Early Human Development 136 (2019) 7–13

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Early Human Development

journal homepage: www.elsevier.com/locate/earlhumdev

Preterm children with suspected cerebral palsy at 19 months corrected age T

in the Canadian neonatal follow-up network
⁎
Anne Synnesa, , Jenna Gillonea,1, Annette Majnemerb, Abhay Lodhac, Dianne Creightonc,
Diane Moddemannd, Prakesh S. Shahe, on behalf of the Canadian and Neonatal Network,
Canadian and Neonatal Follow-up Network
a
Department of Pediatrics, University of British Columbia and BC Women's Hospital and Health Centre, 4500 Oak St, Vancouver, BC, V6H 3V4, Canada
b
McGill University, 3605 de la Montagne, room 113, Montreal, H3G 2M1 Montreal, Canada
c
Department of Paediatrics, University of Calgary, 28 Oki Drive NW, Calgary, Alberta, T3B 6A8, Canada
d
University of Manitoba, 1128-1155 Notre dame Ave, Winnipeg, Manitoba R3E 3G1, Canada
e
University of Toronto, 600 University Avenue, Room 19-231, Toronto, Ontario M5G 1X5, Canada

A R T I C LE I N FO A B S T R A C T

Keywords: Background: The ability to definitively diagnose cerebral palsy (CP) at 18–24 months is unknown.
Cerebral palsy Aims: To describe very preterm children who, at 19 months, have suspected CP defined as neither having a
Prematurity definitive diagnosis of CP nor no CP and compare them with children with and without CP.
Motor impairments Study design and methods: Longitudinal national cohort study of births < 29 weeks' gestation with linked
Canadian Neonatal Network and Canadian Neonatal Follow-up Network data with 19 month assessments and 3-
year questionnaires (Ages and Stages-3 and Health Status Classification System-Preschool). CP, no CP and
suspected CP groups, classified at 19 months, were compared using chi square and ANOVA.
Results: Of 3086 survivors, 2280 had complete 19-month corrected age (CA) and 1261 had 3-year CA data.
Suspected CP (3.6%), CP (6.4%) and no CP (90%) groups differed (p < 0.05) in birth weight, gestational age,
complications of prematurity and NICU length of stay. Children with suspected CP had Bayley-III motor, cog-
nitive and language composite scores at 18 months midway between CP and no CP, had the lowest sensory
impairment rates and highest hospital readmission rates. At 3 years, gross motor, fine motor, problem-solving,
communication and social skill abilities differed: abnormal outcomes were intermediate for children with sus-
pected CP (p < 0.01).
Conclusions: CP incidence varied from 6.4% to 10% with exclusion or inclusion of children with suspected CP.
Children with suspected CP have characteristics mostly midway between those with and without CP and de-
velopmental concerns persist to 3 years and require surveillance beyond 19 months.

1. Introduction CP is an umbrella term encompassing permanent disorders of

Cerebral palsy (CP) is the most common cause of physical impair-
ment in childhood [1]. Overall prevalence in America, Europe and
Australasia is reported at 2–3 per 1000 live births [1–4]. In preterm
children, the risk of CP is elevated to 50 fold as compared to term
children, with a prevalence of 6 to 26% [4,5].
movement and posture affecting function in everyday activities [6]. The
clinical manifestations of CP evolve as the brain matures so there is a
period of time during infancy or early childhood where the diagnosis of
CP may be suspected but uncertain [2,7–10]. Early diagnosis of CP is
important to enhance motor and cognitive outcomes, prevent secondary
complications and improve caregiver well-being [11]. A diagnosis of

Abbreviations: ASQ-3, Ages and Stages Questionnaire third edition; Bayley-III, Bayley Scales of Infant and Toddler Development-Third Edition; BPD, broncho-
pulmonary dysplasia; CA, corrected age; CNFUN, Canadian Neonatal Follow-Up Network; CNN, Canadian Neonatal Network™; CP, cerebral palsy; GA, gestational
age; GMFCS, Gross Motor Function Classification System; HSCS-PS, Health Status Classification System- Preschool version, NICU- neonatal intensive care unit; NDI,
neurodevelopmental impairment; SNAP-II, Score for Neonatal Acute Physiology second version; sNDI, significant neurodevelopmental impairment
⁎
Corresponding author at: Room 1N57, BC Women's Hospital and Health Centre, 4500 Oak St, Vancouver, BC, V6H 3V4, Canada.
E-mail addresses: asynnes@cw.bc.ca (A. Synnes), annette.majnemer@mcgill.ca (A. Majnemer), Abhay.Lodha@albertahealthservices.ca (A. Lodha),
diter@telusplanet.net (D. Creighton), DModdemann@hsc.mb.ca (D. Moddemann), Prakeshkumar.Shah@sinaihealthsystem.ca (P.S. Shah).
1
Current address: Neonatal Department, Royal Victoria Infirmary, Newcastle Upon Tyne. NE14LP. United Kingdom.

