449: Alcohol exposure in pregnancy affects phosphorylation of the JNK and p38 cell signaling pathways

of the JNK and p38 cell signaling pathways Robin Roberson, Thea Kuddo, Daniel Abebe, Catherine Spong NICHD NIH, UPDN DIR, Bethesda, MD OBJECTIVE: Prenatal alcohol affects 1 in 100 births in the United States resulting in neurodevelopmental and learning abnormalities. Development of the nervous system, including myelination and differentiation, are dependent on soluble and membrane bound receptors. Alterations in these may underlie abnormal development due to inutero alcohol exposure. Prenatal therapy with neuropeptides (NAP SAL) prevents some of the developmental and behavioral abnormalities. The objective of this study was to evaluate the role of alcohol and NAP SAL in cellular signaling pathways. STUDY DESIGN: We used the well characterized Webster mouse model of fetal alcohol syndrome. Pregnancy was identified by vaginal plug and treatment with alcohol (0.03mL/kg IP), alcohol NAP SAL (20 g IP) or control (saline) was administered on gestational day 8. Embryos were harvested after 30 minutes, 60 minutes or 10 days. MAP kinase, SRC and STAT cell signaling pathways were studied using a microsphere-based multiplex immunoassay (Luminex xMAP, Millipore) and normalized to total protein concentration. Statistical analysis included ANOVA with Fishers post hoc for multiple comparisons; P .05 significant. RESULTS: Prenatal alcohol increased phosphorylation of JNK in the embryo at 30 and 60min compared with controls (both P 0.01). Pretreatment with NAP SAL returned levels to control at 60min (Figure). Similarly alcohol increased phosphorylation of p38 at 30min and NAP SAL returned levels to control. These findings persisted at 10 days. No differences were found in the phosphorylation of ERK. The levels at these timepoints were undetectable for the SRC and STAT pathways. CONCLUSION: Phosphorylation of the JNK and p38 cell signaling pathways are affected by alcohol exposure in pregnancy. Targeting cell signaling pathways, such as with NAP SAL, should have a significant impact on prevention of alcohol-induced abnormalities. 450 Is prematurity associated with neonatal mortality in severe isolated congenital diaphragmatic hernia after fetal tracheal occlusion? Rodrigo Ruano, Marcos Silva, Marcilia Grassi, Maria Ceccon, Uenis Tannuri, Marcelo Zugaib Medical School, University of Sao Paulo, Obstetrics and Gynecology, Sao Paulo, Brazil, Medical School, University of Sao Paulo, Pediatric Surgery, Sao Paulo, Brazil, Medical School, University of Sao Paulo, Neonatology, Sao Paulo, Brazil, Baylor College of Medicine, Obstetrics and Gynecology, Houston, TX OBJECTIVE: Fetoscopic tracheal occlusion (FETO) has been indicated for severe isolated CDH. However, this fetal intervention is related with prematurity (mean gestational age at delivery 35 weeks). In this study, we sought to evaluate if prematurity was associated with mortality after FETO. STUDY DESIGN: This is a prospective cohort study of 35 fetuses with severe isolated CDH that underwent FETO between 26-30 weeks. Preterm birth ( 37 weeks) and extreme preterm birth ( 32 weeks) were analyzed according to neonatal mortality using Fisher exact test. Other variables were also evaluated such as the lung-to-head ratio (LHR) prior to FETO, gestational age at FETO, duration of tracheal occlusion and duration of the procedure using t-test and Man-Whitney U test. RESULTS: Survival rate after FETO was 54.3%. Mean gestational age at delivery was 35.9 2.4 weeks in survivors and 34.9 2.8 weeks in those that died (p 0.28). Preterm birth and extreme preterm birth were not associated with mortality (p 0.51 and p 0.34, respectively). The only variable associated with mortality was the LHR prior to FETO (0.73 0.02 vs. 0.84 0.09; p 0.01). CONCLUSION: In the present cohort of fetuses with severe CDH that underwent FETO, preterm birth and extreme preterm birth were not associated with mortality. The LHR prior to FETO can be used to predict outcome after tracheal occlusion performed between 26-30 weeks.