ARTICLE

Level of NICU Quality of Developmental Care and

Neurobehavioral Performance in Very Preterm Infants
AUTHORS: Rosario Montirosso, PsyD,a,b Alberto Del Prete, WHAT’S KNOWN ON THIS SUBJECT: Although developmental care
MD,c Roberto Bellù, MD,c Ed Tronick, PhD,d,e and Renato in NICUs reduces the stress experienced by preterm infants, the
Borgatti, MD,b and the Neonatal Adequate Care for Quality actual level of developmental care may vary and little is known
of Life (NEO-ACQUA) Study Group about how the level of developmental care relates to preterm
aCentre for the Study of Social Emotional Development of the at
infants’ neurobehavioral performance.
Risk Infant, and bDepartment of Child and Adolescent Neurology
and Psychiatry, Scientific Institute “E. Medea,” Bosisio Parini,
WHAT THIS STUDY ADDS: The study demonstrates the
Lecco, Italy; cNICU, Manzoni Hospital, Lecco, Italy; dChild
Development Unit, Department of Psychology, University of relationship between variations in developmental care in NICUs
Massachusetts Boston, Boston, Massachusetts; and eDepartment and the neurobehavior of preterm infants. Infants from NICUs with
of Newborn Medicine, Brigham and Women’s Hospital, Harvard high-quality developmental care compared with infants from units
Medical School, Boston, Massachusetts with low quality of care evidenced a better neurobehavioral
KEY WORDS profile.
preterm infant, very low birth weight, developmental care, pain
management, neurobehavioral examination, NNNS
ABBREVIATIONS
ANCOVA—analysis of covariance
ANOVA—analysis of variance
ICC—infant-centered care abstract
IPM—infant pain management
NEO-ACQUA study—Neonatal Adequate Care for Quality of Life
OBJECTIVE: To examine the relation between the neurobehavior of very
study preterm infants and the level of NICU quality of developmental care.
NIDCAP—Neonatal Individualized Developmental Care and Assess-
METHODS: The neurobehavior of 178 very preterm infants (gestational
ment Program
NNNS—NICU Network Neurobehavioral Scale age #29 weeks and/or birth weight #1500 g) from 25 NICUs
QCC—quality-of care checklist participating in a large multicenter, longitudinal study (Neonatal
SES—socioeconomic status Adequate Care for Quality of Life, NEO-ACQUA) was examined with
VON-RA—Vermont Oxford Network Risk Adjustment
a standardized neurobehavioral assessment, the NICU Network
Dr Montirosso was one of the principal investigator and
responsible for study design, data collection, analysis, and
Neurobehavioral Scale (NNNS). A questionnaire, the NEO-ACQUA Quality
interpretation of data, and manuscript preparation; Dr Del Prete, of Care Checklist was used to evaluate the level of developmental care in
one of the principal investigators, made substantial contributions each of the NICUs. A factor analyses applied to NEO-ACQUA Quality of Care
to conception and design, provided supervision with all aspects of
Checklist produced 2 main factors: (1) the infant-centered care (ICC)
the research including study design, and data collection,
performed examinations on infants hospitalized in NICU, made index, which measures parents’ involvement in the care of their infant
substantial contributions to interpretation of results, and and other developmentally oriented care interventions, and (2) the infant
critically revised the manuscript, final approval of the version to pain management (IPM) index, which measures the NICU approach to
be published; Dr Bellù was one of the principal investigators,
made substantial contributions to study design, data analysis, and the procedures used for reducing infant pain. The relations between
and interpretation of results, and critically revised the NNNS neurobehavioral scores and the 2 indexes were evaluated.
manuscript, and gave final approval of the version to be
published; Dr Tronick, one of the principal investigators, provided
RESULTS: Infants from NICUs with high scores on the ICC evidenced higher
assistance with the manuscript preparation, including review and attention and regulation, less excitability and hypotonicity, and lower
critique of each version of the manuscript, and critically revised stress/abstinence NNNS scores than infants from low-care units.
the manuscript; and Dr Borgatti was one of the principal
Infants from NICUs with high scores on the IPM evidenced higher
investigators, made substantial contributions to study design,
provided assistance with this manuscript preparation, obtained attention and arousal, lower lethargy and nonoptimal reflexes NNNS
funding, and gave final approval of the version to be published. scores than preterm infants from low-scoring NICUs.
NEO-ACQUA Study Group: Dr Mosca made substantial contributions
to acquisition of data, critically revised the manuscript, and CONCLUSIONS: Very preterm infant neurobehavior was associated
gave final approval of the version to be published; with higher levels of developmental care both in ICC and in IPM, sug-
gesting that these practices support better neurobehavioral stability.
(Continued on last page) Pediatrics 2012;129:e1129–e1137

