Neonatal–Perinatal Medicine Research

Dr. Lina Chalak in her lab

Faculty in the Division of Neonatal-Perinatal Medicine pursue new knowledge through high-quality research that explores unanswered questions. We work collaboratively to generate important discoveries that improve the care provided for neonates worldwide.

Our research spans a wide range of topics, including pulmonary vascular biology, neonatal resuscitation, and long-term follow-up care. The Division doubled its NIH funding from 2022 to 2024.

Recent and ongoing studies are listed below by category:

Basic Sciences Research
- Pulmonary and vascular biology, oxidative stress, and pulmonary hypertension: Phil Shaul, Chieko Mineo, Danielle Callaway
  - Pathogenesis of bronchopulmonary dysplasia/chronic lung disease and novel therapies
  - Molecular basis of vascular disease
  - Molecular mechanisms and novel therapies for pregnancy complications in antiphospholipid syndrome (APS)
  - Hyaluronan (hyaluronic acid) and its role in inflammation and endothelial function
  - The NLRP3 inflammasome in the pathogenesis of BPD
  - Pulmonary endothelial function, nitric oxide, persistent pulmonary hypertension
  - Oxidative stress and free radical injury
- Cardiovascular system and metabolic syndrome: Phil Shaul
  - Mechanisms linking obesity with insulin resistance and hypertension
- Microbiome and necrotizing enterocolitis: Julie Mirpuri-Hathiramani
  - The gut microbiome and its effects on immune mechanisms of inflammatory bowel conditions in the developing gut
  - Maternal high-fat diet and its effects on the gut microbiota in offspring
- Effect of anemia on multiple organs and necrotizing enterocolitis: Mohan Krishnan
Translational Research
- Neonatal neurology: Lina Chalak
  - Hypoxic-ischemic encephalopathy: Mechanism of injury; assessment of new recognition tools such as the amplitude EEG; translational research utilizing a piglet model of asphyxia; optimizing neuro-protection offered by hypothermia; rewarming after hypothermia; cerebrovascular hemodynamic modulation of asphyxiated infants; neurodevelopment, near-infrared spectroscopy, Doppler measurement of resistive index
  - Cerebral neurovascular autoregulation - advanced wavelet methodologies for real-time, noninvasive assessment of neonatal brain injury
- Microbiome, gastrointestinal tract, necrotizing enterocolitis, and growth: Julie Mirpuri-Hathiramani, Eric Ortigoza, Katherine Stumpf
  - Use of noninvasive technologies to obtain physiologic measurements of the gastrointestinal system in premature babies and to study postnatal gastrointestinal development and feeding intolerance in premature newborns
  - Microbiome in preterm infants versus gastrointestinal motility, anemia and transfusion, antibiotic usage, necrotizing enterocolitis, nutrition, and growth
- Placenta pathology: Lina Chalak, Imran Mir, Rachel León
  - Fetal-placental crosstalk occurs through fetal cytokine synthesis and placental clearance
Clinical Research, Quality Improvement, and Other Scholarship
- Resuscitation: Myra Wyckoff, Vishal Kapadia, Noorjahan Ali, Venkat Kakkilaya, Shalini Ramachandran, Luc Brion
  - Randomized trials: temperature control, oxygen delivery, resuscitation educational interventions
  - Observational studies: ETCO2 guidance of CPR, effectiveness of epinephrine dosing
  - Studies using the resuscitation database, which includes detailed information about all resuscitation team calls since 2005
  - Delivery room endotracheal intubation, CPAP
  - Titration of oxygen delivery vs. morbidity and mortality
  - Analysis of resuscitation data from national database
  - Retention of NRP skills post NICU rotation
  - Studies using CMC resuscitation database, which includes detailed information about all codes in CMC NICU since 01/01/2011
  - Studies using multicenter resuscitation database (from 01/01/2011 until 12/31/2016), which includes all codes at CMC NICU, Seattle Children's Hospital, Children's Hospital of Pittsburgh, and Children's Hospital of Colorado
- Neonatal neurology: Lina Chalak, Rachel León, Kikelomo Babata, Dimitrios Angelis
  - Term-equivalent MRI in very preterm infants
  - Hypoxic-ischemic encephalopathy: assessment of new recognition tools such as the amplitude EEG; optimizing neuroprotection offered by hypothermia; rewarming after hypothermia; cerebrovascular hemodynamic modulation of asphyxiated infants; neuroimaging; neurodevelopment, near-infrared spectroscopy, Doppler measurement of resistive index
  - Prospective research on infants with mild encephalopathy: the PRIME study
  - Intraventricular hemorrhage
  - Lenticulostriate vasculopathy
  - Magnetic resonance imaging at term equivalent
  - Neonatal neurology fellowship (1-year training following either a neonatal-perinatal medicine fellowship or a pediatric neurology fellowship)
  - Posthemorrhagic hydrocephalus
  - Neonatal nutrition vs. head growth and neurodevelopment
- Preterm lung disease, bronchopulmonary dysplasia, and pulmonary hypertension: Phil Shaul, Vishal Kapadia, Sushmita Yallapragada, Luc Brion
  - Pathogenesis of bronchopulmonary dysplasia/chronic lung disease, and novel therapies
  - Pulmonary hypertension in bronchopulmonary dysplasia
  - Use of oxygen during initial stabilization phase and during hospital stay in neonates
  - Treatment of air leak syndrome
- CPAP in preterm and term infants: Venkat Kakkilaya, Vishal Kapadia, Myra Wyckoff, Luc Brion, Lorraine Bautista
  - Randomized study comparing two modes of weaning CPAP
