Preterm infants born at less than 31 weeks’ gestation
have improved growth in cycled light compared with
continuous near darkness
Debra H. Brandon, RN, PhD, Diane Holditch-Davis, RN, PhD, FAAN, and Michael Belyea, PhD
Objectives: Our purpose was to evaluate the benefits of cycled light (CL)
versus near darkness (ND) on health in preterm infants born at <31 weeks’
gestational age.
Study design: Randomized, interventional study comparing infants receiving (1) CL from birth, (2) CL at 32 weeks’ postconceptional age (PCA), and
(3) CL at 36 weeks’ PCA in transition for discharge home. Statistical significance was assessed with segmented mixed general linear models, analysis of
covariance, general estimating equations, χ2, and Fisher’s exact procedure.
Results: Infants receiving CL at birth and 32 weeks’ PCA gained weight
faster than infants not receiving CL until 36 weeks’ PCA. There were no
differences among the groups in length of hospitalization stay or number
of ventilator days, but the power was low for these variables.
Conclusions: These findings suggest that CL has significant weight gain
benefits over ND, and there are no short-term advantages of ND over cycled
light for health in preterm infants. (J Pediatr 2002;140:192-9)
The fetus develops in an environment
rich with auditory, tactile, and kinesthetic sensory stimuli, circadian
rhythms provided by the mother, and
near darkness (ND). The term infant
continues to develop in a cycled light
(CL) environment with increasing circadian influences and multiple sensory
stimuli.1,3 Thus, the needs of preterm
infants cannot be extrapolated from
what is known to be best for fetuses or
healthy term infants. Unlike the fetus
or term infant, preterm infants must
use immature organ systems, including
the auditory and visual system, to deal
with their particular environment.2
The neonatal intensive care unit
(NICU) environment, including continuous bright light levels, may have
negative effects on the growth and
development of preterm infants.1,2
Yet, little attention has been given to
From the Duke University School of Nursing, the Duke Perinatal Research Institute, Durham, and the University of
North Carolina at Chapel Hill School of Nursing, North Carolina.
Supported by National Research Service Award, National Institute of Nursing Research grant
No. NR07180-02, the UNC-CH School of Nursing Biobehavioral Lab, and the Duke Perinatal
Research Institute.
Submitted for publication May 17, 2001; revision received Oct 17, 2001; accepted Nov 28, 2001.
Reprint requests: Debra Brandon RN, PhD, Duke University School of Nursing, Box 3322
DUMC, Durham, NC 27710.
Copyright © 2002, Mosby, Inc. All rights reserved.
0022-3476/2002/$35.00 + 0 9/21/121932
doi:10.1067/mpd.2002.121932
192
identification of how much and when
light is appropriate for neonates.3 Studies of nurseries have demonstrated wide
variations in light levels (400 to 900
lux).4 Attempts to modify nursery light
levels have focused on providing continuous ND to mimic the intrauterine
environment.5 However, it is currently
impossible to replicate the womb for
preterm infants.
BAER
CL
IVH
LOS
NBRS
ND
NICU
PCA
ROP
Brainstem auditory evoked response
Cycled light
Intraventricular hemorrhage
Length of stay
Neurobiologic Risk Scale
Near darkness
Neonatal intensive care unit
Postconceptional age
Retinopathy of prematurity
Light has both positive and negative
potential effects on health and development. Continuous bright light has
been related to infant stress as manifested in increased activity levels, decreased sleep, and bradycardia.1,2,5,6
Yet, CL has the potential to promote
circadian rhythms with health benefits
including hormonal regulation, activity-rest cyclicity, and vital sign regulation.7,8 Thus, growth might either be
decreased with the stress related to exposure to bright light or increased
with the development of circadian patterns and rest-activity rhythms when
exposed to CL. Length of hospitalization is directly related to the infant’s
ability to gain enough weight to reach
discharge weight criteria; thus promotion of growth is a primary goal of
neonatal care.
