EHD-03959; No of Pages 6 Early Human Development xxx (2014) xxx–xxx
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A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants Samuel Vásquez-Ruiz a, José Alfonso Maya-Barrios b, Patricia Torres-Narváez b, Benito Rubén Vega-Martínez a, Adelina Rojas-Granados c, Carolina Escobar c, Manuel Ángeles-Castellanos c,⁎ a b c
Neonatology Department, Hospital Juárez de México, Secretaría de Salud Neonatology Department, Hospital General Dr. Manuel Gea González, Secretaría de Salud Department of Anatomy, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF 04510, México
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Article history: Received 25 November 2013 Received in revised form 10 April 2014 Accepted 12 April 2014 Available online xxxx Keywords: Circadian rhythms Chronotherapy Melatonin Neonatology
a b s t r a c t Background: Bright constant light levels in the NICU may have negative effects on the growth and development of preterm infants Objective: The aim of this study is to evaluate the benefits of an alternating light/dark cycle in the NICU on weight gain and early discharge from the therapy in premature infants. Patients and methods: A randomized interventional study was designed comparing infants in the NICU of Hospital Juarez de México, exposed from birth either to an LD environment (LD, n = 19) or to the traditional continuous light (LL, n = 19). The LD condition was achieved by placing individual removable helmets over the infant's heads. Body weight gain was analyzed, as the main indicator of stability and the main criteria for discharge in preterm infants born at 31.73 ± 0.31 week gestational age. Results: Infants maintained in an LD cycle gained weight faster than infants in LL and therefore attained a shorter hospital stay, (34.37 ± 3.12 vs 51.11 ± 5.29 days; P N 0.01). Also, LD infants exhibited improved oxygen saturation and developed a daily melatonin rhythm. Conclusions: These findings provide a convenient alternative for establishing an LD environment for preterm healthy newborns in the NICU and confirm the beneficial effects of an alternating LD cycle for growth and weight gain and for earlier discharge time. Here we provide an easy and practical alternative to implement light/dark conditions in the NICU. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction Infants in the Neonatal intensive Care Units (NICU) are exposed to constant light (LL) and controlled conditions. In adults circadian organization is disrupted by LL environments. Previous studies have reported that bright light levels in the NICU may have negative effects on the growth and development of preterm infants [1,4]. Mann et al. [8] reported that providing a light/dark (LD) cycle in the NICU increased sleeping time in infants, decreased the time spent feeding, and increased weight gain as compared to that of infants remaining in a typical LL nursery environment. In another study, infants exposed to an LD cycle from the 34th week of life acquired earlier the activity/rest rhythmicity [16]. The purpose of this study was to evaluate the benefits of an alternating LD cycle in the NICU of a Mexican public Hospital on weight gain and
⁎ Corresponding author. Tel.: +52 55 5623 2422. E-mail address: [email protected] (M. Ángeles-Castellanos).
early discharge in preterm infants, and to objectively evaluate the effect of reducing intensity of light at night in the development of premature newborns. 2. Subjects and methods The study was conducted with thirty-eight premature infants with an average birth age of 31.73 ± 0.31 (range from 28 to 36.3 weeks) and satisfied the inclusion criteria. The infants were under 24 h surveillance in the NICU of the neonatology service of the Hospital Juárez de Mexico. All infants were kept in individual incubators with a bed mattress (Isolette, Air- Shields, Dräger Medical and Siemens Company, Germany). Along the 24-h the temperature in the incubator was regulated to maintain a body temperature of 36.5 °C to 37 °C. Infants were assigned by sequential randomization method, where the first infant was assigned to the control constant light (LL) group (n = 19), the second to the experimental light/dark cycle (LD) group (n = 19) and so on. Patients were recruited and the lighting conditions were supervised by three resident investigators. Two
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Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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investigators, who were blinded to the patients' conditions analyzed and interpreted the data. Infants were cleaned and nursed every 3 h by 3 nurses blinded to the infants assigned group also there, heart rate, pulse oximetry were assessed. A informed consent was signed by the parents, and this study was approved by the ethical committee of the Facultad de Medicina, UNAM and the Research Committee of Hospital Juárez de Mexico; HJM1794/09.11.24-R. 2.1. Lighting conditions
meals without respiratory difficulty and mainly a constant body weight gain surpassing 2000 g. 2.2.5. Melatonin determination In eight infants, four in LL and four in LD, saliva samples were obtained in the morning (8:00 h) and in the evening (21:00 h), on the day of admission and on days 1, 5, 10, 15 and 20 during their stay in the NICU. Concentration of salivary melatonin was determined with a kit for ELISA method (enzyme immunoassay for direct quantitative determination of melatonin in human saliva; of IBL International).
In the NICU background lighting at the level of the incubators was 249 ± 11 lux, with light provided by overhead fluorescent white lamps. Control LL infants were exposed to the daily CL conditions of the NICU. Infants to the experimental LD condition remained in the same room, but the LD condition was achieved by placing from 19:00 to 07:00 an acrylic helmet (Adult Oxy-Hood of 30 cm diameter; IDEM, México), covered with blue surgical drapes (50 × 60 cm, Medline Industries. Inc. USA); the surgical cloths were placed on helmets, and the frontal part was open allowing good airflow (see Fig. 1). This helmet was placed individually above the head and thorax of each baby as shown in Fig. 1, resulting in a reduced illumination, with a light intensity of 27 lux ± 0.8 at the level of the eyes.
Data of body weight gain, food intake, melatonin concentration, heart rate and pulse oximetry were classified by group and postnatal days as repeated measures and were compared using a two-way analysis of variance (ANOVA), followed by a Tukey post hoc test with significant values set at P b 0.05; initial weight, gestational age and in-hospital days were compared using a Student “t”-test with significant values set at p b 0.05. Statistical analysis was performed with the program STATISTICA version 4.5 (StatSoft, Inc. 1993) and graphs were elaborated with Sigma Plot version 10.
2.2. Criteria for general state improvement
3. Results
2.2.1. Weight gain Infants were weighed daily, in the morning (8 am), with the incubator scale; weight gain was organized by groups to determine the daily bodyweight gain during the first 21 days of hospitalization.
A total of 38 infants were enrolled for this study. The characteristics of these infants are shown in Table 1. Among the different groups, the infants were similar in postmenstrual age, birth weight and weight at discharge.
