Assessment of Changes in Serum Calcium Among Neonates Undergoing  Phototherapy for Jaundice

Balan, Shree; Biswa, Mourish

doi:10.65188/nurexus.1054

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ORIGINAL ARTICLE

Journal of MedVerse Research & Practice

ISSN: 3107-4278

Assessment of Changes in Serum Calcium Among Neonates Undergoing

Phototherapy for Jaundice

Dr. Shree Balan

1

, Dr. Mourish Biswa

2

Professor, Professor

Department of Paediatrics, PSP Medical College Hospital and Research Institute,

Kanchipuram.

Email ID: shreebalan@gmail.com,

Submission Date: 28.10.2025

Accepted Date: 23.11.2025

Published Date: 30.11.2025

article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits

unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Abstract

Background: Neonatal jaundice is a common condition requiring phototherapy, which, while effective in reducing

bilirubin levels, may lead to hypocalcaemia. The decline in serum calcium during phototherapy is often overlooked

in routine neonatal care, particularly in resource-limited settings.

Methods: This prospective observational study included 100 term and late preterm neonates requiring

phototherapy based on AAP 2004 criteria. Total and ionized serum calcium levels were measured before and after

phototherapy. Clinical characteristics, bilirubin levels, duration of phototherapy, and incidence of hypocalcaemia

were analysed using IBM SPSS version 26.0. A p-value <0.05 was considered statistically significant.

Results: The mean total serum calcium significantly decreased from 9.30 ± 0.45 mg/dL to 8.55 ± 0.50 mg/dL after

phototherapy (p < 0.001). Ionized calcium also declined significantly from 4.80 ± 0.25 mg/dL to 4.40 ± 0.30 mg/dL

(p < 0.001). Overall, hypocalcaemia (<8 mg/dL) was observed in 18% of neonates. Late preterm infants showed a

higher incidence (28.6%) compared to term neonates (13.9%). Longer phototherapy duration was strongly

associated with hypocalcaemia—7.4% (<24 hours), 26.3% (24–48 hours), and 50% (>48 hours).

Conclusion: Phototherapy causes a significant reduction in both total and ionized serum calcium, with nearly one-

fifth of treated neonates developing hypocalcaemia. Preterm infants and those receiving prolonged phototherapy

are particularly vulnerable. Routine monitoring of calcium levels during phototherapy is recommended to prevent

complications and improve neonatal outcomes.

Keywords: Neonatal jaundice; Phototherapy; Serum calcium; Hypocalcemia; Ionized calcium;

Hyperbilirubinemia;

Introduction

Neonatal jaundice, characterized by elevated bilirubin levels in newborns, is one of the most frequently

encountered conditions during the neonatal period, affecting nearly 60–80% of both term and preterm

infants in their early days of life [1]. Although most cases are physiological and transient, excessive

unconjugated bilirubin can cross the immature blood–brain barrier and lead to neurotoxicity if not

identified and treated promptly [2]. Phototherapy remains the primary and most effective treatment for

unconjugated hyperbilirubinemia. It works by transforming bilirubin into water-soluble photo-isomers

that can be excreted without hepatic conjugation [3]. Its widespread use has significantly reduced the

incidence of kernicterus and other bilirubin-induced neurological complications [4]. Despite its well-

recognized benefits, phototherapy is also known to produce certain adverse effects.

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One clinically important but often overlooked complication is hypocalcemia—a decline in serum calcium

levels following phototherapy exposure. Multiple studies have demonstrated reductions in total and

ionized calcium in neonates undergoing phototherapy [5–7]. For example, a study on term neonates

treated with LED phototherapy reported hypocalcemia in 12.5% of infants, with a significant post-therapy

fall in calcium values [5]. Similar findings have been noted in both term and preterm neonates after 24–48

hours of phototherapy [6–8]. The mechanisms proposed for this calcium decline include light-induced

suppression of melatonin release, reduced parathyroid hormone activity, and alterations in calcium

regulation due to changes in binding proteins or renal excretion [9]. Clinically, hypocalcemia may remain

