Clinical Research - Fetal and Neonatal Institute

The division is active in several areas of clinical research including neuroprotection, pulmonary hypertension, hemodynamics, patent ductus arteriosus and respiratory failure. Here are few examples of on-going studies:

High dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Study

Neonatal hypoxic-ischemic encephalopathy (HIE) has an estimated incidence of 1 to 8 per live births in the United States and can lead to mortality or significant neurodevelopmental morbidity including cerebral palsy, hearing and/or visual impairment, epilepsy and developmental/behavioral problems. Current neuroprotective strategy involves hypothermia therapy, lowering the body temperature to 33.5 degrees Celsius for 72 hours. However, almost 40% of infants still suffer from death or severe disability. As such, additional neuroprotective therapies are urgently needed. 

Erythropoietin (EPO), commonly known for its red blood cell generating properties, has been found to reduce neuroapoptosis (neuro cell self-destruction) and exhibit neuroregenerative properties in animal models of neonatal brain injury. Furthermore, small human trials have shown pilot safety and pharmacokinetic data, along with significantly reduced brain injury on MRI for newborns with HIE receiving EPO. 

In this phase III multi-center randomized control trial, Dr. Tai-Wei Wu as the site primary investigator, is investigating whether high dose EPO reduces composite primary outcome of death or neurodevelopmental impairment at 22-26 months of age for newborns undergoing hypothermia therapy for brain injury.  

Intravenous Remodulin (Treprostinil) as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension (PPHN) of the Newborn: A Randomized, Placebo-Controlled, Safety and Efficacy Study

This study aims to explore the safety and treatment effect of intravenous (IV) Remodulin as add-on therapy in neonates with PPHN compared to placebo. Treprostinil is a chemically stable tricyclic analogue of prostacyclin (PGI2), which is approved for the treatment of pulmonary arterial hypertension (PAH) in the US, European Union, and many other countries under the brand name Remodulin. This study enrolls neonate subjects with PPHN who do not show an adequate response to inhaled nitric oxide (iNO) with the hypothesis that the addition of Remodulin will reduce the rate of clinical worsening defined as death, the need for ECMO, or the need for additional pulmonary vasodilator therapy as compared to placebo. Additionally, this study aims to evaluate the dosing and pharmacokinetics of Remodulin in the neonatal population.

Primary Investigators: Dr. Friedlich and Dr. Chapman

Co-investigators: Dr. Bliss, Dr. Iyer, Dr. Noori, and Dr. Szmuskovics

In Utero Percutaneous Endoscopic Correction of Myelomeningocele: Laparotomy versus Percutaneous - A pilot study

The objective of this study is to evaluate the feasibility of a fetoscopic surgical technique for antenatal correction of fetal myelomeningocele. One of two approaches may be used based on placental location and patient preference. The percutaneous approach (closed abdomen/closed uterus) will be offered to patients with a posterior placenta. The laparotomy/uterine exteriorization approach (open abdomen/closed uterus) will be offered to patients with an anterior placenta, or patients that prefer this method. The intervention, regardless of approach, involves placement of a collagen patch over the placode and closure of the fetal skin over the patch. This replaces the classic layer-by-layer closure, which requires dissection of the placode (embryonic tissue layer) from the skin and dura mater. The collagen patch results in development of neoduramater (a new membrane that covers the spinal cord) and produces a watertight seal of the defect. A total of 10 subjects will be enrolled between two recruiting sites. A maximum of 10 subjects will be enrolled at CHLA. This pilot study of 10 subjects plans to explore whether a less invasive, simplified approach, through the use of fetoscopy, allows the benefits of prenatal repair of spina bifida with less maternal and pregnancy-related risks.

Primary Investigator: Dr. Chmait

Co-investigators: Dr. Chu, Dr. Friedlich, Dr. Ho, Dr. Krieger, Dr. Smith, Dr. Van Speybroeck, and Dr. Vanderbilt

Hemodynamic Effects of Gastroschisis Repair in Neonates

Gastroschisis is a congenital abdominal wall defect that allows abdominal contents to protrude from a baby’s body during fetal development. Neonatal intensive care and surgical intervention are required immediately after birth. Returning the eviscerated structures back into the abdomen can place the abdominal contents under pressure, leading to compromised blood flow to vital organs and possibly even cardiac dysfunction. The objectives of this study are to determine the hemodynamic and organ perfusion effects of surgical intervention for gastroschisis in neonates, and to determine the cardiovascular and hemodynamic predictors of clinical outcomes in neonates with gastroschisis. Hemodynamic assessments are performed with functional echocardiography and non-invasive monitoring devices surrounding the time of surgical repair.

Primary Investigator: Dr. Shepherd

Co-investigators: Dr. Wu, Dr. Gayer, Dr. Noori

A Randomized, Placebo-Controlled Trial of Early Caffeine in Preterm Neonates

Caffeine is routinely given to extremely premature infants to improve respiratory drive. Studies have demonstrated that early caffeine therapy is associated with decreased incidence of chronic lung disease of infancy and improved developmental outcomes when given in the first days of life. However, caffeine given shortly after birth has not been thoroughly studied. This is a multi-site, randomized, placebo-controlled, double-blinded trial that is being conducted at delivery centers affiliated with USC and CHLA. We hypothesize that caffeine administered to preterm infants born at less than 32 weeks’ gestation within the first 2 hours of life compared to 12 hours of life will decrease the need for insertion of a breathing tube. A secondary hypothesis is that very early caffeine use will improve cardiac output, given its hemodynamic effects. Clinical outcomes are collected, and detailed hemodynamic measurements are performed on a subset of participants. This study is funded by The Gerber Foundation.

