(total direct and indirect costs unless noted)

COBRE for Reproductive Health – Phase I

(total direct $7,500,000)

Program Director: Surendra Sharma, MD, PhD, Professor of Pediatrics

Deputy Director: Paul Dislivestro, MD. Professor of Obstetrics and Gynecology

Project 1: Beatrice Lechner, MD, Associate Professor of Pediatrics

“Extracellular Matrix Mechanisms of PPROM”

Project 2: Shibin Cheng, MD, PhD, Associate Professor of Pediatrics
“Mechanism of Protein Misfolding and Aggregation in Preeclampsia”

Project 3: Lynae Brayboy, MD, Assistant Professor of Obstetrics and Gynecology
“Cumulus Transcriptome Predicts Preeclampsia and Gestational Diabetes in IVF”

Project 4: Jessica S. Schuster, PhD, Instructor in Pediatrics

“Transcriptional Profiling of Circulating Exosomes Defines Molecular Phenotypes of Preeclampsia”

COBRE for Perinatal Biology – Phase III

(total direct costs $3,750,000)

Program Director: Sunil Shaw, PhD, Assistant Professor of Pediatrics

Pilot Project 1: Don Tseng, PhD, Associate Professor of Pediatrics

“A novel PRKAG2 mutation- an early-onset hypertrophic cardiomyopathy phenotype and treatment”

Pilot Project 2: Joe Bliss, MD, Associate Professor of Pediatrics
“Contribution of Galectin-3 to Host Defense against Neonatal Candidiasis”

Pilot Project 3: Tanbir Najrana, PhD, Instructor in Pediatrics
“Role of mechanical stretch induced EV-miRNA in lung development”

Pilot Project 4: Martin Keszler, MD, Professor of Pediatrics

“NIPPV vs. CPAP at equal mean airway pressure (NICA Trial)”

COBRE Subcontracts

COBRE for Computational Biology of Human Disease – Brown University

Subcontract to Women & Infants Hospital (total direct costs $800,000)

Project 5: Alper Uzun, PhD, Assistant Professor of Pediatrics

“Computational Genomics of Preeclampsia”

ECHO

Pediatric Clinical Trials Network $1,704,713

Principal Investigator: Phyllis Dennery, MD, Professor of Pediatrics

Co- Principal Investigator: Abbot Laptook, MD, Professor of Pediatrics

Environmental Influences on Neurodevelopment Outcomes $19,539,050

Principal Investigator: Barry Lester, PhD, Professor of Psychiatry

Co-Investigator: Sharon Rounds, MD, Professor of Medicine, Professor of Pathology and Laboratory Medicine

Advance – CTR: Center for Clinical and Translational Science

Brown Sub NIH $19,500,000

Principal Investigator: Sharon Rounds, MD, Professor of Pediatrics  

NICHD Cooperative Multicenter Neonatal Research Network $1,492,230

Principal Investigator: Abbot Laptook, MD, Professor of Pediatrics

Co- Principal Investigator: Martin Keszler, MD, Professor of Pediatrics

1) AMPK activation as a therapeutic strategy for PRKAG2 hypertrophic cardiomyopathy;  Oh-Zopfi  $20,000

Principal Investigator::Tseng, YT, Assoc. Professor of Pediatrics.

 2) Bioinformatic approach to identifying potential virulence pathways of Candida parapsilosis 

Co- PI’s Uzun, Bliss, Shaw Oh-Zopfi $20,000.00        

3) Dietary Supplementation of MCT Oil to Reduce Candida Colonization in Preterm Infants, R21 - b

Co-Principal Investigator: Joseph Bliss, MD, Assoc. Professor of Pediatrics.

4) Inter Alpha Inhibitors: Novel Neuroinflammatory Modulator of Neonatal Brain Injury. R21  $440,550

Principal Investigator: Barbara Stonestreet, Professor of Pediatrics

5) Cytokines and the Blood Brain Barrier in the Ovine Fetus  R01 $2,281,120

Principal Investigator: Barbara Stonestreet, Professor of Pediatrics

6) $440,550  

Principal Investigator: Barbara Stonestreet, Professor of Pediatrics

7) Inter-Alpha Inhibitors in Hypoxic-Ischemic Brain Injury SBIR  $589,027

Co- Investigator: Barbara Stonestreet, Professor of Pediatrics

The Brown Center for Children has a number of funded research projects. Titles of these projects plus the projects' major goals can be found on our funded research page.

