Translational Research
Visual Development in Preterm Infants Study
Approximately 12 of every 100 babies that are born each year in the U.S. are preterm i.e. delivered at less than 37 weeks gestation. Premature birth is the most common cause of neonatal morbidity and mortality in the developed world. It is estimated the socio economic burden from prematurity alone was roughly $26 billion in 2005. Despite efforts to prevent premature birth the incidence has continued to rise. Part of the problem in preventing preterm birth is that there are many causes for a baby being born premature. Our understanding of the various pathways that culminate in preterm birth is still rudimentary. In a large majority of cases there are signs of subclinical infection or inflammation. Still another problem is in being able to accurately predict early which pregnancies are most at risk for developing preterm labor. Early prediction can assist in more effective application of preventive measures.
The focus of the Madan laboratory is to elucidate the molecular pathways underlying inflammation induced preterm labor and to develop an assay that is predictive of preterm labor early in pregnancy. With this goal in mind her lab has developed an inflammation induced mouse model of preterm labor. Several studies are being conducted using standard molecular biological techniques as well as novel technologies such as Proteomics using the mouse model. In addition, translational research studies to take this work from the bench to the bedside are underway.
The aims of the study:
- This study compares the development of visual acuity between preterm infants (< 1500g BW) and term infants by using the sweep visual evoked potential (sVEP), an electrophysiologic measure of different visual functions. In addition, this aim will establish normative data for visual acuity thresholds for preterm infants. We hope that development of a sensitive measure of visual acuity in infants will help in early diagnosis of visual impairment and institution of rehabilitative treatment.
- Preterm infants are also at risk for development of intraventricular hemorrhage (IVH), which increases the risk of CVI and a poor neurodevelopment outcome. In order to measure the impact of IVH on visual development, similar studies will be conducted in preterm infants that have sustained IVH in the neonatal period.
- Diffusion tensor imaging (DTI)-MRI is a sensitive tool that has been used to detect early signs of injury predictive of neurodevelopmental impairment in preterm infants. A detailed structural analysis of the visual pathway is conducted on all enrolled infants. A structure-function analysis is done by comparing the results of the MRI to that of threshold acuities measured in the sVEP study. This study will assist in early detection (at the time of hospital discharge) of visual impairment in at risk infants and referral for early intervention and rehabilitative treatment.
Proteomic Investigations in Neonatal-Perinatal Medicine
In collaboration with Drs. Harvey Cohen and Yasser El-Sayed we have undertaken proteomic investigations whose aim is to identify differences in plasma protein expression that may be biomarkers of various morbidities in preterm newborns and for which there is little insight to the mechanism of the disease. This discovery-driven research is a collaborative effort with members of the Biotechnology core in Pediatrics which is being used to:
- Identify proteins in the cord blood of preterm infants that maybe predictive of development of severe retinopathy of prematurity (ROP), a condition that can result in visual impairment
- Detect proteins in the plasma of extremely preterm infants that develop necrotizing enterocolitis (NEC), a major cause of mortality and morbidity in preterm infants. The goal is to identify a biomarker predictive of development of NEC and a biomarker predictive of severity of disease.
- Preterm birth is a major cause of morbidity and mortality. Our understanding of the pathogenesis of preterm labor is limited. “Identification of the serum proteomic profiles in preterm labor” is a study designed to detect a biomarker predictive of preterm labor as well as determine the normal proteomic profile at different stages of pregnancy. This is a collaborative effort with the Division of Maternal-Fetal Medicine.
Pregnancy-Related Mortality in California
Pregnancy-related mortality in California has been increasing over the past several years. Between 1998 and 2003 pregnancy-related mortality increased 43% and is 3.5 times higher than the Healthy People 2010 target. Pregnancy-related mortality is an indicator of maternal health in general, and increasing maternal mortality suggests that serious maternal morbidity is also increasing.
In 2006 the Maternal, Child and Adolescent Health Program, California Department of Public Health and the California Maternal Quality Care Collaborative (CMQCC) formed the California Pregnancy-Related and Pregnancy-Associated Mortality Review (CA-PAMR) committee to analyze maternal deaths in California with a focus on identifying opportunities for improvement and systems change. This is the first ever California state-wide maternal mortality review. This project is assessing all women who died within a year of a live birth or fetal death, beginning with the 2002 cohort of births. The goal is to determine whether maternal death was pregnancy-related, the cause of death, and what factors (community, patient, health care facility, and health care professional) contributed to the death.
Because of the concern about the continuing disparity in mortality rates between African-American and other women, CA-PAMR is paying particular attention to deaths by African-American women and selecting a higher proportion of them for study than women of other race/ethnicities. Selected cases undergo full medical record review and cases are then reviewed by the CA-PAMR Advisory Committee. CA-PAMR results and recommendations will be implemented through the quality improvement efforts of CMQCC. The reviews will continue through other years and are an important tool for identifying priority quality improvement projects for CMQCC.
