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185]

Original Article

Prevalence of hypocalcemia, its correlation with duration

of phototherapy and persistence in healthy term newborns
after intensive phototherapy: A prospective observational
hospital‑based observational study
Jehangir Allam Bhat, Sajad Ahmad Sheikh1, Zubair Ahmad Wani2, Roshan Ara3
Department of Pediatrics, World College of Medical Sciences, Jhajjar, Haryana, 1 Department of Gastroenterology, Vikas Hospital Pvt. Ltd,
New Delhi, 2Department of Pediatrics, Government Medical College, Srinagar, Jammu and Kashmir, 3Department of Pediatrics,
Kurji Holy Family Hospital, Patna, Bihar, India

Abstract Aims and Objectives: The aim is to study the prevalence of hypocalcemia, its correlation with duration of
phototherapy and its persistence in health new‑borns after intensive phototherapy.
Materials and Methods: A prospective hospital‑based observation study was conducted on 380 newborns
who received intensive phototherapy in  Neonatal intensive care unit (NICU). Pre, post, and at the 10th day
after phototherapy calcium levels were estimated in the study neonates. Neonates were observed for
clinical manifestations of hypocalcemia during phototherapy treatment and up to 10 days after discharge
from hospital. All the data were collected and analyzed for statistical significances in relevant software.
Results and Observations: Prevalence of hypocalcemia in this study was 12.63%. Only two infants
developed symptomatic hypocalcemia. Statistically significant (P < 0.001) decrease in calcium levels
were recorded between pre‑ and post‑phototherapy. However, there was no statistical change in
calcium levels when prehototherapy and at the 10 th day after phototherapy calcium levels were
compared and no baby developed clinical manifestations of hypocalcemia during observation for
10 days. Thus, phototherapy‑induced hypocalcemia is short lived without any long‑term effect. Duration
of phototherapy has negative but not significant correlation with phototherapy‑induced change in
calcium levels.
Conclusion: To conclude, there occurs significant asymptomatic phototherapy‑induced hypocalcemia,
correlation of this hypocalcemia with duration of phototherapy is negative but insignificant and effect of
phototherapy‑induced hypocalcemia on long‑term outcome of neonates is nil. Thus, calcium therapy is not
required in hypocalcemia associated with phototherapy, because it is asymptomatic and recovers of its own.

Keywords: Hyperbilirubinemia, hypocalcemia, intensive phototherapy, phototherapy‑induced hypocalcemia

Address for correspondence: Dr. Jehangir Allam Bhat, World College of Medical Sciences, Jhajjar, Haryana, India.
E‑mail: ajaalam333@gmail.com
Received: 07.03.2019, Accepted: 10.03.2019

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How to cite this article: Bhat JA, Sheikh SA, Wani ZA, Ara R. Prevalence of
hypocalcemia, its correlation with duration of phototherapy and persistence
DOI: in healthy term newborns after intensive phototherapy: A prospective
10.4103/ijas.ijas_2_19 observational hospital-based observational study. Imam J Appl Sci
2019;4:57-61.

© 2019 Imam Journal of Applied Sciences | Published by Wolters Kluwer - Medknow 57

