​​Current Research

​One of the primary goals of our division and the shared vision of all our faculty and staff is to provide better care, health, and outcomes for infants. To promote this goal, we support a range of investigator initiated and sponsor intitated research focused on improving health for infants today and tomorrow. Find more about some of the active research within the Division of Neonatology below.

  • Active Research
  • Interested in Participating
  • Recent Publications
  • Supporting Our Research

Active Research

Investigator Intiated Research:

Genomics of Lung Inflammation in Preterm Infants
Bronchopulmonary Dysplasia (BPD) is a frequent complication of preterm birth resulting in respiratory complications and abnormal lung development. Macrophages are a type of white blood cell that help fight infection by ingesting foreign organisms that can cause lung disease. Macrophages are found in tissues throughout the body, including in the lungs. The purpose of this study is to look at the macrophages that are found in the fluid from the lungs of infants that have needed respiratory support. In studying these cells, the researchers are looking to find a connection between lung disease development and the study the macrophages found in the lungs. 

Primary Investigator: Dr. Lawrence Prince

Clinical Trials:

​NCHD-2013-ABS01- Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP)

A Phase 2b Multicenter, Single Dose, Randomized, Double Blind, Placebo Controlled, Parallel Group Study Evaluating the Safety and Efficacy of Two Doses of Stannsoporfin in Combination with Phototherapy

NCHD-2013-ABS01- Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP)

Interested in participating?

The following studies are recruiting:

  1. A Phase 2b Multicenter, Single Dose, Randomized, Double Blind, Placebo Controlled, Parallel Group Study Evaluating the Safety and Efficacy of Two Doses of Stannsoporfin in Combination with Phototherapy
  2. The UCSD Milk Biorepository
  3. KidPrint, Non-Contact Biometric Infant Identification for Resource Limited Settings
  4. INSPIRE: What is Normal Milk? Sociocultural, Evolutionary, Environmental, and Microbial Aspects of Human Milk Composition

If you're interested in one of the studies listed above, please contact our research team for more information or email us at neoresearch@ucsd.edu.

Research by Division Faculty

Lawrence (Lance) Prince, MD, PhD

  • Mechanisms linking lung inflammation and abnormal development in bronchopulmonary dysplasia
  • Developmental biology of lung macrophages
  • Development of novel imaging approaches for understanding neonatal lung disease.

Lars Bode, PhD

  • Biosynthesis and physiological function of human milk oligosaccharides
  • Role of breast milk and unbound complex glycans in development of the intestinal innate immune response.
  • Development of oligosaccharide based therapies to prevent infectious disease and necrotizing enterocolitis.

David Golembeski, MD

  • Board member for the National Children’s Study.
  • Co-PI for the Boston University Birth Defects Monitoring Project.

Gregory P. Heldt, MD

  • Development of synthetic and novel lung surfactants.
  • Neural-activated synchronized ventilation and its applications in critically ill neonates.
  • Basic molecular and cellular mechanisms of group-B streptococcal infections in neonates.

Jose Honold, MD

  • Clinical innovation and interventions that improve outcome in critically ill neonates at highest risk of neurodevelopmental impairment.

Eustratia (Tia) Hubbard, MD

  • Clinical investigations aimed at improving outcomes in late preterm infants and patients at risk of feeding difficulties.

Farhad Imam, MD, PhD

    Using novel approaches and experimental models to study the molecular and genetic responses to environmental stress.
  • Testing the effects of cellular stress on embryogenesis, particularly heart and brain development, in zebrafish

Jae Hong Kim, MD, PhD

  • Understanding development of gastrointestinal motility in preterm infants.
  • Developing novel noninvasive approaches to personalize critical care management in neonates.

Michelle Leff, MD

  • nteractions between maternal diet, breast milk composition, and development of obesity and diabetes.

Krishelle Leong Marc-Aurele, MD

  • Development of novel approaches for counseling families in the prenatal and postnatal setting as part of a multi-disciplinary palliative care model developed specifically for  newborns.

Sanjay Nigam, MD

  • Systems biology approaches to identify mechanisms of kidney branching morphogenesis.
  • Developmental regulation and function of organic acid transporters and the elimination and metabolism of drugs and toxins.

Dawn Reeves, MD

  • Use of detailed echocardiographic data to predict nonsurgical closure of a patent ductus arteriosus in extremely preterm neonates.

