Andrea Weintraub

Osteopontin deficiency in rat vascular smooth muscle cells is associated with an inability to adhere to collagen and increased apoptosis.

Osteopontin (OPN) is an extracellular matrix protein that has been implicated in vascular smooth muscle cell (VSMC) adhesion. We have previously described the generation of OPN-deficient VSMC that displayed altered adhesion to collagen. We have examined further the causes and consequences of this altered adhesion. OPN-deficiency was associated with a significant reduction in surface expression of α1 and β1 integrins (mean fluorescence intensity α1: OPN-deficient 0.135 ± 0.04 vs. control 0.313 ± 0.05, p < 0.0001; β1: OPN-deficient 0.398 ± 0.09 vs. control 0.570 ± 0.05, p < 0.004). Treatment of normal VSMC with antibody to α1 recapitulated the adhesion defect. OPN-deficient cells without collagen exposure had an apoptotic fraction of 1.9%, which increased to 95.7% after 24 hours exposure to collagen. Exogenous OPN added to cultures within 15 minutes of plating restored normal cell adhesion, but did not prevent cells from undergoing apoptosis. Normal VSMC had no detectable apoptosis after 24 hours incubation in suspension, whereas OPN-deficient cells had an apoptotic fraction of 37.5% when incubated in suspension under the same conditions. The data suggest that OPN-deficient VSMC have two distinct abnormalities: an α1β1-mediated inability to adhere normally to collagen and an increased propensity for apoptosis.

Antibiotic use in newborns with transient tachypnea of the newborn.

Background: Initiation of empiric antibiotic treatment for possible early-onset sepsis is recommended for late preterm and term neonates with respiratory distress. There is no evidence base to this approach. Objectives: To determine the incidence of adverse infectious events in neonates with transient tachypnea of the newborn (TTN) managed with a risk-factor-based restrictive antibiotic use policy. Methods: This is a single institution retrospective cohort study of neonates with primary diagnosis of TTN between 2004 and 2010. The relationship between antibiotic exposure and infectious outcomes during the neonatal hospitalization was evaluated. An infectious outcome was defined as pneumonia, bacteremia, clinical sepsis, or death. Analysis included t test, χ2 test, and analysis of variance as appropriate. Results: 745 neonates with TTN met inclusion criteria. None of the 494 antibiotic-naive infants, and 212 of the 251 antibiotic-exposed infants had identifiable risk factors for sepsis. No infectious outcomes occurred in infants who did not receive antibiotics. Eight neonates with TTN received full antibiotic treatment for early-onset sepsis. Each was appropriately identified for early receipt of antibiotics based on historical or clinical risk factors for early-onset sepsis. Conclusions: This study suggests that empiric postnatal antibiotic treatment may not be warranted for late preterm and term infants with TTN in the absence of specific infectious risk factors.

Neonatal Care of Infants with Head and Neck Anomalies

This article reviews the most common serious head and neck congenital anomalies and traumatic injuries that present at or around the time of birth from the perspective of neonatal caregivers. The focus is on the steps necessary to manage these infants in the delivery room and during the first days of life. An organized multidisciplinary team approach is critical to success.

Maternal clinical disease characteristics and maternal and neonatal outcomes in twin and singleton pregnancies with severe preeclampsia