2.2.2. Milk intake All infants were left 12 h in fasting after birth for bowel rest, and started enteric feeding with a dose of 12.5 ml/kg/day of maternal milk, which was increased every 12 h to reach a maximum of 200 ml/ kg/day. In all cases, infants received oral feeding. When infants reached 1600 g of weight, breast-suckling was initiated to prepare for discharge. The results are represented as means ± SE/day. 2.2.3. Heart rate and pulse oximetry Heart rate and pulse oximetry were monitored continuously along the 24 h with a monitoring equipment of vital signals (Criticare Poet Plus 8100, Soma Technology, Inc. USA), and readings were consulted every 3 h daily from the day of admission to day 21. 2.2.4. Hospital discharge Healthy preterm infants with adequate growth curve were considered ready for discharge when they met the following criteria: the ability to maintain the temperature in an open crib, the ability to perform all
2.3. Statistical analysis
3.1. Milk intake Infants were nursed every 3 h (8 meals) and received the total dose calculated for body weight distributed in 24 h. During the first 10 days in the NICU, more intolerance was reported in the LL group as compared to the LD group; 11 infants of LL and 5 infants of the LD group showed symptoms of food intolerance (vomiting, diarrhea, abdominal distension), and low milk intake according to the calculated daily dose. On day 12 a recovery in food consumption was observed and most infants of the LD group consumed higher volume of milk than LL infants (Fig. 2A). The two-way ANOVA indicated statistically significant differences between groups (F(1,294) = 985.9; p b 0.0001), along time (F(20,294) = 910.11; p b 0.0001), and in the interaction of groups × time (F20,294) = 47.2; p b 0.0001). 3.2. Body weight gain Infants of both groups lost weight ranging from 20 to 100 g after birth. Children assigned to LL lost body weight during the first 10 days
Fig. 1. Photograph showing the lighting conditions of the infants in the study: A) the control group remained under constant lighting conditions, as commonly found in the NICU (light: 249 ± 11 lux), and B) the experimental group were under a 12:12 light/dark, light (249 ± 11 lux) 7:00 am to 07:00 pm, and darkness (27 ± 0.8 lux) from 7:00 pm to 7:00 am (with the head covered by a cloth, as shown in the picture).
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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Table 1 The characteristics of these infants enrolled for this study. N
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Average SEM P value
Gestational age (wk)
Birth weight (g)
Length of stay (d)
Discharge weight (g)
Discharge age (wk)
Control
Experimental
Control
Experimental
Control
Experimental
Control
Experimental
Control
Experimental
33.2 32 31 33 32 33 31 32 29 33.6 31 31 31 35 31 30 32 30 32 31.73 0.31 N.S
33 30 33 31 33.4 28 30 30 35 30 33.1 36.3 30 29 29 31 35 32 35 31.67 0.55
1676 1310 2430 1400 1850 2600 1300 1680 1270 1480 1530 1020 1180 1200 820 1570 1280 720 1280 1452.42 101.88 N.S
1525 1472 1810 1352 1660 780 1090 1140 3250 1150 1520 2440 1080 1460 1010 1330 1250 2000 2390 1563.63 130.68
52 66 40 30 31 96 35 20 98 64 26 66 40 35 78 36 36 86 66 51.11 5.29 0.014
26 30 25 22 21 78 41 36 30 31 29 38 45 63 57 35 28 29 11 34.37 3.12
2450 2200 2430 2050 2010 3020 2030 1870 2820 2320 1980 2020 2200 2040 2870 2010 2030 3270 2350 2314.21 87.60 N.S
2356 2400 2100 2560 1910 2460 2030 1890 2030 1970 2200 2020 1900 2210 2240 2030 2100 2340 2580 2175.05 48.0005
39.5 39.1 36.5 37.2 36.3 46.5 36 34.6 43 42.2 34.5 40.3 36.5 40 42.1 35.1 37.1 42.2 37.1 38.7 0.75 0.017
36.5 34.2 36.4 34.1 36.4 39.1 36.1 35.1 39.2 34.2 37.2 41.6 36.3 38 37.1 36 39 36.1 36.4 36.8 0.43
in the NICU started to gain weight after day 11 and recovered the initial birth weight on day 20 in the NICU. Infants in LD conditions started to gain weight after 8 days and had reached their initial birth weight on day 10 (Fig. 2B). On day 21 the difference of body weight gain was 150 g, with the highest levels for LD infants. The two-way ANOVA indicated statistically significant differences between groups (F(1,560) = 120.06; p b 0.0001) and factor time (F(19,560) = 5.78; p b 0.0001), but not in the interaction of groups × time (F19,560) = 1.32;p N 0.0760. 3.3. Heart rate Control infants maintained in LL exhibited an irregular pattern in the number of heart beats per minute: some days their mean heart rate was very high and other days low. In contrast, infants kept under LD exhibited a stable mean heart rate along days starting from postnatal day 3 (Fig. 3A). The two-way ANOVA indicated statistically significant differences between groups (F(1,294) = 9.96; p b 0.001), along time (F(20,294) = 3.44; p b 0.00001), and for the interaction of both factors (F(20,294) = 2.99; p b 0.0001).
3.4. Pulse oximetry An improvement in peripheral oxygen saturation, monitored by pulse oximetry, was observed in the LL group after day 7 of stay in the NICU, while in the LD group an improvement in peripheral oxygen saturation was observed on day 3 in LD, and a major concentration of oxygen during the following days of stay in the NICU, compared with the control group (see Fig. 3B). The two-way ANOVA showed statistically significant differences in the factor groups (F (1,294) = 395.23; p b 0.0001), also in the factor time (F(20,294) = 129; p b 0.0001), and in the interaction of groups × time (F20,294) = 7.492; p b 0.0001). 3.5. Salivary melatonin In the LL group melatonin levels in the morning and in the evening were equally high and constant during the first 20 days in the NICU; the two-way ANOVA did not show statistically significant differences between the day and night values (F(1,38) = 0.0052; p = N.S; see Fig. 4A). Interestingly in the LD group saliva melatonin exhibited
Fig. 2. Graphs showing in white circles (O) the control group and in black circles (●) the experimental group. A) Milk consumption per day by the two groups. The experimental group tolerated more food since the first days compared to control; there is a significant difference between the groups. *P b 0.001. B) Graph showing the weight gain of the two groups, a significant difference after the first 7 days can be observed. This result reflects the best adaptation to food and probably a better digestive response. *p b 0.001.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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Fig. 3. A) The heart rate of the control group maintained in constant illumination exhibited an irregular pattern, and the experimental group kept under a light/dark cycle exhibited a stable mean heart rate along days starting from day 3 of exposure to LD conditions, *p b 0.0001). B) Pulse oximetry in the experimental group showed an improvement in peripheral oxygen saturation on the third day under light/dark cycle, and a major concentration of oxygen during the following days of stay in the NICU, compared with the control group; *p b 0.0001), (o) control group and (●) experimental group.
lower levels in the light phase as early as day 5 and higher melatonin levels during the dark phase, resulting a daily rhythm in melatonin concentration (see Fig. 4B). The two-way ANOVA indicated statistically significant differences between light and dark phases (F(1,38) = 41.75; p b 0.00001), also in the factor time (F(5,38) = 2.225; p b 0.01), and in the interaction of groups × time (F5,38) = 3.3553; p b 0.0001).