PEDIATRICS Volume 129, Number 5, May 2012 e1129

Preterm infants in NICUs are exposed to differences in the actual level of quality review boards, and written informed
numerous stressors, including painful of developmental care incorporated in consent was obtained from all infants’
stimuli, disruption of sleep, excessive a NICU’s standard care has seldom been parents.
noise and light levels, frequent han- evaluated and the relation between level
Perinatal Data Collection
dling associated with medical or nursing of care and infant neurobehavior has not
procedures, and maternal separation been investigated. Perinatal variables collected included
and disrupted parenting.1–3 In an effort The goal of this study was to evaluate gender, gestational age, birth weight,
to improve developmental outcomes, the relations of variation of the quality multiple birth, Apgar scores, type of
management has shifted toward neuro- of NICU developmental care “routinely” delivery, intrauterine growth status
protective strategies and early neuro- carried out in 25 NICUs to the neuro- classified as appropriate for gestational
developmental support.4 Several studies behavioral functioning of a large co- age or small for gestational age.15
suggest that modifications of the care hort of very preterm infants. Given that Socioeconomic Status
practices that reduce the stress and pain there is no generally accepted definition
Socioeconomic status (SES) was as-
experienced by infants improve their of developmental care,14 we developed
sessed by using the Hollingshead 4-
clinical and neurobehavioral function- a questionnaire, the Neonatal Adequate
factor index of SES (A. B. Hollingshead,
ing.5–7 However, not all studies have Care for Quality of Life (NEO-ACQUA)
unpublished observations, 1975). The
demonstrated beneficial effects of devel- Quality of Care Checklist (QCC) to evalu-
more prestigious occupational level
opmental care.8–10 One possible reason ate the level of developmental care in
of either parents was considered as
for a lack of consistent findings is that, NICUs, including parental involvement
family SES score ranging from 0 to 90:
even though a NICU ascribes to carrying and pain management. We compared in-
lower scores reflect lower SES.
out developmental care, the actual level fants from NICUs with low and high levels
of developmental care may vary among of developmental care practices. We
Neonatal Risk Adjustment Score
different NICUs or over time.11,12 expected that infants from NICUs with
high-quality neonatal developmental Neonatal clinical condition was assessed
The seminal work of Als13 led to the
care compared with infants from units with the Vermont Oxford Network Risk
development of the her Neonatal In-
with low-quality care would evidence Adjustment index (VON-RA).16 The VON-RA
dividualized Developmental Care and
better neurobehavioral performance. index considers clinical and demogra-
Assessment Program (NIDCAP). NIDCAP
phical variables, such as gestational age,
was designed to create a NICU envi- METHODS
presence of congenital anomaly, multiple
ronment that minimized the stress ex- The research was conducted as part of gestation, Apgar score at 1 minute, gender,
perienced by the infant by utilizing a large multicenter, longitudinal study delivery typology (vaginal or caesarean),
naturalistic observations of the infant in a collaborative of 25 regional tertiary- and out-born status. Low scores indicate
before, during, and after caregiving level Italian NICUs, named the Neo- less serious of preterm clinical outcomes.
procedures, such as control of external natal Adequate Care for Quality of Life
stimuli (eg, vestibular, auditory, visual, (NEO-ACQUA). One hundred seventy-eight Neurobehavioral Evaluation
tactile), clustering of nursery care ac- healthy very preterm infants (90 female, Infant neurobehavior was evaluated
tivities, and positioning or swaddling of 50.6%) were recruited consecutively by using the NICU Network Neuro-
the preterm infant. Over the years, the between January 2006 and December behavioral Scale (NNNS). The NNNS is
concept of developmental care has 2007. Inclusion criteria were gestational a well-standardized test to evaluate
been elaborated. Recently, 5 core mea- age #29 weeks and/or birth weight the neurobehavioral status of high-risk
sure sets for evidence-based develop- #1500 g; no documented neurologic pa- infants.17 The scale has 45 individual
mental care were identified: protected thologies as shown by cerebral ultra- neurologic and neurobehavioral items
sleep, pain and stress assessment and sound, intraventricular hemorrhage up to that are clustered into state-dependent
management, developmental activities stage 1 or 2; no sensory deficits; and no “packages”; in addition, there are 21
of daily living, family-centered care, and malformation syndromes and/or major individual summary items. Individual
a healing environment.14 Consequently, malformations. Mothers were included scores are summarized by 13 sum-
apart from a specific developmental care if they were aged .18 years, had no mary scales (see Table 1).18 The NNNS
program (eg, NIDCAP), NICUs might apply manifest psychiatric or cognitive pathol- was administered by certified, blinded
different aspects of so-called devel- ogies and no drug addiction, and were research assistants at NICUs when in-
opmental care in their routine manage- not a single parent. The study was ap- fants were clinically stable (postconcep-
ment of their infants. To our knowledge, proved by the hospitals’ institutional tional age range, 35–43 weeks).

e1130 MONTIROSSO et al
 ARTICLE

TABLE 1 Short Definitions and Score Ranges of NNNS Summary Scales score for the ICC and IPM indices was
1 Habituation Response decrement to repeated auditory and visual stimuli computed for each NICU. The ICC index
during sleep (range 1–9) ranged from 0 to 8, with higher scores
2 Attention Ability to localize and track animate and inanimate auditory and
visual stimuli (range 1–9) indicating higher levels of ICC. The IPM
3 Arousal Level of arousal maintained during the examination, including index ranged from 0 to 10, with higher
state and motor (range 1–9) scores indicating higher levels of IPM.
4 Regulation Capacity to modulate arousal and organize motor activity,
physiology, and state in response to stimulation (range 1–9)
To distinguish the quality of care level,
5 Handling Extent to which handling strategies were used during attention each NICU was assessed as being a low-
sequence to maintain alert state (range 0–1) care group or high-care group based on
6 Quality of movement Attributes of motor control, including smoothness, maturity, and median splits for the ICC and IPM. This
lack of startles and tremors (range 1–9)
7 Excitability High levels of motor, state, and physiologic reactivity (range 0–15) approach had the advantage of avoiding
8 Lethargy Low levels of motor, state, and physiologic reactivity (range 0–15) bias from extreme scores. For the ICC
9 Asymmetric reflexes Number of asymmetric responses to elicited reflexes (median = 7.00, mean = 6.65, SD = 2.12):
(range 0–16)
10 Nonoptimal reflexes Number of poor scores to elicited reflexes (range 0–15) 12 NICUs had low-quality care (97 in-
11 Hypertonicity Hypertonic responses in arms, legs, trunk, or general tone fants) and 13 NICUs had high-quality care
(range 0–10) (81 infants). For the IPM (median = 6.00;
12 Hypotonicity Hypotonic response in arms, legs, trunk, or general tone
(range 0–10)
mean = 5.74, SD = 2.38): 14 NICUs had
13 Stress/abstinence Number of stress and abstinence signs observed during the low-quality care (91 infants) and 11
examination (range 0–1) NICUs had high-quality care (87 infants).
Scores on the summary scales indicate “higher/more” or “lower/less” of the behavior, not a “better” or “worse” performance.

