A neurobehavioral intervention and assessment program in very low birth weight infants: outcome at 24 months
A Neurobehavioral Intervention and Assessment Program in Very Low Birth
Karen Koldewijn, PT, Aleid van Wassenaer, MD, PhD, Marie-Jeanne Wolf, PhD, Dominique Meijssen, MSc,
Bregje Houtzager, MSc, PhD, Anita Beelen, PhD, Joke Kok, MD, PhD, and Frans Nollet, MD, PhD
Objective To determine whether the Infant Behavioral Assessment and Intervention Program (IBAIP) improvesdevelopment and behavior in very low birth weight (VLBW) infants at 24-month corrected age. Study design In a multicenter, randomized, controlled trial 86 infants received postdischarge intervention until 6-month corrected age. The intervention consisted of supporting infants’ self-regulation and development, and facil-itating sensitive parent-infant interactions; 90 control infants received regular care. At 6 months, positive interven-tion effects were found. At 24 months, development and behavior were evaluated with the Bayley Scales of InfantDevelopment-II (BSID-II) and the Child Behavior Check List (CBCL). Results Eighty-three intervention and 78 control infants were available for follow-up. After adjustment for differ-ences in perinatal characteristics, an intervention effect of 6.4 points (Æ standard error, 2.4) on the PsychomotorDevelopmental Index favored the intervention infants. Groups did not differ on the Mental Developmental Index,the Behavioral Rating Scale of the BSID-II, or on the CBCL. Subgroup analyses revealed improved motor as wellas improved mental outcomes in intervention infants with bronchopulmonary dysplasia and with combined biolog-ical and social risk factors. Conclusions The IBAIP shows sustained motor improvement in VLBW infants until 2-year corrected age. (J Pe-diatr 2010;156:359-65).
Growingconcernaboutthedevelopmental,social-emotional,andhealthproblemsinverypreterminfantsthatpersist
into early adulthoodhave led to the design of various types of early postdischarge intervention programs that aim toimprove the long-term outcome of these children. Recent meta-analysereported a significant impact of postdi-
scharge intervention on cognitive outcomes at infant and preschool age. There is heterogeneity of the programs, and furtherstudies are needed to identify intervention components that are most effective. Apart from biological factors, the infant’s self-regulatory competenceas well as parental sensitivity and responswere noted as crucial for the quality of parent-infant interactions. These, in turn, influenced the infant’s developmental course after preterm The Infant BehavioralAssessment and Intervention Program ), based on the synactive theory by Als,is designed to support infants withdevelopmental risk from term to approximately 8 months of age. This program aims to support the infant’s self-regulatorycompetence as well as the infant’s multiple developmental functions in an integrative way, via responsive and positive par-ent-infant interactions. We conducted a randomized, controlled trial to study the effect of the IBAIP on very low birth weightinfants (VLBW). At 6-month corrected age, we found that the program improved the mental, motor, and behavioral outcomesof VLBW infants.Neurobehavioral assessment demonstrated increased attention and engagement in interactions over time,accompanied by less stress behavior in the intervention infants compared with control infants. The principal outcome measuresof our trial were child development at 6 months, shortly after termination ofthe intervention, and at 24 months. We report infant outcomes at 24-monthcorrected age.
From the Department of Rehabilitation (K.K., M.-J.W.,A.B., F.N.), the Department of Neonatology (A.v.W.,M.-J.W., B.H., J.K.), Academic Medical Center,University of Amsterdam, The Netherlands; and theDepartment of Pediatric Psychology (D.M.), TilburgUniversity, Tilburg, The Netherlands
Supported by grants from the Innovatiefonds Zorgver-
zekeraars (project No. 576) and ZonMw (Zorg OnderzoekNederland) (project No. 62200032). Innovatiefonds
Zorgverzekeraars supported the implementation of the
intervention program, and Zorg Onderzoek Nederland
supported the first author, who wrote the first draft of themanuscript. The sponsors had no involvement in study
design; collection, analysis, or interpretation of the data;
writing of the report; or the decision to submit the man-uscript for publication.