Currently, there is little evidence to
support either CL or ND as more bene-
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ficial for preterm infants. Studies have
examined the effects of ND only in
combination with other interventions.1,5
Preterm baboons have suprachiasmatic
nuclei innervated by the retina and responsive to light at an age believed to be
comparable to 25 weeks’ human gestation, but it remains unclear whether
young preterm infants can develop discernible circadian rhythms.9 Most studies that have evaluated effects of a CL
in the NICU have used continuous
bright light for comparison.6,10,11 In
convalescent preterm infants (mean
gestational age >31 weeks), Mann et al6
found that those in CL exhibited more
weight gain and sleep 2 to 3 months
after discharge and spent less time feeding in the nursery than infants in
constant light. Infants with a mean gestational age of 28 weeks gained more
weight, were fed orally sooner, and had
fewer ventilator days when they were in
a CL environment.11 These findings are
consistent with findings on the negative
consequences of constant light revealed
in animal studies.12 One study has previously evaluated the short-term effects
of ND and CL.13 No beneficial environmental light effects on the development
of circadian rhythms were observed,
but the intervention may not have been
early or long enough to detect group
differences before discharge. The infants in this study did not receive CL
until they were transferred to the intermediate nursery, and the intervention
was received for a minimum of 10 days
to a maximum of 6 weeks.13
The purpose of this study was to evaluate the timing and short-term effects of
CL (day–night) and continuous ND on
the health of preterm infants born at
<31 weeks’ gestation.
METHODS
Patients
Infants born at <31 weeks’ gestation
(n = 62) were enrolled over 14 months
between May 1998 and July 1999. Infants with known anomalies associated
with neurologic or visual problems (eg,
congenital glaucoma, genetic disorders)
were excluded from study participation.
There were 4 refusals to participate and
2 study withdrawals secondary to group
assignment. Infants were stratified on
the basis of 2 weight categories at birth
(≤1000 grams and >1000 grams) and
randomly assigned with the aid of a
computer-generated random list. Multiple births were included, but each set of
multiples was randomly assigned to the
same intervention group. A target sample size of 60 had been selected, based
on a power analysis for detecting 2% differences11 in average weight gain with
an α level of .05 and an average intervention period of 6 weeks between
study groups and a minimum statistical
power of 93%, using methods developed
by Muller and Barton.14 Weight gain
was chosen for the power analysis because it has the greatest impact on
length of hospitalization (LOS).
Setting
The setting was the 24-bed intensive
care (ICN) and the 12-bed transitional
care nurseries (TCN) of Duke University Medical Center and the 12-bed
level II special care nursery (SCN) of
Durham Regional Hospital. None of
the units have external windows. The
same nursing staff cares for infants in
the ICN and TCN. All recruitment took
place in the ICN with follow-up of patients on transfer to the TCN and SCN
level II units. The Institutional Review
Boards of Duke University Medical
Center and Durham Regional Hospital
approved the study.
Intervention Groups
Neonates were assigned randomly to
one of 3 light intervention groups: (1)
CL from birth, (2) CL at 32 weeks’
postconceptional age (PCA), and (3)
CL at 36 weeks’ PCA in transition for
discharge home. The 3 intervention
groups allowed for comparison of continuous ND and CL as well as the timing of the onset of CL. Thirty-two
weeks was selected as the crossover
time for group 2 because maturation of
the visual system appears ready to handle light stimulation by 32 weeks’ gestation.15,16 The group receiving CL at 32
weeks’ PCA was hypothesized to have
more positive health outcomes than the
CL from birth or CL at 36 weeks’ gestation groups because preterm infants
would be exposed to light at a developmentally appropriate time. In addition,
the infants receiving CL from birth
would have better health outcomes than
the infants receiving CL at 36 weeks because the effects of CL on circadian
rhythm development would be more
beneficial than any stress.
Light was provided with Philips Cool
White fluorescent lamps (Philips, Somerset, NJ) measured as illuminance.
Each lamp emits 5.5% as UVA light and
94.5% as visible light. Filters over the
lamps filtered out UVA light, so only
visible light reached the infant. ND (510 lux) was provided by using protective devices during the daytime and
either dimming the room light or using
protective devices at nighttime. Infants
receiving ND were exposed to 5 to 10
lux light throughout the day except during 6:30 to 7:30 AM and 6:30 to 7:30 PM,
when lighting levels varied based on
change of shift nursing care needs.
These transition hours were applied to
all groups. CL was provided in an 11hour-on, 11-hour-off pattern with one
transition hour at the change of shifts.
The incubator cover was folded on top
of the incubator or the bassinet cover
was off to achieve daylight at 200 to 225
lux between 7:30 AM and 6:30 PM.
