Maternal Nutrient Metabolism and Neonatal Heart Function in Diabetes: A pilot study

Todd Cade, Physical Therapy and Medicine

Washington University, Barnes-Jewish Hospital, St. Louis Children's Hospital

This proof-of-concept/feasibility study aims to focus on alterations in maternal lipid metabolism (maternal kinetics and maternal and fetal concentrations) in DM and to examine its relationship to and prediction of neonatal heart structure and function. Currently, nothing is known regarding the role of lipid metabolism in cardiac abnormalities in IBDM. Data from this study would address an important knowledge gap regarding the potential role of abnormal lipid metabolism in the prediction of the development of cardiac abnormalities in IBDM. The determination of these associations is critical in the pathway to determining the mechanisms of cardiac morphologic and functional alterations in IBDM, in order to develop interventions to ameliorate these cardiac deficits and decrease the future risk of cardiovascular disease and heart failure in these infants.

Weight Management in Obese Pregnant Underserved African American Women

Sam Klein, Internal Medicine

Washington University

The objective of our study is to test an innovative lifestyle intervention program (PAT+), compared to a control condition (standard PAT [PAT-only]), both delivered by PAT parent educators during prenatal and post-partum home visits, in improving our primary outcome of % of women exceeding IOM recommendations for GWG. In addition, we will compare the two conditions in improving various secondary outcomes, including maternal post-partum weight retention, insulin sensitivity; neonatal/infant weight and neurodevelopment; and other maternal and neonatal/infant metabolic and health outcomes. Another objective is to evaluate translation factors to determine the applicability of the PAT+ intervention in real world settings. For this purpose, we will measure programmatic reach, implementation, acceptability, and sustainability.

Early Prediction and Aspirin for Prevention of Preeclampsia

Anthony Odibo, Obstetrics & Gynecology

Washington University

A prospective randomized control trial to estimate the efficacy of low dose aspirin for preventing preeclampsia in women identified as high risk from a first trimester preeclampsia prediction model. Women will be randomized on a 1:1 ratio to either placebo or low dose aspirin. The intervention will be taken daily from recruitment to 37 weeks or delivery whichever comes first. A total of 684 women will be randomized. Recruitment will take place in the Center for Advance Medicine, BJH prenatal clinic from women undergoing ultrasound examination at 9 – 14 6/7 weeks gestation. We will also obtain maternal blood, cord blood and placenta specimen for basic science studies to attempt to dissect biological mechanisms of aspirin effects. In addition we will conduct a cost-benefit analysis to determine the cost effectiveness of screening and using aspirin prophylaxis for screen positive women.

Adipokines and Reprodicutive Outcomes in Obese Women with Infertility

Emily Jungheim, Obstetrics & Gynecology

Washington University

This study involves analysis of various hormones in serum and follicular fluid collected from women undergoing in-vitro fertilization and makes associations between these hormones and reproductive outcomes. More specifically, we are trying to see if there is an association between hormones made by fat tissue (adipokines) and reproductive outcomes in obese women. We will analyze the follicular fluid, and serum for fee fatty acid and adipokines content. We will analyze the granulosa cells for apoptosis. This information will be correlated with clinica data (eg, body mass index, IVF outcomes, and pregnancy outcomes) to determine if there are any associations among these pieces of information.

Polymicrobial Synergy in Adverse Pregnancy Outcomes

Amanda Lewis, Microbiology

Washington University

Prematurity is one of the largest contributors to adverse neonatal outcomes. The March of Dimes estimates that over 500,000 babies are born prematurely in the United States each year. Of these, approximately 1% do not survive and 20% experience life-long disabilities. Culture-independent approaches reveal evidence of intrauterine infection in a substantial proportion of preterm deliveries. However, there are inadequate screening and diagnostic modalities for identification of women at greatest risk for infection-related adverse pregnancy outcomes. Many studies have evaluated correlations between preterm birth and a single infectious disease entity or condition. Here we are investigating whether specific combinations of microbes present in the urogenital tracts of pregnant women synergize to result in a greater risk of adverse outcomes such as preterm birth. The WIHSC project is providing longitudinal urine and vaginal specimens from pregnant women for these studies. Animal models of infection are being performed in parallel with human studies to define mechanisms of polymicrobial synergy.