0022-3476/$ - see front matter. Copyright Ó 2010 Mosby Inc.
All rights reserved. 10.1016/j.jpeds.2009.09.009
THE JOURNAL OF PEDIATRICS www.jpeds.com
Neurobehavioral intervention focuses on overall develop-
mental and behavioral support. In line with the outcomemeasures at 6 months, the Dutch version of the Bayley Scales
The Medical Ethics Committee of all hospitals involved ap-
of Infant Development-II (BSID-II) was used to assess infant
proved the study design. We carried out a multicenter, random-
developmA mental developmental index score (MDI)
ized, controlled trial in 7 Amsterdam hospitals. Infants with
and a psychomotor developmental index score (PDI) were
gestational ages (GA) of <32 weeks and/or birth weights of
calculated for the corrected age of the child. MDI and PDI
<1500 g, with parents living in Amsterdam, were eligible for
in the normal population have a mean of 100 (SD, 15). Ob-
the study. Infants with severe congenital abnormalities, infants
servations of infants’ behavior during the developmental test
whose mothers had a documented history of illicit drug use or
administration were rated using the Behavior Rating Scale
severe physical or mental illness, infants from non–Dutch-
(BRS) of the BSID-II. According to the Dutch manual, the
speaking families for whom an interpreter could not be
percentile scores of the ‘‘orientation/engagement and emo-
arranged, and infants who participated in other trials on postdi-
tional regulation’’ factor and the ‘‘motor quality factor’’
scharge management were excluded. Randomization into a con-
were studied separately and summed up to a total score,
trol or intervention group was computer-generated, stratified
with higher scores on the BRS reflecting more adequate test-
for GA (<30 and $30 weeks) and recruitment site. Interven-
ing behavior. A score of $26 is classified as normal, 25 to 11 is
tions were carried out by 6 experienced pediatric physical ther-
questionable, and #10 is nonoptimal test behavior.
apists who had received 1 year of training in the IBAIP from the
The Dutch version of the Child Behavior Check List 11⁄
author of this program (Rodd Hedlund). IBAIP training in-
5 (CBwas used to evaluate the child’s behavioral and
volved the reliable assessment and support of neurobehavioral
socio-emotional performance, as rated by the parent. It is
competence, the facilitation of affective, social, cognitive, and
a standardized questionnaire with good reliability and valid-
motor functioning of the infant in an integrated way, and the
ity, containing 100 items on problem behavior occurring
use of a strength and process-based approach to support the
now or in the previous 2 months. An Internalizing, External-
parent-infant relationship. A detailed written report with rec-
izing, and a Total problem score can be calculated. Raw
ommendations was provided to the parents after every session.
scores are transformed into T-scores, accounting for differ-
These reports, along with regular contact with the supervisor
ences in sex and age. A T-score of <60 is classified as normal,
(K.K.) and monthly reflection sessions, served to maintain the
60 to 63 is borderline, and >63 is in the clinical range.
The neurological examination according to Touwenwas
Intervention infants and their parents received 1 IBAIP
used to examine neurological functioning at 24 months. Ab-
session shortly before discharge and 6 to 8 home interven-
normal development is severe abnormality of tone, posture,
tions until the baby was 6 months of corrected age. Control
and movement leading to an impairment and/or delay in
infants received standard care and, if required (non-IBAIP
motor development. Mildly abnormal development is a mod-
trained), pediatric physical therapy. Regular outpatient visits
erate abnormality of tone, posture, and movement leading to
to the pediatrician were standard in both intervention and
a minor impairment and/or minor developmental delay.