  - Use of less invasive surfactant administration (LISA)
  - CPAP vs. intubation in the delivery room in preterm infants
  - CPAP failure
  - Association between CPAP in delivery room and air leak in late-preterm and term neonates
- Cardiovascular system and metabolic syndrome: Mambarambath Jaleel, Phil Shaul, Noorjahan Ali, Luc Brion
  - Potential risk of metabolic syndrome in infancy among very low birth weight infants: Evidence for abnormal weight-to-length ratio, increased adiposity, glomerular hyperfiltration, and high blood pressure in very low birth weight infants followed at the Thrive Clinic and beyond the first decade of life
  - Patent ductus arteriosus
  - Nutritional interventions to prevent disproportionate growth
  - Simulation curriculum on delivery room and immediate postnatal management of cardiac lesions
- Nutrition and growth: Eric Ortigoza, Pritha Nayak, Julie Mirpuri-Hathiramani, Katherine Stumpf, Luc Brion
  - Fish oil in short gut syndrome and neonatal cholestasis
  - Randomized clinical trial comparing individualized versus optimized supplementation of human milk in preterm infants
  - Multidisciplinary collaborative plan for optimizing breast milk and breastfeeding while meeting nutritional needs, improving growth assessment and weight-length proportionality, improving neurodevelopment, and reducing risk of metabolic syndrome in preterm infants
  - Prevention of hyperlipidemia
  - Necrotizing enterocolitis: risk factors, prevention
  - Intestinal rehabilitation program: comparison of types of enteral feeds on growth trajectory and time to full feeds in infants with intestinal failure
  - Long-term neurodevelopmental outcome in infants with short gut
  - Urine sodium in infants with short gut
- Neonatal infection, placenta pathology: Imran Mir, Lina Chalak, Shamaila Gill
  - Screening and serial neutrophil counts in early and late neonatal sepsis
  - Fetal-placental crosstalk occurs through fetal cytokine synthesis and placental clearance
  - Antibiotic stewardship
- Participation in NIH Neonatal Research Network: Myra Wyckoff (site PI), Luc Brion (alternate PI), Lina Chalak (hypoxic-ischemic encephalopathy), Mambarambath Jaleel (patent ductus arteriosus)
  - The Division of Neonatal-Perinatal Medicine actively participates in NIH Neonatal Research Network randomized trials, observational studies, and follow-up studies.
- Medical informatics: Timothy Brannon, Christina Chan, Jawahar Jagarapu, Joseph Schneider
  - Does Problem-List Designation of Bronchopulmonary Dysplasia Impact Processes of Care in the Neonatal Intensive Care Unit?
- Development care and follow-up:
  - Developmental follow-up of complex high-risk and very low birth weight infants and infants enrolled in NICHD NRN studies and internal studies
  - Community advocacy
  - Parental Perception of Child Vulnerability in the NICU and Developmental Outcomes: A Randomized Controlled Trial of Preventive Intervention with Cognitive Behavioral Therapy
  - Bayley language development in preterm infants with oral feeding difficulty
- Neonatal Abstinence Syndrome: Venkat Kakkilaya, Lorraine Bautista
  - Predictors of longer length of treatment for infants with neonatal abstinence syndrome
  - Assessment tools for drug withdrawal
  - Treatment of pain, sedation, and withdrawal of therapy
- Educational scholarship: Luc Brion
  - Improving Timeliness of Submission of Fellow Evaluations by Neonatology Faculty
  - Case of the week: Improving bedside teaching in the Parkland Memorial Hospital NICU
  - Improving completion of fellow evaluations by parents
- Observational studies using available databases: Myra Wyckoff, Luc Brion, Vishal Kapadia, Noorjahan Ali, Sushmita Yallapragada
  Several research studies and quality improvement projects use information from available databases, including:
  - The neonatal resuscitation databases (Parkland, William P. Clements Jr. University Hospital [CUH])
  - The neonatal resuscitation database at Children’s Medical Center (CMC)
  - The NICU databases at Parkland and CMC
  - The NICHD Neonatal Research Network Databases: Generic Database (Parkland, CUH), Follow-up Database, and Moderate Preterm Registry
  - The Vermont-Oxford Network (Parkland, Texas Health Resources, and CUH NICU)
  - The Child Health Neonatal Consortium Database (CMC NICU): focus groups including congenital diaphragmatic hernia, resuscitation, pre/post op management, pain, bronchopulmonary dysplasia/pulmonary hypertension, necrotizing enterocolitis
- Quality improvement (QI): Venkat Kakkilaya, Mambarambath Jaleel, Becky Ennis, Shamaila Gill, Noorjahan Ali, Luc Brion, Lorraine Bautista
  There is a significant amount of quality improvement occurring in all of our NICUs (see above). Multiple QI projects are currently ongoing. A sample of those projects includes:
  - Improving non-invasive ventilation use in the delivery room (Parkland)
  - Improving the number of attempts needed for successful intubation (CMC)
  - Reducing antibiotic utilization in late preterm and term infants suspected of early onset sepsis
  - Institution of TPN bundle to decrease triglyceride levels in preterm neonates; decreasing rates of admission to the NICU for hypoglycemia (CUH)
  - Improving resuscitation of neonates beyond the delivery room (CMC)
  - Assessment of growth patterns using accurate serial length measurements in critical neonates
  - Clinical Safety and Efficacy (CSE) course at UT Southwestern Medical Center

Abbreviations: CMC, Children’s Medical Center; CUH, Clements University Hospital