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ORIGINAL RESEARCH
published: 06 October 2020
doi: 10.3389/fped.2020.539451
Frontiers in Pediatrics | www.frontiersin.org 1October 2020 | Volume 8 | Article 539451
Edited by:
Oswin Grollmuss,
Université Paris-Sud, France
Reviewed by:
Jo Wray,
Great Ormond Street Hospital for
Children National Health Service
(NHS) Foundation Trust,
United Kingdom
Benjamin Bierbach,
University Hospital Bonn, Germany
*Correspondence:
Anne Gallagher
anne.gallagher@umontreal.ca
Specialty section:
This article was submitted to
Pediatric Cardiology,
a section of the journal
Frontiers in Pediatrics
Received: 01 March 2020
Accepted: 18 August 2020
Published: 06 October 2020
Citation:
Fourdain S, Caron-Desrochers L,
Simard M-N, Provost S, Doussau A,
Gagnon K, Dagenais L,
Presutto É, Prud’homme J,
Boudreault-Trudeau A, Constantin IM,
Desnous B, Poirier N and Gallagher A
(2020) Impacts of an Interdisciplinary
Developmental Follow-Up Program on
Neurodevelopment in Congenital
Heart Disease: The CINC Study.
Front. Pediatr. 8:539451.
doi: 10.3389/fped.2020.539451
Impacts of an Interdisciplinary
Developmental Follow-Up Program
on Neurodevelopment in Congenital
Heart Disease: The CINC Study
Solène Fourdain1,2 , Laura Caron-Desrochers1,2, Marie-Noëlle Simard 1,3, 4, Sarah Provost 1,2 ,
Amélie Doussau4, Karine Gagnon4, Lynn Dagenais4, Émilie Presutto4,
Joëlle Prud’homme4, Annabelle Boudreault-Trudeau2, Ioana Medeleine Constantin1,2 ,
Béatrice Desnous5, Nancy Poirier1,4,6 and
Anne Gallagher1,2,4*on behalf of the CINC interdisciplinary team
1Sainte-Justine University Hospital Research Center, Montreal, QC, Canada, 2Department of Psychology, Université de
Montréal, Montreal, QC, Canada, 3School of Rehabilitation, Université de Montréal, Montreal, QC, Canada, 4Clinique
d’Investigation Neurocardiaque (CINC), Sainte-Justine University Hospital Center, Montreal, QC, Canada, 5Division of
Neurology, Department of Pediatrics, La Timone Hospital, Marseille, France, 6Faculty of Medicine, Université de Montréal,
Montreal, QC, Canada
Objectives: This study investigates the impact of an early systematic interdisciplinary
developmental follow-up and individualized intervention program on the
neurodevelopment of children with complex congenital heart disease (CHD) who
required cardiac surgery.
Study Design: We prospectively enrolled 80 children with CHD: 41 were already
followed at our neurocardiac developmental follow-up clinic from the age of 4 months,
while 39 were born before the establishment of the program and therefore received
standard health care. We conducted cognitive, motor, and behavioral assessments at
3 years of age. We used one-way multivariate analyses of variance to compare the
neurodevelopmental outcome of both groups.
Results: Between-group analyses revealed a distinct neurodevelopmental profile with
clinically significant effect size (P<0.001, partial η2=0.366). Children followed at
our clinic demonstrated better receptive language performances (P=0.048) and
tended to show higher scores on visuo-constructive tasks (P=0.080). Children who
received standard health care exhibited greater performances in working memory tasks
(P=0.032). We found no group differences on global intellectual functioning, gross and
fine motor skills, and behaviors. Referral rates for specific remedial services were higher in
patients followed at our neurocardiac clinic compared to the historical cohort (P<0.005).
Conclusions: Overall, the impact of the developmental follow-up and individualized
intervention program on neurodevelopmental outcomes remains subtle. Nevertheless,
results, although limited by several factors, point toward an advantage for the children
who took part in the program regarding receptive language skills over children
Fourdain et al. Impacts of Neurocardiac Follow-Up Program
who received standard health care. We hypothesize that group differences may be
greater with growing age. Further research involving larger cohorts is needed to
clearly assess the effectiveness of neurocardiac developmental follow-up programs at
school age.
Keywords: congenital heart disease, neurodevelopment, neurocardiac program, early intervention,
interdisciplinary, preschool age, developmental assessment
INTRODUCTION
Congenital heart disease (CHD) is the most common congenital
anomaly, affecting up to 1% of live births (1–4), with the more
severe cardiac malformations requiring surgery or catheter-based
interventions to ensure survival (5,6). Advances in prenatal
diagnosis, surgical techniques, and medical therapies have led
to a significant rise in the survival rates of children with CHD
(5,7). This, however, has been associated with an increase in long-
term neurodevelopmental comorbidity (7), with up to 50% of
children with CHD presenting impairment in motor, language,
and/or cognitive functions (8–19), along with behavioral
and psychosocial maladjustment (20). These comorbidities
generally limit academic achievement, employability, earnings,
and insurability, and ultimately reduce the quality of life of
patients and their families (10,20–23).
Given the aforementioned comorbidities, several studies
have highlighted the need for an early and close developmental
follow-up of children with CHD (24–29). In 2012, the American
Heart Association and the American Academy of Pediatrics
recommended systematic developmental surveillance, screening,
and evaluation of patients with CHD throughout childhood
to promote early diagnosis, implement relevant supportive
strategies, and ultimately improve neurodevelopmental
prognosis (30). Subsequently, many cardiac developmental
follow-up programs have emerged in pediatric centers worldwide
(26,30,31). At the Sainte-Justine University Hospital Center
(Montreal, QC, Canada), we founded the Clinique d’Investigation
Neurocardiaque (CINC) in 2013 to provide early systematic
and interdisciplinary developmental follow-up for all children
with critical CHD without genetic syndrome (e.g., trisomy 21).