Group status was maintained during
lighting for medical procedures by protecting the eyes with eye pads. All infants were exposed to unavoidable
retinal light stimulation through routinely scheduled ophthalmologic examinations at 4 to 6 weeks of age and every
1 to 2 weeks thereafter. The standard of
care in the study nursery is to place
preterm infants in an incubator as soon
as possible after admission; therefore,
all study infants were in incubators
within 24 hours of age. Infants remain
in incubators regardless of severity of
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Table I. Illness-specific variables by intervention group
Near darkness/cycled light
(n = 19)
Variable
Oxygen days
Phototherapy days
Day of life start feeds
Day of life to full feeds
Calories/kg/d*
NBRS†
Variable
RDS
R/O Sepsis and sepsis
IVH (all grades)‡§
PDA
NEC
Transferred to SCN
Mean ± SD
40.8 ± 46.5
7.3 ± 2.5
5.5 ± 3.8
35.3 ± 31.2
108.5 ± 27.3
4.2 ± 3.8
n (%)
14 (73.7)
9 (47.4)
7 (37.8)
9 (47.4)
3 (15.8)
9 (47.4)
Cycled light
(n = 22)
Near darkness
(n = 21)
Mean ± SD
42.0 ± 53.1
7.2 ± 4.5
9.0 ± 18.9
42.8 ± 43.1
116.0 ± 55.8
3.5 ± 2.8
n (%)
19 (86.4)
11 (50.0)
6 (27.3)
7 (31.8)
3 (13.6)
8 (36.4)
Mean ± SD
58.4 ± 49.2
9.4 ± 4.6
7.0 ± 8.2
42.0 ± 28.0
108.3 ± 30.2
4.1 ± 3.5
n (%)
17 (81.0)
15 (71.4)
4 (19.1)
11 (52.4)
4 (19.1)
7 (33.3)
RDS, respiratory distress syndrome; PDA, patent ductus arteriosus; NEC, necrotizing enterocolitus; SCN, special care nursery.
*Average calories/kg per day over all postconceptional age weeks.
†<5 = low-risk, ≥5 = high-risk.18
‡Papile classification.
§Statistically significant differences between groups, Fisher’s exact test (P < .0001).
illness or ventilator modality. Compliance with the intervention for each
group was evaluated through documentation on the nursing flow sheets and biweekly spot checks by the investigator.
Compliance with the protocol ranged
from 92% to 94% in all nurseries. Light
and ND measures were taken weekly at
each study infant’s bedside to monitor
any unknown environmental differences that may have occurred during
the study period. The day of the week
sampled rotated weekly such that each
day was sampled over a 7-week period.
The mean lux measures remained in the
ranges established for ND (5-10 lux)
and light (200-225 lux) throughout the
study for all infants.
Measures
GROWTH. Infants were weighed daily
on calibrated scales. The weights were
summed and averaged to determine
weekly weight gain for each week of the
infant’s hospitalization.
NUMBER OF VENTILATOR DAYS AND
LENGTH OF STAY. Lung maturation and
disease, reflected by total number of
194
ventilator days, and physiologic health,
measured by total hospital days, were
determined to evaluate the intervention
potential to decrease hospital cost. Because days of mechanical ventilation and
length of stay (LOS) were highly
skewed, the natural logarithm of each
patient’s score was used in analyses.
ducted weekly, biweekly, or monthly,
beginning at 1 month of age (6 weeks
of age for infants born at <25 weeks’
gestation) until the infant had mature
retina or retinopathy of prematurity
(ROP) disease had resolved. The International Classification of ROP was
used to categorize disease.
HEARING (BRAINSTEM AUDITORY
EVOKED RESPONSE). The nursery audiologist conducted the brainstem auditory evoked response (BAER) as close to
discharge as possible so that infants were
no longer requiring antibiotic therapy or
at risk for other conditions that might affect hearing. All infants were tested with
the use of the Algo 2 brainstem auditory
evoked instrument (Natus Medical, San
Carlos, Calif). Results were categorized
as pass (35 dB or no more than a mild
hearing loss) or fail (a hearing loss cannot be ruled out, and further audiologic
testing was conducted after discharge).
Passing results are at the 99.8% confidence level.17
COVARIATES. Baseline descriptive and
illness specific data were obtained from
the medical record. With the exception
of intraventricular hemorrhage (IVH)
(which differed among the groups), the
covariates were added to analyses to
be conservative and attempt to rule out
other explanatory variables. Birth
weight and average weekly caloric intake were used in analysis of weight
gain, birth weight, severity of neurologic insults (Neurobiologic Risk Scale
[NBRS]),18 and length of time to reach
growing calories without regression
were used in the analysis of ventilator
days and LOS, and birth weight,
NBRS, IVH, and number of ventilator
days were used in the analysis of ROP.