3.6. Hospital discharge time The first baby of the LL group was discharged from the hospital on postnatal day 20 (35 wk) and the last baby of this group was discharged from the hospital on postnatal day 98 (43 wk). Contrasting with the LD group, in which the first child was discharged from the hospital on postnatal day 11 (36.6 wk) and the last baby of this group was discharged on day 63 of age (38 wk; see Table 1 and Fig. 5A). Thus the average days of stay in the NICU were significantly lower (P b 0.01) for infants exposed to an alternating light/dark cycle (Fig. 5B).
4. Discussion In this study we observed that heart rate stability, percentage of oxygen saturation in the periphery, as well as a daily difference in the levels of daytime vs. nighttime salivary melatonin were established between the third and fifth days after exposure to a cycle of light/dark. Also the LD cycle promoted a better tolerance to milk and accelerated body weight gain which was directly reflected in reduced hospital stay, suggesting that the LD cycle immediately after birth promotes beneficial effects on the development of premature infants. At birth the experimental and control groups were similar in weight and gestational age; therefore we can conclude that the light/dark cycle promoted adaptive responses in the baby, while the constant light environment has detrimental effects causing heart rate instability and decreasing peripheral oxygen saturation, important physiological parameters during this critical stage of development [10]. A controversy exists on whether a light/dark cycle at this early age is necessary and whether it exerts any effects on development. Kennedy
Fig. 4. Graph showing salivary melatonin levels every 5 days. A) Constant light control group, the gray bars indicate the light phase (day), while the stripe-pattern bars indicate the dark phase (night); melatonin levels in the morning and equally in the night were high and stable during the first 20 days. B) Experimental group, the gray bars indicate the light phase (day) and the black bars of the dark phase (night). Interestingly, this group showed lower levels of salivary melatonin in the light phase and higher levels during the dark phase starting from day 5 under the LD conditions. *P b 0.0001.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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Fig. 5. A) The dynamics of hospital discharge. It was observed that infants under the LD cycle were discharged earlier than those who were kept in LL. B) The average number of hospital stay days in the control group was longer than the experimental group who were discharged 20.5 days earlier. *p b 0.001. (o) Control group and (ν) experimental group.
et al. [7] did not find benefit or detrimental effects on weight gain by reducing the light reaching the eyes of premature infants. In such study goggles were placed during the night on infants which resulted in a 97% light reduction during the 4–6 first weeks of life of the newborn; the design of that study differs from ours, since they decreased the intensity steadily and we believe that the positive results of our study are mainly due to the effect of the light/dark cycle as a temporal signal. In a first stage of the present study we likewise tried to use goggles; however, we observed restlessness in the babies and movements directed to remove the goggles and therefore decided to use the acrylic helmets which do not touch the body and head and thus do not disturb the baby. Mirmiran et al. [12] also did not find significant differences between neonates maintained in a constant dim light nursery (below 20 lux) and neonates in incubators that were covered with an opaque blanket from 19:00 h to 07:00 h, to produce a regular light/dark cycle. The conditions of dim light may resemble constant darkness and do not affect the biological clock as a constant bright light. We speculate that in Mirmiran's paper the beneficial effects of the LD cycle probably were masked when contrasted with a group with low or no effects due to the lighting conditions. Moreover, Boo et al. [2] by maintaining infants in constant dim light or constant darkness also did not report statistically significant difference between groups on body weight gain by day 14. Other studies have reported beneficial effects on infants' development similar to the present study. Mann et al. [8] reported that exposing infants to light/dark cycles improved infant weight gain, and promoted increased sleep episodes in 24 h; which did not occur in infants under constant illumination patterns. This effect was reflected in a shorter hospital stay and decreased mechanical support, especially when exposure to the LD cycle started before 36 weeks of age [3]. A meta-analysis published in the Cochrane Database of Systematic Reviews 2011 [13,14] analyzing the potential benefits of a light/dark cycle, reported the beneficial effects of the alternating light/dark cycle for infants, characterized by a decrease in the number of days requiring supplemental oxygen [11], as well as earlier and better food tolerance leading to increased average weight gain. The same study reported that the average number of hours awake during 24 h was decreased in the group exposed to the alternating light/dark cycle [8]. Also, infants under a light/dark cycle accomplish a temporal organization in general activity with respect to the constant-light group before discharge [17], confirming the beneficial effects on circadian development reflected in the present study in melatonin. These results support the findings of our study, indicating the need for a light/ dark cycle in the NICU. An important consequence of the alternating light/dark cycle in the NICU is an increase in sleep episodes; due to the anabolic effect of
sleep, it may have promoted infants' growth, shown by the weight gain. There is evidence that the endogenous circadian rhythm of sleep/wake is spontaneously developed in the human infant, and that the light/dark cycle accelerates and synchronizes its appearance [15]. Full term newborns exhibit ultradian rhythms of rest–activity; thus they sleep both during the night and day, and spend about 16–17 h sleeping. At the age of 3 to 6 postnatal weeks, sleep time is reduced to 14 or 15 h, and the normal circadian pattern starts to appear. This process is delayed in premature infants [19]; however, previous results combined with the present data suggest that the sleep–wake cycle can be induced and can improve due to the light/dark cycle as described by Parmelee et al. [15]. In this study we found that preterm infants in the control group showed a very unstable heart rate in accordance to a previous report indicating that premature infants have very unstable control of both heart rate and blood pressure compared with term infants [21]; moreover, the stress generated by constant lighting conditions can contribute to this problem in the NICU. Here we show that an alternating light/dark cycle can promote stabilization of heart rate as soon as 3 days after exposure to this manipulation. In preterm infants sleep has a significant effect on heart rate variability, and it has been suggested that the instability of heart rate in these infants is due to the increasing global sympathetic activity, along with the increased locomotive activity characteristic of