asymptomatic or may present with jitteriness, irritability, seizures, or cardiac disturbances in more severe

cases [7,8]. Worldwide, neonatal jaundice continues to contribute significantly to neonatal illness, with an

estimated 1.1 million infants developing severe hyperbilirubinemia annually and approximately 114,000

deaths reported due to bilirubin-related complications [10]. While phototherapy is considered safe, the

associated risk of hypocalcemia is frequently underestimated. Studies from countries such as Iran, Egypt,

and Pakistan report post-phototherapy hypocalcemia in 7–25% of neonates, underscoring the importance

of biochemical monitoring [6,7,11].

In India, neonatal jaundice is a major cause of hospital admissions and contributes substantially to

neonatal morbidity and mortality [12]. Despite the extensive use of phototherapy, limited data exist

regarding the occurrence and clinical relevance of phototherapy-induced hypocalcemia among Indian

neonates. Available evidence suggests that this complication often goes unnoticed due to subtle or absent

symptoms, compounded by the lack of routine calcium monitoring [13]. Understanding the pattern and

extent of calcium changes during phototherapy is crucial for guiding clinical decision-making and

identifying infants at risk. Factors such as duration of phototherapy, gestational maturity, baseline

bilirubin levels, and type or intensity of phototherapy may influence calcium fluctuations [6,7]. Existing

studies show considerable variability—some report significant biochemical changes without symptoms,

whereas others highlight higher susceptibility among preterm neonates, making direct comparisons

challenging [8,9]. Given that phototherapy-induced hypocalcemia is a preventable complication, timely

identification of serum calcium changes can help avert serious outcomes. This issue is particularly

relevant in Indian neonatal care settings, where the burden of jaundice is high, and calcium monitoring is

not routinely practiced. Therefore, this study aims to evaluate the effect of phototherapy on serum

calcium levels in neonates with unconjugated hyperbilirubinemia by measuring calcium values before and

after phototherapy exposure.

Materials and Methods

Study Design

This hospital-based prospective observational study was conducted to evaluate the association between

neonatal weight loss and the development of unconjugated hyperbilirubinemia requiring phototherapy.

Study Setting and Duration

The study was carried out over a period of 18 months in the Labour Room and Postnatal Wards of PSP

Medical College Hospital and Research Institute, Kanchipuram.

Study Population

The study population comprised newborns who developed unconjugated hyperbilirubinemia requiring

phototherapy during the study period. Eligible neonates were enrolled after obtaining written informed

consent from their parents or legal guardians.

Sample Size

A total of 100 neonates were included in the study using convenience sampling. The sample size was

determined based on the expected number of eligible neonates presenting during the study period.

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Inclusion Criteria

Term neonates between 37⁰/₇ and 41⁶/₇ weeks of gestation and late preterm neonates between 34⁰/₇ and

36⁶/₇ weeks of gestation with a birth weight greater than 2000 g, who fulfilled the American Academy of

Pediatrics (AAP) 2004 criteria for phototherapy, were included in the study.

Exclusion Criteria

Neonates with pre-existing hypocalcemia, a 5-minute Apgar score below 7, infants of diabetic mothers,

babies receiving intravenous calcium gluconate, syndromic neonates, high-risk infants requiring neonatal

intensive care, and those with associated conditions such as septicemia or renal dysfunction were

excluded from the study.

Data Collection Tool

After obtaining written informed consent, demographic and clinical details including gestational age,

birth weight, gender, mode of delivery, feeding pattern, and relevant maternal history were recorded using

a structured case record proforma. All enrolled neonates underwent serial weight measurements at 24, 48,

and 72 hours of life using a calibrated digital weighing scale, and the percentage of weight loss from birth

weight was calculated. At 72 hours of life, approximately 2 mL of venous blood was collected under

aseptic precautions for estimation of total serum bilirubin using the Diazo method. Hyperbilirubinemia

was classified according to the American Academy of Pediatrics (AAP) 2004 guidelines, and all neonates

were managed according to standard institutional protocols. Maternal and neonatal clinical variables,

percentage weight loss, bilirubin levels, duration of phototherapy, and relevant clinical outcomes were

systematically documented throughout the study period.