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Bhat, et al.: Prevalence and correlation of jaundice with phototherapy
INTRODUCTION
Neonatal hyperbilirubinemia is one of the most common
newborn entities which lead to frequent admission
to NICU during the newborn period. Due to its
devasting complication like kernicterus,[1] treatment of
neonatal hyperbilirubinemia becomes mandatory when
it crosses the physiological range. Various modalities of
treatment such as phototherapy, exchange transfusion,
pharmacological therapy like IVIG for Rh incompatibility,[2]
and zinc protoporphyrins[3] are usually used to control it.
Phototherapy is mainstays of intervention for neonatal
hyperbilirubinemia. It converts the hazardous bilirubin
into less hazardous stereoisomers which less likely cross
the blood‑brain barrier to enter the central nervous
system, thus reducing neurotoxicity. [4] To make the
phototherapy more effective, double surface intensive
phototherapy must be used in neonatal jaundice care.
The American Academy of Pediatrics (AAP) defines
intensive phototherapy as a spectral irradiance of at least
30 μW/cm2/nm over the relevant bandwidth.[5] Besides
useful effect, some complications such as diarrhea, skin
rash, excessive irritability, hyperthermia, DNA damage,
and hypocalcemia[6] are seen with phototherapy treatment.
Prevalence of hypocalcemia with phototherapy treatment has
been extensive research during the last decade. Association
with the duration of phototherapy and its persistence is least
studied and important for treatment part of hypocalcemia.
Thus, the main aim of our study was framed to keep these
elements in mind so, correlation of hypocalcemia with
duration of phototherapy and its persistence in healthy term
newborn were the main aims designed for this study.
MATERIALS AND METHODS
This was a prospective observational study conducted
in City max hospital and research center Haryana from
July 2013 to July 2016. Newborn were selected on the basis
of some predefined inclusion criteria.
Inclusion criteria
Term healthy babies who developed non physiological
hyperbilirubinemia and required treatment as per American
academy of pediatrics-based guidelines.
Normal calcium level before starting phototherapy.
Exclusion criteria
Newborn suffering from perinatal asphyxia, sepsis,
hypothyroidism, jaundice due inborn error of metabolism
baby needed exchange transfusion, Rh incompatibility, and
baby of diabetic mother.
58 Imam Journal of Applied Sciences | Volume 4 | Issue 2 | July-December 2019
After applying the above defined criteria, a total of 380
neonates were selected for study after taking proper consent
from their parents and hospital ethical and scientific
committee. Neonates were thoroughly examined and
3 ml of the sample was collected and sent to laboratory
for calcium and bilirubin estimation. Serum bilirubin was
estimated by microbilirubin (Jendrassik and Grof method),
for that venous blood is taken in four microcapillaries
and centrifuged at the rate of 10000 rpm for 5 min and
quantitative estimation of calcium was done by Arsenazo
reagent method.
All phototherapy machines were properly checked
and calibrated before starting this study, such that all
neonates received intensive phototherapy as defined
by AAP.[5] Hypocalcemia was defined as total calcium
level  <8  mg/dl.[7] During the session of phototherapy,
parents were counseled and taught about the signs and
symptoms of hypocalcemia. Thus, advised to report
urgently to the hospital if any clinical manifestation of
hypocalcemia developed after discharge at home or report
on the 10th day if baby remained well.
Statistical analysis
Demographic data, serum bilirubin, and calcium level
recorded were analyzed using IBM SPSS Statistics for
Windows, Version 23.0. (Armonk, NY: IBM Corp.) and
MedCalc Software 18.11.3. (Acacialaan 22, 8400 Ostend,
Belgium). Mean, standard deviation and independent and
paired Student’s t‑test was used to compare the data. The
correlation was done by Pearson’s correlation analysis. P <
0.05 was considered statistically significant. In this study,
we studied the correlation of difference of pre and post
phototherapy calcium levels with duration of phototherapy
because to assess the correlation of change of calcium
levels so as to make it statistically relevant.
RESULTS AND OBSERVATIONS
Out of a total of 380 neonates included in the study,
200  (52.63%) were male and 180  (47.37%) female.
217 newborn were vaginally and 163 lower segment
caesarean section delivered [Table 1]. Mean gestational
Table 1: Demographic profile of neonates
Parameter Mean±SD
Gestational age (week) 38.2±1.7
Weight (kg) 2.71±0.49
Serum bilirubin (mg/dl) 17.51±1.9
Gender (male (%)/female (%)) 200 (52.63)/180 (47.37)
Mode of delivery LSCS/VD 163/217
Duration of phototherapy
SD: Standard deviation, LSCS/VD: Lower segment caesarian section/
Vaginal delivery
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Bhat, et al.: Prevalence and correlation of jaundice with phototherapy