IVH was coded grades I through IV (I,
isolated germinal matrix hemorrhage;
RETINOPATHY OF PREMATURITY. Ophthalmologic examinations were con-
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Table II. Mixed model results with 95% confidence intervals
Variable
Intercept*
CL from birth†
CL at 32 wk†
PCA‡
PCA2§
32-wk effect
PCA CL at 32 wk¶
PCA CL from birth¶
PCA 32-wk effect#
Parameter
estimate
103.89
7.10
18.79
27.73
0.77
37.53
11.39
8.51
–31.49
SE
DF
t value
Lower
Upper
95% confidence 95% confidence
P value
interval
interval
12.06
11.09
11.35
5.09
0.47
17.09
4.46
4.17
9.13
569
569
569
59
569
569
569
569
569
8.61
0.64
1.66
5.45
1.64
2.20
2.55
2.04
–3.45
< .0001
.5224
.0984
< .0001
.1011
.0285
.0110
.0415
.0006
80.19
–14.69
–3.51
17.55
–0.15
3.96
2.62
0.33
–49.43
127.58
28.89
41.09
37.92
1.69
71.10
20.15
16.69
–13.55
*Intercept equals standard score at 32 weeks.
†Parameter estimate difference for cycled light (CL) at birth and CL at 32 weeks when compared with CL at 36 weeks group.
‡PCA effects equal the linear slope.
§PCA2 effects equal curvilinear slope.
Modeled 2 slopes for each group, one before and after 32 weeks’ PCA.
¶Interaction effects between PCA and the CL at 32 weeks and CL at birth groups when compared with CL at 36 weeks group.
#Interaction effect between PCA and t32.
II, IVH with normal ventricular size;
III, IVH with acute ventricular dilation;
IV, IVH with parenchymal hemorrhage), according to Papile’s classification.19 The length of time to reach
growing calories without regression
was defined as the number of days until
the infant was taking growing caloric
enteral feedings (100 mL/kg/day) and
continued taking growing calories until
discharge. Because days of mechanical
ventilation were highly skewed, the natural logarithm of each patient’s score
was used in analyses.
The NBRS18 was used as an overall
severity of neurologic insult score. It
summarizes 7 neurologic insults received by an infant throughout hospitalization on a 0 to 4 scale, with a total
score possible range of 0 to 28. The 7
medical indicators (duration of mechanical ventilation, acidosis, infection,
seizures, IVH, periventricular leukomalacia, hypoglycemia) used to calculate
the NBRS were collected as part of the
illness-specific data. Data were obtained
weekly from the medical record. The
NBRS has a correlation of 0.60 with
neurologic examinations at 6 and 15
months of age.18 Because the scale is
based on the entire hospitalization, data
at discharge were used. A score of <5 is
an indicator of low risk, and ≥5 is an indicator of high risk.18
PROCEDURE. Parents were approached
for consent after delivery, or as soon as
the mother had recovered from delivery
and the study procedures could be explained. Infants were enrolled within 48
hours of admission into the intensive
care nursery. The intervention was initiated after group assignment and continued until the infants were discharged
from the hospital.
RESULTS
Characteristics of Study Infants
Infants were similar with respect to
gestational age (27.1 ± 2.0 weeks) and
birth weight (1000 ± 223 g) across the 3
intervention groups. Most infants were
nonwhite (75%), and approximately
half were female. The only variable differing among the groups was the incidence of IVH (grades I through IV)
(Table I). The group receiving CL at 36
weeks had the least IVH, and the group
receiving CL at 32 weeks had the most
IVH. However, between birth and 7
days of age, when most IVH occurs, infants in both of these groups had the
same intervention, ND.
Weight Gain
The cumulative average weekly
weight gain was 117 ± 138 g for infants
receiving CL from birth, 122 ± 149 g for
infants receiving CL at 32 weeks, and
93 ± 112 g for infants receiving CL from
36 weeks.
A segmented, mixed general linear
model was used to analyze the pattern
of weekly weight gain.20, 21 The analysis
examined changes in weight gain over
time by group before and after 32
weeks’ PCA and whether the groups
differed in the amounts and developmental pattern of change.20,21 This
technique was essential because two of
the intervention groups (2 and 3) were
receiving the same intervention (ND)
before 32 weeks’ PCA and two of the
intervention groups (1 and 2) were receiving the same intervention (CL)
after 32 weeks’ PCA. Mixed models are
a recent analytic procedure, which deals
with the analysis of individual differences. These analyses are referred to as
general linear mixed model, random coefficient modeling, multilevel modeling,
and hierarchical linear modeling. In the
mixed models, approach 3 components
are estimated: fixed effects, random effects, and a random error component.
