Application of a Light/Dark Cycle in Preterm Neonates and Its Association With Shorter In-hospital Stay

Introduction Worldwide, Neonatal Intensive Care Units (NICU) are often maintained under 24-hour constant bright light (CBL) conditions, without significant variations in light intensity. As such, infants under these conditions are exposed to chaotic temporal signals, as opposed to predictable temporal signals, without cyclic variations in terms of sounds and light. Interestingly, the level of light to which premature infants are exposed represents an accessible environmental variable that can be easily controlled. Premature infants are generally maintained under CBL conditions for prolonged intervals, thus hampering their growth and development. CBL conditions can generate harmful effects to newborn eyes, and experimental studies have shown that newborn rats exposed to a CBL environment from the first day of birth develop damage in the cellular organization of the retina.

Previous studies have shown that a 12:12 hour light/darkness cycle (LDC) can promote an increase in infant sleep time, decrease feeding time and improve weight gain, compared with infants maintained in constant light or constant dark conditions. Further, evidence shows that infants exposed to a LDC since birth acquire circadian rhythmicity of activity/rest patterns as early as week 34 of life.

This study presents the results from a multicentric trial which sought to determine the benefits of implementing a LDC in the NICU of three different hospitals in Mexico. The primary endpoint was weight gain; secondary endpoints included early hospital discharge, salivary melatonin levels and the effect of reducing the intensity of nocturnal light in development of premature infants.

Methods Study Design and Participants This prospective, open-label, randomized multicentric clinical trial recruited patients in three different public-setting hospitals in Mexico between 2016 and 2020. Eligible patients were premature infants (gestational age <37 weeks) who were hospitalized in the low risk and high-risk neonatal units of participating institution, with a non-severe diagnosis for hospitalization, without concomitant illness, and classified as stable. Exclusion criteria included infants hospitalized with severe illness, congenital malformations, or important neurological diseases, while elimination criteria included infants initially classified as having a non-severe illness who progress to severe illness, infants who received intensive treatment for over a week due to medical complications (i.e. bacterial infections), as well as infants whose parents requested withdrawal from participating in the study. The parents or legal guardians of all included patients provided written informed consent to participate in this study. Participating institutions included Centro Medico Nacional "La Raza", Mexico City; Hospital General de Zona No.1 "Dr. Demetrio Mayoral Pardo" Oaxaca City, Oaxaca, Mexico (both hospitals from the public healthcare system "Mexican Institute for Social Security IMSS"), and General Hospital "Dr. Aurelio Valdivieso", Oaxaca City, Oaxaca, Mexico (from the public healthcare system of the Health Secretariat [SSA]). The study was approved by the scientific and bioethical committees of each participating institution (CMNR-No. 3504-35, HGZ 1 IMSS Oaxaca R-2001-2015-8, SSO-R. 023/2018 y UNAM-094/2014). The study was performed in accord with the declaration of Helsinki and the principles of good clinical practice. This study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines.

Sample Size The sample size was calculated for a two-sample comparison, given an 80% sensitivity and a 60% specificity and with a confidence interval of 90%. A total of 150 patients per group was estimated, for a total sample size of 300 subjects.