Statistical Analysis
Measurement of involvement, such as the possibility for Preliminarily statistical analyses eval-
Developmental Care parents to spend the night in the unit; uated the following: (1) general char-
The NEO-ACQUA QCC assesses a variety use of parental kangaroo care as a rou- acteristics of the units (eg, number of
of procedures and practices of de- tine procedure; the average duration per beds, total admissions per year), (2)
velopmental care used in NICUs.14,19 The day of kangaroo care; and 1 item as- perinatal data, and (3) sociodemographic
QCC covers the following areas: de- sessed the presence of nursing inter- variables. Categorical variables were
velopmental care practices, policies to- ventions to support infant development examined by using x 2 tests. Continuous
ward parents, control of environment, by decreasing infant energy expenditure variables were evaluated with sepa-
and infant pain management. Further- and promoting stability, such as infant rate analyses of variance (ANOVAs) by
more, general information about the containment, postural maneuvers, and using a 2 (ICC index: low and high level of
unit is obtained, such as number of beds reduction of disturbing tactile stimula- care) 3 2 (IPM index: low and high level
and admissions per year. For each NICU, tions. (2) The infant pain management of care). To determine if the care quality
a neonatologist with at least 5 years (IPM) index accounted for 9% of the level was related to preterm infants’
of clinical experience who was not in- variance. The IPM index included 5 items. neurobehavioral performance, sepa-
volved in the direct care of the infants Two items measured the number of rate analyses of covariance (ANCOVAs)
filled out the QCC. A factor analyses ap- pharmacologic and nonpharmacologic were applied to 13 NNNS scales with a 2
plied to QCC responses revealed 3 main procedures used for reducing pain dur- ICC 3 2 IPM factorial design, with the
factors*; however, given the goal of this ing invasive medical procedures (eg, VON-RA to estimate any confounding ef-
study, 2 indices of developmental care intravenous lines, drainage tubes, and fect of the neonatal clinical conditions.
were used. (1) The infant centered care endotracheal tubes), 1 item measured For covariate analysis, the regression
(ICC) index accounted for 20% of the the use of pharmacologic analgesia or coefficients (B) were given to better
variance. The ICC index included 4 items. sedation during continuous mechanical describe the effect. Significant effects
The first 3 items assessed the parent’s ventilation, 1 item measured the kind were evaluated in pairwise compari-
of blood collection procedure (ie, heel son post hoc tests with the P value for
*The third principal factor, labeled “nursing stick), and the last item measured the significance adjusted with Bonferroni
staffing,” which accounted for 12% of the variance, use of a clinical evaluation scale of correction. Effect size was evaluated
included items such as number of physicians per newborn pain and/or a protocol written by using the partial h squared (h2p).
bed, number of graduate students, fellows, or
consultants per bed, nurse chiefs per bed, nurses for the management of newborn pain. All analyses were performed at a sig-
per bed, and nursery nurse, assistants per bed. Based on factor weightings, a composite nificance level P # .05.

PEDIATRICS Volume 129, Number 5, May 2012 e1131

RESULTS TABLE 2 Summary of General Characteristics of the NICUs, Perinatal and Sociodemographic
Variables, Separately Subdivided on the Basis of the Developmental Care Quality Level
NICU Features and Infants’ (Mean and SDs)
Characteristics ICC Index IPM Index
Descriptive statistics, separately sub- Low (NICU = 13) High (NICU = 12) Low (NICU = 11) High (NICU = 14)
divided for quality of care level, are (n = 97, 47 F) (n = 81, 43 F) (n = 91, 44 F) (n = 87, 46 F)
presented for each variable in Tables 2 Mean SD Mean SD Mean SD Mean SD
and 3. No differences were found in Total admissions per year 406.58 224.45 675.46 475.50 471.36 226.00 641.91 536.22
general characteristics of the units, Number of beds 19.08 9.27 22.92 12.96 20.79 10.06 21.46 13.17
perinatal data, and sociodemographic, Birth weight, g 1161.56 229.36 1091.75 258.16 1129.08 249.15 1130.54 241.36
Gestational age at birth, wk 29.12 1.96 28.81 2.41 28.97 2.02 29.00 2.35
with the exception of the VON-RA score, Length of hospitalization, d 59.88 20.38 61.32 24.76 60.69 23.01 60.37 21.92
F(1, 173) = 5.34, P = .02, h2p = 0.03. Pre- VON-RA score 0.05 0.07 0.09 0.15 0.07 0.11 0.07 0.12
term infants from high ICC NICUs had (range, 0.01 4 0.99)
Postmenstrual age at test, wk 37.12 1.39 37.21 1.64 37.04 1.30 37.30 1.69
a higher VON-RA score than those from Chronological age at NNNS, d 52.94 16.69 55.70 19.40 53.32 16.78 55.11 19.19
units with low ICC. Mother’s age, y 33.31 5.02 33.92 4.61 33.27 4.95 33.92 4.72
Father’s age, y 35.82 5.21 36.60 6.33 35.75 5.36 36.59 6.09
Education mother, y 12.42 3.90 12.97 3.73 12.36 4.14 12.98 3.47
Level of Quality of Developmental Education father, y 11.39 3.38 11.72 3.62 11.42 3.53 11.66 3.46
Care and Neurobehavioral Profile SES score 50.83 23.47 53.33 18.44 49.89 23.26 54.19 18.88
Table 4 shows the mean scores, the SDs, F, female.