OBJECTIVE Based on anecdotal observations, there is concern that severe preeclampsia leads to greater morbidity and mortality for mothers and neonates of twin pregnancies than for mothers and neonates of singleton pregnancies. Because few studies have been done, this study compared maternal disease characteristics and maternal/neonatal clinical outcomes of twin and singleton pregnancies complicated by severe preeclampsia. STUDY DESIGN An historical cohort study of patients hospitalized at the Mount Sinai Hospital in New York City, NY, USA, from 2006 to 2010, compared 63 twin and 339 singleton pregnancies complicated by severe preeclampsia via chart review. Women were analyzed in two groups: hospitalized ≤34 weeks gestational age (GA) and hospitalized >34 weeks GA. Univariable analysis (using Chi-square test, Fishers Exact test, Students t-test, or Wilcoxon Rank-Sum test, as appropriate) then multivariable analysis (using multivariable linear regression or multivariable logistic regression, as appropriate) compared maternal disease characteristics and maternal/neonatal clinical outcomes in twin and singleton pregnancies. RESULTS Women with twins were older [mean age 34.9 years (standard deviation (SD) 7.9 years) vs. 29.4 years (SD 7.4 years), P-value<.001] and women with singletons had a higher prevalence of chronic hypertension (21% vs. 8%, P=.02) and higher prevalence of history of preeclampsia (13% vs. 2%, P=.006). Women with twins were admitted for severe preeclampsia at an earlier gestational age (GA) [median twin 34.9 weeks GA (interquartile range, IQR, 32.7, 36.1) vs. median singleton 37.1 weeks GA (IQR 35.0, 38.9), P<.001]. Among women presenting ≤34 weeks GA (27 twins; 108 singletons), women with singletons had a higher mean systolic blood pressure (BP) (181.1 vs. 163.5, P<.001), higher mean diastolic BP (108.4 vs. 100.1, P=.002), and higher prevalence of headache (56% vs. 30%, P=.02). Among women presenting >34 weeks GA (36 twins; 231 singletons), women with singletons had a higher prevalence of headache (54% vs. 28%, P=.004). CONCLUSION Mothers and neonates of twin pregnancies complicated by severe preeclampsia do not appear to have greater morbidity and mortality compared to mothers and neonates of singleton pregnancies complicated by severe preeclampsia.

Group B Streptococcus Exposure and Self-Limited Respiratory Distress in Late Preterm and Term Neonates

Background: Self-limited respiratory distress is a common neonatal respiratory morbidity for which effective treatments are lacking. Supportive care with non-invasive respiratory support is the norm. Animal models suggest that intrapartum exposure to group B Streptococcus (GBS) may cause mild pulmonary hypertension in the neonate, resulting in self-resolving respiratory distress. Treatments for pulmonary hypertension are currently not provided to neonates with self-limited respiratory distress empirically. Objectives: This study examines the hypothesis that the incidence and severity of self-limited respiratory distress are altered by intrapartum exposure to GBS and antibiotic prophylaxis (IAP) in a human population. Methods: This is a 10-year single-center cohort study of retrospective data of late preterm and term neonates diagnosed with self-limited respiratory distress. Multiple logistic models were fitted to examine associations between exposure to GBS and IAP, and markers of self-limited respiratory distress severity. Additional linear regression models were fitted to examine the association between exposure to GBS and IAP, and duration of respiratory support for self-limited respiratory distress. Finally, crude and gestational age-adjusted incidence of self-limited respiratory distress among GBS-exposed and -unexposed infants, as well as the odds of self-limited respiratory distress based on GBS exposure were calculated. Results: 584 neonates met study criteria. Neither GBS exposure nor IAP exposure was associated with severity of self-limited respiratory distress in multiple models. Crude and adjusted incidence of self-limited respiratory distress among neonates did not differ by GBS exposure history. Conclusions: Although animal studies indicate that GBS-mediated pulmonary hypertension may contribute to self-limited respiratory distress, neither exposure to GBS nor IAP was associated with an increased severity or incidence of self-limited respiratory distress in our human study population. Treatments for pulmonary hypertension are unlikely to speed symptom resolution for patients with self-limited respiratory distress.

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.

FAILURE OF VASCULAR SMOOTH MUSCLE CELL (VSMC) ATTACHMENT TO COLLAGEN MATRICES RESULTS IN PROLONGED GROWTH ARREST • 150

FAILURE OF VASCULAR SMOOTH MUSCLE CELL (VSMC) ATTACHMENT TO COLLAGEN MATRICES RESULTS IN PROLONGED GROWTH ARREST • 150