infants with sleep disturbance, noting that there is an imbalance between the sympathetic/parasympathetic modulation of heart rate, and that the maturation of this system is achieved with age [20]. The ontogeny of melatonin production in infants has been studied by measuring the urinary metabolite of melatonin (6-sulfatoxymelatonin). In infants born at term the melatonin circadian rhythm is observed after 8 weeks of age, while preterm infants only express a rhythmic melatonin production after 12 weeks of age [5,6]. This value was obtained in preterm infants maintained in constant light conditions with lighting intensity ranging from 400 to 700 lux at the infants' eye level and such intensity has been described to inhibit melatonin production in adults [18]. In the present study infants were maintained in constant light conditions (249 ± 11 lux), and melatonin remained constant and did not decrease at night. Such observations are supported by a previous study where high levels of melatonin and rhythm disturbance were observed in infants admitted to the ICU in conditions of constant light [9]. On the other hand, in the present study infants exposed to 249 ± 11 lux during the day and to 27 ± 0.8 lux during the night exhibited a daily rhythmicity of saliva melatonin. This finding indicates that a well established alternation of a light/dark cycle condition can be beneficial for the maturation of the baby's physiology including a rhythmic pattern in daily melatonin production.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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5. Conclusions In summary, we found that exposing premature infants to a light/ dark cycle improved physiological development, promoted a rapid weight gain, and especially decreased the hospital discharge time. The latter implies benefits for the baby who is quickly incorporated to the family and by leaving the hospital the risk of exposure to nosocomial diseases is reduced. Furthermore, the direct and indirect economic costs in health services are also reduced. Here we provide an easy and practical alternative to implement light/dark conditions in the NICU. Contributor's statement Samuel Vásquez Ruiz: Dr. Vasquez conceptualized and designed the study, supervised the collection of samples and carried out the initial analyses, drafted the initial manuscript, and approved the final manuscript as submitted. José Alfonso Maya Barrios: Dr. Maya supervised the collection of samples and carried out the analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. Patricia Torres Narváez: Dra. Torres revised the manuscript, and approved the final manuscript as submitted. Benito Vega Martínez: Dr. Vega revised the manuscript, and approved the final manuscript as submitted. Adelina Rojas-Granados: Dra. Granados participated in the discussion of results and in the final structure and revised the manuscript, and approved the final manuscript as submitted. Carolina Escobar: Dra. Escobar conceptualized and designed the study, participated in the discussion of results and in the final structure of the manuscript, along with Dr. Angeles-Castellanos, reviewed the manuscript critically and approved the final manuscript submitted Manuel Ángeles-Castellanos: Dr. Ángeles-Castellanos conceptualized and designed the study, supervised the collection of samples and data collection, performed analyses and graphs, drafted the final version of the manuscript and reviewed the manuscript critically and approved the final manuscript submitted. Conflict of interest We declare no conflict of interest with respect to the data reported in this study. Acknowledgments This study was supported by grants DGAPA IN-209712 and IN 205809, and the special Cathedra “DR. ALBERTO GUEVARA ROJAS”. Authors wish to thank María Elisa Vega Memije, Lorena Hernández
Delgado Hospital Manuel Gea Gonzales; Mexico City, and the medical and nursing staff of the NICU for their cooperation in this study. References [1] Blackburn S. Environmental impact of the NICU on developmental outcomes. J Pediatr Nurs 1998;13:279–89. [2] Boo NY, Chee SC, Rohana J. Randomized controlled study of the effects of different durations of light exposure on weight gain by preterm infants in a neonatal intensive care unit. Acta Pediatr 2002;91:674–9. [3] Brandon DH, Holditch-Davis D, Belyea M. Preterm infants born at less than 31 weeks' gestation have improved growth in cycled light compared with continuous near darkness. J Pediatr 2002;140:192–9. [4] Gottfried A. Environmental neonatology. In: Gottfried A, Gaiter J, editors. Infant stress under intensive care. Baltimore (MD): University Park Press; 1985. p. 252–7. [5] Kennaway DJ, Goble FC, Stamp GE. Factors influencing the development of melatonin rhythmicity in humans. J Clin Endocrinol Metab 1996;81:1525–32. [6] Kennaway DJ, Stamp GE, Goble FC. Development of melatonin production in infants and the impact of prematurity. J Clin Endocrinol Metab 1992;75:367–9. [7] Kennedy KA, Fielder AR, Hardy RJ, Tung B, Gordon DC, Reynolds JD, et al. Reduced lighting does not improve medical outcomes in very low birth weight infants. J Pediatr 2001;139(4):527–31. [8] Mann NP, Haddow R, Stokes L, Goodley S, Rutter N. Effect of night and day on preterm infants in a newborn infants: randomised trial. Br Med J (Clin Res Ed) 1986;293:1265–12667. [9] Marseglia L, Aversa S, Barberi I, Salpietro CD, Cusumano E, Speciale A, et al. High endogenous melatonin levels in critically ill children: a pilot study. J Pediatr 2013;162(2):357–60. [10] Merritt TA, Pillers D, Prows SL. Early NICU discharge of very low birth weight infants: a critical review and analysis. Semin Neonatol 2003;8(2):95–115. [11] Miller C, White R, Whitman T, O'Callaghan M, Maxwell S. The effects of cycled versus noncycled lighting on growth and development in preterm infants. Infant Behav Dev 1995;18:87–95. [12] Mirmiran M, Baldwin RB, Ariagno RL. Circadian and sleep development in preterm infants occurs independently from the influences of environmental lighting. Pediatr Res 2003;53(6):933–8. [13] Morag I, Ohlsson A. Cycled light in the intensive care unit for preterm and low birth weight infants. Cochrane Database of Systematic Reviews. The Cochrane Library; 2011 [10, Art. No.CD006982]. [14] Morag I, Ohlsson A. Cycled light in the intensive care unit for preterm and low birth weight infants. Cochrane Database of Systematic Reviews. The Cochrane Library; 2013 [3,8, Art. No.CD006982]. [15] Parmelee Jr AH, Schulz HR, Disbrow MA. Sleep patterns of the newborn. J Pediatr 1961;58:241–50. [16] Rivkees SA. Developing circadian rhythmicity in infants. Pediatrics 2003;112(2): 373–81. [17] Rivkees SA, Mayes L, Jacobs H, Gross I. Rest–activity patterns of premature infants are regulated by cycled lighting. Pediatrics 2004;113:833–9. [18] Skene DJ, Arendt J. Human circadian rhythms: physiological and therapeutic relevance of light and melatonin. 2006;43(Pt 5):344–53. [19] Waterhouse JM, Minors DS. Circadian rhythms in the neonate and in old age: what do they tell us about the development and decay of the body clock in humans? Braz J Med Biol Res 1996;29(1):87–94. [20] Yiallourou SR, Witcombe NB, Sands SA, Walker AM, Horne RSC. The development of autonomic cardiovascular control is altered by preterm birth. Early Hum Dev 2013;89(3):145–52. [21] Viskari-Lähdeoja S, Hytinantti T, Andersson S, Kirjavainen T. Acute cardiovascular responses in preterm infants at 34–39 weeks of gestational age. Early Hum Dev 2012;88:871–7.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants Samuel Vásquez-Ruiz a, José Alfonso Maya-Barrios b, Patricia Torres-Narváez b, Benito Rubén Vega-Martínez a, Adelina Rojas-Granados c, Carolina Escobar c, Manuel Ángeles-Castellanos c,⁎ a b c