and the results of ANCOVAs for the NNNS

scales, stratified for ICC and IPM in- TABLE 3 Summary of General Characteristics of the NICUs, Perinatal and Sociodemographic
Variables, Separately Subdivided on the Basis of the Developmental Care Quality Level
dexes. Significant ICC effects were ob- (Number and Percentage)
served for the 5 scales: infants from high ICC Index IPM Index
ICC NICUs exhibited higher attention and
Low High Low High
regulation, less excitability, and lower (NICU = 13) (NICU = 12) (NICU = 11) (NICU = 14)
scores on the hypotonicity and stress/ (n = 97, 47 F) (n = 81, 43 F) (n = 91, 44 F) (n = 87, 46 F)
abstinence than infants from low-care
n % n % n % n %
units. Significant IPM effects emerged
Birth weight #1000 g 27 27.8 33 40.7 31 34.1 29 33.3
for 4 scales: infants from high IMP NICUs Gestational age #29 wk 55 56.7 48 59.3 54 59.3 49 56.3
showed higher attention and arousal, Multiple birth 0 0.0 3 3.7 1 1.1 2 2.3
and had lower scores on the lethargy and Small for gestational age 18 18.6 21 25.9 18 19.8 21 24.1
Antenatal corticosteroids 72 75.0 68 86.1 65 73.0 75 87.2
nonoptimal reflexes than preterm infants Patent ductus arteriosus 28 28.9 24 30.0 28 31.1 24 27.6
from low-care units. ANCOVA revealed Conventional ventilation 64 66.0 40 50.0 58 64.4 46 52.9
an effect of VON-RA score for the fol- High-frequency ventilation 10 10.3 8 10.0 9 10.0 9 10.3
Oxygen dependency at 36 wk 5 6.0 11 16.9 6 7.8 10 13.9
lowing scales: attention, nonoptimal
Proven or suspected 1 1.0 0 0.0 1 1.1 0 0.0
reflexes, asymmetric reflexes, and hy- necrotizing enterocolitis
potonicity. These findings suggest that IVH (grade 1 or 2) 14 14.4 13 16.0 17 18.7 10 11.5
a higher VON-RA score was associated Sepsis 8 8.2 2 2.5 10 11.0 0 0.0
F, female; IVH, intraventricular hemorrhage.
with a decreased capacity to attend to
visual and auditory stimuli, more sub-
optimal reflexes, and higher abnormal exception of the stress/abstinence scale, We expected, for example, that low
muscle tone. No interactions emerged where the ICC effect was of medium size scores on both the ICC and IPM would be
between the 2 main factors (ICC and (range, 6.0–13.9%) associated with poorer neurobehavioral
IPM). Furthermore, no significant inter- performance in comparison with infants
actions emerged between VON-RA and 2 Neurobehavior Related to the from high ICC- and IPM-scoring NICUs,
main factors suggesting that the dif- Different Combinations of and that NICUs with 1 high and 1 low
ferences on NNNS scales among the ICC and IPM score would not differ from each other
levels of care quality did not vary as Given these findings, we asked if dif- but might differ from the high-high and
a function of the neonatal clinical con- ferent combinations of levels of ICC and low-low NICUs. To analyze what may be
ditions. The h2p effect sizes, in general, IPM might be related to a preterm in- thought of as cumulative effects of ICC
were small (range, 1%–5.9%), with the fant’s neurobehavioral performance. and IPM, we defined 4 groups of NICUs

e1132 MONTIROSSO et al
 ARTICLE

TABLE 4 Descriptive Statistics of the NNNS Scales Across the NICUs Stratified for Quality Care Level and ANOVAs Results
NNNS Scales ICC Index IPM Index Main Effects Covariatea

Low (NICU = 12) High (NICU = 13) Low (NICU = 14) High (NICU = 11) ICC IPM VON-RA index

Mean SD N Mean SD N Mean SD N Mean SD N F h2p F h2p B h2p

Habituation 7.51 1.63 62 7.33 1.83 52 7.69 1.44 54 7.20 1.92 60 0.45 0.00 3.05 0.03 2.61 0.03
Attention 5.59 1.20 92 5.97 1.41 76 5.46 1.25 86 6.08 1.31 82 4.42b 0.03 10.44d 0.06 22.00b 0.03
Arousal 3.89 0.66 95 3.74 0.55 76 3.73 0.64 88 3.92 0.58 83 3.20 0.02 4.41b 0.03 0.02 0.00
Regulation 5.65 0.84 94 5.96 0.66 76 5.76 0.90 87 5.82 0.62 83 7.06c 0.04 0.03 0.00 20.56 0.01
Handling 0.47 0.26 90 0.44 0.23 74 0.46 0.26 83 0.45 0.24 81 1.18 0.01 0.03 0.00 0.16 0.01
Quality of movement 4.52 0.58 93 4.64 0.73 74 4.62 0.66 86 4.54 0.65 81 1.63 0.01 1.14 0.01 20.17 0.00
Excitability 2.51 1.79 96 1.88 1.59 77 2.11 1.76 89 2.36 1.70 84 6.23b 0.04 1.52 0.01 0.21 0.00
Lethargy 3.73 2.28 97 3.60 1.98 81 4.00 2.39 91 3.33 1.80 87 0.18 0.00 4.24b 0.02 0.95 0.00
Nonoptimal reflexes 5.05 2.48 97 4.35 2.59 81 5.20 2.72 91 4.24 2.27 87 3.21 0.02 6.37c 0.04 3.30b 0.02
Asymmetric reflexes 1.21 1.71 97 0.86 1.56 81 1.04 1.79 91 1.06 1.50 87 2.92 0.02 0.03 0.00 2.42b 0.03
Hypertonicity 0.03 0.18 95 0.01 0.11 77 0.05 0.21 88 0.00 0.00 84 0.49 0.00 3.35 0.02 0.06 0.00
Hypotonicity 0.18 0.56 95 0.06 0.25 77 0.10 0.48 88 0.15 0.42 84 5.04b 0.03 0.79 0.00 0.82c 0.04
Stress/abstinence 0.18 0.07 96 0.13 0.08 77 0.16 0.08 89 0.16 0.08 84 21.31d 0.11 0.30 0.00 20.02 0.00
a For covariate analysis, values are reported for the regression coefficients (B) that allow an easier data interpretation of effect direction.
b P # .05.
c P # .01.
d P # .001.