The establishment of the CINC program (i.e., identification of
systematic time points for assessments, selection of assessment
tools, recruitment of clinicians, etc.) is grounded on evidence
from literature on the CHD population and similar clinical
populations (e.g., preterm), and is gradually refined and adjusted
according to probative research findings and hospital resources
(19). The CINC interdisciplinary team is composed of a nurse
practitioner coordinator, a pediatric cardiac surgeon, pediatric
neurologists, cardiologists, developmental pediatricians,
physical therapists, occupational therapists, a psychologist, a
speech-language pathologist, and a nutritionist. Our program
begins at the age of 4 months and consists of systematic and
standardized developmental assessments at multiple pre-
established ages. These include neurological and physical exams,
motor and cognitive assessments, as well as socio-affective and
behavioral screenings using parental questionnaires. While direct
participation of professionals varies across assessments (e.g.,
4-month neurologic exams are performed by developmental
pediatricians or pediatric neurologists and 24-month cognitive
and motor assessments are conducted by a neuropsychologist),
all clinicians are invited to interdisciplinary clinical meetings,
thus having a potential indirect involvement with every patient
regardless of age. The timeline of the CINC developmental
follow-up program is presented in Figure 1.
Early generalized and systematic intervention is also offered.
It includes educational support to the child’s family, such as
information about infant growth and development, explanations
of child behavior, and feedback from a professional on the
parents’ interaction with the child. Children may also obtain
additional care according to their specific needs, therefore based
on the results of the systematic assessments. This additional
care consists of individualized recommendations to parents for
educational activities, daily home exercises, or direct intervention
with a therapist. Data from the scientific literature and the
clinical experience of the CINC professionals have led to establish
fixed criteria to determine the child’s eligibility for further
intervention (19,32,33). For instance, a child performing below
the 10th percentile on the Alberta Infant Motor Scale (34) at
4 months will be considered at risk of gross motor delay (32,
33) and will receive individual sessions for motor intervention
with the physical therapist (35). Similarly, a child with a score
below the 2nd percentile in one scale of the MacArthur–Bates
Communicative Development Inventories (MBCDI) (36), at the
10th percentile on the Communicative Gestures scale of the
MBCDI, or below the 10th percentile in all of its scales will
receive an extensive language assessment by a speech-language
pathologist to determine the needs for speech therapy (19). A
score in the monitoring zone or below the cutoff at the Ages
and Stages Questionnaire, Third Edition (37), will also lead to a
referral to a speech-language pathologist for evaluation. Finally,
a child showing a failure to thrive, that is, an insufficient weight
gain for age, an inappropriate weight loss, or a weight inferior
to the 2nd percentile according to standards of growth, will be
referred to a nutritionist.
In 2017, we published a case study (38) showing significant
motor improvement in a 12-month-old girl with complex CHD
who received early intervention with a physical therapist as
part of the CINC program. Recently, Fourdain and colleagues
described a substantial improvement of gross motor abilities in
CINC patients aged up to 24 months, particularly in children
at risk of motor delay who received physical therapy on a
regular basis (35). Although these results suggest a positive
impact of the CINC program, they could also be associated with
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Fourdain et al. Impacts of Neurocardiac Follow-Up Program
FIGURE 1 | Timeline of developmental follow-up from 4 to 42 months of age Clinique d’Investigation Neurocardiaque (CINC). Systematic screening and assessments
are represented in plain lines; additional examinations based on screening are represented in dotted lines. ASQ-3, Ages and Stages Questionnaire, Third edition;
ASQ-SE, Ages and Stages Questionnaire: Social–emotional; MBCDI, MacArthur–Bates Communicative Development Inventories; MCHAT, Modified Checklist for
Autism in Toddlers; BASC-2, Behavioral Assessment System for Children, Second Edition; SP, Sensory profile; CBCL, Child Behavior Checklist.
spontaneous recovery after surgery (39,40). Further research
is therefore needed to quantify the benefits of neurocardiac
follow-up programs on neurodevelopment. To this end, this
study aimed to assess the impact of the CINC early systematic
interdisciplinary developmental follow-up and individualized
intervention program compared to standard health care on
motor, cognitive, and behavioral development in 3-year-old
children with critical CHD.
MATERIALS AND METHODS
Patient Population
Since 2013, families of Sainte-Justine University Hospital
Center’s patients presenting with moderate to severe CHD
requiring cardiac surgery have been offered a referral to the
interdisciplinary neurocardiac clinic [Clinique d’Investigation
Neurocardiaque (CINC)]. Children with genetic syndromes (e.g.,
trisomy 21) and children with severe or profound intellectual
disability were not referred to the CINC as they already received
specialized services in thematic clinics or rehabilitation centers.
Since its opening, 16 (4%) families of the patients referred to
the CINC declined the developmental interdisciplinary follow-
up. Reasons for declining included being followed in another
pediatric hospital in the Montreal area for 3 (19%), being
followed in another specialized clinic in the Sainte-Justine
University Hospital Center for 2 (13%), having been referred
early to a pediatric rehabilitation center for 1 (6%), or being
satisfied with the standard health care for 1 (6%). Nine (56%)
families did not specify any reason for refusing the CINC follow-
up. Currently, we provide early systematic and interdisciplinary
developmental follow-ups to 338 children with CHD.