https://doi.org/10.1016/j.earlhumdev.2019.06.009
Received 6 April 2019; Received in revised form 18 June 2019; Accepted 21 June 2019
0378-3782/ © 2019 Elsevier B.V. All rights reserved.
A. Synnes, et al.
CP, assessed at 18–24 months corrected age (CA) has been used as a
primary outcome or part of a composite outcome in several neonatal
trials [12,13]. In contrast, many CP registers have not ‘registered’ cases
until after 2 years of age [1]. The developmental trajectory of children
with suspected CP is unknown.
The Canadian Neonatal Follow-up Network (CNFUN) [14] collects
information on neurodevelopmental assessments of children born <
29 weeks gestational age at a targeted age of 18 to 21 months CA, with
linkage to neonatal data from the Canadian Neonatal Network™ (CNN)
[15]. The need for a “suspected CP” category was identified by the
expert clinicians on the CNFUN database committee to capture the
children where the clinician believes the child may have CP but does
not meet the definitive criteria for CP [6]. The aim of this study was to
describe the neonatal and 18–24 month CA characteristics of children in
the CNFUN database identified as having suspected CP at the median
age of 19-months CA and also report their trajectory to 3 years. Our
hypothesis was that children with suspected CP have characteristics
from birth to 3 years that are in between those of children with and
without definitive CP.
2. Methods
2.1. Participants and assessments
This retrospective national cohort study included children born
at < 29 completed weeks' gestation between April 1, 2009 and
September 30, 2011 admitted to a neonatal intensive care unit (NICU)
and followed prospectively in a CNFUN neonatal follow-up program
participating in the Maternal Infant Care study. The Maternal Infant
Care study linked Canadian Neonatal Network™ (CNN) data from 28
participating sites with CNFUN data from all 26 Canadian neonatal
follow-up programs and captured about 90% of Canadian NICU ad-
missions during this time period [14]. Ethics approval for data collec-
tion was obtained from the participating sites as part of the Maternal
Infant Care Study and in addition the Children's and Women's Research
Ethics Board in Vancouver approved this study. Written informed
consent was obtained from participating families at the 19 month
CNFUN visit and as part of the 3 year questionnaire as per local research
ethics boards' requirements .
2.2. CNN data collection
Data collection has been previously described and validated [15].
Gestational age at birth, birth weight, proportion with high severity of
illness as defined by a Score for Neonatal Acute Physiology second
version (SNAP-II) score [16] above 20, neonatal morbidities including
bronchopulmonary dysplasia (BPD) defined as receipt of oxygen at or
beyond 36 weeks' gestational age, brain injury defined as grade 3–4
intraventricular hemorrhage [17] or periventricular leukomalacia, late
onset sepsis defined as a positive blood or cerebrospinal fluid culture,
necrotizing enterocolitis of Bell's stage 2 or higher [18], retinopathy of
prematurity (ROP) of stage > 3 in either eye or treated with laser or
anti-vascular endothelial growth factor, duration of CNN NICU admis-
sion and NICU discharge on any respiratory support were compared in
groups with definitive CP, suspected CP and no CP.
2.3. CNFUN data collection
CNFUN has a standardized assessment at 18 to 21 months CA with a
database and manual of operations and definitions [19]. The neurolo-
gical examination was completed by experienced physicians (neona-
tologists, pediatricians or developmental pediatricians) in participating
Follow-Up Programs without additional training for reliability. Stan-
dard definitions and classifications of cerebral palsy [6,19] were used.
For children with CP, the Gross Motor Function Classification System
(GMFCS) [20] was utilized as a measure of functional gross motor
8
Early Human Development 136 (2019) 7–13
severity. Variables included in the analyses were: age at assessment,
Bayley Scales of Infant and Toddler Development 3rd edition (Bayley-
III) [21] motor, cognitive and language composite scores, visual and
hearing impairment, sociodemographic variables, comorbidities, re-
source utilization including supports, referrals and medication use as
previously described [19]. In addition, physicians identified whether
there were other diagnoses or issues that likely affected development
including fetal alcohol spectrum disorder, chromosomal or genetic
disorders, extensive hospitalization, congenital heart disease, and par-
ental illicit substance use.
2.4. CNFUN data collection: 3-year CA questionnaire
Parents completed two questionnaires at 36-months CA: the Ages
and Stages Questionnaire–Third Edition [22] (ASQ-3) and Health Status
Classification System- Preschool [23–24] (HSCS-PS) version. These
were mailed to families by 21 participating CNFUN sites, scored at the
coordinating site, uploaded into the CNFUN database and linked using a
unique identifier. The ASQ-3 is a developmental screening tool re-
commended for use in preterm populations [25]. It includes the fol-
lowing domains: communication, fine and gross motor skills, problem
solving, and personal-social skills. The HSCS-PS is a multidimensional
measure of overall health, including vision, hearing, mobility, dex-
terity, self-care, emotion, learning and remembering, thinking and
problem solving, pain, and behavior validated for preschool-aged
children born preterm [24].
2.5. Statistical analyses
Analyses were performed on 1) the entire cohort of eligible children
with CNN and 19-month CA CNFUN data and 2) the subset of children
with CNN, 19-month and 3-year CA data. For the suspected, definitive
and no CP groups, neonatal, 19-month CA and 3-year characteristics
were described and the 3 groups compared statistically. Cell counts
containing values < 5 were not reported to avoid identification of in-
dividuals according to network policy. Proportions and means were
compared using Pearson Chi Square or Fisher test for categorical vari-
ables and ANOVA F test for continuous variables as appropriate.
Corrections were not made for multiple comparisons and p values <
0.05 were considered of interest in this hypothesis generating study.
3. Results
As shown in Fig. 1, 3108 participants survived to NICU discharge,
3086 were known to survive to 19 months CA (22 post NICU deaths)
and 2340 were seen at a median of 19 months corrected age and
complete data was available for 2280. There were 146 (6.4%) children
with definitive CP, 81 (3.6%) with suspected CP and 2053 (90%)
without CP at the 19-month CA assessment. Questionnaires were
completed at 3 years CA by 1261 caregivers. Families who didn't
complete the 3 year questionnaire were more likely to have children
with a slightly higher birth weight, have a primary language other than
English or French, be non-english speaking, younger and single parents.
(eTable 1; supplement) In the cohort with complete 3 year CA data
(n = 1257), comparisons were made between 70 children with CP, 47
with suspected CP and 1140 without CP.
3.1. Neonatal characteristics
Children with CP were born earlier, smaller, were more severely ill,
were more likely to have had neonatal morbidities and had longer NICU
stays (Table 1). Children with suspected CP were in between those with
and without CP with respect to gestational age, all neonatal morbidities
and length of NICU admission.
A. Synnes, et al. Early Human Development 136 (2019) 7–13