representing combinations of high and with low and high IPM (see Fig 1). The that the pain control is crucial to
low ICC index and high and low IMP in- size effects were small to moderate. ameliorating some aspects of the
dex: low ICC-low IPM (NICU = 7; 54 neurologic immaturity. Interestingly,
infants); low ICC-high IPM (NICU = 5; 43 DISCUSSION the NICU features and infants charac-
infants) or high ICC-low IPM (NICU = 7; 37 teristics were homogeneously distrib-
The main objective of this study was to
infants); and high ICC-high IPM (NICU = 6; uted across units, with the exception
investigate whether the level of quality
44 infants). Univariate ANOVAs were of the VON-RA clinical status score. In
of developmental care found in a large
applied to 13 NNNS scales with the 4 particular, infants from high ICC NICUs
number of NICUs was associated with
groups of NICUs as between-subjects had higher VON-RA scores, indicating
neurobehavioral performance of very
variables.† Significant effects were more challenging clinical conditions.
preterm infants. The overall quality of
found for 3 scales of the NNNS: attention, It should be noted that, regardless of
developmental care was measured by 2
F(3, 164) = 5.61, P = .000, h2p = 0.09; the level of quality of care, the neo-
indices of a broad range of care prac-
nonoptimal reflexes, F(3, 174) = 3.11, P = natal clinical conditions affected the
tices “routinely” used in NICUs. The
.03, h2p = 0.05; and stress/abstinence, infants’ performance (primarily, neu-
findings indicate that, after controlling
F(3, 169) = 7.63, P = .000, h2p = 0.12. The rologic items). Nevertheless, the lack
for neonatal clinical conditions, the ICC
Bonferroni post hoc test showed that of significant interactions between the
and IPM have specific relations to neu-
preterm infants from high ICC-high IPM VON-RA scores and the ICC index make
robehavioral performance. Regardless
NICUs exhibited a significantly higher it unlikely that the differences in neuro-
of the level of pain management, a low
attention score than infants from all behavioral profile between infants from
level of ICC was associated with de-
other types of units. Preterm infants high ICC NICUs and those from units with
creased capacity of regulation and in-
from low ICC-low IPM NICUs exhibited low ICC can be explained by the neona-
creased signs of stress, less attention,
more nonoptimal reflexes than those tal clinical conditions. Furthermore,
higher excitability, and abnormal muscle
from high ICC-low IPM and high ICC-high given that there were no differences
tone, indicating that some infant-centered
IPM NICUs. Preterm infants from low- in the time of exposure to the devel-
developmental care interventions were
quality-of-care NICUs for ICC, both with opmental care (ie, the length of hospi-
critical to moderating infant distress
low and high IPM, had higher scores on talization and the chronological age at
and scaffolding their infants’ regulatory
stress/abstinence than infants from time of assessment), it may be that the
and motor capacities. By contrast, re-
high-quality-of-care NICUs for ICC, both high score of VON-RA for infants from
gardless of the level of ICC, a low level
of IPM was associated with less at- high ICC NICUs is a spurious finding.
†Given the lack of interaction between the
covariate and the main factors (ICC and IPM), the tention and arousal, more lethargy, and In NICUs with a higher ICC score, infants
VON-RA scores did not enter into this analysis. more suboptimal reflexes, suggesting had betterattention and self-regulation,

PEDIATRICS Volume 129, Number 5, May 2012 e1133

FIGURE 1
Mean of the scores for attention (A), nonoptimal reflexes (B), and stress/abstinence (C) and their relation to the different combinations of ICC and IPM.
* P # .05.

