VULNERABILITY TO PRENATAL GLUCOCORTICOIDS PROGRAMS INFANT DEVELOPMENT
Poggi Elysia, Assistant Professor
University Of California Irvinecity: Irvine country: United States (us)
Grant 5R01HD065823-02 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Synthetic glucocorticoids (GCs) are widely administered to pregnant women at risk for preterm delivery to enhance fetal lung maturation and have established benefits for respiratory functioning and survival among preterm infants (Crowley, 1995). Ironically, this common prenatal treatment given to promote survival among preterm infants may increase the risk of preterm birth and developmental impairments, particularly among vulnerable fetuses. This is plausible because (i) GC treatment stimulates placental CRH production resulting in a 1.5 fold increase in CRH concentrations that persists for at least one week (Korebrits et al., 1998; Marinoni et al., 1998), (ii) elevated placental CRH during this gestational period is associated with preterm birth and may be in the causal pathway (Sandman et al., 1994; Wadhwa et al., 1998; Sandman et al., 1999; Smith et al., 2002; Sandman et al., 2003; Wadhwa et al., 2004; Sandman et al., 2006; Smith et al., 2009) and (iii) prenatal exposure to elevated CRH is associated with developmental impairments (Sandman et al., 1999; Davis et al., 2005; Class et al., 2008; Ellman et al., 2008, Preliminary Studies). The goal of the present application is to characterize the placental CRH response to GC therapy and to identify fetuses who are most susceptible to negative consequences resulting from GC treatment. This application will determine if the magnitude of the placental CRH response to GC treatment is associated with birth outcome and infant development. The placental response to synthetic GC treatment will be determined with the serial collection of maternal plasma samples in 150 African American and Caucasian women with singleton pregnancies who present with signs of preterm labor. Samples will be collected before and during the week following glucocorticoid treatment. Infant development will be evaluated with standardized laboratory measures at 6 and 12 months. This project will determine if the magnitude of the placental CRH response to glucocorticoid treatment will be associated with risk for (i) accelerated time to delivery among women in preterm labor, (ii) increased infant physiological stress reactivity, (iii) infant fearful temperament and (iv) infant mental and neuromotor delays. Prenatal treatment with synthetic glucocorticoids is a common therapy given to women in preterm labor. This investigation will identify fetuses who are vulnerable to the negative consequences of prenatal glucocorticoid treatment for birth outcome and infant development
Keywords: Acceleration; Address; Adrenal Glands; Adult; Affect; African American; Animal Model; Animals; Behavior; Biological; biological adaptation to stress; Birth; Brain; Caucasians; Caucasoid Race; Child; Childhood; Cognitive; cognitive function; Collection; Corticotropin-Releasing Hormone; Data; Detection; Development; Developmental Delay Disorders; Emotions; Environment; Evaluation; Event; Exposure to; fetal; Fetal development of the mammalian embryo or fetus; Fetal Lung; Fetus; Genes; Gestational Age; Glucocorticoids; Goals; Human; Hydrocortisone; Hypertrophy; Impairment; improved; Individual; infancy; Infant; Infant Development; Investigation; Laboratories; Length; Life; lung maturation; Measures; Medical; Methods; neonate; Neurologic; nonhuman primate; Outcome; Pain; Pathway interactions; Perinatal Exposure; Physiological; Placenta; Plasma; Predisposition; Pregnancy; Pregnant Women; Premature Birth; Premature Infant; Premature Labor; prenatal; prenatal exposure; Production; programs; Promoter Regions (Genetics); Proteins; Psyche structure; public health relevance; Regulation; Reporting; Research; Respiratory physiology; response; Risk; Rodent; Sampling; Sheep; Signal Transduction; Steroid biosynthesis; Stress; Temperament; Time; Uterine Contraction; Visit; Woman
Relevance: Prenatal treatment with synthetic glucocorticoids is a common therapy given to women in preterm labor. This investigation will identify fetuses who are vulnerable to the negative consequences of prenatal glucocorticoid treatment for birth outcome and infant development
Project start date: 2010-08-10
Project end date: 2015-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-07-070
5R01HD065823-02 (2011): $525871
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Grants awarded to Poggi Elysia
PRENATAL GLUCOCORTICOIDS INFLUENCE BRAIN AND BEHAVIOR
Poggi Elysia, Assistant Professor
University Of California Irvinecity: Irvine country: United States (us)