Neonatology Department, Hospital Juárez de México, Secretaría de Salud Neonatology Department, Hospital General Dr. Manuel Gea González, Secretaría de Salud Department of Anatomy, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF 04510, México
a r t i c l e
i n f o
Article history: Received 25 November 2013 Received in revised form 10 April 2014 Accepted 12 April 2014 Available online xxxx Keywords: Circadian rhythms Chronotherapy Melatonin Neonatology
a b s t r a c t Background: Bright constant light levels in the NICU may have negative effects on the growth and development of preterm infants Objective: The aim of this study is to evaluate the benefits of an alternating light/dark cycle in the NICU on weight gain and early discharge from the therapy in premature infants. Patients and methods: A randomized interventional study was designed comparing infants in the NICU of Hospital Juarez de México, exposed from birth either to an LD environment (LD, n = 19) or to the traditional continuous light (LL, n = 19). The LD condition was achieved by placing individual removable helmets over the infant's heads. Body weight gain was analyzed, as the main indicator of stability and the main criteria for discharge in preterm infants born at 31.73 ± 0.31 week gestational age. Results: Infants maintained in an LD cycle gained weight faster than infants in LL and therefore attained a shorter hospital stay, (34.37 ± 3.12 vs 51.11 ± 5.29 days; P N 0.01). Also, LD infants exhibited improved oxygen saturation and developed a daily melatonin rhythm. Conclusions: These findings provide a convenient alternative for establishing an LD environment for preterm healthy newborns in the NICU and confirm the beneficial effects of an alternating LD cycle for growth and weight gain and for earlier discharge time. Here we provide an easy and practical alternative to implement light/dark conditions in the NICU. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction Infants in the Neonatal intensive Care Units (NICU) are exposed to constant light (LL) and controlled conditions. In adults circadian organization is disrupted by LL environments. Previous studies have reported that bright light levels in the NICU may have negative effects on the growth and development of preterm infants [1,4]. Mann et al. [8] reported that providing a light/dark (LD) cycle in the NICU increased sleeping time in infants, decreased the time spent feeding, and increased weight gain as compared to that of infants remaining in a typical LL nursery environment. In another study, infants exposed to an LD cycle from the 34th week of life acquired earlier the activity/rest rhythmicity [16]. The purpose of this study was to evaluate the benefits of an alternating LD cycle in the NICU of a Mexican public Hospital on weight gain and
⁎ Corresponding author. Tel.: +52 55 5623 2422. E-mail address: [email protected] (M. Ángeles-Castellanos).
early discharge in preterm infants, and to objectively evaluate the effect of reducing intensity of light at night in the development of premature newborns. 2. Subjects and methods The study was conducted with thirty-eight premature infants with an average birth age of 31.73 ± 0.31 (range from 28 to 36.3 weeks) and satisfied the inclusion criteria. The infants were under 24 h surveillance in the NICU of the neonatology service of the Hospital Juárez de Mexico. All infants were kept in individual incubators with a bed mattress (Isolette, Air- Shields, Dräger Medical and Siemens Company, Germany). Along the 24-h the temperature in the incubator was regulated to maintain a body temperature of 36.5 °C to 37 °C. Infants were assigned by sequential randomization method, where the first infant was assigned to the control constant light (LL) group (n = 19), the second to the experimental light/dark cycle (LD) group (n = 19) and so on. Patients were recruited and the lighting conditions were supervised by three resident investigators. Two
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Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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investigators, who were blinded to the patients' conditions analyzed and interpreted the data. Infants were cleaned and nursed every 3 h by 3 nurses blinded to the infants assigned group also there, heart rate, pulse oximetry were assessed. A informed consent was signed by the parents, and this study was approved by the ethical committee of the Facultad de Medicina, UNAM and the Research Committee of Hospital Juárez de Mexico; HJM1794/09.11.24-R. 2.1. Lighting conditions
meals without respiratory difficulty and mainly a constant body weight gain surpassing 2000 g. 2.2.5. Melatonin determination In eight infants, four in LL and four in LD, saliva samples were obtained in the morning (8:00 h) and in the evening (21:00 h), on the day of admission and on days 1, 5, 10, 15 and 20 during their stay in the NICU. Concentration of salivary melatonin was determined with a kit for ELISA method (enzyme immunoassay for direct quantitative determination of melatonin in human saliva; of IBL International).
In the NICU background lighting at the level of the incubators was 249 ± 11 lux, with light provided by overhead fluorescent white lamps. Control LL infants were exposed to the daily CL conditions of the NICU. Infants to the experimental LD condition remained in the same room, but the LD condition was achieved by placing from 19:00 to 07:00 an acrylic helmet (Adult Oxy-Hood of 30 cm diameter; IDEM, México), covered with blue surgical drapes (50 × 60 cm, Medline Industries. Inc. USA); the surgical cloths were placed on helmets, and the frontal part was open allowing good airflow (see Fig. 1). This helmet was placed individually above the head and thorax of each baby as shown in Fig. 1, resulting in a reduced illumination, with a light intensity of 27 lux ± 0.8 at the level of the eyes.
Data of body weight gain, food intake, melatonin concentration, heart rate and pulse oximetry were classified by group and postnatal days as repeated measures and were compared using a two-way analysis of variance (ANOVA), followed by a Tukey post hoc test with significant values set at P b 0.05; initial weight, gestational age and in-hospital days were compared using a Student “t”-test with significant values set at p b 0.05. Statistical analysis was performed with the program STATISTICA version 4.5 (StatSoft, Inc. 1993) and graphs were elaborated with Sigma Plot version 10.
2.2. Criteria for general state improvement
3. Results
2.2.1. Weight gain Infants were weighed daily, in the morning (8 am), with the incubator scale; weight gain was organized by groups to determine the daily bodyweight gain during the first 21 days of hospitalization.
A total of 38 infants were enrolled for this study. The characteristics of these infants are shown in Table 1. Among the different groups, the infants were similar in postmenstrual age, birth weight and weight at discharge.