age, mean weight, mean serum bilirubin, and duration of
phototherapy are shown in Table 1.
Only two babies developed symptoms of hypocalcemia
during phototherapy treatment. One developed jitteriness
which did not need any calcium therapy and other
developed seizures which was managed by calcium as per
protocol for the management of hypocalcemia.
Out of total 380 neonates, calcium level of only 320 patients
was checked on follow‑up because 34 patients did not come
on the 10th day as advised. Reset 26 neonates developed
illness such as septicemia, bronchopneumonia, meningitis,
or other form of illness thus were excluded from calcium
examination on the 10th day.
Our study revealed 48, i.e., 12.63% newborn out of
total 380 developed hypocalcemia and rest 332 (87.37%)
had nor mal calcium level during phototherapy
treatment [Table 2].
Table 3 depicts the statistical values of bilirubin and calcium
levels during various stages. It is worthy to observe that
mean calcium pre, post, and at after the 10th of phototherapy
was 8.3530  mg/dl, 7.4733  mg/dl, and 8.2812  mg/dl,
respectively. Mean of the difference of calcium between
pre‑ and post‑phototherapy was 0.8979 mg/dl and mean
duration of phototherapy was 38.05 h.
Table 2: Prevalence of hypocalcemia due to double surface
intensive phototherapy
Calcium status No. of neonates (%)
Hypocalcemia 48 (12.63)
Normocalcemia 332 (87.37)
Total 380 (100)
Comparison of pre‑  and post‑phototherapy and at
the 10 th  day after phototherapy levels of calcium
showed statistical significance between pre‑  and
post‑phototherapy  (P  ‑  0.000) and post phototherapy
and at the 10th day after phototherapy (P  =  0.00) levels
with P <  0.05 as shown in Table  4. Pre and at 10th day
after phototherapy levels of calcium comparison showed
statistically insignificance (P = 0.183).
Correlation analysis of duration of phototherapy
with a change in calcium levels (difference of pre and
postphototherapy calcium levels) showed negative but
insignificant correlation with coefficient (r) of  −0.008 and
P = 0.878 [Table 5 and Figure 1].
DISCUSSION
Transcranial illumination of blue light during phototherapy
causes the inhibition of melatonin secretion from the pineal
gland. Decreased melatonin leads to decreased the production
of corticosterone, thus decreasing bone resorption of calcium
from bones which results in hypocalcemia.[8]
Prevalence of hypocalcemia in our study was 12.63%
which is similar to the prevalence of 15% and 14.4%
shown in their study by Karamifar et al.[9] and Ehsanipoor
et al.,[10] respectively. In our study there occurred significant
decrease in calcium level of neonates during phototherapy,
which was supported by significant statistical difference
when comparison of pre and post phototherapy calcium
levels was done (P = 0.00). This result was supported by
a study of Bahbah et al.[11] who also showed P < 0.0001
in their study when pre‑ and post‑phototherapy calcium
levels were compared.

Table 3: Descriptive statistics of bilirubin and calcium level in neonates

Statistics Bilirubin Calcium Difference of Duration of
Prephototherapy Postphototherapy Prephototherapy Postphototherapy 10th day after calcium pre‑ and phototherapy
phototherapy post‑phototherapy
Mean 17.5184 10.981 8.3530 7.4733 8.2812 0.8797 38.0500
SD 1.94390 1.34 0.73295 0.49714 0.75447 0.79524 8.23950
Minimum 13.40 5.4 7.40 6.10 7.10 −1.10 25.00
Maximum 23.00 12.3 10.00 8.90 10.00 3.40 65.00
Variance 3.779 2.455 0.537 0.247 0.569 0.632 67.889
Range 9.60 8.76 2.60 2.80 2.90 4.50 40.00
SD: Standard deviation

Table 4: Comparison of calcium levels and their statistical significance of differences

Calcium Paired differences Significant (two‑tailed)
Mean SD SEM 95% CI of the difference
Lower Upper
Pre‑ and post‑phototherapy 0.87971 0.79524 0.04080 0.79950 0.95992 0.000
Postphototherapy and at 10th day of life −0.80789 0.92184 0.04729 −0.90088 −0.71491 0.000
Prephototherapy and at 10th day of life 0.07182 1.04976 0.05385 −0.03407 0.17770 0.183
SD: Standard deviation, CI: Confidence interval, SEM: Standard error of the mean