Number of infants born at <29 weeks

gestational age admitted to a NICU
N = 3993

Moribund infants 65
Major anomalies 228
Death 592

Infants discharged alive

n = 3108

No link to CNFUN Linked to CNFUN

n = 276 n = 2832

Post NICU death 22

Eligible survivors
n = 2810

Not seen at 18 months CA Assessed at18 months CA

n = 470 n = 23401

No data at 3 years CA Data at 3 years CA

n = 1079 n = 12612

1
60 patients were missing CP information
2
4 patients were missing CP information at 18 months

Fig. 1. Flow diagram of study population.

1
60 patients were missing CP information
2
4 patients were missing CP information at 18 months.

Table 1 3.2. Eighteen month characteristics

Neonatal characteristics.
CP Suspected CP No CP P value
Median CA at the time of assessment was 19 months for all 3 groups
N = 146 N = 81 N = 2053 and did not differ statistically between groups. Children with CP per-
formed significantly worse not only on the Bayley-III motor composite
GA, weeks, median (IQR) 26 (25, 27) 26 (25, 27) 27 (25, 28) < 0.01 score but also the cognitive and language composite scores (Table 2)
Birth weight, grams, 880 (720, 930 (760, 928 (770, 0.04
and in 24% of children the Bayley-III could not be administered. Of the
median (IQR) 1040) 1090) 1100)
SNAP-II > 20, n (%) 67 (47.2) 29 (35.8) 514 (25.1) < 0.01 129 children with CP with further information, 120 (93%) had spastic
BPD, n (%) 84 (57.5) 43 (53.1) 894 (43.6) < 0.01 CP and 60% had less severe CP with a GMFCS score < 3 (eTable 2
Brain injury, n (%) 84 (57.5) 20 (25.0) 164 (8.2) < 0.01 supplement). Children with suspected CP were successfully tested using
Late onset sepsis, n (%) 58 (39.7) 32 (39.5) 549 (26.7) < 0.01
the Bayley-III in > 95% and scored midway between those with and
Severe ROP, n (%) 36 (24.7) 13 (16.1) 218 (10.6) < 0.01
Treated PDA, n (%) 87 (59.6) 41 (50.6) 905 (44.1) < 0.01 without CP on all 3 domains. Visual and hearing impairments were rare
NICU length of stay, days, 105 (67, 94 (67, 120) 73 (48, 101) < 0.01 in the suspected CP group, lower than both other groups. Children with
median (IQR) 135) CP had more adverse sociodemographic features than those without CP
Discharge on respiratory 81 (55.5) 41 (50.6) 781 (38.0) < 0.01 and, again, children with suspected CP were in between (Table 2).
support, n (%)
Children with suspected CP did differ from both other groups with
CP-cerebral palsy; GA- gestational age; wks-weeks; IQR-interquartile range; − respect to likelihood of re-hospitalizations for at least one-night post
grams; SNAP-II - Score for Neonatal Acute Physiology second version; BPD- NICU discharge, especially for respiratory infections (28.4%), non-in-
bronchopulmonary dysplasia; ROP-retinopathy of prematurity; PDA-patent fectious conditions (19.8%) and also for feeding and growth concerns
ductus arteriosus, NICU‑neonatal intensive care unit. (6.2%). For children with suspected CP who were re-hospitalized, the
number of readmissions was not higher. More children with suspected
CP had received a prescription medication (59.3%) in the 3 months
prior to the 19-month CA visit and had higher rates of using a re-
spiratory aid (supplemental oxygen, respiratory support, pulse oximetry

