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Indian Pediatr 2021;58:836-838 |
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Vitamin D, Bone Mineral
Density and Serum IGF-1 Level in Non-ambulatory Children With
Cerebral Palsy
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Namita Gwasikoti,
1
Kapil Bhalla,1
Jaya Shankar Kaushik,1
Veena Singh Ghalaut,2
Zile Singh Kundu3
From Departments of 1Pediatrics, 2Biochemistry
and 3Orthopedics, Pt. BD Sharma PGIMS, Rohtak, Haryana.
Correspondence to: Dr Kapil Bhalla, Department of
Pediatrics, Pandit Bhagwat Dayal Sharma Post Graduate Institute of
Medical Sciences, Rohtak 124 001, Haryana.
Email: [email protected]
Received: November 23, 2020;
Initial review: December 14, 2020;
Accepted: February 20, 2021.
Published online: April 17, 2021;
PII:S097475591600312
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Objective: To compare serum 25-hydroxy vitamin D (25-OHD) status,
bone mineral density and Insulin-like growth factor (IGF-1) level among
children with cerebral palsy (CP) aged 1 to 8 years with age- and
gender-matched controls. Methods: A cross-sectional study
enrolled 30 children in each group: CP with epilepsy, CP without
epilepsy, and healthy controls. Bone mineral density (BMD), serum 25-OHD
levels, and serum insulin like growth factor (IGF)-1 levels were
measured. Results: z-scores of BMD [-1.80 (1.03), -2.12
(0.85) vs -1.40 (0.90); P<0.01], 25-OHD levels [19.26 (8.28),
20.59 (8.92) Vs 26.79 (12.76) ng/mL; P<0.01] and IGF-1 levels
[20.90 (6.42), 23.37 (8.11) vs 31.77 (11.21) ng/mL; P<0.01] were
significantly low among children with CP with epilepsy, CP without
epilepsy when compared to controls . Conclusion: Children with CP
with or without comorbid epilepsy were prone to vitamin D deficiency,
low bone mineral density and growth hormone axis suppression with low
IGF-1 levels.
Keywords: Antiepileptic drugs, BMD, Dyskinetic cerebral palsy,
Epilepsy, Osteoporosis.
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C
erebral palsy (CP) is a group of
non-progressive disorders of movement and posture that result in
activity limitation [1]. The motor disorder of cerebral palsy is
often accompanied by disturbance of sensation, cognition,
behavior, and epilepsy [2]. The risk factors that predispose
children with CP to low bone mineral density include physical
inactivity, lack of adequate sunlight exposure, poor nutrition,
and intake of antiepileptic drugs [3-6]. Low bone mineral
density predisposes to osteoporotic fractures leading to further
inactivity and functional loss [7]. Non-ambulatory children with
CP are also prone to vitamin D deficiency, low intake of calcium
and low sunlight exposure [3,8].
Insulin like growth factor-1 (IGF-1)
stimulates the synthesis of bone-specific proteins and
osteoblasts in cell and organ cultures [9,10]. Both bone mineral
density (BMD) and IGF-1 levels were found significantly low in
children with spastic CP with higher gross motor functional
classification system GMFCS [11]. Few antiepileptic drugs (AEDs)
can cause decrease in BMD attributed to the increased enzyme
induction and expression of CYP21 leading to increased
inactivation of vitamin D [12]. The spectrum of CP in India is
shifting from quadriplegic CP to more of diplegic CP over last
10 years [13]. Indian children with cerebral palsy are also at
high risk of malnutrition [14]. There is limited literature on
BMD among Indian children with CP. Hence, the present study was
conducted to evaluate the vitamin D levels, IGF-1 levels, and
BMD in non-ambulatory patients with CP.
METHODS
This was a cross-sectional study conducted in
a tertiary care hospital from January, 2018 to April, 2019.
Patients were recruited from pediatric and pediatric neurology
outpatient units. Clearance was obtained from the institutional
ethics committee and a written informed consent was obtained
from the caregiver.
Thirty children aged 1-8 years were recruited
in each of the following three groups: Group I – CP with GMFCS
III-V with epilepsy (on AEDs for at least two years), Group II -
CP without epilepsy, and Group III – age- and gender-matched
healthy controls who belonged to same community. Children on
vitamin D or calcium supplementation in last six months, and
those with ambiguity in clinical diagnosis were excluded from
the study.