Perinatal variables were taken from the medical records at
The content of the IBAIP has been more extensively de-
discharge. GA was determined by maternal history and ultra-
scribed elseand is available from the Internet.
sound examination in early pregnancy and confirmed post-
The implementation of the IBAIP by pediatric physical ther-
natally with the Dubowitz-score if antepartum information
apists resulted in a comprehensive intervention model in
was inconclusive.Bronchopulmonary dysplasia (BPD)
which ‘‘prevention’’ and ‘‘treatment’’ overlapped to a large
was defined as moderate to severe BPD when the infant
extent, supporting the parents as well as the evolving in-
was oxygen dependent $36 Sociodemographic
fant-parent relationship and the infant’s emerging functions.
data were obtained by a parent questionnaire. A multiple
Guided by the infant’s behavior, the interventionist provides
risk factor was created to explore the possible additive effect
suggestions to encourage parents to support their infant’s
of biological and social risk, including low maternal educa-
self-regulatory efforts and/or competence; to adjust the
tion and abnormal cranial ultrasound and/or BPD.
environment to their infant’s needs; to support positiveparent-infant interactions; and to enhance postural controland successful infant explorations without distress. Parents
were given detailed information about their infant’s develop-
At 24-month corrected age, pediatric, neurological, and de-
ment to guide parents along their infant’s next developmen-
velopmental assessment took place at the follow-up clinic
tal steps and to support realistic expectations of their child’s
of the Academic Medical Center and was carried out by an
functioning. Central to the IBAIP intervention is the support
experienced pediatrician and psychologist, blinded for group
of the parent to raise their child. In addition, mindful atten-
assignment. Parents were aware of the group assignment and
tion to their infant’s behavioral expressions and development
were instructed not to inform any of the outcome assessors.
may enhance the parents’ emotional availability, intrinsic
The CBCL was sent to the parents 2 weeks before the follow-
motivation, feelings of joy, and confidence in themselves
up visit, to be completed by the parent that was most respon-
sible for the care-taking of the child. 315 eligible participants
refused to participate (38)died (11)child factors (12)language reasons (11)parental factors (12)
176 randomized
older brother/sister in trial (3)participating in other trial (52)
86 intervention infants 90 control infants 85 received intervention/ 1 did not receiveFollow-up at 6 months: 86 Follow-up at 6 months: 85 Follow-up at 24 months: 83 Follow-up at 24 months: 78 withdrawn (1); moved to other country (2)died (1); withdrawn (2); moved to other country (2); lost to follow up (2)
ing significantly between the intervention and control group
Primary outcome measures were the MDI and PDI of the
(the use of indomethacin, dopamine, surfactant, and septic
BSID-II. Secondary outcomes were the BRS, CBCL, and neu-
Secondary analysis of the MDI and PDI were performed to
explore the interaction between intervention and BPD, cra-
nial ultrasound abnormality, gestational age, low maternal
The sample size for this trial was selected to provide 90%
education, as well as multiple risk (low maternal education
power to detect a difference between intervention and con-
and abnormal cranial ultrasound and/or BPD). Post hoc
trol groups in BSID-II (PDI and/or MDI) at 6-month cor-
t tests were performed to compare the outcomes of sub-
rected age of 0.5 With the initial sample size of 176
groups of infants with BPD and multiple risk. An a level of
children and an assumed dropout rate at 24 months of
0.05 was used for all tests of significance. All analyses were
10%, the resultant sample size would provide slightly less
based on intention to treat. The trial is registered with
than 90% power to detect a difference of 0.5 SD.
Data were analyzed using the SPSS 15.0 program (SPSS,
Chicago, Illinois). Independent-samples t tests and c2 tests
were performed to compare the 2 groups. Multivariate linearregression analyses were used to assess the effect of the inter-
The 176 participating infants in this trial until 24-month cor-
vention on the MDI, PDI, total-BRS, and CBCL scores, ad-
rected age are tabulated in the One of 86 intervention
justing for baseline differences. Weeks of gestation, sex,
infants did not receive the planned intervention because of
cranial ultrasound abnormalities, and oxygen therapy $28
severe psycho-social problems of the mother. According to
days were entered as fixed factors considering their potential
the intention-to-treat principle, this infant was included in
influence on developmental and behavioral outcome. Al-
the intervention group. At 24 months, 83 (97%) intervention
though the number of low-educated mothers did not differ
infants and 78 (89%) of the surviving control infants were
between the groups, the factor was added given its potential
available for follow-up. Perinatal and demographic charac-
influence on infant developmental and behavioral outcome.
teristics of the group that was not available for follow-up
Other factors associated with the primary outcomes, differ-
did not differ from the group that was assessed at 24 months.