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A. Synnes, et al. Early Human Development 136 (2019) 7–13

Table 2
19 month corrected age characteristics.
CP Suspected CP No CP P value
N = 146 N = 81 N = 2053

Corrected age at assessment, median (IQR) 19 (18, 20) 19 (18, 20) 19 (18, 19) 0.35
Bayley III motor, median (IQR) 70 (58, 79) 82 (70, 94) 94 (88, 100) < 0.01
Bayley-III cognitive, median (IQR) 85 (70, 95) 90 (80, 105) 95 (90, 105) < 0.01
Bayley-III language, median (IQR) 81 (65, 94) 86 (74, 97) 91 (79, 100) < 0.01
Bayley-III not administered, n (%) 35 (24.0) <5 107 (5.2) < 0.01
Bilateral visual impairment, n (%) 18 (14.2) 0 15 (0.8) < 0.01
Hearing aids or cochlear implants, n (%) 20 (14.0) <5 34 (1.7) < 0.01
Other factors affecting development
One or more factors that may affect development, n (%) 23 (15.9) 18 (22.2) 123 (6.0) < 0.01
a
Fetal Alcohol Spectrum Disorder, n (%) <5 <5 8 (0.4) 0.20
a
Chromosomal or genetic abnormalities, n (%) <5 <5 5 (0.2) 0.17
a
Extensive hospitalization, n (%) 9 (6.2) 7 (8.6) 54 (2.6) < 0.01
a
Congenital heart disease, n (%) 0 0 <5 0.58
a
Parental illicit drug/alcohol use during pregnancy, n (%) 5 (3.4) 0 19 (0.9) 0.02
a
Other, n (%) 12 (8.2) 8 (9.9) 65 (3.2) < 0.01
Sociodemographic characteristics
Caregiver with completed post-secondary, n (%) 69 (54.8) 42 (56.0) 1251 (65.6) 0.01
Employed caregiver, n (%) 110 (84.0) 67 (84.8) 1770 (90.8) 0.01
One adult in the home, n (%) 16 (12.8) 6 (7.8) 129 (6.9) 0.05
2+ adults in the home, n (%) 109 (87.2) 71 (92.2) 1735 (93.1)
Resource utilization
Number of rehospitalizations, median (IQR) 2 (1, 3) 2 (1, 3) 1 (1, 2) < 0.01
Proportion rehospitalized, n (%) 71 (50.4) 44 (54.3) 708 (35.0) < 0.01
a
Hospital readmissions for respiratory infections, n (%) 27 (18.5) 23 (28.4) 358 (17.4) 0.04
a
Hospital readmissions for respiratory non-infections, n (%) 11 (7.5) 16 (19.8) 133 (6.5) < 0.01
a
Hospital readmissions for surgery, n (%) 31 (21.2) 10 (12.4) 185 (9.0) < 0.01
a
Hospital readmissions for infections, n (%) 10 (6.9) 8 (9.9) 65 (3.2) < 0.01
a
Hospital readmissions for growth/feeding, n (%) 5 (3.4) 5 (6.2) 52 (2.5) 0.12
a
Hospital readmissions for other reasons, n (%) 24 (16.4) 10 (12.4) 116 (5.7) < 0.01
Receiving prescription medications, n (%) 73 (50.7) 48 (59.3) 823 (40.7) < 0.01
a
Use of a motor aid, n (%) 53 (37.1) 14 (17.3) 69 (3.4) < 0.01
a
Use of a respiratory aid, n (%) 47 (32.9) 29 (35.8) 342 (16.8) < 0.01
Referrals (service received or referral made)
a
Dietitian, n (%) 56 (39.4) 31 (40.8) 400 (25.9) < 0.01
aa
Early intervention program, n (%) 75 (53.6) 35 (46.1) 604 (38.9) < 0.01
a
Neurologist, n (%) 74 (52.1) 17 (22.7) 87 (5.7) < 0.01
a
Occupational therapist, n (%) 118 (82.5) 56 (73.7) 627 (40.4) < 0.01
a
Physiatrist, n (%) 24 (17.1) 8 (11.1) 44 (2.9) < 0.01
a
Physiotherapist, n (%) 137 (95.1) 65 (85.5) 749 (48.3) < 0.01
a
Psychologist, n (%) 13 (9.2) 5 (6.6) 44 (2.9) < 0.01
a
Rehabilitation centre, n (%) 64 (45.1) 22 (29.7) 139 (9.1) < 0.01
a
Social worker, n (%) 38 (27.0) 21 (27.6) 127 (8.3) < 0.01
a
Speech therapist n (%) 89 (63.1) 45 (59.2) 638 (41.4) < 0.01