After taking a thorough history, each
participant underwent detailed clinical evaluation including
anthro-pometric and functional ability assessment GMFCS. Bone
mineral density (BMD) of lumbar vertebrae (L2-L4) was
determined by dual energy X-ray absorptiometry (DXA).
Serum 25-hydroxy vitamin D (25-OHD) levels were measured by
radioimmunoassay (RIA). Serum IGF-1 levels were measured by
ELISA method using
DRG IGF-1 600 ELISA (EIA-4140) kit.
Considering the proportion of vitamin D
deficiency to be 66% in children with CP and 36.7% in healthy
controls based on previous published data [3], a sample size of
28 (rounded to 30 in each group) was computed assuming an alpha
error of 0.05 and power of 90%.
Statistical analysis: Outcome variables
were compared between the three groups by using analysis of
Variance (ANOVA) for multi-group comparisons followed by Tukey
test. Logistic regression analysis was performed to determine
the predictors of low BMD. A P value <0.05 was considered
as significant.
RESULTS
A total of 90 children (30 in each of three
groups) were enrolled in the study. Baseline characteristics
were mostly comparable between the groups (Table I).
Of the 30 children with comorbid epilepsy, 21 (70%) were on
valproate, 2 (2.1%) were on levetiracetam, 10 (33.3%) children
were on clonazepam, 3 (10%) on vigabatrin and one child was on
phenytoin.
Table I Baseline Characteristics of Children With Cerebral Palsy and Controls
| Baseline |
Cerebral palsy |
Cerebral palsy |
Controls |
| characteristics |
with epilepsy |
without epilepsy |
(n=30) |
|
(n=30) |
(n=30) |
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|
Age in yearsa
|
3 (1.75-5.25) |
3.5 (2-7) |
4 (2-6.25) |
| Male gender |
22 (73.3) |
21 (70) |
19 (63.3) |
| BMIb,c |
14.89 (2.58) |
14.07 (2.29) |
16.21 (2.6) |
|
WFA <-3 SDd
|
4 (13.3) |
8 (26.7) |
1 (3.3) |
| WFH <-3 SD |
5 (16.7) |
7 (23.3) |
2 (6.7) |
|
HFA <-3 SDe |
4(13.3) |
11(36.7) |
12 (40.0) |
| Type of cerebral palsy |
|
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| Diplegia |
6 (20) |
7 (23.3) |
- |
| Hemiplegia |
6 (20) |
2 (6.7) |
|
| Quadriplegia |
13 (43.3) |
18 (60) |
|
| Dyskinetic |
1 (3.3) |
2 (6.7) |
|
| Mixed |
4 (13.3) |
1 (3.3) |
|
| Etiology |
|
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| HIE |
21 (70) |
18 (60) |
- |
| Prematurity |
5 (16.7) |
5 (16.7) |
|
| Kernicterus |
0 |
2 (6.7%) |
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| Meningitis |
1 (3.3) |
5 (16.7%) |
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| GMFCS |
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| Grade III |
12 (40) |
8 (26.7) |
- |
| Grade IV |
16 (53.3) |
20 (66.7) |
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| Grade V |
2 (6.7) |
2 (6.7) |
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Data expressed as no. (%), amedian (IQR) or bmean
(SD). GMFCS:Gross motor functional classification
system. cP<0.001, dP<0.05, ep=0.05, BMI: body mass
index; WFA: weight for age; WFH: weight for height;
HFA: height for age; HIE: hypoxic ischemic
encephalopathy. |
The serum 25-OHD levels, IGF-1 levels and BMD
z-score in the three groups are shown in Table II.
Post hoc analysis revealed that BMD Z-scores (P=0.37),
serum IGF-1 levels (P=0.53) and 25-OHD levels (P=0.87)
were comparable between CP with epilepsy and CP without
epilepsy. There was a significant correlation between serum
IGF-1 levels and serum 25-OHD levels (r=0.88; P<0.001).
Regression analysis model revealed that low BMD was predicted by
lower age [OR (95% CI): 1.05 (1.02-1.08); P=0.005] and
GMFCS level [OR (95% CI): 0.86 (0.71-1.01); P=0.038].