A Neurobehavioral Intervention and Assessment Program in Very Low Birth Weight Infants: Outcome at 24 Months
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Children who could not complete the developmental assess-
Table I. Sociodemographic and perinatal characteristics
ment (>5 missing/incomplete items per scale) were excluded
from the analyses (Parents of 62 intervention infants
(75%) and of 50 control infants (64%) returned the CBCL
).The child’s parents were from various ethnic
backgrounds; half of them were born in The Netherlands.
Despite random assignment, more infants in the intervention
group were <28 weeks GA than in the control group (21 vs 8;
P = .013). In addition, there were more boys in the interven-
tion group. More intervention infants had an abnormal cra-
nial ultrasound, they had more septic episodes, and were
oxygen dependent for a longer period (O2 $28 days and
$36 weeks). Also, more intervention infants received indo-
methacin or surfactant and were hospitalized for a longer
On the mental domain of the BSID-II, 69% intervention vs
63% control children were classified as normal (MDI >85);
on the psychomotor domain, 50% intervention vs 45% con-
trol children were classified as normal (PDI >85).
The mean (Æ standard deviation [SD]) MDI scores were
91.7 Æ 17 in the intervention group and 90.9 Æ 18 in the con-
trol group (P = .72). Mean PDI scores were 87.5 Æ 16 and
83.8 Æ 14, respectively (P = .12). After adjustment for perina-
tal and background variables a significant intervention effect
was found on the motor scale of 6.4 Æ 2.4 (P = .006). No in-
tervention effect was found on the mental scale (2.4 Æ 2.8,
P = .38). The effects of factors that independently influenced
the primary outcomes and the adjusted means are summa-
In total, there were 30 infants with BPD and 21 infants with
multiple risk; 12 infants with BPD were included in the mul-
tiple risk group. Intervention children with BPD and with
multiple risk had higher mental as well as higher motor scores
compared with control children with these problems. In the
children with BPD the mean Æ SD MDI scores were 88.5 Æ
17.5 in the intervention children vs 73.0 Æ 18 in the control
children (P = .05, n = 23 vs7); the mean PDI scores were 81.8
Æ 17.6 in the intervention children vs 61.6 Æ 10.0 in the con-
trol children (P = .009, n = 20 vs 7). In children with multiple
risk, the mean MDI scores were 86.7 Æ 17.1 in the interven-
tion children vs 68.7 Æ 11.0 in the control children (P = .029,
n = 15 vs 6); the PDI mean scores were 85.7 Æ 16.6 in the in-
tervention children vs 63.8 Æ 14.1 in the control children
PMA, postmenstrual age. Numbers are given as number of infants unless otherwise stated.
displays the multivariate linear regression analy-
Independent-samples t tests and c2 tests. *Small for gestational age was defined as <1 SD below the mean for Dutch reference data.
ses, which demonstrates the significant interaction between
intervention and BPD and between intervention and multi-
zEither breast-fed or expressed milk. xCerebral hemorrhage (IVH) was defined according to periventricular leukomalacia
ple risk. No significant interaction was found between treat-
ment and GA <28 and $28 weeks, cranial ultrasoundabnormalities, or low maternal education. Performing theanalyses with only 1 child per family in the case of multiplets,to explore a possible nesting effect, did not change the results.
izing mean Æ SD T-score was 48.0 Æ 8.8 and 45.7 Æ 9.7, re-
Table II. Multivariate regression models: Independent
spectively, the total problem score was 45.81 Æ 9.09 in
effect of factors on MDI, PDI, and BRS of the BSID-II at
intervention children and 45.2 Æ 8.9 in control children.