Evan Y. Snyder, MD, PhD

  • Stem cell biology
  • Discovery of novel molecular and cellular mechanisms that regulate stem cell pluripotency and neuronal differentiation.
  • The use of induced pluripotent stem cells to investigate basic disease mechanisms and   discover novel treatments specific for individual patients.​

Prospective, Randomized, Cross-over, Observation Study Comparing NAVA to NSIMV in Preterm Infants
Infants with respiratory distress are typically ventilated with breaths that are not synchronized with the infant's own breathing and instead are generated by fixed inspiratory pressures and rates.  Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation that delivers synchronized assist in time and in proportion to the electrical activity of the infant's diaphragm on a breath-by-breath basis.  It is approved by the FDA and based on the preliminary results of a previous feasibility study, has had a favorable patient effect when compared to standard nasal synchronized intermittent mandatory ventilation (NSIMV).  This protocol expands upon our previous feasibility study and will provide a prospective, randomized cross-over comparison of the physiologic effects of NAVA versus NSIMV under steady-state conditions, while controlling for mean airway pressure (Paw) and level of ventilation.

PHASE II/III DRUG STUDIES

A Phase 2b Multicenter, Single Dose, Randomized Double Blind, Placebo Controlled, Parallel Group Study Evaluating the Safety and Efficacy of Two Doses of Stannsoporfin in Combination with Phototherapy
Neonatal jaundice (or accumulation of bilirubin) is the most common cause of hospital readmission for term and near term infants and its management poses a significant burden on the healthcare system. Infants who are born with increased breakdown of their red blood cells (such as ABO or Rh incompatibility, or G6PD deficiency) have increased bilirubin production. Newborn infants have immature liver function and do not breakdown bilirubin well, which results in jaundice. Thus, bilirubin levels may rise rapidly and intervention may be required. At present, phototherapy (PT) is the most frequently used treatment for jaundice; it converts bilirubin to less toxic chemicals in the body that are then passed in the urine. Infants who do not respond to PT are treated by an exchange blood transfusion (ET), considered a therapy of last resort due to its associated morbidity and mortality risks. Both PT and ET enhance the elimination of, but have no impact on the production of bilirubin. Stannsoporfin is a drug that acts to reduce bilirubin production and is being developed for the management of neonatal jaundice. Previous clinical studies have demonstrated that a single IM injection of stannsoporfin at doses of 3.0 or 4.5 mg/kg can reduce bilirubin levels. The present study will evaluate the benefits and safety of using this drug for infants who reach the need for PT.

Antibiotic Safetey in Infants with Complicated Intra-Abdominal Infections (SCAMP)
The most commonly used antibiotics in infants with complicated intra-abdominal infections are not labeled for use in this population because safety and efficacy data are lacking. This multicenter study will provide the safety information required for labeling. This study is being coordinated by Duke University through the Duke Clinical Research Institute, the Pediatric Trials Network and The Best Pharmaceuticals for Children Act (BPCA) Program and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). NICHD activities related to BPCA are intended to improve pediatric drug therapeutics through preclinical and clinical testing that lead to drug labeling change. The primary objective of this study is to evaluate the safety of drug regimens consisting of ampicillin, metronidazole, clindamycin, piperacillin-tazobactam, and gentamicin in infants with complicated intra-abdominal infections.  The secondary objectives are to evaluate the efficacy of these antibiotic regimens, to evaluate the pharmacokinetics of these regimens, to assess biomarker association with disease severity and antibiotic exposure, and the comparison of intestinal microbiota between treatment arms.

Efficacy of intravenous levetiracetam in the treatment of neonatal seizures (Phase II)
There are no FDA approved treatments for neonatal seizures (seizures occurring in the first 28 days of life). More effective and less toxic treatments are urgently required. While appropriately holding orphan drug status, neonatal seizures are a common problem within the field of child neurology and cause significant morbidity. Current standard of care treatments Phenobarbital and phenytoin are unsatisfactory as each agent is effective in less than 50% of subjects, and both have significant acute and chronic side effects. Levetiracetam (LEV) has great potential as a treatment for neonatal seizures, but is not approved for use in children less than 2 years of age. LEV has established efficacy and an excellent safety profile in older patients. In animal models this agent does not cause neuronal apoptosis and is neuroprotective. However, the efficacy of LEV has not been systematically studied in neonates and cannot be assumed.  Drugs that are effective in terminating seizures in adults may be less effective and have more toxicity in neonates. This study aims to obtain essential data regarding the efficacy and safety of LEV in this vulnerable and under researched population.