For this research study, we prospectively recruited a cohort
of 43 children with complex CHD, followed longitudinally at
the CINC. A total of 59 CINC patients were approached to
participate in the present study: 14 (23.7%) did not respond to
the invitation, 2 (3.4%) refused to participate due to lack of time,
and 43 (72.9%) accepted the invitation and were scheduled for a
research interdisciplinary standardized assessment at 3 years of
age. Two (4.7%) children did not offer sufficient collaboration
during the assessment to gather valid data. This resulted in 41
children whose data were included in this study and constituted
the Surveillance Group. Among these, 5 (12.2%) did not attend
the 4-month-old evaluation, 2 (4.9%) did not attend the 12-
month assessment, and 2 (4.9%) did not attend the 24-month
follow-up, with all children being present for at least two of
these assessments.
To compare neurodevelopmental outcomes at the age
of 3, we prospectively recruited a group of children with
moderate to severe CHD who were born before the CINC
was established and, as such, were not followed within the
clinic’s framework. These children received standard health care
(pre-established follow-ups with the cardiologist and regular
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Fourdain et al. Impacts of Neurocardiac Follow-Up Program
medical appointments with the pediatrician or family physician).
As for the CINC referral criteria, we only included children
who did not present genetic syndrome or severe or profound
intellectual disability. Among the 63 eligible families contacted
to participate in the study, 4 (6.3%) did not respond to the
invitation, 19 (30.2%) refused to participate, and 40 (63.5%)
accepted the invitation and were scheduled for the same research
interdisciplinary standardized assessment at 3 years of age. The
reasons provided when refusing to participate were lack of time
for 6 (31.6%), long distance between home and the hospital for 6
(31.6%), stating that the child has no developmental delay for 4
(21%), parent or child having to undergo surgery for 2 (10.5%),
and child being too afraid of hospitals for 1 (5.3%). One child did
not offer sufficient collaboration during the assessment to gather
valid data, resulting in 39 enrolled children who constituted the
Historical Control Group.
A description of the timeline of participants’ recruitment and
assessment is presented in Figure 2. The study was approved
by the institutional research ethics board of the Sainte-Justine
University Hospital Center. All participants’ parents gave written
informed consent.
Research Interdisciplinary Evaluations
Participants of the Surveillance Group and the Historical
Control Group received an interdisciplinary neurodevelopmental
evaluation as part of this research project. It included a cognitive
assessment by neuropsychologists (SF and LCD), a gross motor
assessment by a physical therapist (LD), a fine motor assessment
by occupational therapists (KG and JP), and a behavioral
assessment using a parental questionnaire. Interdisciplinary
research assessments were conducted at the Sainte-Justine
University Hospital Center during one full morning (90 min
for the cognitive assessment, and 15 and 60 min for the fine
and gross motor evaluations, respectively). Due to the young
age of the participants, parents were present in the room
with the child for the whole duration of the assessment. At
the end of the meeting, professionals provided to parents a
retroaction on the child’s cognitive and motor performances,
and behavioral skills during an interdisciplinary feedback session.
Finally, the assessment findings and the resulting relevant
recommendations were summarized in an interdisciplinary
written report.
Cognitive assessment was performed using the Wechsler
Preschool and Primary Scale of Intelligence, Fourth Edition
(WPPSI-IV) (41). For 3-year-olds, it includes three verbal
subtests (Receptive Vocabulary, Information, and Picture
Naming), two visuospatial subtests (Block Design and Object
Assembly), and two working memory subtests (Picture Memory
and Zoo Locations). It provides a global cognitive score
(Full-Scale IQ) as well as three primary index scales (Verbal
Comprehension, Visual Spatial, and Working Memory). Mean
performances of 10 [standard deviation (SD) =3] and
100 (SD =15) are expected on the subtest and scale
levels, respectively.
Gross motor skills were assessed using the Peabody
Developmental Motor Scale, Second Edition (PDMS-2)
(42), which includes three gross motor subtests (Stationary,
Locomotion, and Object Manipulation). It produces standard
scores (Mean =10; SD =3) for each subtest as well as
a Gross Motor Quotient (Mean =100; SD =15). Fine
motor assessment was done using the Manual Dexterity
scale of the Movement ABC, Second Edition (M-ABC-2)
(43). It measures manipulative skills through three subtests
(Posting Coins, Threading Beads, and Drawing Trail), each
providing a standard score (Mean =10; SD =3). The M-
ABC-2 also provides a Manual Dexterity composite score
(Mean =100; SD =15).
Behavioral assessment was performed using the Parent Rating
Scale of the Behavior Assessment System for Children, Second
Edition (BASC-2), preschool version (44). It provides a T
score (Mean =50; SD =10) for 12 syndrome scales and
four composite scales (Externalizing Problems, Internalizing
Problems, Behavioral Symptoms Index, and Adaptative Skills).
Perinatal, surgical, critical, and demographic variables were
collected from medical records for participants of both groups.
Anatomic CHD classification (45) and RACHS-1 scores (46)
were extracted from the descriptions of heart defects and
surgical procedures by a pediatric neurologist (BD). Information
regarding the use of remedial services was collected through
a parental report for both groups. For the Surveillance Group,
FIGURE 2 | Timeline of participants’ births (plain lines) and research assessments (dotted lines) for the Historical Control Group and the Surveillance Group.
Frontiers in Pediatrics | www.frontiersin.org 4October 2020 | Volume 8 | Article 539451
Fourdain et al. Impacts of Neurocardiac Follow-Up Program
additional information on remedial services was also retrieved
from the CINC records.
Statistical Analyses
Descriptive statistics [means, medians, SDs, and 95% confidence
intervals (95% CI)] were calculated for continuous variables,
and number of participants and percentages were calculated for
dichotomous and categorical variables. Unpaired t-tests, Mann–
Whitney U-tests, and Chi-squared tests were used to compare
both groups on continuous, categorical, and dichotomous
variables, respectively.