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The patterns of weight gain before and
after 32 weeks’ PCA were significantly
different (P = .03), and there was a significant interaction effect between the
change at 32 weeks and the linear trend
(P = .001). The CL at 32 weeks and CL
from birth groups’ growth accelerated
significantly earlier than the group receiving CL at 36 weeks’ PCA (P = .01
and P = .04, respectively) (Figure).
Ventilator Days and Length
of Stay
Figure. Weight gain over time segmented before and after 32-week PCA.
The fixed effects and random error are
similar to the usual multiple regression
parameters. The random effects are the
difference between the patient’s regression line and the population regression
line. Mixed models accommodate repeated observations within individuals
by modeling the covariance structure
within patients. In these models, individual differences over time are
captured by random coefficients. The
advantage of this technique over traditional approaches, such as repeatedmeasures analysis of variance, is that it
can describe group changes over time,
does not have restricted and unrealistic
assumptions, can easily handle missing
data and nonuniform time intervals, and
allows time-varying covariates.21,22
In a preliminary mixed model, weight
gain was regressed over PCA as both
linear and quadratic trends and segmented change at 32 weeks. Segmenting the groups at 32 weeks modeled 2
slopes for each group, one before and
one after 32 weeks’ PCA. The interactions between the PCA trends and
group were also included in the initial
196
model. Birth weight and caloric intake
(calories/kg/day), although not significantly different among the groups, were
initially included as covariates to control for their potential influence on
weight gain. The intercept, PCA, and
intervention group were included in the
random effect component to allow each
infant to have an individual developmental trajectory. A second screening
analysis was conducted with intercept,
PCA, and all variables that reached
P < .10 in the preliminary analysis. Variables remaining after this screening
procedure were used in a final model
analysis if they reached significance at
P < .05. This procedure simplified the
model until only the linear and quadratic trends of PCA, the 32-week effect,
intervention groups, and the interaction
between intervention group and linear
PCA were left as explanatory variables
(Table II).
There was a significant linear trend
(P = .0001) for all groups (Figure). In
addition, there were significant differences in the trajectory of weight gain
among the 3 groups over time (PCA).
Ventilation days and LOS were each
dependent variables in an analysis of covariance, between-groups design controlling for birth weight, NBRS, and time to
reach growing enteral calories. Ventilator
days (CL from birth, 17 ± 23 days; CL at
32 weeks, 23 ± 26 days; CL at 36 weeks,
26 ± 27 days) and LOS (CL from birth,
78 ± 43 days; CL at 32 weeks, 74 ± 41
days; CL at 36 weeks, 86 ± 40 days),
group means, trended in the direction of
the hypotheses that the CL groups would
perform better, but there were no statistically significant differences among treatment groups. The covariates birth weight
F (1, 54) = 21.20; P < .0001, severity of
neurologic insult F (1, 54) = 4.07; P < .05),
and time to reach growing enteral calories F (1, 55) = 27.23; P < .0001, best predicted LOS and the covariates birth
weight F (1, 55) = 4.06; P < .05, and severity of neurologic insult F (1, 55) = 9.47;
P < .0001, best predicted number of ventilator days.
Auditory Functioning
Auditory functioning (BAER) was
analyzed by means of χ2 and Fisher’s
exact procedure. There were no statistically significant differences among
groups in the failure of each ear analyzed separately, but the infants receiving CL at 32 weeks had significantly
more failures (n = 7) in one or both ears
than the infants receiving CL at 36
weeks (n = 1). However, there were no
significant differences between the infants receiving CL from birth and the
infants receiving CL at 36 weeks.
BAER examinations repeated after dis-
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Table III. Number of patients with maximum ROP stage by intervention group at hospital discharge
Near darkness/cycled light
(n = 19)
Normal retina
Immature retina
ROP stage 1
ROP stage 2
ROP stage 3
ROP stage 4
Infants requiring laser surgery
4
4
4
3
2
0
2
Cycled light
(n = 22)
Near darkness
(n = 21)
5
6
3
3
4
0
1
0
3
4
5
5
0
3
No significant differences among groups. Fisher’s exact procedure, P = .63.
charge revealed subsequent passing
scores that resulted in no significant differences between the infants receiving
CL at 32 and 36 weeks.