Prescription med = any meds excluding vitamins and iron, Motor aid = braces, walker or stroller.
Respiratory aid = apnea monitor, oximeter, supplemental oxygen, CPAP or tracheostomy.
Feeding or GI aid = gavage feeding, jejunostomy, ileostomy, or colostomy.
IQR-interquartile range; Bayley-III-Bayley scales of infant and toddler development 3rd edition.
a
One patient may have more than one selection.

or an apnea monitor). Referral to a dietitian was highest in the sus-
pected CP group but they were less likely than children with CP to
require gavage feeding, gastrostomy or have a stoma. For other ser-
vices, referral to or provision of other health care was in between
children with and without CP. For both definite CP and suspected CP
respectively, physiotherapy (95.1% and 85.5%) and occupational
therapy (82.5% and 73.7%) referrals or care provision was common.
3.3. Three-year status
At three years of age, characteristics of children with CP, suspected
CP and without CP are shown in Table 3. There were significant be-
tween group differences for all domains of the HSCS-PS and ASQ
(all < 0.01). Children with suspected CP continued to be in between
children with and without CP at 3 years of age for both incidence and
severity. For example, on the HSCS-PS, the proportion of children who
get around in a typical fashion is 84.3% for children without CP, 51.1%
for children with suspected CP and 20.9% for children with CP. Self-
care was the domain that children with suspected CP scored the worst.
A similar pattern of developmental concerns was seen with the ASQ-3.
Problem solving concerns on the ASQ-3 were slightly more frequent for
the suspected CP than definitive CP.
4. Discussion
In this national cohort of very preterm children, 3.6% could not be
categorized using the internationally recognized definition of CP6, as
having or not having CP at a median age of 19 months CA. Since it is not
clear whether children with suspected CP should be classified as CP or
no CP, the incidence of CP would range from 6.4% to 10% and absence
of CP from 90% to 93.6% depending on whether these children are
included in the CP or no CP groups.
The challenge of definitively diagnosing CP at 18 to 24 months CA is
not surprising. The current definition of CP is “a group of permanent
disorders of the development of movement and posture, causing ac-
tivity limitation, that are attributed to non- progressive disturbances
that occurred in the developing fetal or infant brain. The motor dis-
orders of cerebral palsy are often accompanied by disturbances of

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A. Synnes, et al. Early Human Development 136 (2019) 7–13

Table 3
Three-year corrected age outcomes.
CP Suspected CP No CP P value
N = 70 N = 47 N = 1140