e1134 MONTIROSSO et al
 ARTICLE

were less excitable, had less hypotonia, findings are consistent with previous re- Although the primary goal of this study
and were less stressed, suggesting that search. They suggest that invasive pro- was not to develop or evaluate the QCC,
these infants had greater physiologic cedures affect preterm infants’ arousal the findings support its usefulness. The
and behavioral stability. A higher score levels and likely induce physiologic and factor analysis revealed the robustness
of the ICC index identifies several prac- behavioral changes, energy expenditure, of the instrument. The range of scores
tices used by a NICU, including parents and instability.26 Moreover, invasive pro- on the ICC and IPM suggest that QCC is
being allowed to spend the night in the cedures expose preterm infants to nu- sensitive to differences in the extent of
unit whenever they chose, even when an merous nociceptive events, and several developmental quality of care even in
infant’s condition is critical; parents be- lines of evidence suggest that repeated a group of NICUs that ascribe to using
ing allowed to practice kangaroo care as and prolonged pain exposure has detri- similar levels of care. Although additional
a routine procedure as well as being mental consequences.27–29 Although we research is needed, the relation of the 2
encouraged to hold their infants, both of did not directly assess infant pain re- indexes to neurobehavioral performance
which they do more of the time than in activity to invasive procedures (eg, ob- provides evidence to support the sensi-
NICUs with a low ICC index; and, in ad- serving facial expressions), our findings tivity and specificity of the QCC and its
dition, the high ICC index NICUs have suggest that, during the neonatal period, usefulness in discriminating differences
implemented more nursing interven- less protection from repetitive painful in quality of developmental care level
tions to decrease infant energy expen- experiences alters neurobehavioral func- among NICUs. The QCC appears to be
diture and promote stability. Previous tioning. These findings have important useful for evaluating how different levels
research has documented that infants of implications for the control of pain during of developmental care relate to infant
parents involved in the care of their in- the infants’ NICU experience, because the outcomes (eg,motordevelopment, stress
fant and preterm infants who received effects of early exposure to negative reactivity). The QCC would also be useful
kangaroo care showed improvements environments may be at least partially not only for tracking changes, but also for
in neurobehavioral functioning.20–22 Fur- ameliorated by minimizing of the number maintaining and improving the quality of
thermore, positioning and containing of painful procedures performed and by care within a NICU over time.
(eg, use of blanket rolls) have positive using treatments that can alleviate pro- The study has limitations. The 25 NICUs
effects by reducing physiologic distress cedural pain in neonates.30 Thus, in agree- sampled self-selected themselves into
and increasing motor organization and ment with others, these findings suggest the NEO-ACQUA study and cannot be
self-regulatory ability.23,24 The ICC is a it is important to prevent and minimize considered representative of develop-
global index, and it is not possible to the number and intensity of painful events mental care quality in the ∼120 Italian
identify which specific practices are for preterm infants,31 and they support NICUs. This limitation applies to its ap-
related to the neurobehavioral perfor- the use of evidence-based guidelines for plication to NICUs in other countries.
mance of infants. Nonetheless, taken preventing or treating neonatal pain and The indexes emerged from factor anal-
together, the findings from the ICC cor- its adverse consequences.32 yses of the information gathered on
roborate previous findings suggesting The findings highlight that ICC and IPM developmental care, but not all aspects
that a greater use of developmental care can act together in relation to preterm of development care were examined, and
practices lead to better neurobehavioral infants’ neurobehavioral functioning. other aspects of care may have influ-
stability and neuromaturation.8,25 Better attentional performance was re- enced the infants’ performance. It also
The findings also indicate that IPM is lated to NICUs that scored higher on both would be useful to evaluate the relations
related to the neurobehavioral perfor- indices. Fewer nonoptimal reflexes were of the QCC to a broader array of clinical
mance of preterm infants. The IPM index seen in NICUs that scored high on ICC variables. Furthermore, because the in-
denotes the number of pharmacologic than in NICUs with low scores in both in- dexes aggregated several aspects of care
and nonpharmacologic treatments used dexes. Preterm infants from low -quality- practices, it is not possible establish
to alleviate pain associated with proce- of-care NICUs for ICC, both with low and which particular aspects affected the
dures, the presence and use of a protocol high IPM, had more signs of stress than infants’ functioning. However, with more
for measuring infant pain, and guidelines preterm infants from NICUs with high ICC experience in the use of the QCC, it would
for preventing or treating neonatal pain. scores, both with low and high IPM. It be possible to disaggregate the var-
In the NICUs with a lower IPM score, seems likely that different aspects of iables. The use of a self-administered
infants had reduced levels of attention quality of care may contribute to specific questionnaire is an additional limitation,
and arousal, were more lethargic, and adverse neurobehavioral performance and it is not possible to rule out evalua-
had more nonoptimal reflexes. These both separately and cumulatively. tion biases by those who filled out the

