83 (0.52-0.98) and specificity of 0.94 (0.79-0.99).Conclusions: Circulating early transcriptomic markers for preeclampsia can be found either by untargeted profiling of the cellular transcriptome or by focusing on placental cell-specific mRNAs. The untargeted cellular mRNA signature was consistently increased in early preeclampsia after 22 weeks of gestation, and individual mRNAs of this signature were significantly increased as early as 11-17 weeks of gestation. Several single-cell placental signatures predicted future development of the disease at 11-17 weeks and were also increased in women already diagnosed at 32-34 weeks of gestation. [ABSTRACT FROM AUTHOR]

Objective: In the last few decades, attention has been focused on morbidity and mortality associated with late preterm delivery (34-36 + 6/7 weeks), accounting for 60-70% of all preterm births. This study is aimed to determine (1) the prevalence of late preterm deliveries (spontaneous and medically indicated) in our population; and (2) the rate of neonatal morbidity and mortality as well as maternal complications associated with the different phenotypes of late preterm deliveries. Study design: This retrospective population-based cohort study, included 96,176 women who had 257,182 deliveries, occurred between 1988 and 2011, allocated into three groups: term (n = 242,286), spontaneous (n = 10,063), and medically indicated (n = 4833) late preterm deliveries. Results: (1) Medically indicated late preterm deliveries were associated with increased maternal morbidity, as well as neonatal morbidity and mortality, in comparison with other study groups (p < .01 for all comparisons); (2) medically indicated late preterm delivery was an independent risk factor for composite neonatal morbidity (low Apgar score at 5', seizures, asphyxia, acidosis) after adjustment for confounding factors (maternal age and ethnicity and neonatal gender) and stratification according to gestational age at delivery; and (3) the proportion of medically indicated late preterm deliveries affected the neonatal mortality rate. Below 35% of all late preterm deliveries, indicated late preterm birth were associated with a reduction in neonatal mortality; however, above this threshold medically indicated late preterm deliveries were associated with an increased risk for neonatal death. Conclusions: (1) Medically indicated late preterm deliveries were independently associated with adverse composite neonatal outcome; and (2) to benefit in term of neonatal outcome from the tool of medically indicated late preterm birth, their proportion should be kept below 35% of all late preterm deliveries, while exceeding this threshold increases the risk of neonatal mortality. [ABSTRACT FROM AUTHOR]

Objectives: To investigate mechanisms of in utero death in normally formed fetuses by measuring amniotic fluid (AF) biomarkers for hypoxia (erythropoietin [EPO]), myocardial damage (cardiac troponin I [cTnI]) and brain injury (glial fibrillary acidic protein [GFAP]), correlated with risk factors for fetal death and placental histopathology. Methods: This retrospective, observational cohort study included intrauterine deaths with transabdominal amniocentesis prior to induction of labor. Women with a normal pregnancy and an indicated amniocentesis at term were randomly selected as controls. AF was assayed for EPO, cTnI and GFAP using commercial immunoassays. Placental histopathology was reviewed, and CD15-immunohistochemistry was used. Analyte concentrations >90th centile for controls were considered "raised". Raised AF EPO, AF cTnI and AF GFAP concentrations were considered evidence of hypoxia, myocardial and brain injury, respectively. Results: There were 60 cases and 60 controls. Hypoxia was present in 88% (53/60), myocardial damage in 70% (42/60) and brain injury in 45% (27/60) of fetal deaths. Hypoxic fetuses had evidence of myocardial injury, brain injury or both in 77% (41/53), 49% (26/53) and 13% (7/53) of cases, respectively. Histopathological evidence for placental dysfunction was found in 74% (43/58) of these cases. Conclusion: Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. Hypoxic myocardial injury was an attributable mechanism of death in 70% of the cases. Non-hypoxic cases may be caused by cardiac arrhythmia secondary to a cardiac conduction defect. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and type of histopathologic lesions in placentas delivered by women with a normal pregnancy outcome. Methods: This retrospective cohort study included placental samples from 944 women with a singleton gestation who delivered at term without obstetrical complications. Placental lesions were classified into the following four categories as defined by the Society for Pediatric Pathology and by our unit: (1) acute placental inflammation, (2) chronic placental inflammation, (3) maternal vascular malperfusion and (4) fetal vascular malperfusion. Results: (1) Seventy-eight percent of the placentas had lesions consistent with inflammatory or vascular lesions; (2) acute inflammatory lesions were the most prevalent, observed in 42.3% of the placentas, but only 1.0% of the lesions were severe; (3) acute inflammatory lesions were more common in the placentas of women with labor than in those without labor; (4) chronic inflammatory lesions of the placenta were present in 29.9%; and (5) maternal and fetal vascular lesions of malperfusion were detected in 35.7% and 19.7%, respectively. Two or more lesions with maternal or fetal vascular features consistent with malperfusion (high-burden lesions) were present in 7.4% and 0.7%, respectively. Conclusion: Most placentas had lesions consistent with inflammatory or vascular lesions, but severe and/or high-burden lesions were infrequent. Mild placental lesions may be interpreted either as acute changes associated with parturition or as representative of a subclinical pathological process (intra-amniotic infection or sterile intra-amniotic inflammation) that did not affect the clinical course of pregnancy. [ABSTRACT FROM AUTHOR]