HSCS-PS
Getting around -typical, n (%) 14 (20.9) 24 (51.1) 922 (84.3) < 0.01
Getting around –some difficulty, n(%) 25 (37.3) 19 (40.4) 163 (14.9)
Getting around –difficult, n (%) 28 (41.8) <5 9 (0.8)
Hands and fingers – typical, n (%) 38 (55.9) 35 (74.5) 1040 (95.1) < 0.01
Hands and fingers–some difficulty, n(%) 21 (30.9) 8 (17.0) 43 (3.9)
Hands and fingers –difficult, n (%) 9 (13.2) <5 11 (1.0)
Taking care of self -typical, n (%) 18 (16.9) 14 (30.4) 692 (63.5) < 0.01
Taking care of self –some difficulty n(%) 16 (23.9) 21 (45.7) 325 (29.8)
Taking care of self–difficult, n (%) 33 (49.3) 11 (23.9) 72 (6.6)
Pain –typical, n (%) 47 (70.2) 34 (73.9) 921 (84.4) < 0.01
Pain –more than usual, n (%) 15 (22.4) 11 (23.9) 161 (14.8)
Pain -considerable, n (%) 5 (7.5) <5 9 (0.8)
ASQ
Gross motor below cut-off, n (%) 48 (72.7) 19 (42.2) 145 (13.2) < 0.01
Gross motor monitoring zone, n (%) 7 (10.6) 12 (26.7) 145 (13.2)
Fine motor below cut-off, n (%) 23 (35.4) 11 (25.6) 96 (8.9) < 0.01
Fine motor monitoring zone, n (%) 12 (18.5) 5 (11.6) 175 (16.2)
Problem solving below cut-off, n (%) 24 (37.5) 16 (37.2) 129 (11.9) < 0.01
Problem solving monitoring zone, n (%) 7 (10.9) 8 (18.6) 144 (13.3)
Communication below cut-off, n (%) 21 (32.3) 11 (25.0) 114 (10.4) < 0.01
Communication monitoring zone, n (%) 11 (16.9) 8 (18.2) 108 (9.9)
Personal- social below cut-off, n (%) 30 (45.5) 11 (23.9) 113 (10.2) < 0.01
Personal- social monitoring zone, n (%) 6 (9.1) 9 (19.6) 90 (8.2)

sensation, perception, cognition, communication, and behaviour; by
epilepsy, and by secondary musculoskeletal problems.” 6(p9) This is a
clinical definition without distinct age-specific diagnostic criteria. The
distinction between ‘normality’ and CP is not a clear cut one, but more
of a continuum along which abnormalities become apparent.
Abnormalities of tone associated with transient dystonia of prematurity
are common in the first 12 months of life [8]. In the Collaborative
Perinatal Project, approximately half of all children diagnosed with CP
at their first birthday “outgrew” or lost the motor signs of CP by the age
of seven [9]. Conversely, relatively nonspecific motor signs, such as
hypotonia, that can be seen in early life may evolve over the first few
years into spasticity and extrapyramidal abnormalities [2]. Axon
myelination and neuronal maturation must be present for spasticity,
dystonia, and athetosis to become apparent. Some conditions such as
visual impairment or prolonged hospitalization may affect movement,
posture, or attainment of developmental milestones and make the di-
agnosis of CP more difficult. Furthermore, antecedent conditions such
as ROP and BPD are also associated with an increased risk of CP. Most
CP registries require children to be 5 years of age before CP can be
confirmed and a minimum age of 4 years is recommended [26].
Previously, care of the child with CP was supportive and the need
for a diagnosis non-urgent. Progress in the management of children
with CP has led to a paradigm shift [11] supporting earlier diagnosis
and intervention. This shift towards earlier diagnosis and intervention
[27] highlights the importance of understanding the early life trajec-
tories of children with suspected CP. Validated neurological assess-
ments such as the General Movements Assessment [28] and the Ham-
mersmith Infant Neurological Exam [29] are now recommended [11]
but were not used by CNFUN during this study. Concurrent assessments
with the Hammersmith Infant Neurological Exam in children with
suspected CP would be of great interest.
Our study shows that children with suspected CP fall on a spectrum
between CP and no CP as neonates and at 19-months CA for most
characteristics. The differences are also observed at 3 years CA sug-
gesting that the neurological abnormalities noted by clinicians persist
to at least 3 years CA. As the children in our study did not have a
neurological exam to assess for CP at 3 years, the type and incidence of
eventual neurodevelopmental diagnoses received by children with
suspected CP is unknown. Possible outcomes include CP, other motor
impairments and global developmental delay. Some types of CP, such as
dystonic CP, are typically diagnosed at a later age and there is dis-
agreement whether hypotonia should be included under the umbrella of
CP [26]. Other non-CP motor impairments such as developmental co-
ordination disorder [30] are typically diagnosed after 3 years of age but
are associated with worse infant motor performance [29]. Our study
also demonstrates that, in general, children with suspected CP have
lower Bayley-III cognitive and language scores at 18–21 months CA
than their CP free peers. Motor impairments may have affected Bayley-
III cognitive scores. At 3 years, over 50% of children with suspected CP
have concerns in the problem-solving domain of the ASQ. Some of these
children may therefore have a more global developmental delay.
An interesting finding was the high rate of respiratory aids, hospital
readmissions, especially for respiratory indications, and prescription
medications amongst children with suspected CP. In the suspect CP
group we found a pattern of post NICU resource use typical for children
with BPD and children with BPD are more likely to have neuromotor
problems [31]. However, in our cohort, the incidence of BPD was in
between that of CP and no CP.
Our study has several implications. When precision is required, as in
trials andstudies, CP should not be used as an isolated outcome but
rather combined with a validated supplementary motor function as-
sessment. Nineteen months of age is too early for a definitive diagnosis
of motor disorders. Neonatal follow-up programs should be encouraged
to follow children born preterm beyond 18 months CA both for audit
and clinical reasons. Children with suspected CP need ongoing support
and intervention to support their development while their neurodeve-
lopmental diagnostic status evolves. The recent recommendations for
diagnostic criteria for an early interim diagnosis of “high risk of cere-
bral palsy” [11] may benefit children with suspected CP.
5. Limitations
The neurological examination was completed by physicians in
participating Neonatal Follow-Up Programs without additional training
for reliability. However, these physicians are typically responsible for
identifying CP in at-risk children and therefore reflect the clinical rea-
lity. Complete data on CP status was available for 82% of eligible
children in the CNFUN database. Canada is the second largest country