ROP Development
The general estimating equation procedure (GEE)22 was used to evaluate
differences in the development of ROP.
The GEE can be thought of as ordinal
logistic regression for correlated outcomes. It has the same advantages of
the mixed model analysis discussed previously. ROP was coded as immature
retina = 0, and the stages of disease = 1
through 4. To determine if the intervention groups were predictive of ROP, a
general estimating equation was calculated for ROP with the intercept, intervention group, PCA as both a linear
and quadratic trend, and the interactions between the PCA trends and intervention group. A model reduction
procedure with each variable was entered into a preliminary GEE analysis.
Birth weight, number of ventilator days
(log), NBRS, and IVH were initially included as covariates in the model because of their potential to be predictive
of ROP. A second GEE analysis was
conducted with intercept, PCA linear
and quadratic trends, intervention
group, the interactions between PCA
and intervention group, and all variables that reached P < .10 in the preliminary analysis. The variables remaining
after this screening procedure were
used in a final mixed model analysis,
which included only those variables
with a value of P < .05. One infant died
at 33 weeks’ PCA and 6 infants were
transferred or discharged without ROP
data; therefore, only 55 infants are included in this analysis.
The maximum severity of ROP
throughout hospitalization assessed
with Fisher’s exact test was not significantly different among the 3 groups
(Table III) (P = .63). However, in the
GEE analysis, ROP demonstrated a
significant linear increase in severity
over time for each of the intervention
groups (parameter = 0.20; P = .0001)
and was best predicted by birth weight
(parameter = –0.002; P = .0001). The
ND group appeared to have more severe ROP earlier (parameter = 0.32;
P = .09).
DISCUSSION
The findings of this study suggest that
CL has short-term advantages over
continuous ND for the health of
preterm infants. Like other CL studies,6,11 infants receiving CL from birth
or beginning at 32 weeks’ PCA gained
weight significantly faster than infants
that were in ND until 36 weeks’ PCA.
There were no group differences in
LOS and ventilator days; however, they
were not the primary outcomes on
which sample size was calculated. The
study was not sufficiently powered to
detect LOS and ventilator day differences, given the variability among the
groups. However, the trend toward de-
creased LOS and ventilator days in the
CL groups supports the significant
weight gain differences among the
groups.
Although previous findings have suggested that continuous bright light is
detrimental to the health of preterm infants,6,10,11 findings of this study would
suggest that CL does not have the same
deleterious effects. Negative effects
previously associated with continuous
bright light, including increased activity, decreased sleep, and more apnea
and bradycardia, were observed at
higher illumination levels than in this
study.1,2,5,6 The standard nursery light
levels in this study were low (200-225
lux) compared with previous research
(400-900 lux).4 Lower illumination levels may be less stressful to the preterm
infant, as evidenced by the finding that
the infants receiving CL at 32 weeks
and from birth had similar mean weekly weight gains before and after 32
weeks. Additionally, any stress associated with light exposure before 32
weeks may have been outweighed by
the benefits of CL. Causal mechanisms
contributing to the group differences in
weight gain could include differences in
sleep-wake activity cycles, gastrointestinal hormone secretion, or endocrine functioning.
Auditory outcomes were evaluated to
ensure the safety of CL because premature stimulation of one sensory system
is known to influence the development
of other sensory systems.23,24 The finding of a higher BAER failure rate in the
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BRANDON, HOLDITCH-DAVIS, AND BELYEA
infants receiving CL at 32 weeks versus
36 weeks was unexpected. Because infants receiving CL from birth and at 36
weeks did not differ in BAER failure
rates and there were no significant differences on later testing between the infants receiving CL at 32 weeks and CL
at 36 weeks, these failure differences
may be related to false-positives or
problems with testing rather than a true
maturational difference in auditory development.