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Bhat, et al.: Prevalence and correlation of jaundice with phototherapy
Table 5: Correlation of difference between pre‑ and
post‑phototherapy calcium levels with duration of
phototherapy
Correlation r CI for r Significant (P)
Negative −0.008 −0.003–0.0234
r: Coefficient of correlation, CI: Confidence interval
Figure 1: Scatter plot of: Correlation of difference between pre
phototherapy and post phototherapy calcium levels and duration of
phototherapy
Only two babies developed symptoms of hypocalcemia in
our study which is in accordance with study of Karamifar
et al.[9] who revealed no neonate developed symptoms of
hypocalcemia while under phototherapy. Development of
hypocalcemia in two babies in our study could be explained
by large sample size (380) as compared to size (153) taken
by Karamifar et al.[9]
The study revealed that while observing the neonates
up to the 10th day of phototherapy, no one developed
symptoms of hypocalcemia and calcium estimation on
that day showed a mean value of 8.2812. Comparison
of the 10th day calcium level with pre phototherapy level
showed no significant difference (P  =  0.183). Thus,
phototherapy‑induced hypocalcemia is transient and
asymptomatic.  (No study is present on follow‑up of
phototherapy‑induced hypocalcemia neonates and their
subsequent calcium levels).
Phototherapy causes a decrease in level calcium, but there
is no effect of duration of phototherapy on the level of
calcium, i.e., negative (phototherapy causes a decrease
in the level of calcium) but insignificant correlation.
However, a study conducted by Chandrashekar[12] revealed
increase number of neonates developed hypocalcemia
with increase in duration of phototherapy but in his study
cutoff value for hypocalcemia was <7 mg/dl, which could
be the reason for the difference in our results. Thus, more
60 Imam Journal of Applied Sciences | Volume 4 | Issue 2 | July-December 2019
research is needed to support this question of correlation
of hypocalcemia with duration of phototherapy.
CONCLUSION
0.878
There occurs significant asymptomatic phototherapy
induced hypocalcemia, correlation of this hypocalcemia
with the duration of phototherapy is negative but
insignificant and effect of phototherapy induced
hypocalcemia on long‑term outcome of neonates is nil
because no infant developed symptoms and signs of
hypocalcemia during 10 days observation and no statistical
difference was seen between prephototherapy and the
10th day calcium levels.
Recommendations
Calcium therapy is not required In hypocalcemia associated
with phototherapy, because it is asymptomatic and recovers
of its own.
Acknowledgment
We are highly thankful to our hospital administration and
parents of study new‑borns, who permitted us to conduct
this research. We also thank our senior and junior colleagues
for their valuable support.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Volpe  JJ. Neurology of the Newborn. 5th  ed. Philadelphia: W  B
Saunders; 2008. p. 619‑51.
2. Kappas A, Drummond GS, Henschke C, Valaes T. Direct comparison
of sn‑mesoporphyrin, an inhibitor of bilirubin production, and
phototherapy in controlling hyperbilirubinemia in term and near‑term
newborns. Pediatrics 1995;95:468‑74.
3. Gottstein  R, Cooke  RW. Systematic review of intravenous
immunoglobulin in haemolytic disease of the newborn. Arch Dis
Child Fetal Neonatal Ed 2003;88:F6‑10.
4. Mreihil K, Madsen P, Nakstad B, Benth JŠ, Ebbesen F, Hansen TW,
et al. Early formation of bilirubin isomers during phototherapy for
neonatal jaundice: Effects of single vs. double fluorescent lamps vs.
photodiodes. Pediatr Res 2015;78:56‑62.
5. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia.
Management of hyperbilirubinemia in the newborn infant 35 or more
weeks of gestation. Pediatrics 2004;114:297‑316.
6. Xiong T, Qu Y, Cambier S, Mu D. The side effects of phototherapy
for neonatal jaundice: What do we know? What should we do? Eur J
Pediatr 2011;170:1247‑55.
7. Cloherty  JP, Eichenwald  EC, Hansen  AR, Martin  CR, Stark  AR,
editors. Cloherty and Stark’s Manual of Newborn Care: Neonatal
Hyperbilirubinemia. 7th  ed. Wolter Kluwer: Philadelphia; 2008.
p. 336‑7.
8. Hunter KM. Hypocalcemia. In: Cloherty JP, Eichenwald CE, Stark AR,
[Downloaded free from http://www.e-ijas.org on Tuesday, August 27, 2019, IP: 180.252.79.185]

Bhat, et al.: Prevalence and correlation of jaundice with phototherapy

editors. Manual of Neonatal Care. 5th  ed. Philadelphia: Lippincott
Williams & Wilkins; 2004. p. 579‑88.
9. Karamifar H, Pishva N, Amirhakimi GH. Prevalence of phototherapy
induced hypocalcemia. Int J Mol Sci 2002;4:166‑8.
10. Ehsanipoor F, Khosravi N, Jalali S. The effect of hat on phototherapy
induced hypocalcemia in icteric newborn. Razi J Med Sci 2008;15:25‑9.
11. Bahbah MH, El Nemr FM, El Zayat RS, Khalid Aziz EA. Effect of
phototherapy on serum calcium level in neonatal jaundice. Menoufia
Med J 2015;28:426-30.
12. Chandrashekar  B. Effect of duration of phototherapy on serum
calcium level in newborn with neonatal jaundice. Pediatr Rev Int J
Pediatr Res 2014;1:88‑92.

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