One-way multivariate analyses of variance (MANOVA) were
computed for intergroup comparisons on neurodevelopmental
assessment scores. Post-hoc unpaired t-tests were carried out to
identify significant differences between groups. Significance level
was set to α=0.05. Alpha adjustment for multiple comparisons
was done according to false discovery rate (47).
RESULTS
Patients’ Characteristics
A total of 80 participants were included in this study: 41
children in the Surveillance Group and 39 in the Historical
TABLE 1 | Clinical and demographical characteristics of infants with CHD.
Groups
Total
(N=80)
Surveillance
(n=41)
Control
(n=39)
p-values
Male sex, n37 (46.3) 17 (41.5) 20 (51.3) 0.38
Prenatal diagnosis, n41 (60.3) 23 (69.7) 18 (51.4) 0.12
Gestational age at birth, weeks 38.7 (1.8) 38.5 (1.8) 38.9 (1.9) 0.31
Birth weight, kg 3.2 (0.6) 3.08 (0.6) 3.2 (0.7) 0.23
Apgar score at 5 min 8.5 (1) 8.5 (1.1) 8.6 (0.9) 0.63
Confirmed genetic abnormality, n7 (9.3) 5 (13.5) 2 (5.3) 0.22
Cyanotic heart lesions, n46 (57.5) 26 (63.4) 20 (51.3) 0.27
Anatomic classification of CHDa,n0.35
Class I 50 (62.5) 28 (68.3) 22 (56.4)
Class II 25 (31.3) 10 (24.4) 15 (38.5)
Class III 2 (2.5) 1 (2.4) 1 (2.6)
Class IV 3 (3.8) 2 (4.9) 1 (2.6)
Primary cardiac surgery
Age at surgery, days 18 (67) 27 (143) 13 (30.8) 0.09
Cardiopulmonary bypass, n54 (76.1) 32 (84.2) 22 (66.7) 0.08
Cardiopulmonary bypass time, min 165 (80.4) 177 (100) 147.5 (32.2) 0.19
Open chest after surgery, n20 (31.3) 13 (37.1) 7 (24.1) 0.26
RACHS-1 scoreb,c,n0.29
Category 1 3 (3.8) 0 (0.0) 3 (8.1)
Category 2 30 (38.5) 16 (39.0) 14 (37.8)
Category 3 25 (32.1) 17 (41.5) 8 (21.6)
Category 4 18 (23.1) 6 (14.6) 12 (32.4)
Category 6 2 (2.6) 2 (4.9) 0 (0.0)
Primary hospital admission
Hospital length stay, days 17 (23) 20 (23) 16 (21.8) 0.44
Pediatric intensive care unit length stay, days 6.5 (5) 7 (5.5) 6 (5.3) 0.78
Maternal education level, n0.75
High school 24 (30.4) 13 (31.7) 11 (28.9)
Vocational school 21 (26.6) 11 (26.8) 10 (26.3)
College/university 34 (43) 17 (44.7) 17 (41.5)
Age at neurodevelopmental assessment, months 44.1 (1.2) 44.3 (1.2) 43.9 (1.2) 0.13
Data expressed as number of participants (percentages) for dichotomous and categorical variables and mean (SD) for continuous variables. Data for age at surgery,hospital length stay,
and PICU length stay are expressed as median (IQR).
aAnatomic classification of CHD defined according to Clancy et al. (45). Class I: two-ventricle heart without arch obstruction; class II: two-ventricle heart with arch obstruction; class III:
single-ventricle heart without arch obstruction, and class IV: single-ventricle heart with arch obstruction (45).
bData unavailable for two participants of the Historical Control Group.
cSurgical risk category defined according to Jenkins and Gauvreau (46).
Frontiers in Pediatrics | www.frontiersin.org 5October 2020 | Volume 8 | Article 539451
Fourdain et al. Impacts of Neurocardiac Follow-Up Program
Control Group. Perinatal, surgical, critical, and demographic
characteristics of the participants are presented in Table 1.
The most common heart defects were transposition of the
great arteries (39% in the Surveillance Group and 31% in the
Historical Control Group), coarctation of the aorta (14% in
the Surveillance Group and 28% in the Historical Control Group),
and Tetralogy of Fallot (17% in the Surveillance Group and 18%
in the Historical Control Group). We found a statistical tendency
for a greater proportion of children of the Surveillance Group
who required cardiopulmonary bypass during surgery compared
to the Historical Control Group (P=0.084). There were no
other differences in perinatal, surgical, critical, and demographic
characteristics between groups.
We found no differences between the 80 participants (41
in the Surveillance Group and 39 in the Historical Control
Group) and children who declined participation in the study
(16 CINC patients and 23 children born before the CINC was
established; all P>0.05) regarding sex or medical characteristics
(i.e., gestational age at birth, prenatal diagnosis, anatomic CHD
classification, birth weight, APGAR score at 5, age at surgery,
CPB time, hospital length stay, PICU length stay, and open chest
after surgery). No data were available regarding socio-economic
status for those who declined participation.