Since ND has become the standard
of care in nurseries using the developmental recommendations by Als et al,5
ROP incidence was evaluated to ensure the safety of CL. As expected,
each intervention group had similar
maximum severity of ROP disease, but
the trend that the ND group developed
more severe ROP earlier in gestation
was unexpected. There have been conflicting reports about the effect of light
on the development of ROP.25-27 Glass
et al24 found a higher incidence of
ROP in preterm infants exposed to
continuous bright light, especially infants with birth weight <1000 g, and
they hypothesized that light may cause
alterations in retinal metabolism and
cellular damage. Other studies26,27
found no differences in the incidence
of ROP when infants were shielded
from light by blankets or eye patches
for all or part of the day. The period of
ND provided by the CL may have enabled retinal photoreceptors to recover
or light may have promoted retinal
maturation. Appropriate visual stimulation is known to be necessary for visual development,15 and excessive light
exposure is known to damage the retina.12,28 However, whether appropriately timed moderate light exposure
may facilitative retinal development is
unknown. Light exposure earlier than
normal for an organism can facilitate
some aspects of intersensory development.23,24 It is also possible that ND is
harmful to the retina. In healthy
adults, retinal oxygen consumption is
increased in darkness, with a concurrent increase in retinal blood flow to
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FEBRUARY 2002
increase oxygen delivery.29 If retinal
oxygen consumption is also increased
in darkness in preterm infants, the immaturity of the autonomic nervous system and cerebral blood flow regulation
mechanisms may not preserve retinal
perfusion during episodes of low blood
pressure. It is unclear whether the rate
at which ROP develops is related to
long-term visual outcomes and should
be evaluated further.
Future research should evaluate further the best time to introduce CL to
preterm infants to maximize physical
growth and visual and auditory development. In addition, the development of
circadian rhythmicites in preterm
infants exposed to prolonged CL environments in the hospital should be evaluated. The presence of significant
circadian rhythms provided by maternal chemical and rest-activity cycles in
the intrauterine environment suggests
that they are important for human development. Implementation of CL at
the most appropriate time for the
preterm infant may help promote the
development of circadian rhythms and
growth and development before and
after hospital discharge.
6.
7.
8.
9.
10.
11.
12.
13.
14.
REFERENCES
1. Blackburn S. Environmental impact of
the NICU on developmental outcomes.
J Pediatr Nurs 1998;13:279-89.
2. Gottfried A. Environmental neonatology. In: Gottfried A, Gaiter J, editors.
Infant stress under intensive care. Baltimore (MD): University Park Press;
1985. p. 252-7.
3. Rivkees S, Hao H. Developing circadian rhythmicity. Semin Perinatol 2000;
24:232-42.
4. Lotas MJ. Effects of light and sound in
the neonatal intensive care unit environment on the low-birth-weight infant.
NAACOG’s Clin Issues Perinat Womens Health Nurs 1992;3:34-44.
5. Als H, Lawhon G, Brown E, Gibes R,
Duffy FH, McAnulty G, et al. Individualized behavioral and environmental
care for the very low birth weight
preterm infant at high risk for bronchopulmonary dysplasia: neonatal in-
15.
16.
17.
18.
19.
20.
tensive care unit and developmental
outcome. Pediatrics 1986;78:1123-32.
Mann NP, Haddow R, Stokes L, Goodley S, Rutter N. Effect of night and day
on preterm infants in a newborn infants: randomised trial. BMJ 1986;
293:1265-7.
Rivkees S. Developing circadian rhythmicity: basic and clinical aspects. Pediatr Clin North Am 1997;44:467-87.
Scanlon M. Endocrine functions of the
hypothalamus and alterations in neuroendocrine function—focus on thyrotropin and growth hormone. Prog
Brain Res 1992;93:19.
Rivkees S, Hofman P, Fortman J.
Newborn primate infants are entrained
by low intensity lighting. Proc Natl
Acad Sci U S A 1997;94:292-7.
Blackburn S, Patterson D. Effects of
cycled light on activity state and cardiorespiratory function in preterm infants. J Perinat Neonat Nurs 1991;
4:47-54.
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.
Bellhorn RW. Lighting in the animal environment. Lab Anim Sci 1980;30:440.
Mirmiran M, Ariagno RL. Influence of
light in the NICU on the development
of circadian rhythms in preterm infants.
Semin Perinatol 2000;24:247-57.
Muller KE, Barton CN. Approximate
power for repeated measures ANOVA
lacking sphericity. J Am Stat Assoc
1989;84:549-55.
Isenberg S. The eye in infancy. 2nd ed.
St Louis (MO): Mosby; 1994.
Robinson J, Fielder AR. Pupillary diameter and reaction to light in preterm
neonates. Arch Dis Child 1990;65:35-8.
Ruth RA, Lambert PR. Auditory
evoked potentials. Otolaryngol Clin
North Am 1991;24:349-70.
Brazy J, Eckerman CO, Oehler JM,
Goldstein RF, O’Rand AM. Nursery
neurological risk score: important factors in predicting outcome in very low
birth weight infants. J Pediatr 1991;
188:783-92.