2.2.2. Milk intake All infants were left 12 h in fasting after birth for bowel rest, and started enteric feeding with a dose of 12.5 ml/kg/day of maternal milk, which was increased every 12 h to reach a maximum of 200 ml/ kg/day. In all cases, infants received oral feeding. When infants reached 1600 g of weight, breast-suckling was initiated to prepare for discharge. The results are represented as means ± SE/day. 2.2.3. Heart rate and pulse oximetry Heart rate and pulse oximetry were monitored continuously along the 24 h with a monitoring equipment of vital signals (Criticare Poet Plus 8100, Soma Technology, Inc. USA), and readings were consulted every 3 h daily from the day of admission to day 21. 2.2.4. Hospital discharge Healthy preterm infants with adequate growth curve were considered ready for discharge when they met the following criteria: the ability to maintain the temperature in an open crib, the ability to perform all
2.3. Statistical analysis
3.1. Milk intake Infants were nursed every 3 h (8 meals) and received the total dose calculated for body weight distributed in 24 h. During the first 10 days in the NICU, more intolerance was reported in the LL group as compared to the LD group; 11 infants of LL and 5 infants of the LD group showed symptoms of food intolerance (vomiting, diarrhea, abdominal distension), and low milk intake according to the calculated daily dose. On day 12 a recovery in food consumption was observed and most infants of the LD group consumed higher volume of milk than LL infants (Fig. 2A). The two-way ANOVA indicated statistically significant differences between groups (F(1,294) = 985.9; p b 0.0001), along time (F(20,294) = 910.11; p b 0.0001), and in the interaction of groups × time (F20,294) = 47.2; p b 0.0001). 3.2. Body weight gain Infants of both groups lost weight ranging from 20 to 100 g after birth. Children assigned to LL lost body weight during the first 10 days
Fig. 1. Photograph showing the lighting conditions of the infants in the study: A) the control group remained under constant lighting conditions, as commonly found in the NICU (light: 249 ± 11 lux), and B) the experimental group were under a 12:12 light/dark, light (249 ± 11 lux) 7:00 am to 07:00 pm, and darkness (27 ± 0.8 lux) from 7:00 pm to 7:00 am (with the head covered by a cloth, as shown in the picture).
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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Table 1 The characteristics of these infants enrolled for this study. N
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Average SEM P value
Gestational age (wk)
Birth weight (g)
Length of stay (d)
Discharge weight (g)
Discharge age (wk)
Control
Experimental
Control
Experimental
Control
Experimental
Control
Experimental
Control
Experimental
33.2 32 31 33 32 33 31 32 29 33.6 31 31 31 35 31 30 32 30 32 31.73 0.31 N.S
33 30 33 31 33.4 28 30 30 35 30 33.1 36.3 30 29 29 31 35 32 35 31.67 0.55
1676 1310 2430 1400 1850 2600 1300 1680 1270 1480 1530 1020 1180 1200 820 1570 1280 720 1280 1452.42 101.88 N.S
1525 1472 1810 1352 1660 780 1090 1140 3250 1150 1520 2440 1080 1460 1010 1330 1250 2000 2390 1563.63 130.68
52 66 40 30 31 96 35 20 98 64 26 66 40 35 78 36 36 86 66 51.11 5.29 0.014
26 30 25 22 21 78 41 36 30 31 29 38 45 63 57 35 28 29 11 34.37 3.12
2450 2200 2430 2050 2010 3020 2030 1870 2820 2320 1980 2020 2200 2040 2870 2010 2030 3270 2350 2314.21 87.60 N.S
2356 2400 2100 2560 1910 2460 2030 1890 2030 1970 2200 2020 1900 2210 2240 2030 2100 2340 2580 2175.05 48.0005
39.5 39.1 36.5 37.2 36.3 46.5 36 34.6 43 42.2 34.5 40.3 36.5 40 42.1 35.1 37.1 42.2 37.1 38.7 0.75 0.017
36.5 34.2 36.4 34.1 36.4 39.1 36.1 35.1 39.2 34.2 37.2 41.6 36.3 38 37.1 36 39 36.1 36.4 36.8 0.43
in the NICU started to gain weight after day 11 and recovered the initial birth weight on day 20 in the NICU. Infants in LD conditions started to gain weight after 8 days and had reached their initial birth weight on day 10 (Fig. 2B). On day 21 the difference of body weight gain was 150 g, with the highest levels for LD infants. The two-way ANOVA indicated statistically significant differences between groups (F(1,560) = 120.06; p b 0.0001) and factor time (F(19,560) = 5.78; p b 0.0001), but not in the interaction of groups × time (F19,560) = 1.32;p N 0.0760. 3.3. Heart rate Control infants maintained in LL exhibited an irregular pattern in the number of heart beats per minute: some days their mean heart rate was very high and other days low. In contrast, infants kept under LD exhibited a stable mean heart rate along days starting from postnatal day 3 (Fig. 3A). The two-way ANOVA indicated statistically significant differences between groups (F(1,294) = 9.96; p b 0.001), along time (F(20,294) = 3.44; p b 0.00001), and for the interaction of both factors (F(20,294) = 2.99; p b 0.0001).
3.4. Pulse oximetry An improvement in peripheral oxygen saturation, monitored by pulse oximetry, was observed in the LL group after day 7 of stay in the NICU, while in the LD group an improvement in peripheral oxygen saturation was observed on day 3 in LD, and a major concentration of oxygen during the following days of stay in the NICU, compared with the control group (see Fig. 3B). The two-way ANOVA showed statistically significant differences in the factor groups (F (1,294) = 395.23; p b 0.0001), also in the factor time (F(20,294) = 129; p b 0.0001), and in the interaction of groups × time (F20,294) = 7.492; p b 0.0001). 3.5. Salivary melatonin In the LL group melatonin levels in the morning and in the evening were equally high and constant during the first 20 days in the NICU; the two-way ANOVA did not show statistically significant differences between the day and night values (F(1,38) = 0.0052; p = N.S; see Fig. 4A). Interestingly in the LD group saliva melatonin exhibited
Fig. 2. Graphs showing in white circles (O) the control group and in black circles (●) the experimental group. A) Milk consumption per day by the two groups. The experimental group tolerated more food since the first days compared to control; there is a significant difference between the groups. *P b 0.001. B) Graph showing the weight gain of the two groups, a significant difference after the first 7 days can be observed. This result reflects the best adaptation to food and probably a better digestive response. *p b 0.001.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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Fig. 3. A) The heart rate of the control group maintained in constant illumination exhibited an irregular pattern, and the experimental group kept under a light/dark cycle exhibited a stable mean heart rate along days starting from day 3 of exposure to LD conditions, *p b 0.0001). B) Pulse oximetry in the experimental group showed an improvement in peripheral oxygen saturation on the third day under light/dark cycle, and a major concentration of oxygen during the following days of stay in the NICU, compared with the control group; *p b 0.0001), (o) control group and (●) experimental group.
lower levels in the light phase as early as day 5 and higher melatonin levels during the dark phase, resulting a daily rhythm in melatonin concentration (see Fig. 4B). The two-way ANOVA indicated statistically significant differences between light and dark phases (F(1,38) = 41.75; p b 0.00001), also in the factor time (F(5,38) = 2.225; p b 0.01), and in the interaction of groups × time (F5,38) = 3.3553; p b 0.0001).