Midwives and nurses have a key role in monitoring postpartum period. They represent the first line professional figure in quantifying blood loss, initiating early diagnosis of obstetric hemorrhage, and mobilizing a team response, if needed. These actions are crucial in determining maternal outcome in postpartum hemorrhage (PPH). In our review we aimed to: (1) Provide a picture of PPH including its pathophysiology, epidemiology, and associated complications; (2) Discuss diagnosis of this dangerous postpartum event; and, (3) Especially evaluate the efficiency of the employment of visual blood loss estimation as a rapid way to suspect PPH and activate the patient assessment. [ABSTRACT FROM PUBLISHER]

Objectives: The aim of this study was to evaluate the role of cervical length measurement in early third trimester (28–32 weeks) as a predictor of preterm delivery (PTD), in women presenting with preterm parturition. Methods: Cervical length was measured prospectively, in singleton pregnancies at 28–32 weeks with preterm contractions (PTC). A multivariate linear regression model was performed to assess the association between cervical length and gestational age at delivery. Logistic regression analysis with PTD before 34 and 37 weeks of gestation as the outcome variable was performed to control for confounders. Results: Fifty-six women were included, mean gestational week at presentation and at delivery were 29.88 ± 1.13 and 37.05 ± 2.86, respectively. There was a direct association between short cervical length at admission and gestational week at delivery (p = 0.027). This association remained significant even after controlling for confounders. Short cervical length was significantly associated with PTD before 34 (p = 0.045) or 37 (p = 0.046) weeks of gestation. Conclusions: Third trimester cervical length measurement in patients with PTC is associated with gestational week at delivery, as well as PTD prior to 34 and 37 weeks of gestation. Therefore, examining cervical length is clinically valuable and probably cost-effective during early third trimester. [ABSTRACT FROM PUBLISHER]

Objective: The rate of placenta accreta, a life threatening condition, is constantly increasing, mainly due to the rise in the rates of cesarean sections. This study is aimed to determine the effect of a history of placenta accreta on subsequent pregnancies., Study Design: A population based retrospective cohort study was designed, including all women who delivered at our medical center during the study period. The study population was divided into two groups including pregnancies with: (1) a history of placenta accreta (n=514); and (2) control group without placenta accreta (n=239,126)., Results: (1) A history of placenta accreta is an independent risk factor for postpartum hemorrhage (adjusted OR 4.1, 95% CI 1.5-11.5) as were placenta accreta (adjusted OR 22.0, 95% CI 14.0-36.0) and placenta previa (adjusted OR 7.6, 95% CI 4.4-13.2) in the current pregnancy, and a prior cesarean section (adjusted OR 1.7, 95% CI 1.3-2.2); (2) in addition, placenta accreta in a previous pregnancy is associated with a reduced rate of mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51, 95% CI 0.26-0.98); (3) however, in spite of the higher rate of neonatal deaths in the study group, a history of placenta accreta was not an independent risk factor for total perinatal mortality (adjusted OR 1.0, 95% CI 0.5-1.9) after adjusting for confounders., Conclusion: A history of placenta accreta is an independent risk factor for postpartum hemorrhage. This should be taken into account in order to ensure a safety pregnancy and delivery of these patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)