Carolyn Salafia

Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses

Objective To identify placental histopathology associated with absent and reversed end-diastolic flow demonstrated by umbilical artery (UA) Doppler velocimetry in fetal growth restriction (FGR). Methods Between January 1989 and June 1995, 64 consecutive, nonanomalous singletons at less than the tenth percentile for birth weight were admitted to the neonatal intensive care unit, with UA Doppler velocimetry obtained within 3 days of delivery; 54 of the 64 (84%) had placental histopathology. Umbilical artery Doppler wave forms were classified as having end-diastolic flow (n = 26), and either absent (n = 20) or reversed end-diastolic flow (n = 8). Blinded review of placental histology scored lesions in categories of intraplacental vaso-occlusion, uteroplacental vascular pathology, chronic inflammation, and coagulation. Results Using cases of FGR with end-diastolic flow present as the control population, we found that absent end-diastolic flow cases had significantly more fetal stem vessels with medial hyperplasia and luminal obliteration, and cases of reversed end-diastolic flow had significantly more poorly vascularized terminal villi, villous stromal hemorrhage, “hemorrhagic endovasculitis,” and abnormally thin-walled fetal stem vessels (each P <.005). Conclusion In FGR, UA Doppler velocity wave forms do not demonstrate a continuum of placental lesions in which reversed end-diastolic flow reflects more severe placental histopathology than absent end-diastolic flow and enddiastolic flow present. As expected, absent end-diastolic flow cases had more occlusive lesions of the intraplacental vasculature. In reversed end-diastolic flow, lesions suggesting vascular remodeling and/or damage by pathologic conditions of intraplacental flow predominated.

Using proteomic analysis of the human amniotic fluid to identify histologic chorioamnionitis.

OBJECTVE: To estimate the relationship between histologic chorioamnionitis and four amniotic fluid proteomic biomarkers characteristic of inflammation (defensins 2 and 1, calgranulins C and A). METHODS: One hundred fifty-eight women with singleton pregnancies had a clinically indicated amniocentesis to rule out inflammation and infection in the context of preterm labor or preterm premature rupture of membranes. A proteomic fingerprint (Mass Restricted score) was generated from amniotic fluid using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The Mass Restricted score ranges from 0 to 4 (none to all four biomarkers present) in direct relationship with severity of intra-amniotic inflammation. Presence or absence of biomarkers was analyzed in relationship to placental pathology. Criteria for severity of histologic chorioamnionitis were 3 stages and 4 grades of inflammation of the amnion, choriodecidua and chorionic plate. RESULTS: The prevalence of histologic chorioamnionitis was 64% (stage I 12%, stage II 16%, and stage III 37%). The Mass Restricted score significantly correlated with stages of histologic chorioamnionitis (r=0.539, P<.001), grades of choriodeciduitis (r=0.465, P<.001), and amnionitis (r=0.536, P<.001). African-American women were overrepresented in the group with severe inflammation (Mass Restricted score 3–4, P=.022). Of the four biomarkers of the Mass Restricted score, calgranulin C had the strongest relationship with presence of stage III chorioamnionitis, independent of race, amniocentesis-to-delivery interval, and gestational age. CONCLUSION: Proteomic analysis of amniotic fluid provides an opportunity for early recognition of histologic chorioamnionitis. This methodology may in the future identify candidates for antenatal therapeutic interventions. LEVEL OF EVIDENCE: II

Gestational Age-Dependent Extravillous Cytotrophoblast Osteopontin Immunolocalization Differentiates Between Normal and Preeclamptic Pregnancies

PROBLEM: Normal placentation requires modulation of proliferative cytotrophoblast to an invasive phenotype. Preeclampsia is characterized by failed cytotrophoblast invasion and arterial remodeling. Osteopontin (OPN) is an extracellular matrix protein implicated in cell adhesion, spreading, and invasion.