3.6. Hospital discharge time The first baby of the LL group was discharged from the hospital on postnatal day 20 (35 wk) and the last baby of this group was discharged from the hospital on postnatal day 98 (43 wk). Contrasting with the LD group, in which the first child was discharged from the hospital on postnatal day 11 (36.6 wk) and the last baby of this group was discharged on day 63 of age (38 wk; see Table 1 and Fig. 5A). Thus the average days of stay in the NICU were significantly lower (P b 0.01) for infants exposed to an alternating light/dark cycle (Fig. 5B).
4. Discussion In this study we observed that heart rate stability, percentage of oxygen saturation in the periphery, as well as a daily difference in the levels of daytime vs. nighttime salivary melatonin were established between the third and fifth days after exposure to a cycle of light/dark. Also the LD cycle promoted a better tolerance to milk and accelerated body weight gain which was directly reflected in reduced hospital stay, suggesting that the LD cycle immediately after birth promotes beneficial effects on the development of premature infants. At birth the experimental and control groups were similar in weight and gestational age; therefore we can conclude that the light/dark cycle promoted adaptive responses in the baby, while the constant light environment has detrimental effects causing heart rate instability and decreasing peripheral oxygen saturation, important physiological parameters during this critical stage of development [10]. A controversy exists on whether a light/dark cycle at this early age is necessary and whether it exerts any effects on development. Kennedy
Fig. 4. Graph showing salivary melatonin levels every 5 days. A) Constant light control group, the gray bars indicate the light phase (day), while the stripe-pattern bars indicate the dark phase (night); melatonin levels in the morning and equally in the night were high and stable during the first 20 days. B) Experimental group, the gray bars indicate the light phase (day) and the black bars of the dark phase (night). Interestingly, this group showed lower levels of salivary melatonin in the light phase and higher levels during the dark phase starting from day 5 under the LD conditions. *P b 0.0001.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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Fig. 5. A) The dynamics of hospital discharge. It was observed that infants under the LD cycle were discharged earlier than those who were kept in LL. B) The average number of hospital stay days in the control group was longer than the experimental group who were discharged 20.5 days earlier. *p b 0.001. (o) Control group and (ν) experimental group.
et al. [7] did not find benefit or detrimental effects on weight gain by reducing the light reaching the eyes of premature infants. In such study goggles were placed during the night on infants which resulted in a 97% light reduction during the 4–6 first weeks of life of the newborn; the design of that study differs from ours, since they decreased the intensity steadily and we believe that the positive results of our study are mainly due to the effect of the light/dark cycle as a temporal signal. In a first stage of the present study we likewise tried to use goggles; however, we observed restlessness in the babies and movements directed to remove the goggles and therefore decided to use the acrylic helmets which do not touch the body and head and thus do not disturb the baby. Mirmiran et al. [12] also did not find significant differences between neonates maintained in a constant dim light nursery (below 20 lux) and neonates in incubators that were covered with an opaque blanket from 19:00 h to 07:00 h, to produce a regular light/dark cycle. The conditions of dim light may resemble constant darkness and do not affect the biological clock as a constant bright light. We speculate that in Mirmiran's paper the beneficial effects of the LD cycle probably were masked when contrasted with a group with low or no effects due to the lighting conditions. Moreover, Boo et al. [2] by maintaining infants in constant dim light or constant darkness also did not report statistically significant difference between groups on body weight gain by day 14. Other studies have reported beneficial effects on infants' development similar to the present study. Mann et al. [8] reported that exposing infants to light/dark cycles improved infant weight gain, and promoted increased sleep episodes in 24 h; which did not occur in infants under constant illumination patterns. This effect was reflected in a shorter hospital stay and decreased mechanical support, especially when exposure to the LD cycle started before 36 weeks of age [3]. A meta-analysis published in the Cochrane Database of Systematic Reviews 2011 [13,14] analyzing the potential benefits of a light/dark cycle, reported the beneficial effects of the alternating light/dark cycle for infants, characterized by a decrease in the number of days requiring supplemental oxygen [11], as well as earlier and better food tolerance leading to increased average weight gain. The same study reported that the average number of hours awake during 24 h was decreased in the group exposed to the alternating light/dark cycle [8]. Also, infants under a light/dark cycle accomplish a temporal organization in general activity with respect to the constant-light group before discharge [17], confirming the beneficial effects on circadian development reflected in the present study in melatonin. These results support the findings of our study, indicating the need for a light/ dark cycle in the NICU. An important consequence of the alternating light/dark cycle in the NICU is an increase in sleep episodes; due to the anabolic effect of
sleep, it may have promoted infants' growth, shown by the weight gain. There is evidence that the endogenous circadian rhythm of sleep/wake is spontaneously developed in the human infant, and that the light/dark cycle accelerates and synchronizes its appearance [15]. Full term newborns exhibit ultradian rhythms of rest–activity; thus they sleep both during the night and day, and spend about 16–17 h sleeping. At the age of 3 to 6 postnatal weeks, sleep time is reduced to 14 or 15 h, and the normal circadian pattern starts to appear. This process is delayed in premature infants [19]; however, previous results combined with the present data suggest that the sleep–wake cycle can be induced and can improve due to the light/dark cycle as described by Parmelee et al. [15]. In this study we found that preterm infants in the control group showed a very unstable heart rate in accordance to a previous report indicating that premature infants have very unstable control of both heart rate and blood pressure compared with term infants [21]; moreover, the stress generated by constant lighting conditions can contribute to this problem in the NICU. Here we show that an alternating light/dark cycle can promote stabilization of heart rate as soon as 3 days after exposure to this manipulation. In preterm infants sleep has a significant effect on heart rate variability, and it has been suggested that the instability of heart rate in these infants is due to the increasing global sympathetic activity, along with the increased locomotive activity characteristic of infants with sleep disturbance, noting that there is an imbalance between the sympathetic/parasympathetic modulation of heart rate, and that the maturation of