Integration of the Ketogenic-Ketolytic Axis with Metabolic Homeostasis in Newborn Period

Peter Crawford, Cardiology

Washington University

The purpose of this research study is to monitor the blood concentration of ketone bodies that can serve as an alternative energy source to glucose. Based on epidemiological risk factors, and from controls with no identifiable risk factors for hypoglycemia, some newborns in the first 2 days after delivery are at risk for developing hypoglycemia (low blood sugar). We anticipate that de-identified specimens from approximately 100 WIHSC subjects will be needed to demonstrate the ability of ketone bodies to predict the development of hypoglycemia. Approximately one-third of the subjects will be controls that lack identifiable risk factors for neonatal hypoglycemia, and two-thirds will carry epidemiological risk factors, including gestational/maternal diabetes, intrauterine growth restriction, small or large for gestational age birth, and late-preterm gestational deliveries. Because the target population to study consists of neonates without significant confounding illness, infants suffering severe perinatal hypoxia-ischemia, congenital heart disease, and congenital infection will be excluded.

Autologous Umbilical Veins as Conduits for Vascular Reconstruction in Congenital Heart Disease

David Hoganson, Cardiothoracic Surgery

Washington University, St. Louis Children’s Hospital

This is a pilot, feasibility tissue collection study looking at the veins in the umbilical cords of healthy infants. The primary end point of the study will be demonstration of cellular viability and endothelial function of the umbilical vessels cultured in vitro at 4 weeks. The secondary endpoints will be: 1) Development of collection and handling techniques for obtaining the umbilical cords and isolating the vascular structures. 2) Demonstration of initial and preserved (4 weeks) mechanical performance of the umbilical grafts. 3) Evaluation of performance and durability of the valved BT shunt conduit. 4) Determination of the optimal shunt geometry and diameter for valved and non-valved autologous shunts.

Evaluation of Maternal ß-hemolytic Streptococcal Pharyngeal Exposure in Pregnancies Affected by Congenital Heart Disease

Pirooz Eghtesady, Cardiothoracic Surgery

Washington University, St. Louis Children’s Hospital

Hypoplastic Left Heart Syndrome (HLHS) accounts for as much as 25% of all deaths among neonates with congenital heart disease. The dismal outcomes of HLHS relate to its essential feature of a left ventricle that is too small to support circulation. The etiology of HLHS is unknown. Based on familial occurrence, a genetic etiology for the pathogenesis of HLHS has been proposed but a specific gene(s) associated with HLHS has not yet been identified. We propose to test a hypothesis implicating an immunologic cause. Our hypothesis is that HLHS and variant heart defects are a manifestation of rheumatic heart disease (RHD) of the fetus. We believe that antibodies generated in response to an antecedent episode of maternal pharyngitis caused either by groups A (GABHS), G or C ß-hemolytic streptococci (“strep throat”) cross the placenta and result in an inflammatory, immunologic injury to the developing fetal heart. The pathologic mechanism proposed is analogous to that leading to RHD, the most common cause of acquired heart disease worldwide, and a known sequela of pharyngeal GABHS or group G or C ß-hemolytic streptococcal infection, and the most common cause of acquired heart disease worldwide. Finally, the concept of transplacental passage of maternal antibodies that are harmful to the fetus is not novel and has been reported for a variety of diseases of the fetus and newborn, such as congenital heart block. The aim of the proposed study is to determine the potential association of a pregnancy complicated by HLHS with previous strep throat infection(s) in the mother.

Vaginal Microbiome and Preterm Birth

Methodius Tuuli, Obstetrics & Gynecology

Washington University

The purpose is to identify novel microbes which constitute the vaginal microbiome of pregnancy and identify specific patterns which may be linked to preterm birth (PTB). The specific aims are to identify specific vaginal microbiome patterns associated with PTB using 16s rRNA and shotgun sequencing techniques and to identify specific vaginal microbiome patterns associated with cervical shortening using 16s rRNA and shotgun sequencing techniques. Pilot case-control study using already existing vaginal swab specimens obtained during the second or third trimester of pregnancy. Cases of preterm birth will be defined as those who subsequently delivered at less than 37 weeks. Controls will be those who delivered beyond 37 weeks. Exclusion criteria include: use of progesterone at the time the vaginal swab was obtained and lack of delivery outcomes including gestational age of delivery. Patients are consented for enrollment into the WIHSC study and specimen collection according to WIHSC protocols. No further consent will be obtained for use of already existing specimens.

Neuroimaging in Infants with Congenital Heart Disease and Relation to Neurodevelopmental outcomes

Jenny Duncan, Pediatrics

Washington University, St. Louis Children’s Hospital

Infants with congenital heart disease (CHD) are known to be at significant risk of neurodevelopmental impairments within motor, cognitive, language, and behavioral domains. An additional factor that may affect neurodevelopmental outcome is mitochondrial function. Mitochondria are the energy centers of the cell and mitochondrial disorders have been associated with neurodevelopmental problems. There is data to suggest that maternal obesity and diabetes may contribute to mitochondrial deficits in offspring. Maternal obesity and diabetes are also associated with CHD. This study will analyze maternal blood, cord blood and placenta at delivery.