Hepatic Histology in Intrauterine Growth Retardation Following Uterine Artery Ligation in the Guinea Pig

Hepatic histology was examined in guinea pig fetuses in which intrauterine growth retardation (IUGR) was induced by unilateral uterine artery ligation and compared with that of control (well-grown) fetuses from uterine horns with intact circulations. From all animals, sections taken from the six lobes of the liver were prepared using hematoxylin and eosin stains. Periodic acid-Schiff and Prussian blue stains (both on fixed samples) and Oil Red O stains on frozen tissues were performed on a subset of samples. Comparisons revealed greater fat content in hepatocytes (P < .05) and decreased total hepatic hematopoiesis (P < .01) in IUGR animals than in controls. No differences in hepatocyte histology among lobes were observed in control animals. IUGR animals had increased fat content and decreased extramedullary hematopoiesis in the lobes receiving the portal circulation (P < .05). These data indicate significant abnormalities of hepatic lipid metabolism in IUGR animals following uterine artery ligation. An unexpected and counterintuitive finding was the decrease in hepatic hematopoiesis in the right side of the liver.

Use of prophylactic misoprostol in reduction of blood loss at vaginal delivery.

INTRODUCTION: The objective of this study was to assess the effect of prophylactic adjunctive rectal administration of misoprostol on reduction of blood loss at vaginal delivery and incidence of postpartum anemia. METHODS: Open-label, randomized prospective trial of 143 term singleton pregnancies, 2011–2013. Exclusion criteria were grand multiparity, multiple gestations, intrauterine fetal demise, preeclampsia, polyhydramnios, third- or fourth-degree laceration, and cesarean delivery. Group A included 73 patients who received 600 micrograms misoprostol per rectum postpartum in addition to conventional management. Group B included 70 patients who received conventional management with oxytocin administration. Primary outcome was reduction in hemoglobin and hematocrit values from admission to 24 hours after delivery. Baseline demographics, clinical characteristics, and results were analyzed using SPSS 20.0 with one-way analysis of variance and &khgr;2 tests. P<.05 was considered significant. RESULTS: The two groups did not differ with respect to age, parity, ethnicity, degree and type of lacerations, episiotomy, epidural analgesia, presence of postpartum hemorrhage, incidence of operative vaginal delivery, mean blood loss at delivery, average birth weight, body mass index, or mean duration of stages 1, 2, or 3 of labor. More patients in group A received augmentation with oxytocin (P=.039), and five patients developed postpartum endometritis compared with none in group B (P=.032). The mean difference in the reduction of hemoglobin concentration (mg/dL) (A=1.08, B=1.20; P=.484) and hematocrit (%) (A=2.91, B=3.31; P=.491) was not significant. In the presence of lacerations, reduction of hemoglobin was significant in group B (1.43 mg/dL, P=.034) compared with group A (1.18 mg/dL, P=.891). CONCLUSION: Adjunctive administration of prophylactic rectal 600 micrograms misoprostol reduces postpartum anemia in patients with perineal lacerations.

Neonatal Outcomes in Preterm Severe Preeclampsia as Compared to Other Etiologies of Prematurity [25K]

INTRODUCTION: To evaluate neonatal outcomes in pregnancies complicated by severe preeclampsia, delivered 24–33 6/7 weeks vs. GA - matched pregnancies with other etiologies of preterm delivery. METHODS: Retrospective case-control study involving patients with expectantly managed severe preeclampsia and patients with other causes of preterm delivery; Queens Hospital Center, 1/2009–10/30/2014. Inclusion criteria (cases): severe preeclampsia, 24 0/7–33 6/7 weeks. Inclusion criteria (controls): non-preeclampsia causes of preterm delivery, 24 0/7–33 6/7 weeks. Exclusion criteria: fetal anomalies, IUFD, HELLP syndrome, eclampsia, multiple gestations. Comparison parameters: baseline demographics, obstetrical history, comorbidities, IUGR, mode of delivery, birth weight, cord pH, Apgar scores, placental histology. Primary outcomes: length of NICU stay. Other outcomes: rates of RDS, neonatal sepsis, IVH, NEC. Continuous variables were analyzed using ANOVA, Mann-Whitney U tests. RESULTS: Cases group 65 patients; controls 165 patients. Mean GA at delivery was similar between groups (29 weeks) Duration of expectant management was similar: 3.8 days cases, 4.8 days controls. Rates of IUGR, SGA, c-section were significantly higher among cases. No significant difference in the rates of IVH, RDS, NEC, neonatal sepsis, death was noted. Length of NICU stay was significantly higher among cases: 34 vs 27 days (P=.024). CONCLUSION: With similar rates of neonatal complication (RDS, IVH, NEC, sepsis, neonatal death), neonates born prior to 33 6/7 weeks, due to severe preeclampsia, require longer NICU stay than neonates delivered preterm due to other etiologies. Severe preterm preeclampsia has no protective effect with respect to neonatal outcomes.