Papile L, Burstein J, Burstein R, Koffler H. Incidence and evolution of
subependymal and intraventricular hemorrhage: a study of infants with birth
weights less than 1500. J Pediatr
1978;92:529-34.
Diggle PJ, Liang K-Y, Zeger SL.
Analysis of longitudinal data. New
York: Oxford University Press; 1994.
BRANDON, HOLDITCH-DAVIS, AND BELYEA
THE JOURNAL OF PEDIATRICS
VOLUME 140, NUMBER 2
21. Liang K-Y, Zeger SL, Qaqish B. Multivariate regression analyses for categorical data. J R Stat Soc 1992;54:33-40.
22. Lickliter R. Atypical perinatal sensory
stimulation and early perceptual development: insights from developmental
psychobiology. J Perinatol 2000;20:
S45-54.
23. Marshall-Baker A, Lickliter R, Cooper RP.
Prolonged exposure to a visual pattern
may promote behavioral organization in
preterm infants. J Perinat Neonat Nurs
1998;12:50.
24. Glass P, Avery G, Kolinjavadi N. Effect
of bright light in the hospital nursery on
the incidence of retinopathy of prematurity. N Engl J Med 1985;313:401-4.
25. Seiberth V, Linderkamp O, Knorz C,
Liesenhoff H. A controlled clinical trial
of light and retinopathy of prematurity.
Am J Ophthalmol 1994;118:492-5.
26. Reynolds M, Hardy R, Kennedy K,
Spencer R, van Heuven W, Fielder A.
Lack of efficacy of light reduction in
preventing retinopathy of prematurity.
N Engl J Med 1998;338:1572-6.
27. Busch EM, Gorgels TGMF, Roberts J, van
Norren D. The effects of two stereoisomers
of N-acetylcysteine on photochemical damage by uva and blue light in rat retinae. Photochem Photobiol 1999;70:353-8.
28. Havelius U, Hansen F, Hindfelt B,
Krakau T. Human ocular vasodynamic
changes in light and darkness. Invest
Ophthalmol Vis Sci 1999;40:1850-5.
29. Feke GT, Zuckerman R, Green GJ,
Weiter JJ. Response of human retinal
blood flow to light and dark. Invest
Ophthalmol Vis Sci 1983;24:136-41.
50 Years Ago in The Journal of Pediatrics
APLASTIC ANEMIA IN SIBLINGS WITH MULTIPLE CONGENITAL ANOMALIES (THE FANCONI TYPE)
Levy W. J Pediatr 1952;40:24-41.
Five decades ago, Levy reported his observations concerning the clinical course of 2 brothers with Fanconi’s
anemia. He painstakingly detailed the physical anomalies and hematologic decline in the boys, after their symptom
presentation at 6 years old, as the 29th and 30th published cases of Fanconi’s anemia. Treatment with oral iron, diluted hydrochloric acid, thyroid extract, subcutaneous injections of liver extract, a diet adequate in vitamins, and
discharge to a resort for convalescent care were, not surprisingly to modern readers, ineffective. Both boys died
within 10 to 15 months after the development of marrow aplasia, not unexpected in an era when transfusion support was limited to whole blood.
The author interpreted the cases in terms of the prevailing hematologic wisdom of the era. He suggested that the
development of aplastic anemia at the same age in the siblings was because of a “maternal factor” or “imperfections
in the germ plasm responsible for the production of the hematopoietic system leading to its exhaustion.” The congenital malformations associated with Fanconi’s anemia were ascribed to “defective germ plasm” or consanguinity.
Our modern understanding of the multisystem manifestations of Fanconi’s anemia draws extensively on the
publication of detailed clinical descriptions such as this. Although hematologists today have characteristic chromosomal breakage studies after clastogenic stress to confirm a clinical diagnosis of Fanconi’s anemia, and the genes
responsible have been cloned for many kindreds, we still do not understand why bone marrow failure commonly
occurs in early childhood or develops in a specific patient. Levy observed his patients briefly, yet detailed their
cases so carefully that by reading his report, we feel we know them. With modern supportive care, including androgen therapy, blood component transfusion, and the potential for cure with bone marrow transplantation, clinicians today may potentially observe their patients for decades. Yet, can we say that we will know our patients any
better or detail their courses any more clearly than Levy?
Zora R. Rogers, MD
Department of Pediatrics
The University of Texas
Southwestern Medical Center at Dallas
Dallas, TX 75390-9063
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doi:10.1067/mpd.2002.122351
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