11
A. Synnes, et al.
with a huge land mass which creates challenges for follow-up assess-
ments, patient transfers and family relocations. This national cohort
minimizes potential biases of institutional cohorts and provides a large
sample size to study children with suspected CP.
Funding source
This work was supported by the Canadian Institutes of Health
Research through a grant to the CIHR Team in Maternal-Infant Care
(CTP 87518). The study coordinating centre, the Maternal-Infant Care
Research Centre, is supported by program funding from the Ontario
Ministry of Health and Long-Term Care. In addition, participating sites
contributed additional funding for patient outcome assessments. The
funding agencies had no role in the design and conduct of the study;
collection, management, analysis, and interpretation of the data; pre-
paration, review, or approval of the manuscript; and decision to submit
the manuscript for publication.
Authors' contributions
Dr. Synnes is the director of the Canadian Neonatal Follow-Up
Network. Dr. Shah is director of the Canadian Neonatal Network and
takes responsibility for the integrity of the data and the accuracy of the
data analysis.
Conceptualization and methodology:Synnes, Gillone, Majnemer,
Lodha, Creighton, Moddemann,
Data curation and project administration: Synnes, Shah
Validation:Shah, Synnes, Gillone, Majnemer, Lodha, Creighton,
Moddemann.
Writing-original draft: Synnes (Gillone drafted an earlier version
which included only the 18 month CA data).
Writing-review & editing:Gillone, Majnemer, Lodha, Creighton,
Moddemann, Shah.
Declaration of Competing Interest
None declared.
Acknowledgments
Data Access, Responsibility, and Analysis: Dr. Shah and the
Maternal Infant Care coordinating site staff had full access to all the
data in the study and take responsibility for the integrity of the data and
the accuracy of the data analysis.
Canadian Neonatal Network Investigators: Prakesh S Shah, MD,
MSc (Director, Canadian Neonatal Network and site investigator),
Mount Sinai Hospital, Toronto, Ontario; Adele Harrison, MD, MBChB,
Victoria General Hospital, Victoria, British Columbia; Anne Synnes,
MDCM, MHSC, and Joseph Ting, MD, British Columbia Women's
Hospital, Vancouver, British Columbia;; Wendy Yee, MD, Foothills
Medical Centre, Calgary, Alberta; Carlos Fajardo, MD, Alberta
Children's Hospital, Calgary, Alberta; Khalid Aziz, MBBS, MA, MEd, and
Jennifer Toye, MD, Royal Alexandra Hospital and University of Alberta
Hospital, Edmonton, Alberta; Zarin Kalapesi, MD, Regina General
Hospital, Regina, Saskatchewan; Koravangattu Sankaran, MD, MBBS,
and Sibasis Daspal, MD, Royal University Hospital, Saskatoon,
Saskatchewan; Molly Seshia, MBChB, Winnipeg Health Sciences Centre,
Winnipeg, Manitoba; Ruben Alvaro, MD, St. Boniface General Hospital,
Winnipeg, Manitoba; Amit Mukerji, MD, Hamilton Health Sciences
Centre, Hamilton, Ontario; Orlando Da Silva, MD, MSc, London Health
Sciences Centre, London, Ontario; Chuks Nwaesei, MD, Windsor
Regional Hospital, Windsor, Ontario; Kyong-Soon Lee, MD, MSc,
Hospital for Sick Children, Toronto, Ontario; Michael Dunn, MD,
Sunnybrook Health Sciences Centre, Toronto, Ontario; Brigitte Lemyre,
MD, Children's Hospital of Eastern Ontario, Ottawa, Ontario; Kimberly
Dow, MD, Kingston General Hospital, Kingston, Ontario; Ermelinda
12
Early Human Development 136 (2019) 7–13