Intravenous Remodulin (Treprostinil) as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn: A Randomized, Placebo-Controlled, Safety and Efficacy Study
In utero, oxygen passes from the mother to the baby through the umbilical cord, bypassing the lungs. Since the lungs are not used for gas exchange, pulmonary pressure is high so that only a small fraction of the baby's blood is directed to the pulmonary vascular bed. Once the baby is born, pulmonary pressure should decrease, allowing a significant increase in pulmonary blood flow which, in turn, allows for the lungs to oxygenate the blood. When the pulmonary pressure remains high, the appropriate amount of blood cannot reach the lungs for oxygenation, and the baby will become hypoxic. This syndrome is called persistent pulmonary hypertension of the newborn (PPHN). Currently, the standard of care is to treat with inhaled nitric oxide (a vasodilator) delivered during ventilation in order to help relax blood vessels, improving blood flow. Unfortunately, 30-40% of neonates with PPHN do not respond adequately to this treatment. In the current study, we will assess whether the use of Remodulin (Treprostinil) as add on therapy for neonates who do not respond to inhaled nitric oxide (iNO) is safe and effective in the treatment of PPHN.

PARENTERAL NUTRITION and OMEGA-3 FATTY ACIDS

Use of Omegaven for Parenteral Nutrition Associated Cholestasis
In the United States, patients dependent upon parenteral nutrition (PN) receive parenteral fat emulsions composed of soybean oils. Lipids are necessary in PN dependent patients due to their high caloric value and essential fatty acid content. However, they have been implicated in predisposing patients to PN associated liver disease. Phytosterols such as those contained in soybean oils are thought to have a deleterious effect on biliary secretion and accumulation of lipids in the hepatic Kupffer cells may further impair liver function. We hypothesize that omega-6 fatty acid emulsions prevent fatty acid deficiency, but are not cleared in a manner similar to enteral chylomicrons and therefore accumulate in the liver resulting in steatotic liver injury. We further hypothesize that a fat emulsion comprised of omega-3 fatty acids (i.e., fish oil) such as Omegaven™ would be beneficial in the management of steatotic liver injury by its inhibition of de novo lipogenesis, the reduction of arachidonic acid-derived inflammatory mediators, prevention of essential fatty acid deficiency through the presence of small amounts of arachidonic acid, and improved clearance of lipids from the serum. Animal studies have shown that IV fat emulsions (IFE) such as fish oil that are high in eicosapentaenic and docashexaaenoic acid reduce impairment of bile flow which is seen in cholestasis caused by conventional fat emulsions.  Furthermore, we hypothesize that that intravenous omega three fatty acids will be well tolerated and might reduce the inflammatory effect in the liver of prolonged PN exposure and could potentially reverse any hepatic dysfunction due to PN/IFE use.  By administering Omegaven™ in place of conventional phytosterol/soybean fat emulsions we may reverse or prevent the progression of PN associated cholestasis and thus allow the patient to be maintained on adequate PN until they are able to ingest adequate nutrition enterally. In this trial, infants initially on a standard lipid emulsion will be enrolled after a diagnosis of parental nutrition associated liver disease is made.

Omega-3 LCPUFA Supplementation in Very Low Birthweight Infants for the Prevention of Retinopathy of Prematurity: Prospective Randomized Controlled Masked Clinical Trial with Lipidomic and Transcriptomic Analyses
Retinopathy of prematurity (ROP) is a blinding disease affecting infants born prematurely. These infants do not have enough essential fatty acids to structurally support the retina, the nerve tissue in the eye which allows us to see. A recent study showed that giving omega-3 (n-3) fatty acids to these infants soon after birth made them less likely to need invasive treatments for eye disease. We intend to give young infants born prematurely with n-3 fish oil treatment and look at how this changes factors in the blood that promote disease. We will do detailed blood studies comparing infants with and without ROP and will follow these infants over time to assess their eye development.

