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512: Prenatal inflammation: an important therapeutic target to prevent adverse outcomes?
Poster Session III
Doppler Assessment, Fetus, Prematurity
www.AJOG.org
512 Prenatal inflammation: an important therapeutic target to prevent adverse outcomes? Michal A. Elovitz1, Jamie Bastek1, Anita Weber2, Megan McShea1, Markley Foreman3, Sindhu Srinivas1 1 University of Pennsylvania Perelman School of Medicine, Maternal and Child Research Program; Department of OBGYN, Philadelphia, PA, 2 University of Pennsylvania Perelman School of Medicine, CCEB, Philadelphia, PA, 3University of Pennsylvania Perelman School of Medicine, Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Philadelphia, PA
OBJECTIVE: Prenatal inflammation, as noted by histological (HCA) or clinical chorioamnionitis (CCA), has been considered a risk factor for prematurity and adverse neonatal outcomes. However, prior studies have been limited by their retrospective nature with more recent studies suggesting that only gestational age at delivery, not the intrauterine environment, is the main predictor of neonatal outcome. We sought to assess if prenatal inflammation, as measured by HCA, CCA or maternal temperature ⬎38 (T38), was associated with adverse neonatal outcomes. STUDY DESIGN: A prospective cohort of women with singleton pregnancies and preterm labor was performed. HCA was determined by a pathologist and CCA by provider. The highest maternal temperature within 24 hours prior to delivery was recorded. Gestational age at delivery (GA-DEL) and neonatal outcomes within the first 30 days of life were recorded. Associations between categorical variables were determined usgin chi-square analyses. MVLR was performed to determine the association between prenatal inflammation (CCA, HCA, T38) on adverse neonatal outcomes (a composite and individualFigure). RESULTS: 595 women and their infants were studied. The PTB rate was 40%. Rates of exposures and outcomes are on Table I. 30% of women with T38 did not have a diagnosis of CCA. GA-DEL was associated with COMP; for each increase in gestational age by 1 week, COMP was decreased by 33% (0.61-.72, P⬍0.001). HCA was not associated with COMP. In contrast, CCA and T38 were strongly associated with outcomes (FIG 1). Excluding women with CCA, T38 remained associated with adverse outcome (OR 3.5). CONCLUSION: Prenatal inflammation as measured by both CCA and maternal temperature ⬎38 is strongly associated with adverse neonatal outcomes. Whether HCA is a poor marker of intrauterine inflammation or represents a lower risk inflammatory environment than CCA or T38 requires further investigation. These data support the role of prenatal inflammation in adverse neonatal outcomes. Clinical trials that investigate therapies for these mothers/neonates at increased risk should begin. MOD#21FY08-539
S232
513 Antenatal glucocorticoids and postnatal surfactant treatment partially rescues neonatal lethality and pulmonary immaturity in an ERK3-/- knockout (ko) murine model of intrauterine growth restriction (IUGR) Milenka Cuevas-Guaman1, Elena Sbrana2, Cynthia Shope3, R. Alan Harris4, Stephen Welty5, Sylvain Meloche6, Kjersti Aagaard3 1 Baylor College of Medicine, Department of Pediatrics, Division of Neonatology, Houston, TX, 2The University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX, 3Baylor College of Medicine, Obstetrics&Gynecology, Division of Maternal-Fetal Medicine, Houston, TX, 4 Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, TX, 5Baylor College of Medicine, Pediatrics, Division of Neonatology, Houston, TX, 6Universite de Montreal, Institute de Recherche en Immunologie et Cancrologie, Cellular and Molecular Biology, Quebec, Canada
OBJECTIVE: As previously reported in our Erk3-/- (ko) mouse model, 0.4mg/kg antenatal dexamethasone given on E16.5&17.5 rescued pulmonary immaturity (decreased sacculation and increased type II pneumocyte glycogen; PNAS 106:16710) but did not rescue neonatal lethality. Using high throughput discovery platforms (whole transcriptome RNA shotgun sequencing), we then identified the critical molecular mediators in fetal pulmonary maturation (i.e., corticotropin releasing hormone (CRH) and surfactant B (SPB)). Here we sought to functionally validate these molecular discoveries in a relevant translational model, hypothesizing that neonatal surfactant (Survanta) with antenatal glucocorticoids could enhance neonatal survival. STUDY DESIGN: In a double crossover design, we administered 0.4mg/kg prenatal dexamethasone (dex) or saline at E16.5 and E17.5, alongside phospholipids-enriched surfactant (Survanta) or saline at 50mg/kg via inhalation intubation at birth. Confirmation of pulmo-