this system is achieved with age [20]. The ontogeny of melatonin production in infants has been studied by measuring the urinary metabolite of melatonin (6-sulfatoxymelatonin). In infants born at term the melatonin circadian rhythm is observed after 8 weeks of age, while preterm infants only express a rhythmic melatonin production after 12 weeks of age [5,6]. This value was obtained in preterm infants maintained in constant light conditions with lighting intensity ranging from 400 to 700 lux at the infants' eye level and such intensity has been described to inhibit melatonin production in adults [18]. In the present study infants were maintained in constant light conditions (249 ± 11 lux), and melatonin remained constant and did not decrease at night. Such observations are supported by a previous study where high levels of melatonin and rhythm disturbance were observed in infants admitted to the ICU in conditions of constant light [9]. On the other hand, in the present study infants exposed to 249 ± 11 lux during the day and to 27 ± 0.8 lux during the night exhibited a daily rhythmicity of saliva melatonin. This finding indicates that a well established alternation of a light/dark cycle condition can be beneficial for the maturation of the baby's physiology including a rhythmic pattern in daily melatonin production.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
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5. Conclusions In summary, we found that exposing premature infants to a light/ dark cycle improved physiological development, promoted a rapid weight gain, and especially decreased the hospital discharge time. The latter implies benefits for the baby who is quickly incorporated to the family and by leaving the hospital the risk of exposure to nosocomial diseases is reduced. Furthermore, the direct and indirect economic costs in health services are also reduced. Here we provide an easy and practical alternative to implement light/dark conditions in the NICU. Contributor's statement Samuel Vásquez Ruiz: Dr. Vasquez conceptualized and designed the study, supervised the collection of samples and carried out the initial analyses, drafted the initial manuscript, and approved the final manuscript as submitted. José Alfonso Maya Barrios: Dr. Maya supervised the collection of samples and carried out the analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. Patricia Torres Narváez: Dra. Torres revised the manuscript, and approved the final manuscript as submitted. Benito Vega Martínez: Dr. Vega revised the manuscript, and approved the final manuscript as submitted. Adelina Rojas-Granados: Dra. Granados participated in the discussion of results and in the final structure and revised the manuscript, and approved the final manuscript as submitted. Carolina Escobar: Dra. Escobar conceptualized and designed the study, participated in the discussion of results and in the final structure of the manuscript, along with Dr. Angeles-Castellanos, reviewed the manuscript critically and approved the final manuscript submitted Manuel Ángeles-Castellanos: Dr. Ángeles-Castellanos conceptualized and designed the study, supervised the collection of samples and data collection, performed analyses and graphs, drafted the final version of the manuscript and reviewed the manuscript critically and approved the final manuscript submitted. Conflict of interest We declare no conflict of interest with respect to the data reported in this study. Acknowledgments This study was supported by grants DGAPA IN-209712 and IN 205809, and the special Cathedra “DR. ALBERTO GUEVARA ROJAS”. Authors wish to thank María Elisa Vega Memije, Lorena Hernández
Delgado Hospital Manuel Gea Gonzales; Mexico City, and the medical and nursing staff of the NICU for their cooperation in this study. References [1] Blackburn S. Environmental impact of the NICU on developmental outcomes. J Pediatr Nurs 1998;13:279–89. [2] Boo NY, Chee SC, Rohana J. Randomized controlled study of the effects of different durations of light exposure on weight gain by preterm infants in a neonatal intensive care unit. Acta Pediatr 2002;91:674–9. [3] Brandon DH, Holditch-Davis D, Belyea M. Preterm infants born at less than 31 weeks' gestation have improved growth in cycled light compared with continuous near darkness. J Pediatr 2002;140:192–9. [4] Gottfried A. Environmental neonatology. In: Gottfried A, Gaiter J, editors. Infant stress under intensive care. Baltimore (MD): University Park Press; 1985. p. 252–7. [5] Kennaway DJ, Goble FC, Stamp GE. Factors influencing the development of melatonin rhythmicity in humans. J Clin Endocrinol Metab 1996;81:1525–32. [6] Kennaway DJ, Stamp GE, Goble FC. Development of melatonin production in infants and the impact of prematurity. J Clin Endocrinol Metab 1992;75:367–9. [7] Kennedy KA, Fielder AR, Hardy RJ, Tung B, Gordon DC, Reynolds JD, et al. Reduced lighting does not improve medical outcomes in very low birth weight infants. J Pediatr 2001;139(4):527–31. [8] Mann NP, Haddow R, Stokes L, Goodley S, Rutter N. Effect of night and day on preterm infants in a newborn infants: randomised trial. Br Med J (Clin Res Ed) 1986;293:1265–12667. [9] Marseglia L, Aversa S, Barberi I, Salpietro CD, Cusumano E, Speciale A, et al. High endogenous melatonin levels in critically ill children: a pilot study. J Pediatr 2013;162(2):357–60. [10] Merritt TA, Pillers D, Prows SL. Early NICU discharge of very low birth weight infants: a critical review and analysis. Semin Neonatol 2003;8(2):95–115. [11] Miller C, White R, Whitman T, O'Callaghan M, Maxwell S. The effects of cycled versus noncycled lighting on growth and development in preterm infants. Infant Behav Dev 1995;18:87–95. [12] Mirmiran M, Baldwin RB, Ariagno RL. Circadian and sleep development in preterm infants occurs independently from the influences of environmental lighting. Pediatr Res 2003;53(6):933–8. [13] Morag I, Ohlsson A. Cycled light in the intensive care unit for preterm and low birth weight infants. Cochrane Database of Systematic Reviews. The Cochrane Library; 2011 [10, Art. No.CD006982]. [14] Morag I, Ohlsson A. Cycled light in the intensive care unit for preterm and low birth weight infants. Cochrane Database of Systematic Reviews. The Cochrane Library; 2013 [3,8, Art. No.CD006982]. [15] Parmelee Jr AH, Schulz HR, Disbrow MA. Sleep patterns of the newborn. J Pediatr 1961;58:241–50. [16] Rivkees SA. Developing circadian rhythmicity in infants. Pediatrics 2003;112(2): 373–81. [17] Rivkees SA, Mayes L, Jacobs H, Gross I. Rest–activity patterns of premature infants are regulated by cycled lighting. Pediatrics 2004;113:833–9. [18] Skene DJ, Arendt J. Human circadian rhythms: physiological and therapeutic relevance of light and melatonin. 2006;43(Pt 5):344–53. [19] Waterhouse JM, Minors DS. Circadian rhythms in the neonate and in old age: what do they tell us about the development and decay of the body clock in humans? Braz J Med Biol Res 1996;29(1):87–94. [20] Yiallourou SR, Witcombe NB, Sands SA, Walker AM, Horne RSC. The development of autonomic cardiovascular control is altered by preterm birth. Early Hum Dev 2013;89(3):145–52. [21] Viskari-Lähdeoja S, Hytinantti T, Andersson S, Kirjavainen T. Acute cardiovascular responses in preterm infants at 34–39 weeks of gestational age. Early Hum Dev 2012;88:871–7.
Please cite this article as: Vásquez-Ruiz S, et al, A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants, Early Hum Dev (2014), http://dx.doi.org/10.1016/j.earlhumdev.2014.04.015