Pelausa, MD and Lajos Kovacs MD, Jewish General Hospital, Montréal,
Québec; Keith Barrington, MBChB, Hôpital Sainte-Justine, Montréal,
Québec; Christine Drolet, MD, and Bruno Piedboeuf, MD, Centre
Hospitalier Universitaire de Québec, Sainte Foy Québec; S Patricia Riley
MD and Martine Claveau, RN, Montreal Children's Hospital and Daniel
Faucher MD, Royal Victoria Hospital (latter two now merged as McGill
University Health Centre), Montréal, Québec; Valerie Bertelle, MD, and
Edith Masse, MD, Centre Hospitalier Universitaire de Sherbrooke,
Sherbrooke, Québec; Roderick Canning, MD, Moncton Hospital,
Moncton, New Brunswick; Hala Makary, MD, Dr. Everett Chalmers
Hospital, Fredericton, New Brunswick; Cecil Ojah, MBBS, and Luis
Monterrosa, MD, Saint John Regional Hospital, Saint John, New
Brunswick; Wayne Andrews MD and Akhil Deshpandey, MD, MBBS,
Janeway Children's Health and Rehabilitation Centre, St. John's,
Newfoundland; Doug McMillan MD and Jehier Afifi, MB BCh, MSc, IWK
Health Centre, Halifax, Nova Scotia; Andrzej Kajetanowicz, MD, Cape
Breton Regional Hospital, Sydney, Nova Scotia; Shoo K Lee, MBBS, PhD
(Chairman, Canadian Neonatal Network), Mount Sinai Hospital,
Toronto, Ontario.
Canadian Neonatal Follow-Up Network Investigators:
Thevanisha Pillay, MD, Victoria General Hospital, Victoria, British
Columbia; Anne Synnes, MDCM, MHSC, British Columbia Women's
Hospital, Vancouver, British Columbia; Reg Sauvé, MD, MPh, Leonora
Hendson MB.BCH, MSc, Alberta's Children's Hospital, Foothills Medical
Centre, Calgary, Alberta; Amber Reichert, MD, Glenrose Rehabilitation
Hospital, Edmonton, Alberta; Jaya Bodani, MD, Regina General
Hospital, Regina, Saskatchewan; Koravangattu Sankaran, MD, Royal
University Hospital, Saskatoon, Saskatchewan; Diane Moddemann, MD,
Cecilia de Cabo, Winnipeg Health Sciences Centre, St. Boniface General
Hospital, Winnipeg, Manitoba; Chukwuma Nwaesei, MD, Windsor
Regional Hospital, Windsor, Ontario; Thierry Daboval, MD, Children's
Hospital of Eastern Ontario, Ottawa, Ontario; Kimberly Dow, Kingston
General Hospital, Kingston, Ontario; David Lee, Kevin Coughlin, MD,
Children's Hospital London Health Sciences Centre, London, Ontario;
Linh Ly, MD, Hospital for Sick Children, Toronto, Ontario; Edmond
Kelly, MD, Mount Sinai Hospital, Toronto, Ontario; Saroj Saigal, Salhab
el Helou, MD, Hamilton Health Sciences Centre, Hamilton, Ontario;
Paige Church, MD, Sunnybrook Health Sciences Centre, Toronto,
Ontario; Ermelinda Pelausa, MD, Jewish General Hospital, Montréal,
Québec; S Patricia Riley, MD, Montréal Children's Hospital, Royal
Victoria Hospital, Montréal, Québec; Francine Lefebvre, Thuy Mai Luu
MD, MSc, Centre Hospitalier Universitaire Sainte-Justine, Montréal,
Québec; Charlotte Demers, Centre Hospitalier Universitaire de
Sherbrooke, Sherbrooke, Québec; Sylvie Bélanger, MD, Centre
Hospitalier Universitaire de Québec, Québec City, Québec; Roderick
Canning, MD, Moncton Hospital, Moncton, New Brunswick; Luis
Monterrosa, MD, Saint John Regional Hospital, Saint John, New
Brunswick; Hala Makary, MD, Dr. Everett Chalmers Hospital,
Fredericton, New Brunswick; Michael Vincer, MD, Jehier Afifi, MB BCh,
MSc, IWK Health Centre, Halifax, Nova Scotia; Phil Murphy, Charles
Janeway Children's Health and Rehabilitation Centre, St. John's,
Newfoundland.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.earlhumdev.2019.06.009.
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