Grant 5R01HD050662-05 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: The primary aim of this proposal is to determine the effects of prenatal treatment with glucocorticoids (GCs) on the HPA axis, affect regulation, cognition and the brain in children born preterm and term. Animal models have demonstrated that prenatal exposure to elevated levels of GCs has persisting consequences for health and development. The lasting influences of GC exposure on development of the human child are not known. Every year hundreds of thousands of women at risk of premature labor are treated with GCs to facilitate lung development in the fetus. As many as 20% of children who were exposed to prenatal GC treatment subsequently were born at term. This group is important for two reasons. First, they are at risk for the consequences of GC exposure without receiving the medical benefits evident for preterm infants. Second, inclusion of this critical group allows the impact of GC treatment to be evaluated independently from the known and deleterious long-term effects on the brain and behavior of premature delivery. Despite the importance to health and development of exposure to GCs, existing research has not separated their effects from the impact of preterm delivery. Participants will include a racially diverse sample of 300 six to eight year old children (100 controls, 100 GC treatment, 100 multiple treatments). The specific aims are to (i) Assess the influence of prenatal treatment with GCs on hypothalamic pituitary adrenocortical axis (HPA) function and affect regulation. Salivary cortisol levels will be measured at baseline and in response to challenge to assess the integrity of the HPA axis. Parent report measures of fear/anxiety will be employed as a measure of affect regulation, (ii) Evaluate the impact of prenatal treatment with GCs on cognition. Cognition will be assessed using both standardized intelligence measures and neuropsychological tasks that evaluate memory and executive functions, (iii) Determine the effect prenatal treatment with GCs on brain structure, specifically on the volume of the hippocampus, amygdala, and prefrontal cortex (PFC). Magnetic Resonance Imaging (MRI) will be employed, in a subset of 80 children (40 GC exposed), for the in vivo characterization of brain structure. This project will provide the first opportunity to examine the independent influence of fetal exposure to GC´s in a group of children born at term
Keywords: 0-11 years old; 8 year old; Address; Aeroseb-HC; Affect; Ammon Horn; Amygdala; Amygdaloid Body; amygdaloid nuclear complex; Amygdaloid Nucleus; Amygdaloid structure; Animal Model; Animal Models and Related Studies; Animals; Anxiety; Area; Behavior; Behavioral; Behavioral inhibition; Betadexamethasone; Betamethasone; Birth; Brain; brain behavior; brain volume; Celestone; Cetacort; Child; Child Youth; Childhood; children; Children (0-21); Cognition; Cognitive; cognitive function; cohort; Collection; coping; Cornu Ammonis; Cort-Dome; Cortef; Cortenema; Cortisol; Cortispray; Cortril; Data; Dermacort; Development; Effects, Longterm; eight year old; Eldecort; Emotions; Encephalon; Encephalons; Endocrine; endocrine disrupting; Endocrine disruption; Evaluation; executive control; executive function; Exhibits; Exposure to; Fear; fetal exposure; Fetus; Flubenisolone; Fright; Glucocorticoid Receptor; Glucocorticoids; Head and Neck, Saliva; Health; hippocampal; Hippocampus; Hippocampus (Brain); Human Development; Human, Child; Hydrocortisone; Hydrocortone; Hypophysis; Hypophysis Cerebri; hypothalamic; Hypothalamic structure; Hypothalamus; Hytone; Image; imaging; Impairment; in utero; in utero exposure; in vivo; infancy; Infant; Infant, Premature; infantile; instrument; Intelligence; intra-uterine environmental exposure; intrauterine environmental exposure; Labor, Premature; Life; Long-Term Effects; Lung; lung development; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Measures; Medical; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Memory; model organism; MR Imaging; MR Tomography; MRI; Nervous System, Brain; Nervous System, Pituitary; neuropsychological; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Nutracort; offspring; Parents; Participant; Parturition; pediatric; Performance; Perinatal Exposure; Pituitary; Pituitary Gland; Population; Prefrontal Cortex; Pregn-4-ene-3, 20-dione, 11, 17, 21-trihydroxy-, (11beta)-; Pregna-1, 4-diene-3, 20-dione, 9-fluoro-11, 17, 21-trihydroxy-16-methyl-, (11beta, 16beta)-; Pregnant Women; premature baby; Premature Birth; premature childbirth; premature delivery; Premature Infant; premature infant human; Premature Labor; Premature Obstetric Labor; prenatal; prenatal exposure; prenatal influence; prenatally exposed; preterm baby; Preterm Birth; preterm delivery; preterm infant; preterm infant human; Preterm Labor; preterm neonate; Proctocort; Production; programs; Programs (PT); Programs [Publication Type]; Publishing; pulmonary; Regulation; Reporting; Research; Respiratory System, Lung; response; Risk; Saliva; Salivary; Sampling; standardize measure; Stress; Structure; Therapeutic Glucocorticoid; Therapeutic Hydrocortisone; unborn; Woman; youngster; Zeugmatography
Project start date: 2006-04-15
Project end date: 2012-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2012
5R01HD050662-05 (2010): $405561