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Indian Pediatr 2021;58:839-841 |
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Vitamin D Levels in
Neonates With and Without Seizures: A Single Center
Cross-Sectional Study
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Jonnala Chaitanya Reddy, Apurv Barche, Sneha Jaganathan Andrade,
Aditya Verma, Leslie Edward Lewis, Jayashree Purkayastha
From Department of Pediatrics, Kasturba Medical College, Manipal
Academy of Higher Education (MAHE), Manipal, Karnataka.
Correspondence to: Dr Jayashree Purkayastha, Professor, Department of
Pediatrics, Kasturba Medical College, Manipal, Manipal Academy of Higher
Education (MAHE), Karnataka.
Email:
jayashreepurkayastha@yahoo.com
Received: December 28, 2020;
Initial review: February 13, 2021;
Accepted: May 13, 2021.
Published online: May 20, 2021;
PII:S097475591600330
Trial registration: CTR1/2018/12/023028
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Objective: To study the serum vitamin D levels in
neonatal seizures and vitamin D status of the mothers whose babies had
vitamin D deficiency. Methods: For this cross-sectional study,
vitamin D levels were studied in term and late preterm neonates admitted
to NICU with seizures at our tertiary care center. Controls were term
and late preterm healthy neonates admitted in the postnatal ward with
the mothers in the same center. Results: 30 cases and 30 controls
were enrolled. The mean (SD) serum vitamin D was 19.33 (7.76) ng/mL
among cases and 16.83 (6.74) ng/mL among controls (P=0.18). We
tested maternal vitamin D levels in babies with seizures and low vitamin
D levels. The mean (SD) serum vitamin D level among these mothers (n=11)
was 13.25 (6.17) ng/mL. Conclusions: There was no
statistically significant association between serum vitamin D levels and
seizures among neonates in our study.
Keywords: Hypocalcemia, Neonates, Seizures, Vitamin D.
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The incidence of
neonatal seizures is 2-4 per
1000 live births. Seizures may be due to
electrolyte abnormalities, underlying brain
injury, or initial presentation of an underlying inborn error of
metabolism [1,2]. Early recognition and management of
biochemical disturbances in neonatal seizures are important to
prevent further brain damage. Neonates with hypocalcemia may
present with seizures secondary to increased excitability of the
cell membrane, thus resulting in exaggerated startles,
jitteriness, myoclonic jerks, and seizures [2]. Hypocalcemia due
to vitamin D deficiency constitutes a major cause of neonatal
seizures in developing countries [3]. Maternal vitamin D
deficiency results in a poor trans-placental transfer of vitamin
D during pregnancy and reduced stores in the newborns [4,5].
Neonates born to vitamin-deficient mothers are at a
significantly higher risk to develop hypocalcemic seizures [6].
In addition to hypocalcemic seizures, some neonates with
idiopathic seizures also have low vitamin D levels [5].
During early infancy, vitamin D stores depend
on intrauterine accretion and breastmilk, in addition to
sunlight exposure in the mother. Breastfed neonates born to and
nursed by vitamin D deficient mothers have low serum vitamin D
levels [7]. We compared vitamin D levels in neonates with
seizures with those without seizures, and also studied vitamin D
levels among mothers whose babies had seizures and low vitamin D
levels.
METHODS
This was a cross-sectional study done from
November, 2018 to August, 2020 in a tertiary care center in
southern India, after institutional ethics committee clearance.
Term and late preterm (35-40 weeks) neonates
admitted to the neonatal intensive care unit (NICU) of our
institute with seizures were enrolled as cases. Controls were
healthy term and late preterm neonates admitted in the postnatal
ward along with their mothers. Exclusion criteria were: neonates
with congenital anomalies, meningitis, hypoglycemia, birth
asphyxia, or inborn errors of metabolism; neonates with mothers
having hepatic, renal, or bone disorders, mothers on
enzyme-inducing drugs and COVID-positive neonates; and neonates
with vitamin D supplementation or neonates who were administered
antiepileptic drugs before admission.
Blood was drawn for 25-hydroxy vitamin D
levels (25(OH)D) from enrolled neonates admitted with seizures.
The mothers’ vitamin D levels were also evaluated in those
neonates with seizures who had vitamin D deficiency. Controls
were evaluated for vitamin D levels during day 3-7
investigations like serum bilirubin levels.
Informed consent was obtained from both
parents. A detailed antenatal, intranatal and postnatal history
was taken in a pre-designed proforma. Whether mothers had
received antenatal calcium and vitamin D supple-mentation and
compliance history was also taken. Baseline anthropometry was
carried out for all neonates at admission. All babies with
seizures who satisfied the inclusion criteria were examined at
admission with a detailed examination of the central nervous
system. Clinical details of the witnessed seizure episode were
noted and details at the time of first seizure and the type of
seizure were noted. The neonatal seizures were classified as per
Volpe classification into subtle, multifocal tonic, focal
clonic, focal tonic, and myoclonic.
Blood samples of all neonates with seizures
included in the study were sent for vitamin D levels, calcium,
and magnesium along with other investigations like sepsis screen
(to rule out septicemia), ammonia, lactate, pyruvate, ABG,
TMS/GCMS (to rule out IEM), blood glucose, ionized calcium and
total calcium, and serum albumin. Blood samples were taken
immediately after seizures and before administration of any
specific treatment. Second-line investigations were done in
cases, as and when indicated. These included
electro-encephalography (EEG), cerebrospinal fluid analysis, and
neurosonogram/magnetic resonance imaging. Serum vitamin D
estimation was done by electro-chemilu-minescence immunoassay.