Mechanical Labor Induction Using the Foley Catheter Balloon Compared With the Cook Cervical Balloon [96]

INTRODUCTION: This study was conducted to evaluate the outcomes of induction of labor using the Foley catheter balloon compared with the Cook cervical balloon in singleton gestations undergoing induction of labor resulting from an unfavorable cervix. METHODS: A retrospective case–control study of patients undergoing induction of labor at Queens Hospital Center from January 2013 to December 2013. Inclusion criteria were singleton gestation and intact membranes. Gestational age was greater than or equal to 37 weeks. Exclusion criteria were contraindication to vaginal delivery, multiple gestations, intrauterine fetal demise, rupture of membranes, gestational age below 37 weeks, and fetal structural anomalies. Baseline demographic parameters were collected. The primary outcome was the time interval from initiation of cervical ripening to delivery. The secondary outcomes were rate of cesarean delivery, chorioamnionitis, and neonatal outcomes. Spearmans correlation coefficient, analysis of variance, and &khgr;2 were used for statistical analysis. RESULTS: A total of 172 women met study inclusion criteria. Seven patients had both the Cook cervical balloon and Foley catheter balloon used and were excluded from the study. There were 27 patients in the Foley catheter balloon group and 138 patients in the Cook cervical balloon group. The groups were similar with respect to maternal age, body mass index, gestational age, parity, and racial and ethnic background. There was no difference in Bishop scores between Cook cervical balloon and Foley catheter balloon groups irrespective of parity before cervical ripening: nulliparous patients (P=.064); multiparous patients (P=.26), and after cervical ripening: nulliparous patients (P=.36); multiparous patients (P=.36). With respect to the primary outcome, the time period from initiation of cervical ripening to delivery for the Foley catheter balloon was 1,069.2 minutes compared with 1,700.1 minutes for the Cook cervical balloon (P<.001). All secondary outcomes were similar between the patients receiving the Foley catheter balloon and the Cook cervical balloon. CONCLUSION: In singleton gestations with an unfavorable cervix, the use of the Foley catheter balloon for induction of labor is superior to the Cook cervical balloon with respect to time period from initiation of cervical ripening to delivery.

Baseline Maternal Body Mass Index Compared With Body Mass Index at Delivery as a Predictor of Neonatal Outcomes in Obese Pregnant Women [95]

INTRODUCTION: The study was conducted to analyze whether baseline body mass index (BMI, calculated as weight (kg)/[height (m)]2) at initiation of prenatal care in pregnant women with BMIs greater than 30 affects neonatal outcomes more than pregnancy weight gain or BMI at delivery. METHODS: A retrospective cohort study of 175 singleton pregnancies managed at Queens Hospital Center from January 2013 to December 2013 were included in the study. Inclusion criteria were maternal BMI greater than 30 at initiation of prenatal care (before 16 weeks of gestation), singleton gestation, and delivery during the study period. Exclusion criteria were multiple gestations, fetal anomalies, and gestational and pregestational diabetes. Group A had BMI 30–34.9 (114 patients), group B had BMI 35–39.9 (42 patients), and group C had BMI greater than 40 (19 patients). Groups were analyzed with respect to baseline demographic parameters and neonatal outcomes: birth weight, neonatal intensive care unit (NICU) admission, and length of hospital stay. Spearmans correlation coefficient, analysis of variance, and &khgr;2 were used for statistical analysis. RESULTS: Across the three groups, the neonatal birth weight significantly correlated with maternal weight gain in pregnancy and weight gain at delivery but did not correlate with maternal baseline weight and BMI at initiation of prenatal care (P=.04). The mode of delivery, the rate of NICU admission, and length of stay did not demonstrate any association with either baseline BMI or BMI at delivery across all three groups. CONCLUSION: Maternal BMI at delivery and not baseline BMI at initiation of prenatal care is directly associated with neonatal birth weight in pregnancies complicated by maternal obesity. Neither BMI at initiation of prenatal care nor at the time of delivery is associated with mode of delivery, rate of NICU admission, or neonatal hospital stay.