Table II Bone Mineral Density and Other Markers in Children With Cerebral Palsy (CP) and Healthy Controls
| Variable |
CP with |
CP without |
Control |
|
epilepsy |
epilepsy |
(n=30) |
|
(n=30) |
(n=30) |
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| BMD (z- score)a |
-1.80 (1.03) |
-2.12 (0.85) |
-1.40 (0.90) |
|
25-OHD, ng/mLb |
19.26 (8.28) |
20.59 (8.92) |
26.79 (12.76) |
|
IGF-1, ng/mLb |
20.90 (6.42) |
23.37 (8.11) |
31.77 (11.21) |
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Data expressed as mean (SD). aP<0.01 for CP without
epilepsy and control and P=0.23 for CP with epilepsy and
control; bP <0.01 for both CP with epilepsy and controls
and CP without epilepsy and control. BMD – Bone mineral
density; 25-OHD -25 hydroxy vitamin D; IGF-1-Insulin
like growth factor. |
DISCUSSION
The present study revealed that comorbid
epilepsy in children with CP did not affect BMD and serum 25-OHD
levels. However, children with CP without epilepsy had
significantly lower BMD when compared to age-matched controls.
25-OHD levels and IGF-1 levels were significantly low in
children with CP with or without epilepsy when compared to
controls.
The present study findings are in concurrence
with another study which found that severity of functional
ability (GMFCS level 4,5) correlated negatively with BMD [15].
However, majority of patients in the present study belonged to
GMFCS IV and III.
Children with CP are prone to vitamin D
deficiency owing to lower sunlight exposure, non-ambulatory
status and poor nutritional intake. Findings of low vitamin D
level among children with CP in this study were consistent with
previous studies
[8,12,15]. Similar
serum vitamin D levels in those with or without epilepsy could
be with use of non-enzyme inducing drugs in the epilepsy group
in this study.
GH and IGF-1 are principal regulators of
bone-cell function. IGF-1 has stimulatory effects on the
synthesis of bone specific proteins and osteoblastic
proliferation in cell and organ cultures.
Patients with CP have significantly low levels of IGF-1
and low BMD which makes them prone for osteoporotic fractures
[4,11,15]. Low levels of IGF-1 in children with CP could also be
attributed to malnutrition and liver disorders. In this context,
GH level estimation would have been more useful than IGF-1
level. However, GH levels were not estimated as the procedure is
tedious and there is need for hospital admission.
Selection of age- and gender-matched controls
in the present study served as comparator for the observations
of BMD, IGF-1 and vitamin D levels in children with CP. This
study analyzed bone mineral metabolism in terms of suppression
of growth hormone axis (IGF-1), bone mineralization (BMD) and
nutritional status (vitamin D). Limitations of the study include
cross-sectional descriptive study design with limited sample
size and absence of liver function tests. Most of the enrolled
children were non-ambulatory where factors like sunlight
exposure, presence of feeding difficulties and history of use of
dairy products would have been useful; however, these were not
recorded in the study.
The study concludes that spinal BMD, serum
vitamin D levels and serum IGF-1 levels were decreased in
children with CP with and without epilepsy when compared to
healthy controls. Future longitudinal studies are suggested with
larger sample size looking for efficacy of interventions like
structured exercise program, vitamin D, calcium, and GH
supplementation among children with CP.
Ethics clearance: Institutional ethics
committee, PLBD Sharma, PGIMS; No. BREC/Th/19/Ped 15; dated
March 06, 2020.
Note: Presented in 19th Annual Conference
of Neurology Chapter of Indian Academy of Pediatrics, 26-28
July, 2019, Hyderabad, Telengana.
Contributors: KB, JSK: conceptualized the
idea; NG, KB, JSK, VSG, ZSK: involved in data collection and
patient management; NG, KB, JSK: drafted the manuscript; VSG,
ZSK: provided intellectual inputs; all the authors the final
version of the manuscript.
Funding: None; Competing interests:
None stated.
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WHAT THIS STUDY ADDS?
• Non-ambulatory children with cerebral palsy with or
without epilepsy have low bone mineral density, low
serum vitamin D levels, and low IGF-1 levels as compared
to healthy controls.
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