Serum vitamin D concentrations >20 ng/mL was
considered as sufficient, between 12-20 ng/mL as insufficient
and <12 ng/mL as deficient [7]. Neonatal hypocalcemia was
defined as a total serum calcium concentration of <7 mg/dL or an
ionized calcium concentration of <4 mg/dL (1 mmol/L) [8].
Statistical analysis: Statistical
analysis was done by using the statistical package for social
sciences (SPSS) version 20. Mann-Whitney U test was used
to compare median vitamin D levels among cases and controls.
Comparison of mean values was done by paired and unpaired
Student t-test and chi-square test. P value <0.05
was considered significant.
RESULTS
A total of 91 babies with seizures were
admitted to the NICU during the study period, of which 61 were
excluded. Thirty neonates were enrolled as controls. Baseline
characteristics of cases and controls were not significantly
different (Table I).
Table I Baseline Characteristics and Serum Vitamin D Levels in Neonates With Seizures and Controls
| Characteristics |
Cases (n=30) |
Controls (n=30) |
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Birthweight, ga |
3083 (567) |
2896 (488) |
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Low birthweight |
5 (17) |
7 (23) |
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Gestational age, wka |
38.13 (1.3) |
37.5 (1.1) |
| Male gender |
19 (63) |
15 (50) |
| Late preterm |
4 (13) |
6 (20) |
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Maternal age, ya |
29.9 (5.1) |
28.9 (4.3) |
| Cesarean section |
18 (60) |
21 (70) |
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Vitamin D levels, ng/mLb |
19.17 |
15.38 |
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(14.3-21.9) |
(12.3-19.9) |
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All values in no. (%) except amean (SD) or bmedian
(IQR). P>0.05 for all comparisons. All mothers received
vitamin D and calcium supplementation during pregnancy. |
Based on the semiology, the most common
seizures were multifocal clonic type (n=9), followed by
focal clonic (n=7). Mixed type and subtle seizures were
seen in six neonates each, and tonic and myoclonic types in one
each. Based on the etiology, idiopathic seizures were the most
common (n=21) followed by hypocalcemic seizures (n=6).
The serum vitamin D levels were higher in
cases than the controls (P=0.18); although, both groups
had levels in the insufficient range (15-20 ng/mL) (Table I).
There were 16 neonates with seizures with low vitamin D levels
(<20 ng/mL). Out of which, five mothers’ samples could not be
done as they were not willing and/or were not admitted to the
same Institute as the babies were outborn. The mean (SD) serum
vitamin D levels of remaining mothers (n=11) was 13.25
(6.17) ng/mL and the mean serum vitamin D levels of their babies
(n=11) was 13.04 (4.55) ng/mL. There was no significant
association (P=0.84) between maternal and neonatal
vitamin D levels.
There was no significant association (P=0.18)
between onset of seizures (within and beyond 72 hours) and
vitamin D levels. Levels of vitamin D were low among neonates
with hypocalcemic seizures but it was not statistically
significant [ 16.17 (8.79) vs 20.91 (6.88); P=0.11]. Among the
cases, EEG was done in 19 babies. Out of the 19 EEGs, only three
were abnormal.
DISCUSSION
We found that majority of mother-neonate
pairs in this study had low vitamin D levels. Vitamin D levels
were low in both cases and controls, with no significant
association of low vitamin D level in neonates and occurrence of
seizures.
Vitamin D levels were low in controls
probably because low birthweight and late preterm babies were
more among controls than cases, and mean birth weight was less
among controls than cases. Mean vitamin D levels among the
mothers whose babies had low vitamin D levels were also low.
Possibly mothers in this part of the country have low vitamin D
levels as previously also reported [10], which did not improve
even after antenatal vitamin D supplementation. Aparna, et al.
[11] also reported that vitamin D deficiency was highly
prevalent among pregnant women, lactating mothers, neonates,
and/or exclusively breastfed infants. Increasing the dose of
antenatal vitamin D supplementation may be considered, if
similar findings are seen in larger community-based studies.
Previously, one-third of infants have been
reported to have vitamin D levels <10 ng/mL [10]. Fetal and
newborn concentrations of 25 (OH) D depend on and correlate with
maternal serum levels. Thus, newborns of vitamin D-insufficient
mothers are at a greater risk of developing vitamin D deficiency
[12]. Although there was no significant difference in vitamin D
levels among the two groups in this study, it suggests that
vitamin D levels are low among the normal neonate population in
India and the mothers. In a similar study conducted by Singh, et
al. [13], it was found that 85.7% of the neonates were vitamin
D-deficient. Other studies [11,14] also show that majority of
the neonates have vitamin D deficiency even in tropical
climates.
The study population was small and selective
because we did not include extreme, early, and moderate preterm
babies as seizures are less common in these babies and we would
not get matched controls. This study needs to be done in a
larger sample to find the status of vitamin D levels among
mothers and babies in the Indian population.
We conclude that hypovitaminosis D in mothers
is also associated with hypovitaminosis D in neonates. There is
a need to assess the vitamin D status of pregnant and lactating
women and to consider routine vitamin D supplementation or to
increase the dose of vitamin D supplementation among pregnant
and lactating women in this region. Routine vitamin D
supplementation among healthy newborns also need to
strengthened.
Ethics clearance: Institutional ethics
committee of KMC; No. 779/2018 dated November 13, 2018.
Contributors: JP, SJA, AB: conceptualization,
methodology; JCR: data collection, analysis; JP: original draft
preparation. AB, SJA, AV: correction of draft and final
preparation. All authors approved the final manuscript.
Funding: None; Competing interest:
None stated.
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WHAT THIS STUDY ADDS?
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There was no association of neonatal seizures and
vitamin D deficiency.
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