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
Doppler Assessment, Fetus, Prematurity
www.AJOG.org
512 Prenatal inflammation: an important therapeutic target to prevent adverse outcomes? Michal A. Elovitz1, Jamie Bastek1, Anita Weber2, Megan McShea1, Markley Foreman3, Sindhu Srinivas1 1 University of Pennsylvania Perelman School of Medicine, Maternal and Child Research Program; Department of OBGYN, Philadelphia, PA, 2 University of Pennsylvania Perelman School of Medicine, CCEB, Philadelphia, PA, 3University of Pennsylvania Perelman School of Medicine, Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Philadelphia, PA
OBJECTIVE: Prenatal inflammation, as noted by histological (HCA) or clinical chorioamnionitis (CCA), has been considered a risk factor for prematurity and adverse neonatal outcomes. However, prior studies have been limited by their retrospective nature with more recent studies suggesting that only gestational age at delivery, not the intrauterine environment, is the main predictor of neonatal outcome. We sought to assess if prenatal inflammation, as measured by HCA, CCA or maternal temperature ⬎38 (T38), was associated with adverse neonatal outcomes. STUDY DESIGN: A prospective cohort of women with singleton pregnancies and preterm labor was performed. HCA was determined by a pathologist and CCA by provider. The highest maternal temperature within 24 hours prior to delivery was recorded. Gestational age at delivery (GA-DEL) and neonatal outcomes within the first 30 days of life were recorded. Associations between categorical variables were determined usgin chi-square analyses. MVLR was performed to determine the association between prenatal inflammation (CCA, HCA, T38) on adverse neonatal outcomes (a composite and individualFigure). RESULTS: 595 women and their infants were studied. The PTB rate was 40%. Rates of exposures and outcomes are on Table I. 30% of women with T38 did not have a diagnosis of CCA. GA-DEL was associated with COMP; for each increase in gestational age by 1 week, COMP was decreased by 33% (0.61-.72, P⬍0.001). HCA was not associated with COMP. In contrast, CCA and T38 were strongly associated with outcomes (FIG 1). Excluding women with CCA, T38 remained associated with adverse outcome (OR 3.5). CONCLUSION: Prenatal inflammation as measured by both CCA and maternal temperature ⬎38 is strongly associated with adverse neonatal outcomes. Whether HCA is a poor marker of intrauterine inflammation or represents a lower risk inflammatory environment than CCA or T38 requires further investigation. These data support the role of prenatal inflammation in adverse neonatal outcomes. Clinical trials that investigate therapies for these mothers/neonates at increased risk should begin. MOD#21FY08-539
S232
513 Antenatal glucocorticoids and postnatal surfactant treatment partially rescues neonatal lethality and pulmonary immaturity in an ERK3-/- knockout (ko) murine model of intrauterine growth restriction (IUGR) Milenka Cuevas-Guaman1, Elena Sbrana2, Cynthia Shope3, R. Alan Harris4, Stephen Welty5, Sylvain Meloche6, Kjersti Aagaard3 1 Baylor College of Medicine, Department of Pediatrics, Division of Neonatology, Houston, TX, 2The University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX, 3Baylor College of Medicine, Obstetrics&Gynecology, Division of Maternal-Fetal Medicine, Houston, TX, 4 Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, TX, 5Baylor College of Medicine, Pediatrics, Division of Neonatology, Houston, TX, 6Universite de Montreal, Institute de Recherche en Immunologie et Cancrologie, Cellular and Molecular Biology, Quebec, Canada
OBJECTIVE: As previously reported in our Erk3-/- (ko) mouse model, 0.4mg/kg antenatal dexamethasone given on E16.5&17.5 rescued pulmonary immaturity (decreased sacculation and increased type II pneumocyte glycogen; PNAS 106:16710) but did not rescue neonatal lethality. Using high throughput discovery platforms (whole transcriptome RNA shotgun sequencing), we then identified the critical molecular mediators in fetal pulmonary maturation (i.e., corticotropin releasing hormone (CRH) and surfactant B (SPB)). Here we sought to functionally validate these molecular discoveries in a relevant translational model, hypothesizing that neonatal surfactant (Survanta) with antenatal glucocorticoids could enhance neonatal survival. STUDY DESIGN: In a double crossover design, we administered 0.4mg/kg prenatal dexamethasone (dex) or saline at E16.5 and E17.5, alongside phospholipids-enriched surfactant (Survanta) or saline at 50mg/kg via inhalation intubation at birth. Confirmation of pulmo-
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012