Novel non-invasive approach for predicting retinopathy of prematurity in premature neonates

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ABSTRACT: Maldevelopment of the microvasculature in premature neonates plays a major role in complications of prematurity with life-long consequences such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC) and pulmonary hypertension (PHTN) complicating bronchopulmonary dysplasia (BPD), which are major causes of morbidity and mortality in premature infants. Unfortunately, there is no non-invasive method established to assess and monitor systemic microvascular development in premature babies to predict which infant will develop these complications. Nailfold capillaroscopy is a non-invasive technique useful in adults and children with connective tissue diseases to predict relapses, but not currently used in premature neonates to assess capillary development. Our preliminary data suggest that, in very-low-birthweight (VLBW) infants, nailbed capillary network density parameters (e.g. capillary skeletal length per area and branch points per area) significantly decrease during the first month of life. Our data also suggest that babies who ultimately developed ROP had a higher capillary density in the first few weeks after birth compared to those who do not. In this proposal, we will test the hypothesis that nailfold capillaroscopy can non-invasively detect capillary development impairment in premature infants and predict development of ROP requiring medical intervention. Therefore, we will address the following specific aims: 1) Identify the longitudinal developmental changes of nailfold capillaries in premature infants; 2) define capillary nailfold parameters that most reliably predict moderate to severe ROP development in VLBW infants. We have established a multi-disciplinary research team which includes the Northwestern University (NU) Imaging Core, the NU school of engineering and the departments of Ophthalmology and Neonatology at Ann & Robert H. Lurie Children’s Hospital of Chicago. If successful, the scientific premise of this project would include: 1) To non-invasively identify infants with vascular growth impairment which could benefit from novel therapeutic interventions aimed at preventing microvascular complications of prematurity, including ROP, thus improving patient outcomes; 2) To monitor the systemic effect of therapies targeting the microvasculature e.g. anti-VEGF antibodies. For this proof-of-principle study, we will focus on prediction of moderate to severe ROP as its diagnosis is directly based on the extent of retinal capillary maldevelopment. However, we plan in the future to expand our study to other microvascular beds that are less accessible to exam and to determine whether abnormal nailfold capillary development is able to predict other complications of prematurity e.g. NEC, BPD-related PHTN.