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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 4  |  Issue : 2  |  Page : 57-61

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


1 Department of Pediatrics, World College of Medical Sciences, Jhajjar, Haryana, India
2 Department of Gastroenterology, Vikas Hospital Pvt. Ltd, New Delhi, India
3 Department of Pediatrics, Government Medical College, Srinagar, Jammu and Kashmir, India
4 Department of Pediatrics, Kurji Holy Family Hospital, Patna, Bihar, India

Date of Submission07-Mar-2019
Date of Acceptance10-Mar-2019
Date of Web Publication30-Jul-2019

Correspondence Address:
Dr. Jehangir Allam Bhat
World College of Medical Sciences, Jhajjar, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijas.ijas_2_19

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  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 10th 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


How to cite this article:
Bhat JA, Sheikh SA, Wani ZA, Ara R. 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. Imam J Appl Sci 2019;4:57-61

How to cite this URL:
Bhat JA, Sheikh SA, Wani ZA, Ara R. 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. Imam J Appl Sci [serial online] 2019 [cited 2019 Oct 14];4:57-61. Available from: http://www.e-ijas.org/text.asp?2019/4/2/57/263661




  Introduction Top


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/cm[2]/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 Top


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.

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 Top


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 age, mean weight, mean serum bilirubin, and duration of phototherapy are shown in [Table 1].
Table 1: Demographic profile of neonates

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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 normal calcium level during phototherapy treatment [Table 2].
Table 2: Prevalence of hypocalcemia due to double surface intensive phototherapy

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

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Comparison of pre- and post-phototherapy and at the 10th 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).
Table 4: Comparison of calcium levels and their statistical significance of differences

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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].
Table 5: Correlation of difference between pre- and post-phototherapy calcium levels with duration of phototherapy

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Figure 1: Scatter plot of: Correlation of difference between pre phototherapy and post phototherapy calcium levels and duration of phototherapy

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  Discussion Top


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.

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 research is needed to support this question of correlation of hypocalcemia with duration of phototherapy.


  Conclusion Top


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 Top

1.
Volpe JJ. Neurology of the Newborn. 5th ed. Philadelphia: W B Saunders; 2008. p. 619-51.  Back to cited text no. 1
    
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.  Back to cited text no. 2
    
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.  Back to cited text no. 3
    
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.  Back to cited text no. 4
    
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.  Back to cited text no. 5
    
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.  Back to cited text no. 6
    
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.  Back to cited text no. 7
    
8.
Hunter KM. Hypocalcemia. In: Cloherty JP, Eichenwald CE, Stark AR, editors. Manual of Neonatal Care. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 579-88.  Back to cited text no. 8
    
9.
Karamifar H, Pishva N, Amirhakimi GH. Prevalence of phototherapy induced hypocalcemia. Int J Mol Sci 2002;4:166-8.  Back to cited text no. 9
    
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.  Back to cited text no. 10
    
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.  Back to cited text no. 11
  [Full text]  
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.  Back to cited text no. 12
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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