Based on parental reports, 14 (37%) children in the Historical
Control Group received at least one remedial service before
3 years of age through references within standard health
care. As expected, this rate was smaller compared to the
Surveillance Group, in which 37 (90%) children received at
least one remedial service before the age of 3, χ2=24.5,
P<0.001. Among the 14 children of the Historical Control
Group who received services, only 7 (50%) had met more than
one type of health professional, whereas 31 (84%) children
in the Surveillance Group had been followed by at least two
different health professionals, χ2=6.1, P=0.013. Physical
therapists, occupational therapists, speech-language pathologists,
and nutritionists were the most consulted professionals in
both groups. Among the 20 (49%) children in the Surveillance
Group who received speech and language therapy, 30% received
only indirect intervention, such as recommendations of daily
activities to stimulate language development, whereas 70%
received both indirect and direct speech therapy. In comparison,
only 5 (13%) children in the Historical Control Group
received services from a speech-language pathologist. A detailed
description of remedial services received in both groups is
presented in Table 2.
Cognitive, Motor, and Behavioral Results
The mean age at testing was similar in both groups (P=0.129)
with assessments at 43.9 months (SD =1.2) for the Historical
Control Group and at 44.3 months (SD =1.2) for the Surveillance
Group.Table 3 shows groups’ mean scores for cognitive, motor,
and behavioral measures. Each mean score, including indices
and subtests, was in the normal range, except for the Zoo
Locations subtest and the Working Memory Index, which were
both in the high average for the Historical Control Group.
Although in the normal range, distributions of gross motor
scores were slightly down shifted with an increased proportion
TABLE 2 | Participants’ characteristics relating to the use of remedial services.
Groups
Surveillance
(n=41)
Control
(n=38)a
Ever received remedial services, n37 (90) 14 (36.8)
Number of remedial services, n
One 6/37 (16.2) 7/14 (50)
Two 16/37 (43.2) 3/14 (21.4)
Three 8/37 (21.6) 3/14 (21.4)
Four 6/37 (16.2) 1/14 (7.1)
Five 1/37 (2.7) 0/14 (0)
Type of remedial services, n
Speech-language therapy 20/41 (49) 5/38 (13)
Physical therapy 37/41 (90) 7/38 (18)
Occupational therapy 15/41 (37) 8/38 (21)
Psychology therapy 0/41 (0) 2/38 (5)
Special educational support 3/41 (7) 1/38 (3)
Nutrition 17/41 (42) 4/38 (11)
Data expressed as sample size (percentages).
aData unavailable for one participant of the Historical Control Group.
of children performing under clinical cutoffs for both groups
[12 (31%) from the Historical Control Group and 7 (19%) from
the Surveillance Group performed equally to or below the 16th
percentile (1 SD or more below norms)].
Differences Between Groups
The one-way MANOVA revealed significant differences between
groups for performances on cognitive subtests, with a clinically
significant effect size, F(6, 57) =5.491, P<0.001; Wilk’s
3=0.634, partial η2=0.366. Post-hoc t-tests revealed that
the Surveillance Group performed better than the Historical
Control Group (P=0.048) on the Receptive Vocabulary subtest.
Individual results revealed that 3 (7%) children from the
Surveillance Group performed equally to or below the 16th
percentile (1 SD below mean), compared to 6 (16%) from the
Historical Control Group on this subtest. t-tests also showed a
statistical trend toward a greater score on the Object Assembly
subtest and a lower score on the Zoo Locations subtest in the
Surveillance Group compared to the Historical Control Group
(both P=0.08). We also found a significant group difference
in cognitive primary indices, F(4, 49) =3.449, P=0.013; Wilk’s
3=0.810, partial η2=0.190. Post-hoc comparisons indicated
that the mean score for the Working Memory Index was
significantly higher for the Historical Control Group compared
to the Surveillance Group (P=0.032), which is coherent with
the results obtained on the subtest level. We found no significant
effect of group on gross and fine motor scores as well as
behavioral scales.
DISCUSSION
Following the American Heart Association and the American
Academy of Pediatrics recommendations of systematic
Frontiers in Pediatrics | www.frontiersin.org 6October 2020 | Volume 8 | Article 539451
Fourdain et al. Impacts of Neurocardiac Follow-Up Program
TABLE 3 | Neurodevelopmental outcome of children with CHD.
Groups p-values
Surveillance
(n=41)
Control
(n=39)
Mean of scores
(SD)
Missing data
n(%)
Mean of scores
(SD)
Missing data
n(%)
Cognition (WPPSI-IV)
Full-scale IQ (FSIQ) 100 (11.7) 4 (9.8) 100.9 (13) 0 (0) ns
Verbal comprehension index 93.3 (12.1) 1 (2.4) 97.4 (12.1) 0 (0) ns
Receptive vocabulary 11.4 (3.5) 9.5 (2.4) 0.048
Information 8.8 (3.2) 10 (2.9) ns
Picture naming 9 (3) 10 (2.4) ns
Visual spatial index 103.8 (13.5) 3 (7.3) 100.54 (11.6) 0 (0) ns
Block design 10.1 (2.5) 10.4 (2.2) ns
Object assembly 11.3 (2.8) 10 (2.8) 0.080
Working memory index 102.45 (12. 6) 8 (19.5) 111.1 (13.4) 7 (17.9) 0.032
Picture memory 10 (2.5) 10.9 (2.9) ns
Zoo locations 10.8 (3.2) 12.3 (2.9) 0.080
Gross motor (PDMS-2)
Gross motor quotient 94.6 (9.2) 5 (12.2) 94.1 (11.2) 0 (0) ns
Stationary 9.4 (2.1) 9.1 (2.4) ns
Locomotion 9.2 (2) 9.5 (2.3) ns
Object manipulation 8.9 (1.6) 8.6 (1.5) ns
Fine motor (M-ABC-2)
Manuel dexterity score 97.7 (12.3) 2 (4.9) 99.1 (14) 0 (0) ns
Posting coins 9.6 (2.39) 9.4 (3.2) ns
Threading beads 9.5 (3.15) 9.4 (2.9) ns
Drawing trail 8.8 (3) 9.6 (3.4) ns
Behavior (BASC-2) 10 (24.4) 6 (15.4)
Externalizing problems 48.5 (9) 51.1 (8.4) ns
Internalizing problems 55.3 (10.5) 53.4 (8.9) ns
Behavioral symptoms index 48.3 (8.65) 48. 5 (7) ns
Adaptative skills 54 (6.55) 54.9 (7.4) ns
Data expressed as mean (SD). Mean performances of 10 (SD =3) and 100 (SD =15) are expected on subtest and scale levels, respectively. p-values were calculated using unpaired
sample t-tests with alpha adjustment according to false discovery rate.