HUMAN MILK AND MILK COMPONENTS

UCSD Human Milk Biorepository
Breastfeeding is a recommended and encouraged practice in all cases where possible for the first months to a year of life according to the Centers for Disease Control's U.S. Healthy People 2020 guidelines.  The benefits of breast milk in terms of cognitive development, growth, and protection against disease have been documented; however, there is much to be learned about the mechanisms whereby breast milk is of benefit to the infant, how the caloric and other nutrient content of breast milk varies by mother, and if and what changes in breast milk components occur with various conditions and lengths of storage.  In addition, for many medications that might be taken by women, there is little to no information available on potential magnitude and consequences of infant exposure while breastfeeding.  As a result, women are often advised not to breastfeed if taking a medication, or may avoid breastfeeding themselves for lack of information.  Conversely, some drugs are known to pass into breast milk and can compromise infant health (e.g., opioids in a susceptible subpopulation) and a better understanding of which medications should be avoided in women who are breastfeeding (or avoidance of breastfeeding is advisable) is important to the health of infants.  A multidisciplinary group of investigators at UCSD/Rady Children's Hospital have identified this as a group of topic areas that could benefit greatly from access to a shared resource represented by the Repository. Mother/baby dyads are now being enrolled both in the community and among inpatient populations in order to grow a repository of several thousand breast milk samples with along with pertinent medical information about both mother and baby.

Human Milk Oligosaccharides (HMO) in Maternal Urine throughout Pregnancy
Human milk oligosaccharides (HMO) are a diverse group of complex sugars that are found in large amounts in breast milk and are relatively unique to humans. HMO are also found in the urine of pregnant women; as early as the end of the first trimester. It has not yet been described whether inter-and intra-individual variations in HMO composition occur.  Also, whether or not the HMO composition in the urine of pregnant women (antepartum) corresponds to the HMO composition in the milk post-partum has not been characterized. In addition, it is currently unknown whether or not HMO also appear in amniotic fluid and cord blood. Potentially, HMO can be protective against infection, which is a major cause of prematurity. For this study, we are collecting urine samples from pregnant women, and later their infants, as well as amniotic fluid samples, cord blood samples, and breast milk samples to measure the content of HMO. We are also collecting information about preterm delivery, maternal urine infection, and Group B Streptococcus colonization, as well as chorioamnionitis to assess the incidence of these conditions to allow for planning of future studies to potentially correlate certain HMO with risk of the aforementioned conditions.

METABOLOMICS

Untargeted, Large-Scale Metabolomics in Neonatology for Disease Biomarker Discovery
In this study, we aim to discover an association between specific metabolites and a wide variety of common neonatal diseases including prematurity, hypoxic ischemic injury, meconium aspiration syndrome, neonatal abstinence syndrome, Persistent Pulmonary Hypertension of the Newborn, congenital heart disease, and others. We are applying our recently validated mass spectroscopy methodology to perform an unbiased metabolomic analysis of patient samples, measuring thousands of individual metabolites in the blood in order to better understand the organ systems and biological functions that contribute to diseases pathogenesis and/or progression. We hope to identify a unique metabolite signature for each of these diseases. Furthermore, we plan to use metabolic pathway analysis to determine whether differentially regulated metabolites are indicative of a change in a specific signaling pathway or gene, such as in the well-established case of congenital adrenal hyperplasia and particular steroid intermediates. This project is using waste blood leftover from samples drawn at our participating hospitals for routine laboratory investigations and thereby does not expose patients to additional risks and/or procedures.

Transcriptomic and Metabolomic Signature in the Blood of Neonates
It is a paradox that neonatologists often provide oxygen during delivery room resuscitation to produce SpO2 values well in excess of 95% while such levels are not generally accepted once the infant is admitted to a NICU. There is significant biological plausibility that the benefit seen in the term infants when using air versus 100% oxygen may be even greater in the most premature infants.  The development of detection methods such as blood tests would allow monitoring response to optimize the level of supplemental oxygen. Evidence exists that reduced oxygen tension affects cellular metabolism and the microenvironment, including pH level. Nuclear magnetic resonance (NMR) spectroscopy is a commonly used analytical method to analyze the small molecule composition, that is, the metabolome, of body fluids such as urine and blood serum. Variations in metabolite concentrations have been associated with the biochemical status of organisms and reflect changes in metabolism arising from biologic conditions, including disease and response to hypoxic treatment. Another important component in the blood sample is white blood cells (WBCs). They play an important role in neonatal defence system and can reflect changes in tissue transcriptome during low oxygen. For example, previous studies have shown that neonatal hyperoxia exposure induces functional alterations in white blood cells.  Expression arrays have been routinely used to determine gene expression profiles in human tissues and cells. The combination of NMR-based metabolomics and array-based expression profiling might allow to better evaluate the effect of oxygen dysregulation in term and preterm neonates. The results might help to identify new clinical biomarkers that might guide the diagnosis and therapy of the response to hypoxia. This study is being done to find out if variations in the composition of blood in babies at birth can help doctors recognize and treat hypoxia. Information obtained from the study will help to develop a better understanding of the use of supplemental oxygen during resuscitation of infants.