On the internalizing scale, 3 intervention children vs 4 control
children scored above the borderline or clinical range; on the
externalizing scale, 7 intervention versus vs 6 control children;on the total scale, 4 intervention vs 3 control children. No in-
tervention effects were found after adjustment for differences
in perinatal characteristics and low maternal education (not
Neurological. No differences between the groups were
found on neurological outcome measures. At 24 months, 5
intervention infants scored mildly abnormal and 3 interven-
tion infants scored abnormal; in the control group, 3 infants
scored mildly abnormal and 5 abnormal (P = .24). Between
the end of the intervention at 6 months and the assessment
at 24 months, significantly fewer intervention infants re-
ceived paramedical support (pediatric physical therapy
and/or occupational therapy and/or speech therapy) com-
pared with control infants: 10 (13%) vs 21 (24%) infants,
IBAIP post discharge intervention, supporting VLBW infants
until the corrected age of 6 months, improved the child’s mo-
tor development at 24-month corrected age. We found a sig-
nificantly better score on the psychomotor domain of the
BSID-II after adjustment for perinatal factors and the influ-
ence of maternal education, which almost reached the pre-
planned half standard deviation. The positive intervention
Multivariate linear regression analyses: gestation, sex, abnormal ultrasound, O2 $ 28 days,
effect on mental and behavioral development that was found
and maternal education are included in the model as constant factors; the use of indomethacin,
at 6 months was not seen at 24 months. However, in post hoc
dopamine, surfactant, septic episodes, and intervention are entered stepwise. Intervention wasincluded as fixed factor in which intervention was excluded from the model.
analyses, we found improved motor as well as improved
*The adjusted mean Æ SE MDI scores were 92.5 Æ 2 in the intervention infants and 90 Æ 2 in
mental development after IBAIP intervention in subgroups
the control infants. †The adjusted mean Æ SE PDI scores were 88.9 Æ 2 in the intervention infants and 82.4 Æ 2 in
of children with BPD and children with multiple risk. Apart
from the described outcomes, significantly fewer interven-
zThe adjusted mean Æ SE BRS total scores were 57.9 Æ 3 in the intervention infants and55 Æ 4 in the control infants.
tion infants received paramedical services after 6 months,and they were more compliant with follow–up, which under-lines the positive effects of the intervention.
This study demonstrates motor improvement after postdi-
Behavioral. At 24 months, 84% of children in both inter-
scharge early intervention in VLBW infants at 24 months.
vention and control groups scored in the category normal
Benefits on cognitive outcomes from age 2 on were reported
test behavior on the BRS; 11% of the intervention, and 13%
The Infant Health and Development Program
of the control children scored in the category questionable:
(IHDP) found a positive cognitive effect in LBW after 3 years
5% vs 3% scored nonoptimal. No statistically significant dif-
of frequent home visits, attendance at a child development
ferences between the groups were found. The mean total per-
center, and parent group meMore recently, the
centile score Æ SD was 56.6 Æ 31 in the intervention group
APIP reported identical small cognitive gains of a de-
and 56.3 Æ 30 in the control group (P = .89). shows
velopmental education program or a parent adviser program
the effects of factors that independently influenced the out-
after supporting VLBW infants and families for 2 years. The
comes. No intervention effects were found. Also, no signifi-
most vulnerable VLBW infants (<1250 g and those with brain
cant differences were found in problem behavior, as
injuries) benefited most from the developmental curriculum.
measured with the CBCL. The internalizing mean Æ SD
Both programsreported a strong relation between infant
T-score on the CBCL was 44.82 Æ 9.4 in the intervention
outcomes and social factors, such as the mother’s educational
children and 46.2 Æ 10.4 in the control children, the external-
level. We found only 1 short postdischarge early intervention
A Neurobehavioral Intervention and Assessment Program in Very Low Birth Weight Infants: Outcome at 24 Months
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Table III. Multivariate regression models: Independent effect of factors, and interaction between BPD1 and intervention,and a Multirisk factor2 and intervention on MDI and PDI of the BSID-II at 24-month corrected age
Interaction between multiple risk and intervention
1BPD: oxygen dependency $36 weeks. Multivariate linear regressions analyses: gestation, sex, abnormal cranial ultrasound, BPD, interaction BPD* intervention, low maternal education andintervention are included in the model as contant factors; the use of indomethacin, dopmine, surfactant, septic and septic episodes are entered stepwise. 2Multivariate linear regression analyses: gestation, sex, interaction multirisk* intervention, multirisk, and intervention are included in the model as constant factors; the use of indomethacin,dopamine, surfacant, and septic episodes are entered stepwise.
programcomparable in content to the IBAIP. It included
which, in turn, may hinder their environmental explorations.
infants <2000 g and ended at the corrected age of 3 months.