PI: Dr. Shepherd; Co-investigators: Dr. Noori, Dr. Borzage, Dr. Wu, Dr. Nicholas, Dr. Wong, Dr. Ramanathan, and Dr. Friedlich

Brain Development in Fetuses and Children with Congenital Heart Disease

With collaboration from members of multiple disciplines (Neonatology, Cardiology, Radiology, Perinatology, Neuropsychology, Cardiothoracic Surgery, Pediatric Critical Care, etc.), we have an ongoing longitudinal study to learn about the brain development in fetuses and children with congenital heart disease.  Our hope is to learn about the pathogenesis of brain maldevelopment in the child with congenital heart disease, optimize his/her care, and make the future less challenging for each one of these children. Once the mother has had a fetal MRI or the baby has had a normal postnatal cranial ultrasound as part of routine care, we invite the family to participate in our study: MRIs and neurodevelopmental assessments.  The study MRIs are done pre-operatively and post-operatively in the neonatal period and at 6 years of age.  The neurodevelopmental assessments start in the hospital as a newborn and are every three months in the first year, becoming a bit less frequent as each year passes. The last evaluation, MRI and neurodevelopment, is at six years of age. The information is correlated to normal healthy controls and a premature baby cohort who are also offered the same evaluations. We began in 2010 at CHLA, have set-up the same study at Pittsburgh Children’s, have learned a lot, and hope to keep adding to the knowledge base and helping our patients.

Extubation Prediction and Risk Factors for Extubation Failure in Newborn Infants (NEXT) Study

Dr. Iyer’s study focuses on determining the most accurate method for performing a spontaneous breathing trial (SBT), a test that predicts extubation failure, which will allow clinicians to better determine which patients are more likely to be successfully extubated. This fully funded study when complete will answer the question about the best predictive test for determining extubation failure as well describe the prevalence and risk factors of two important causes of extubation failure- upper airway obstruction and respiratory muscle weakness.

Primary Investigator: Dr. Iyer

Co-Investigators: Dr. Khemani, Justin Hotz, RRT, Dr. Newth, Dr. Friedlich and Dr. Ramanathan

Multicenter Study of Saturation Targeting by Automated vs. Manual Adjustment of Inspired Oxygen in Neonates and Infants (STAMINA): A Prospective, Multicenter, Randomized, Cross-over, Safety and Efficacy Study

This multicenter trial is evaluating the safety and efficacy of the investigational automated FiO2 adjustment function in the AVEA ventilator with the new and innovative CLiO2 software system in managing oxygen saturations in neonates and infants receiving invasive and noninvasive respiratory support in comparison to manual adjustment of inspired oxygen during routine clinical care. This trial is a prospective, multicenter, randomized, cross-over, safety and efficacy study which is being conducted in accordance with the US Food and Drug Administration Investigational Device Exemption (IDE) Regulations. If CliO2 software is shown to improve the management of oxygen saturations in neonates, it will allow for more optimal management of oxygen therapy in infants and potentially lead to less retinopathy of prematurity, chronic lung disease and improved overall survival. Dr. Narayan Iyer is the Principal Investigator for the conduct of the study at Children’s Hospital Los Angeles.

Pulse Oximetry Ranges and the Risk of Hyper and Hypoxia in Newborn Infants

Low and high oxygen states are equally harmful in newborn infants, especially preterm infants. The likelihood of hyper- and hypoxia at different pulse oximetry levels is dependent on several factors and the elucidation of these factors along with the exact risk of hyper- and hypoxia at different pulse oximetry levels is not fully understood. Data is used from thousands of paired data of pulse oximetry and actual oxygen saturation to describe levels of pulse oximetry that carry clinically significant risk for hyper- and hypoxemia.

Primary Investigator: Dr. Bachman

Co-Investigators: Dr. Iyer, Dr. Newth, Dr. Ross, Dr. Khemani

Derivation and Utility of Loop Gain in the Diagnosis and Severity Classification of Neonatal Sleep Disordered Breathing

Sleep disordered breathing is very common among preterm infants discharged from the NICU. The diagnosis and severity classification depends on specialized polysomnogram (PSG) assessment, sometimes referred to as a sleep study assessment. However, PSG assessment is time consuming and standards for newborn infants are not fully established. Use of loop gain is a new engineering concept in describing sleep disordered breathing. This study examines the factors that control and affect the regulation of breathing and describe the process of deriving loop gain from PSG and analyze its utility in diagnosing sleep disordered breathing among preterm infants.

Primary Investigator: Dr. Iyer

Co-Investigators: Dr. Nava Guerra, Dr. Ward

Features extracted from breath-by-breath time-series analysis as risk factors for extubation failure

Extubation failure in infants and children is associated with increased morbidity, mortality and prolonged length of hospitalization. Use of time series analysis to better predict extubation outcomes in children has not been described in large cohorts. This study describes different indices derived from breath by breath analysis of spontaneous breathing trials in a large cohort of infants and children with the aim of developing automated tools for accurate prediction of extubation outcomes.

Primary Investigator: Dr. Khemani

Co-Investigators: Dr.Nava Guerra, Dr. Knox, Justin Hotz, RRT, Dr. Sekayan, Dr. Iyer