WPPSI-IV, Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition; PDMS-2, Peabody Developmental Motor Scale, Second Edition; M-ABC-2, Movement ABC, Second
Edition; BASC-2, Behavior Assessment System for Children, Second Edition.
developmental surveillance, screening, and evaluation of
children with CHD (30), many neurocardiac developmental
follow-up programs have emerged worldwide. The feasibility of
implementing such programs has been demonstrated (26,48)
and factors improving follow-ups have been investigated
(49,50). The benefits of early intervention in supporting
neurodevelopment have been shown in other clinical pediatric
populations (e.g., preterms, autistic children) (51–55). Despite
variability with regard to the type of interventions (provided at a
clinic vs. home-based interventions) or professionals involved,
studies have demonstrated a positive impact of early intervention
programs compared to standard health care in enhancing
cognitive and behavioral outcomes of children born preterm
(55–58). In comparison, literature on interventional effect in
CHD is only emerging but is gathering increasing attention. The
aim of the present study was to assess the impact of the CINC
early systematic interdisciplinary developmental follow-up
program on neurodevelopmental outcomes of preschoolers with
critical CHD compared to standard health care.
Cognitive and Language Skills
Children of the Surveillance Group and the Historical Control
Group demonstrated similar global intellectual functioning.
We found a significant difference, with clinically significant
effect size, in performances on the receptive vocabulary subtest
and a statistical tendency on the visuo-constructive subtest
between groups. These skills have been previously reported to
be impaired in children with CHD (16,19,59–61). These results
suggest an advantage of the children who took part in the
CINC early systematic interdisciplinary developmental follow-up
program regarding receptive language competency compared to
children of the Historical Control Group who received standard
health care.
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Fourdain et al. Impacts of Neurocardiac Follow-Up Program
As part of their developmental follow-up and based on the
MBCDI screening results, 20 (49%) children of the Surveillance
Group were referred to a speech-language pathologist for
an extensive language assessment before the age of 3, with
70% who received both direct speech therapy and indirect
intervention in the form of recommendations to stimulate
language development. In comparison, only 5 (13%) parents of
children from the Historical Control Group reported receiving
services from a speech-language pathologist. These children
were referred only when a language delay was already observed
or if parental concerns were present, whereas all children of
the Surveillance Group underwent early systematic language
screening, which may result in earlier detection of language
impairments and higher referral rates. The individualized
intervention received by children from the Surveillance Group
may have strengthened the development of their receptive
language skills, as illustrated by a lower proportion of receptive
difficulties at the age of 3 (7% in the Surveillance Group compared
to 16% in the Historical Control Group being below 1 SD).
Additionally, we found that the children from the Surveillance
Group tend to have better visuo-constructive skills compared
to children from the Historical Control Group. Occupational
therapists of the CINC sometimes recommended visuospatial
and visuo-constructive activities for parents to perform with
their child, including shape sorting games and stacking toys,
to help stimulate perceptual–motor development and hand–
eye coordination abilities. However, it is not possible at this
point to state that we found an effect of the developmental
follow-up program or the specific individualized intervention on
these skills. This potential benefit in preserving the development
of visuo-constructive skills remains to be demonstrated.
Nonetheless, these results allow us to flag this set of competencies
for further assessment at a growing age.
Beyond the benefits of direct intervention, literature has
previously demonstrated the effects of a more global approach
in improving neurocognitive functions in children at risk
for developmental delay. For instance, several studies have
demonstrated that intervention programs including parental
support could benefit the neurodevelopment of preterm children
(55,58,62,63). In the CHD population, McCusker et al.
(64) have documented better cognitive and communicative
abilities in 8-month-old infants with CHD whose mother
participated in the Congenital Heart Disease Program. Through
psychoeducation, coaching, and therapy, this psychosocial
program notably aimed at promoting child development by
supporting maternal adjustment to the diagnosis and teaching
effective coping strategies. The Congenital Heart Disease
Program also demonstrated gains on measures of maternal
mental health and family functioning, which may indirectly
influence the child outcomes (65). In the CINC program,
psychoeducational support is systematically offered to parents.
Every visit is also an opportunity for parents to ask questions to
pediatric specialists. If needed, the nurse practitioner coordinator
also addresses parental concerns and offers additional support.
In addition to the potential impact of the individualized
direct intervention, the affective and psychoeducational support
given to parents may have had a beneficial effect on the
neurodevelopment of children with critical CHD. Additional
research is needed to investigate the potential benefits of the
CINC program in improving family well-being.
We found that children of the Surveillance Group showed
a significantly lower mean score on the Working Memory
Index compared to the children of the Historical Control
Group. However, this result should be taken with caution as
we cannot exclude that the high rate of missing data on this
scale could have biased group comparisons (see Table 3). For
a substantial number of children, we were not able to obtain
adequate collaboration to acquire valid data for the two subtests
composing this index (Zoo Locations and Picture Memory).