The difference between intervention and control infants was
This study applied a modified version of the Mother-Infant
stronger in those with multiple risk factors. This shows the
Transaction Program (MITP)and found less parenting
need to support these often underserved groups with both
stress but no significant benefits in infant outcomes at age
adverse infant and parent characteristics.Unfortunately,
2. The original version of the MITP reported increasing ben-
these post hoc results are based on a small patient group, with
efits in cognitive outcome from 3 years on, also preceded by
fewer infants with BPD and multiple risk in the control
enhanced parenting outcomes (maternal role satisfaction,
group. Further studies are warranted to explore these prom-
maternal self-confidence and maternal perception of infant
ising effects of the IBAIP in high-risk infants.
temperament), which suggests that intervention may have
Although better motor performance is expected to be in-
a delayed effect on cognitive outcome.
tertwined with improvements in behavioral and cognitive
Improved motor outcome in the present study may be ex-
development, this was not seen in the outcomes of all
plained by the basic elements and timing of IBAIP implemen-
our children at 24 months. This may indicate the need of
tation. Movement derives from the interactions between the
consistent and age-specific preventive interventions after 6
individual, the task, and the environment in which the task is
months to further boost the responsiveness of parents to
carried out.We hypothesize that supporting both the in-
their infant’s development and self-regulation during
fant’s individual self-regulatory competencies as well as pro-
increasingly complex skills (eg, social-emotional competen-
viding the environmental and task activities the infant
cies and attention control, language, manipulation, and
expected and could handle, enhanced the infant’s informa-
tion processing and exploratory abilities. During early in-
Given the impact of the IBAIP on motor development at
fancy, the sensory-motor system plays a key role in
24 months and its encouraging effect on mental and motor
explorations as well as in self-regulation. Hence, these posi-
development in the most vulnerable preterm infants, this
tive early experiences may have influenced the organization
neurobehavioral intervention program may contribute to
of the involved brain areas, on which the child could build
the early resilience and developmental outcome of VLBW in-
after the intervention period.Infants with BPD may have
fants after discharge from hospital. We are now studying if
profited most from the intervention because they are partic-
the effect of the IBAIP sustains until early school age. n
ularly vulnerable to stress. Infants with BPD have difficultiesin gaining homeostatic, postural, and state control. These
We thank the following pediatricians of all 7 participating Amsterdam
problems make them more difficult to handle and harder
hospitals for their involvement and cooperation in this study: Rinske
to socially engage without physiological compromise,
Breur, Hans Budde, Frank van den Dungen, Warda Goudsmit,
Marina Keessen, Erik Ree, Janny Samsom (in memoriam), Loekie van
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Sonderen, Louise Spanjerberg, Paolo Valerio, and Bart Wolf.
Infant Behavioral Assessment and Intervention Program to support pre-term infants after hospital discharge: a pilot study. Dev Med Child Neu-rol 2005;47:105-12.
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A Neurobehavioral Intervention and Assessment Program in Very Low Birth Weight Infants: Outcome at 24 Months
EFDAEuropean Fusion Development Agreement Issue 2000/1 I N FORM AT I ON F U SI ON Fusion energy from the sun Fusion Energy: has warmed the earth for billions of years. Today, sci- An Option for the Future entists and engineers have achieved the first demonstra- tions of a process for releas- ing fusion energy similar that which takes place in the sun. This
Liste des médicaments disponibles en conditionnement trimestriel Antidiabétiques Spécialité Dénomination Présentation Conditionnement “Prix public TTC commune internationale (décembre 2007-IMS Health)” Liste des médicaments disponibles en conditionnement trimestriel Politique du médicament/Dim – mars 2008 • 1 Liste des médicaments disponibles e