Funded Research at the Brown Center

This is a randomized clinical trial to determine if cycled phototherapy increases survival compared to continuous phototherapy among extremely low gestation neonates (< 27 weeks or ≤ 750 grams birth weight). The rationale is that phototherapy may be hazardous in extremely preterm infants who have thin, translucent skin.  This study will also determine if bilirubin levels can be adequately controlled with less light exposure.

Enrolled infants are randomized by 24 hours of age and cycled phototherapy is achieved by a timer turning lights on for 15 minutes and off for 45 minutes. If the bilirubin is not adequately controlled, the timer is reset to 30 min on, 30 min off. Sample size is 1,700 infants.

This is a randomized, blinded trial to determine if intratracheal administration of budesonide with surfactant as compared to surfactant alone will reduce bronchopulmonary dysplasia (BPD) or death by 36 weeks among preterm infants < 29 weeks gestation. BPD is the most common morbidity among extremely preterm infants and can negatively impact neurodevelopment. The rationale for this study is to use the anti-inflammatory effect of steroids to benefit the lungs and minimize systemic effects of steroids on other organ systems.

This trial is for infants who develop respiratory distress syndrome at birth or at < 50 hours of age and require intubation. Infants will be given surfactant via an endotracheal tube. Sample size is 1,160 infants.

This is a randomized, blinded trial of continuing caffeine in the hospital (beyond the usual time to stop caffeine, ≈ 34-35 weeks post-menstrual age) to determine if it reduces the number of days of hospitalization from randomization to discharge compared to placebo among moderately preterm infants (29-33 weeks at birth). The rationale for the study is that respiratory events such as apnea, bradycardia and desaturations can keep premature infants in the hospital. Caffeine therapy is used to stop these events but it is unclear what is the optimal time to stop the drug.

Infants randomized to caffeine will be treated for 28 days beyond discharge while the control group will receive placebo after discharge. Sample size is 1,200 infants.

This is a randomized trial of active treatment compared to expectant management of a patent ductus arteriosus (PDA) among preterm infants < 29 weeks gestation on death or BPD at 36 weeks post-menstrual age.  A PDA is a common morbidity of prematurity and can cause clinical problems due to excessive left to right shunting across the PDA with the potential for adverse effects on the lung. Neonatologists often pharmacologically close the PDA with drugs such as indomethacin.  The rationale for this study is to determine whether closure of a PDA does in fact cause injury to the lung.

This is an open label study where infants will be randomized to pharmacologic treatment or continued monitoring without treatment. Infants in the expectant treatment arm can cross over for pharmacologic treatment if they fulfill pre-defined criteria of cardiopulmonary compromise. Sample size is 1,116 infants.

This is a randomized, blinded trial to determine if milrinone improves oxygenation among newborns ≥ 36 weeks with a congenital diaphragmatic hernia. The rationale for this study is that milrinone is often used among infants with congenital diaphragmatic hernia but without any data to show that it is effective.

Infants meeting specific criteria based on an oxygenation index will be randomized to either a 72 hour continuous infusion of milrinone or placebo and blood gases will be compared. This is a pilot study and the sample size is 66 infants.

This is a randomized, blinded trial of rapid compered to slower weaning of pharmacologic therapy on days of opioid exposure for infants with Neonatal Opioid Withdrawal Syndrome (NOWS). Infants exposed to opioids in-utero may manifest abstinence signs related to central nervous system, gastrointestinal or autonomic dysfunction. If non-pharmacologic interventions are not successful, pharmacologic therapy with either morphine or methadone is most often used to control NOWS signs followed by a reduction in the pharmacologic agent until off.

The rationale for this study is that there is no data to support weaning morphine or methadone faster or slower. Sample size for this trial is 502 infants.