As frequently observed by assessors in both groups, these two
subtests specifically appeared to require substantial efforts from
the participants. The high number of missing values could have
resulted in an over-representation of the highest performances,
potentially explaining the mean performance in the high average
at the Working Memory Index for the Historical Control Group.
This could also have reduced statistical power, thus not reflecting
a true difference on memory span and working memory skills
between groups.
Gross and Fine Motor Functions
Overall, gross motor assessment revealed mean scores in the
normal range. However, this developmental domain still appears
as a specific area of concern, with 31% of the Historical Control
Group and 19% of the Surveillance Group performing equally to
or below the 16th percentile (1 SD or more below norms). In both
groups, gross motor disabilities were characterized by difficulties
with standing balance, decreased lower limbs strength, proximal
instability, and difficulty with hand–eye coordination. Although
some studies document a gradual improvement in gross motor
abilities up to the age of 3, difficulties in this domain persist
at school entry where gross motor impairment rate generally
exceeds normative expectations (9,66).
We found no significant differences between groups for gross
motor functions. Since gross motor impairments are known to
be the first manifestations of altered neurodevelopment in infants
with CHD, it is possible that family physicians and pediatricians,
even outside specialized clinics, may be successful at detecting
these difficulties and thus accurately referred patients to relevant
rehabilitation services or offer parental recommendations on
how to foster the child’s motor development (67). Based on
parental reports, 18% of children in the Historical Control Group
had received treatments with a physical therapist in addition
to the standard health care, physical therapy being one of the
most frequently received interventional services. This could have
preserved their gross motor skills and may explain the absence
of significant differences between groups. As discussed by Kynø
et al. (68) in the preterm population, the standard care offered
to all patients with CHD at the pediatric intensive care unit
(e.g., nesting, post-surgical positioning program, parents present
as much as possible, etc.) may also have supported the child’s
development, therefore reducing outcome differences between
groups. Nevertheless, the greater proportion of children in the
Historical Control Group performing below the 1 SD cutoff
suggests that children who did not undergo early systematic
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Fourdain et al. Impacts of Neurocardiac Follow-Up Program
interdisciplinary developmental follow-ups are at higher risk for
gross motor impairments compared to children who took part in
the CINC program. We cannot exclude either that this absence
of significant statistical differences in gross motor skills could be
due to the small sample size.
Regarding fine motor functions, occupational therapists have
observed limitations in the proximal stability of the upper limbs
in a significant proportion of children from both groups. These
limitations caused distal tremors and difficulties with motor
coordination. Children seemed to succeed in compensating for
these difficulties with both groups performing within the normal
range in fine motor tasks. However, children frequently exhibited
non-voluntary mouth movements, revealing that these tasks
required substantial efforts. In future studies, systematic video
recordings of children’s evaluations could help analyze qualitative
observations from specialists and thus allow the tracing of a
more subtle neurodevelopmental profile. We hypothesize that
these subtle limitations may progress into significant deficits
with growing environmental demands. Conducting a follow-up
at school age is thus crucial to document the developmental
trajectory and to detect motor difficulties that could arise and
significantly impact schooling and social life (9).
Behavioral Functioning
Children of the Surveillance Group and the Historical Control
Group demonstrated similar results on the BASC-2, revealing
behavioral functioning in the normative range for both groups.
At that age, only 2 children (5%) of the Historical Control Group
and no children from the Surveillance Group received services
from a psychologist. However, as it is integrated within the
CINC systematic program, psychologists conduct the 24-month-
old developmental evaluation and thus have the possibility to
provide parental counseling and psychological support without
the need to refer the family to external psychological therapy.
During the evaluation, assessors observed behavioral regulation
issues (e.g., oppositional behaviors, hyperactivity, and difficulties
to mobilize cognitive resources) that have not been reported
in the parental questionnaire. Based on our experience and the
literature, behavioral issues appear gradually with age in children
with CHD and become more salient to parents when the child
enters school. We are following these children and expect parents
to report more behavioral issues at school age.
Use of Remedial Services
Referral rates for interventional services were higher in children
who took part in our interdisciplinary developmental follow-
up program (90%) compared to children who received standard
health care (37%). These referral rates are in accordance with a
previous study we conducted on a subsample of CINC patients
where we reported that 79% were identified at the age of 4
months to be at high risk for gross motor delay and were referred
to the CINC physical therapist for interventional treatment
(35). In the current literature, apart from recognizing that
the prevalence of children with CHD who need interventional
services largely exceeds that of healthy children, there is no
clear consensus regarding the referral rate for additional care,
which depends on available public health resources as well
as insurance coverage (50). For instance, Mussatto et al. (39)
reported that 74% of 3-year-old children with CHD received
remedial services from US regional early intervention programs
or private therapy, and Calderon et al. (69) indicated that 53%
of 5-year-old children with CHD from the Paris area received
at least one rehabilitation service. Another study revealed that
40–95% of 8-year-old children with CHD who exhibited specific
developmental delays did not receive the relevant services (28).
In light of these findings, we think that an early systematic
developmental follow-up program results in a potential earlier
detection of neurodevelopmental impairments associated with
CHD, thus generating higher referral rates and at an earlier age.
However, this remains to be documented, and the relevance of
higher referral rates to be demonstrated in future studies.
Clinical Characteristics
While no statistical differences were found for most perinatal,
surgical, and critical characteristics between groups, a greater
proportion of children of the Surveillance Group required
cardiopulmonary bypass during surgery. This factor has
been shown to be associated with worse neurodevelopmental
outcomes (61,70,71). Children from the Surveillance Group
may have been at higher risk of neurologic sequelae after
surgery, thus affecting their neurodevelopmental outcome.
