Beginning to See the Light: Lessons Learned From the Development of the Circadian System for Optimizing Light Conditions in the Neonatal Intensive Care Unit

Abstract

The circadian timing system optimizes health by temporally coordinating behavior and physiology. During mammalian gestation, fetal circadian rhythms are synchronized by the daily fluctuations in maternal body temperature, hormones and nutrients. Circadian disruption during pregnancy is associated with negative effects on developmental outcomes in the offspring, highlighting the importance of regular and robust 24-h rhythms over gestation. In the case of preterm birth (before 37 weeks of gestation), maternal cues no longer synchronize the neonate's circadian system, which may adversely affect the neonate. There is increasing evidence that introducing robust light-dark cycles in the Neonatal Intensive Care Unit has beneficial effects on clinical outcomes in preterm infants, such as weight gain and hospitalization time, compared to infants exposed to constant light or constant near-darkness. However, the biological basis for these effects and the relationship with the functional and anatomical development of the circadian system is not fully understood. In this review, we provide a concise overview of the effects of light-dark cycles on clinical outcomes of preterm neonates in the NICU and its alignment with the development of the circadian system.

Keywords: Neonatal Intensive Care Unit; chronobiology; circadian system; cycled light; development; eye development and function; preterm infants.

FIGURE 1

Overview of light levels used in cycled light studies that have been conducted in Neonatal Intensive Care Units. Light levels reported in studies that investigated the effect of cycled light versus (A) constant light and (B) constant near-darkness. Values are depicted as ranges (shaded rectangles), means (dots), and/or standard deviations (error bars), depending on the values reported in the publication. Yellow/Orange colors indicate “light”, Black/Gray colors indicate “darkness”. *Standard errors reported in Rivkees et al. (2004) are converted to standard deviations by multiplying with the square root of the n per group. **Light intensities measured in the horizontal plane are reported here. ***Unclear whether standard deviations or standard errors are reported; using published values for error bars.

FIGURE 2

Developmental timeline of the human circadian system, based on reviewed human and animal studies. Bold text: developmental time points that are obtained from human studies. Italic text: developmental time points that are inferred from animal studies, using the gestational age equivalent to humans.