PEDIATRICS Volume 129, Number 5, May 2012 e1135

QCC. The relation of the QCC to observed conventional care may promote neuro- Hospital G. Martino); Palma Mammoliti,
actual practices in a large number of maturation of preterm infants, includ- MD (NICU, Ospedale degli Infermi); Cinzia
units would be valuable, but difficult to ing their capacity for regulation and Fortini, MD (NICU, Pediatric University
carry out. Nonetheless, it is important to resilience.33 Hospital); Paolo Tagliabue, MD (Neona-
note that compilation of QCC was done tology, San Gerardo Hospital); Lorenzo
independently from the NNNS assess- Quartulli, MD (NICU, Perrino Hospital);
ACKNOWLEDGMENTS
ment, which was administrated by re- Giuliana Motta, MD (NICU, Niguarda Hos-
Neonatal Adequate Care for Quality of
search assistants blind to all other pital Ca’ Granda); Paola Introvini, MD
Life (NEO-ACQUA) Study Group collabo-
information gathered by QCC. Further- (NICU, Buzzi Hospital); Rosetta Grigorio,
rators are as follows: Fabio Mosca,
more, because the care level of each NICU MD (NICU Umberto I Hospital); Paola
MD; Odoardo Picciolini, MD (NICU, De-
was established on a statistical basis, Mussini, MD (NICU, C. Poma Hospital);
partment of Maternal and Pediatric Sci-
both the informant who filled out the QCC Giulia Pomero, MD (NICU, Santa Croce e
ences, University of Milan Fondazione
and research assistant who adminis- Carle Hospital); Carlo Poggiani, MD (NICU,
IRCCS Ca’ Granda); Stefano Visentin,
tered the NNNS were unaware of the care Istituti Ospitalieri); Ananda Bauchiero,
MD; Nadia Battajon, MD (Neonatol-
level assigned to their unit. MD (Department of Neonatology, S. Anna
ogy and NICU, Ca’ Foncello Hospital);
Maria Lucia Di Nunzio, MD; Fiorina University Hospital).
CONCLUSIONS Ramacciato, MD (NICU Cardarelli Hospi- We thank Massimo Agosti, Guido Calcio-
The view that developmental care and tal); Laura Barberis, MD; Emmanuele lari, and Maria Caterina Cavallo of the
pain control have potential beneficial Mastretta, MD (Division of Neonatology NEO-ACQUA study Advisory Board. We
effects on infant neurodevelopment is and NICU, S. Anna Hospital); Rinaldo Zanini, thank Julie Hofherimer (University of
generally accepted.7,20 However, although MD (NICU, Manzoni Hospital); Giovanna North Carolina at Chapel Hill) and Barry
tremendous advances in the care offered Carli, MD; Michela Alfiero Bordigato, Lester (Brown University Medical Cen-
to high-risk preterm infants have been MD (NICU, Hospital of Camposampiero); ter) for their expertise and support dur-
made over the past decades, variability Valeria Chiandotto, MD; Cristiana Boiti, ing the NNNS training. Thanks go to
in the practice of developmental care MD (Department of Neonatology, Uni- MediData Studi e Ricerche staff in Mod-
remains a constant concern, and the versity Hospital S. M. M.); Rosangela ena for the organizational, technical,
effects of developmental care need fur- Litta, MD; Giovanna Minelli, MD (Divi- and scientific support. We thank the
ther exploration. The findings reported sion of Neonatology and NICU, Ospedali staff of all of the 25 NICUs that partici-
here suggest that incorporating more Riuniti); Marcello Napolitano, MD (NICU, pated in the survey. Finally, we thank
developmental care practices and more Evangelic Hospital Villa Betania); the participating infants and their
pain control practices into a NICU’s Alessandro Arco, MD (NICU, University parents.

REFERENCES
1. Perlman JM. Neurobehavioral deficits in 6. Als H, Duffy FH, McAnulty GB, et al. Early growth in very preterm infants in relation to
premature graduates of intensive care— experience alters brain function and struc- NIDCAP in a Dutch NICU: two years of follow-
potential medical and neonatal environ- ture. Pediatrics. 2004;113(4):846–857 up. Acta Paediatr. 2009;98(2):291–297
mental risk factors. Pediatrics. 2001;108(6): 7. Anand KJ, Scalzo FM. Can adverse neonatal 11. Stevens B, Petryshen P, Hawkins J, Smith B,
1339–1348 experiences alter brain development and Taylor P. Developmental versus conventional
2. Aucott S, Donohue PK, Atkins E, Allen MC. subsequent behavior? Biol Neonate. 2000; care: a comparison of clinical outcomes for
Neurodevelopmental care in the NICU. Ment 77(2):69–82 very low birth weight infants. Can J Nurs
Retard Dev Disabil Res Rev. 2002;8(4):298–308 8. Symington A, Pinelli J. Developmental care Res. 1996;28(4):97–113
3. Newnham CA, Inder TE, Milgrom J. Measur- for promoting development and preventing 12. Ashpaugh A, Leick-Rude MK, Kilbride HW.
ing preterm cumulative stressors within the morbidity in preterm infants. Cochrane Developmental care teams in the neonatal
NICU: the Neonatal Infant Stressor Scale. Database Syst Rev. 2006;(2):CD001814 intensive care unit: Survey on current sta-
Early Hum Dev. 2009;85(9):549–555 9. Westrup B, Kleberg A, von Eichwald K, tus. Am J Perinatol. 1999;19(1):48–52
4. Byers JF. Components of developmental Stjernqvist K, Lagercrantz H. A randomized, 13. Als H. Developmental care in the newborn
care and the evidence for their use in the controlled trial to evaluate the effects of intensive care unit. Curr Opin Pediatr. 1998;
NICU. MCN Am J Matern Child Nurs. 2003;28 the newborn individualized developmen- 10(2):138–142
(3):174–180, quiz 181–182 tal care and assessment program in a 14. Coughlin M, Gibbins S, Hoath S. Core
5. Slevin M, Farrington N, Duffy G, Daly L, Swedish setting. Pediatrics. 2000;105(1 pt measures for developmentally supportive
Murphy JF. Altering the NICU and measur- 1):66–72 care in neonatal intensive care units: the-
ing infants’ responses. Acta Paediatr. 2000; 10. Wielenga JM, Smit BJ, Merkus MP, Wolf MJ, ory, precedence and practice. J Adv Nurs.
89(5):577–581 van Sonderen L, Kok JH. Development and 2009;65(10):2239–2248