The higher neurological burden of the CINC patients may
have contributed to blurring group differences. More clinically
equivalent groups may lead to greater effects of interventional
treatment between groups.
Limitations
First, the small sample size may have prevented us from
clearly demonstrating an advantage of the interdisciplinary
developmental follow-up program over the existing standard
health care, and limits the generalization of our findings to the
whole complex CHD population. The sample size was restricted
in accordance with the hospital’s flow of patients with CHD.
Specifically, the Historical Control Group was recruited and tested
at a time period overlapping the beginning of the CINC program.
Therefore, we reached a maximal sample size since all children
subsequently born with a critical CHD were referred to the CINC.
Second, the use of a historical control group may have introduced
biases due to a different time of enrollment. Although no major
changes in cardiac care (e.g., cardiac surgeon) occurred in the
hospital over this timeframe, subtle changes may have influence
group differences. We might also have conducted the evaluation
too early in the developmental stage to observe significant
differences in high-level cognitive functions, fine motor abilities,
and behavior. We cannot exclude that the CINC program may
have longer-term impacts that would be more precisely measured
in an older cohort as opposed to preschoolers, thus stressing
the importance of following these children up to school age
and even later on. Finally, because evaluations were performed
by the CINC professionals and served for the clinical follow-
up of the CINC patients, it is to be noted that examiners were
not blind to the children’s group, which might have induced an
assessment bias.
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Fourdain et al. Impacts of Neurocardiac Follow-Up Program
Conclusions
Results suggest that the CINC early systematic and
interdisciplinary developmental follow-up program might
prevent the emergence of receptive language difficulties
in preschoolers. While these results are promising, they
remain subtle at this age and several factors limit their
generalization. It is therefore crucial to assess the impact of
early systematic developmental follow-ups at school age when
this impact might be greater and higher-order functions and
learning abilities can be assessed. At the CINC, subsequent
follow-ups occur at 5 and 8 years of age, with extensive
motor, cognitive, and language assessments performed by
occupational therapists, neuropsychologists, and speech-
language pathologists, respectively. In addition, we are currently
following the children from the Historical Control Group, who
are now starting to turn 8 years, and we have been able to recruit
more children in this group to increase statistical power. This
second phase of the current study will allow us to more accurately
assess the impact of our early systematic developmental program
at school age.
While neurodevelopmental assessments show that cognitive,
motor, and behavioral development of children with critical
CHD appears globally within the normal range prior to
entry at school, it is not to exclude that subtle limitations
may progress into deficits at school age with growing
environmental demands. Early systematic assessments with an
interdisciplinary team therefore appear to be of great importance
to document the developmental trajectory of these functions
and to detect subtle impairments that may have a functional
impact on behavior, learning, social functioning, and quality
of life.
DATA AVAILABILITY STATEMENT
The datasets generated for this study will not be made publicly
available due to patient confidentiality.
ETHICS STATEMENT
The studies involving human participants were reviewed and
approved by the Institutional Research Ethics Board of the
Sainte-Justine University Hospital Center. Written informed
consent to participate in this study was provided by the
participants’ legal guardian/next of kin.
AUTHOR CONTRIBUTIONS
SF participated in designing the study and data collection,
conducted the analysis, drafted the initial manuscript, and
reviewed and revised the manuscript. LC-D participated in
data collection and analysis, drafted the initial manuscript, and
reviewed and revised the manuscript. M-NS contributed to
the analysis and reviewed and revised the manuscript. AD,
KG, LD, ÉP, and JP contributed to the design of the study,
collected the data, and reviewed and revised the manuscript. SP,
AB-T, and IC contributed to the data collection and reviewed
and revised the manuscript. NP contributed to the design
of the study and reviewed and revised the manuscript. AG
conceptualized and designed the study, supervised the collection
of the data, contributed to the draft of the initial manuscript,
and revised and critically reviewed the manuscript for important
intellectual content. All authors approved the final manuscript
as submitted and agree to be accountable for all aspects of
the work.
FUNDING
This work was supported by the Heart and Stroke Foundation of
Canada under grant numbers G-16-00012606 and G-17-0018253
as well as a Canada Research Chair held by AG and by Garnier
Kids Foundation.
ACKNOWLEDGMENTS
We are grateful to the families who participated in the CINC
study. We also thank all the staff of the Clinique d’Investigation
Neurocardiaque (CINC) of the Sainte-Justine University Hospital
Center, Montreal, Quebec, Canada: Laurence Beaulieu-Genest,
MD, Valérie Deslauriers, BSc, Erg, Amélie Fauvelle, MSc,
Erg, Marie-Michèle Gagnon, MSc, PT, Julien Harvey, MSc,
SLP, Julien Leroux, DPs, Psych, Magdalena Jaworski, MD,
Geneviève Lupien, BSc, PT, Manuela Materassi, BSc, PT,
Christine Montmigny, BSc, PT, Perrine Peckre, BSc, Erg, Elana
Pinchefsky, MD, Anne-Marie-Vermette, BSc, RD, and Marie-
Claude Vinay, PhD, Psych. We give particular credit to Lionel
Carmant, MD, for his involvement in co-founding the CINC
and his contribution throughout every step of this study. In
memory of our friend and outstanding pediatric neurologist Ala
Birca, MD.
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Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Copyright © 2020 Fourdain, Caron-Desrochers, Simard, Provost, Doussau, Gagnon,
Dagenais, Presutto, Prud’homme, Boudreault-Trudeau, Constantin, Desnous,
Poirier and Gallagher. This is an open-access article distributed under the terms
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Frontiers in Pediatrics | www.frontiersin.org 12 October 2020 | Volume 8 | Article 539451
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