Fellow Name, PGY-Status:
Megan Miller, DO (PGY-6)

Research Mentor:
Dr. Barbara Stonestreet

Project Title:
Effects of hypoxia-ischemia (HI) related brain injury on differential cell death pathways by necroptosis, immunogenic cell death, and pyroptosis after exposure to moderate HI

Project Description:
Novel forms of cell death including pyroptosis, necroptosis, and immunogenic cell death are being examined using a neonatal rat model of hypoxia ischemia. Results will be determined by quantitative analysis of  immunohistochemical staining of the specific cell death processes. In brief, post-natal age 7 neonatal rats undergo an ischemic insult followed by 90 minutes of hypoxia, 72 hours after which brains are harvested. The brain slices are then processed using immunohistochemistry staining for pyroptosis, necroptosis, and immunogenic cell death. After processing, the slides are viewed using a stereology microscope and the amount of cell death is quantified. The effects of HI at 90 min will be compared with 120 min and to sham treated control subjects.

Fellow Name, PGY-Status:
Sanghamitra 'Tiya' Sinha, MD (PGY-5)

Research Mentor:
Dr. Barbara Stonestreet

Project Title:
Characterization of high-mobility group box-1 (HMGB1) and inter- alpha inhibitor protein (IAIP) interaction in the lipopolysaccharide (LPS)-induced pre-term sheep brain.

Project Description:
In-vitro immunohistochemical staining and quantification of IAIP and HMGB1 in LPS-exposed pre-term sheep brain slices. Involved in IHC staining, quantification, and analysis of sheep brain slices.

Fellow Name, PGY Status:
Alison Little, MD, MPH, (PGY-6)

Project Title:
Outcomes of Preterm Infants Discharged from the NICU with Child Protective Services (CPS) Involvement

Mentors:
Dr. Elisabeth McGowan and Dr. Betty Vohr

Project Description:
Using institutional follow-up clinic data to study infants <30 weeks who are discharged from our NICU with CPS involvement. The primary objective is to determine the effects of CPS involvement on baseline demographics and medical risk factors, health care utilization after discharge (e.g., Early Intervention enrollment, emergency room visits), and developmental outcomes at 18-26 months corrected age.

Fellow Name, PGY-Status:
Lauren Boudreau, DO (PGY-5)

Research Mentor:
Dr. Elisabeth McGowan

Project Title:
The Impact of the COVID-19 Pandemic on the Provisions of Human Milk for Preterm Infants

Project Description:
The primary objective of the project is to investigate the impact of the COVID-19 pandemic on maternal provision of human milk at the time of discharge home from the NICU for preterm infants.

Fellow Name, PGY-Status:
Katherine Redford, DO (PGY-5)

Research Mentor:
Dr. Beatrice Lechner

Project Titles:
Influence of DNR Status on End of Life Care in the NICU
Influence of Post-Death Family Meeting on Parental Bereavement

Project Description:
Death and bereavement in the NICU. DNR orders and their degree of importance to families and staff, as well as the effect of post-Mortem exams and their effect on parental bereavement and staff processing and closure.

Fellow Name, PGY-Status:
Dolapo Avungbeto, PGY 4

Research Mentor:
Dr. Martin Keszler

Project Title:
Effects of volume guaranteed ventilation versus Synchronized intermittent mandatory ventilation PS during surfactant administration in preterm infants 

Project Description:
To monitor the effect of ACVG vs SIMV PS on Tidal Volumes, Inspiratory pressures and PCO2 using transcutaneous CO2 monitoring. To access duration of transition to room air.

Fellow Name, PGY-Status:
Lisa Grady, PGY-6

Research Mentor:
Dr. Martin Keszler and Dr. Mara Coyle

Project Title:
NICA trial - NIPPV vs CPAP at Equal Mean Airway Pressure and the REST project – Rapid Evaluation and Stabilization of Tiny Infants: A Quality Improvement Initiative

Project Description:
The NICA trial is an ongoing crossover, non-inferiority clinical trial which has hypothesized the difference between CPAP and NIPPV occurs due to a difference in mean airway pressure or MAP, and when compared at equivalent MAP, NIPPV and CPAP will achieve similar level of support. I am also working on a quality improvement project called REST (Rapid Evaluation and Stabilization of Tiny Infants), which aims to decrease the time required to stabilize the ELBW infant upon arrival to the NICU. The main focus of the project is to complete the stabilization process from NICU admission to incubator top down within one hour.