e1136 MONTIROSSO et al
 ARTICLE

15. Parazzini F, Cortinovis I, Bortolus R, Fedele 21. Feldman R, Eidelman AI. Skin-to-skin contact Biological and Social Context, Progress in
L. Standards of birth weight in Italy [in (Kangaroo Care) accelerates autonomic and Pain Research and Management. Seattle,
Italian]. Ann Ostet Ginecol Med Perinat. neurobehavioural maturation in preterm in- WA:IASP Press; 2003;26:23–55
1991;112(4):203–246 fants. Dev Med Child Neurol. 2003;45(4):274– 28. Grunau RE, Oberlander TF, Whitfield MF,
16. Zupancic JA, Richardson DK, Horbar JD, 281 Fitzgerald C, Lee SK. Demographic and
Carpenter JH, Lee SK, Escobar GJ; Vermont 22. Ohgi S, Fukuda M, Moriuchi H, et al. Com- therapeutic determinants of pain reactivity
Oxford Network SNAP Pilot Project Partic- parison of kangaroo care and standard care: in very low birth weight neonates at 32
ipants. Revalidation of the score for neonatal behavioral ganization, development, and tem- weeks’ postconceptional age. Pediatrics.
acute physiology in the Vermont Oxford Net- perament in healthy, low-birth-weight infants 2001;107(1):105–112
work. Pediatrics. 2007;119(1) Available at: through 1 year. J Perinatol. 2002;22(5):374–379 29. Johnston CC, Stevens BJ. Experience in
www.pediatrics.org/cgi/content/full/119/ 23. Grenier IR, Bigsby R, Vergara ER, Lester BM. a neonatal intensive care unit affects pain
1/e156 Comparison of motor self-regulatory and stress response. Pediatrics. 1996;98(5):925–930
17. Lester BM, Tronick EZ, Brazelton TB. The behaviors of preterm infants across body 30. Axelin A, Salanterä S, Kirjavainen J, Lehtonen
Neonatal Intensive Care Unit Network Neu- positions. Am J Occup Ther. 2003;57(3):289–297 L. Oral glucose and parental holding prefer-
robehavioral Scale procedures. Pediatrics. 24. Short MA, Brooks-Brunn JA, Reeves DS, able to opioid in pain management in pre-
2004;113(3 pt 2):641–667 Yeager J, Thorpe JA. The effects of swaddling term infants. Clin J Pain. 2009;25(2):138–145
18. Lester BM, Tronick EZ, La Gasse L, Seifer R, versus standard positioning on neuromus- 31. Anand KJS; International Evidence-Based
Bauer CR, Shankaran S, Bada HS, Wright LL, cular development in very low birth weight Group for Neonatal Pain. Consensus state-
Smeriglio VL and Lu J. Summary statistics infants. Neonatal Netw. 1996;15(4):25–31 ment for the prevention and management
of neonatal intensive care unit network 25. Feldman R, Eidelman AI, Sirota L, Weller A. of pain in the newborn. Arch Pediatr Ado-
neurobehavioral scale scores from the ma- Comparison of skin-to-skin (kangaroo) and lesc Med. 2001;155(2):173–180
ternal lifestyle study: A quasinormative sam- traditional care: parenting outcomes and 32. Batton DG, Barrington KJ, Wallman C; American
ple. Pediatrics. 2004;113(3 pt 2):668–675 preterm infant development. Pediatrics. 2002; Academy of Pediatrics Committee on Fetus and
19. Greisen G, Mirante N, Haumont D, et al; ESF 110(1 pt 1):16–26 Newborn; American Academy of Pediatrics
Network. Parents, siblings and grandparents 26. Grunau RE. Self-regulation and behavior in Section on Surgery; Canadian Paediatric So-
in the Neonatal Intensive Care Unit. A survey preterm children: Effects of early pain. In: ciety Fetus and Newborn Committee. Preven-
of policies in eight European countries. Acta McGrath PJ, Finley GA, eds. Pediatric Pain: tion and management of pain in the neonate:
Paediatr. 2009;98(11):1744–1750 Biological and Social Context, Progress in an update. Pediatrics. 2006;118(5):2231–2241
20. Als H, Gilkerson L. The role of relationship- Pain Research and Management. Vol 26. 33. DiCorcia JA, Tronick E. Quotidian resilience:
based developmentally supportive newborn Seattle, WA: IASP Press; 2003 exploring mechanisms that drive resilience
intensive care in strengthening outcome of 27. Grunau RE. Self-regulation and behavior in from a perspective of everyday stress and
preterm infants. Semin Perinatol. 1997;21 preterm children: effects of early pain. In: coping. Neurosci Biobehav Rev. 2011;35(7):
(3):178–189 McGrath PJ, Finley GA, eds. Pediatric Pain: 1593–1602

(Continued from first page)

Drs Picciolini, Visentin, Battajon, Di Nunzio, Ramacciato, Barberis, and Mastretta made substantial contributions to acquisition of data, performed examinations on
infants hospitalized in NICU, critically revised the manuscript, and gave final approval of the version to be published; Dr Zanini made substantial contributions to
conception and design, obtained funding, critically revised the manuscript, and gave final approval of the version to be published; Drs Carli, Bordigato, Chiandotto,
Boiti, Litta, Minelli Napolitano, Arco, Mammoliti, Fortini, Tagliabue, Quartulli, Motta, Introvini, Grigorio, Mussini, Pomero, Poggiani, and Bauchiero made substantial
contributions to acquisition of data, performed examinations on infants hospitalized in NICU, critically revised the manuscript, and gave final approval of the version
to be published.
www.pediatrics.org/cgi/doi/10.1542/peds.2011-0813
doi:10.1542/peds.2011-0813
Accepted for publication Jan 5, 2012
Address correspondence to Rosario Montirosso, Scientific Institute “E. Medea,” Via don Luigi Monza, 20-23842 Bosisio Parini, Lecco, Italy. E-mail: rosario.
montirosso@bp.lnf.it
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2012 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: The NEO-ACQUA project was supported by an unrestricted educational grant from Chiesi Farmaceutici S.p.A. Dr Tronick was supported by a grant from
National Institute Child Health & Human Development (R01HD37138; ET, PI) Standardization of the NRN-Neurobehavioral Scale.
COMPANION PAPER: A companion to this article can be found on page e1322, online at www.pediatrics.org/cgi/doi/10.1542/peds.2012-0511.

PEDIATRICS Volume 129, Number 5, May 2012 e1137