Effect of Maternal Third-Trimester Body Mass Index on Maternal and Neonatal Outcomes

INTRODUCTION: High maternal prepregnancy body mass index (BMI) has been linked to adverse maternal and neonatal outcomes. Many patients enter prenatal care late and their prepregnancy health status and pregnancy-related weight gain is not available. We examined effects of maternal third-trimester BMI on maternal and neonatal outcomes. METHODS: Retrospective cohort study of all pregnancies delivered at Queens Hospital Center between November 2012 and February 2013. Only patients with at least one third-trimester prenatal care visit at Queens Hospital Center were included. Multiple gestations, intrauterine fetal demise, and known fetal anomalies were excluded. Outcomes of nonobese (BMI less than 30 kg/m2) compared with obese (BMI greater than 30 kg/m2) pregnancies were compared with respect to mode of delivery, rates of shoulder dystocia, maternal morbidity and neonatal weight, ponderal index, and rate of neonatal intensive care unit (NICU) admission. Categorical variables were compared using contingency tables and &khgr;2. Continuous variables were analyzed using analysis of variance and regression models with P<.05 considered significant throughout. RESULTS: Three hundred forty-six consecutive patient charts were reviewed. Two hundred fifty women fit study inclusion criteria. The obese (n=112) and nonobese (n=138) groups were similar with respect to rates of gestational diabetes, chronic hypertension, gestational hypertension, preeclampsia, and shoulder dystocia. However, the rates of cesarean delivery and chorioamnionitis were greater in the obese group (P=.027 and P=.034, respectively). The mean neonatal birth weight (and ponderal index) in the obese group was higher: 3,324 compared with 3,024 g (P<.001), whereas the rate of NICU admission did not differ between groups: 32 in both groups (P=.34). CONCLUSIONS: Maternal third-trimester BMI greater than 30 kg/m2 is associated with higher chorioamnionitis and cesarean delivery rates, higher neonatal birth weight, and ponderal index but not increased NICU admission rate. Larger future studies are necessary to validate these conclusions.

Gestational Age-Dependent Extravillous Cytotrophoblast Osteopontin(OPN) Immunolocalization in the Basal Plate and Uteroplacental Vasculature Differentiates between Normal and Growth-Restricted Fetuses |[dagger]| 261

Human placentation requires modulation of proliferative cytotrophoblasts to an invasive phenotype to create the intervillous space. Preeclampsia is characterized by failed trophoblast invasion and remodeling of the maternal spiral arteries. OPN is a secreted extracellular matrix protein found in many tissues including human trophoblast, and has been implicated in cell adhesion, invasion, spreading, and migration. To investigate gestational age-specific expression of OPN, immunohistochemical staining of post-partum placental tissue from 13 healthy women was performed using a monoclonal antibody against OPN (MPIIIB10-1). OPN protein was localized to the cytoplasm of invasive extravillous trophoblast from 24-28 wks (N=7). After 28 wks (N=6), OPN was undetectable in the extravillous trophoblast, and was not identified in non-invasive intravillous cytotrophoblast and syncytiotrophoblast at any gestational age (N=13). To investigate the role of OPN in uteroplacental vascular pathology, immunohistochemical staining of post-partum placentas from pregnancies complicated by preeclampsia (N=6) or intrauterine growth retardation (N=2) was performed using MPIIIB10-1 and compared to staining of placentas from gestational age-matched controls without pregnancy-induced maternal vascular disease (N=13). In the preecclampsia group, there was prominent proliferation of cytotrophoblast in the basal plate with intense OPN staining, in association with morphologic evidence of compromised uteroplacental perfusion. This staining pattern was identified in all preeclamptic placentas at 24-40 wks. In contrast, the normal and IUGR placentas did not display prominent cytotrophoblast proliferation or evidence of decreased uteroplacental perfusion: OPN staining was limited to the invasive extravillous cytotrophoblast and detected only until 28 wks. The data suggests a role for OPN in trophoblast invasion of the maternal vasculature and extracellular matrix during normal placentation, where OPN may serve as a marker for uteroplacental vascular remodeling in the human fetus. In the preeclamptic pregnancy, extravillous cytotrophoblast continues to express OPN even at advanced gestational ages, which supports the speculation that intervillous fibrin/fibrinoid may be actively involved in the remodeling of the intervillous space. OPN may be critical in this process, the successful maintenance of which may necessary for fetal compensation.