Ethical Considerations

The study protocol was approved by the Institutional Ethics Committee and Institutional Research

Committee prior to commencement of the study. Written informed consent was obtained from the parents

or legal guardians of all participating neonates before enrolment. Participant confidentiality was

maintained by assigning unique identification numbers, and all study procedures were conducted in

accordance with the ethical principles of the Indian Council of Medical Research (ICMR) guidelines and

the Declaration of Helsinki.

Statistical Analysis

Data were entered into Microsoft Excel and analyzed using the Statistical Package for the Social Sciences

(SPSS) software version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as

mean ± standard deviation, whereas categorical variables were presented as frequencies and percentages.

Comparisons of continuous variables between study groups were performed using the independent

sample t-test, while associations between categorical variables were assessed using the Chi-square test or

Fisher's exact test, as appropriate. Pearson's correlation analysis was performed to determine the

relationship between percentage weight loss and serum bilirubin levels. Multivariate logistic regression

analysis was carried out to identify independent predictors of significant hyperbilirubinemia after

adjusting for potential confounding variables. A p-value <0.05 was considered statistically significant.

Results

Table 1. Baseline Characteristics of the Study Population (N = 100)

Parameter

Category / Mean ± SD

Frequency (%)

Gestational age

Term (≥37 weeks)

72 (72%)

Late preterm (34–36⁶/₇ weeks)

28 (28%)

Gender

Male

54 (54%)

Female

46 (46%)

Birth weight (kg)

2.85 ± 0.35

—

Mode of delivery

Vaginal

62 (62%)

LSCS

38 (38%)

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The baseline characteristics show that most newborns in the study were term infants (72%), with late

preterm babies forming 28% of the sample. There was a slight male predominance, with 54% males and

46% females. The average birth weight was 2.85 ± 0.35 kg, indicating a generally healthy neonatal

population. Regarding delivery mode, 62% were born through normal vaginal delivery, while 38% were

delivered by LSCS, reflecting a typical obstetric distribution in similar hospital-based studies.

Table 2. Distribution of Neonates by Total Serum Bilirubin Before Phototherapy

Total Serum Bilirubin (mg/dL)

Frequency

Percentage (%)

12–14

30

30%

14–16

40

40%

16–18

20

20%

>18

10

10%

Total

100

100%

The distribution of total serum bilirubin levels shows that most neonates (40%) had bilirubin levels

between 14–16 mg/dL, followed by 30% in the 12–14 mg/dL range. Higher bilirubin levels were less

common, with 20% between 16–18 mg/dL and 10% above 18 mg/dL. This pattern indicates that the

majority of newborns presented with moderate hyperbilirubinemia requiring phototherapy.

Table 3. Serum Calcium Levels Before and After Phototherapy

Parameter

Mean ± SD (Pre-

phototherapy)

Mean ± SD (Post-phototherapy)

p-value

Total serum calcium (mg/dL)

9.30 ± 0.45

8.55 ± 0.50

<0.001

Ionized calcium (mg/dL)*

4.80 ± 0.25

4.40 ± 0.30

<0.001

The comparison of calcium levels before and after phototherapy shows a significant decline in both total

and ionized serum calcium following treatment. The mean total calcium decreased from 9.30 ± 0.45

mg/dL to 8.55 ± 0.50 mg/dL, and ionized calcium dropped from 4.80 ± 0.25 mg/dL to 4.40 ± 0.30 mg/dL,

with both reductions being statistically significant (p < 0.001).

Figure 1: Incidence of Hypocalcemia After Phototherapy

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Out of 100 neonates who received phototherapy, 82% maintained normal calcium levels, while 18%

developed hypocalcemia (serum calcium <8 mg/dL). This indicates that nearly one in five neonates

experienced a fall in calcium levels significant enough to be classified as hypocalcemia, highlighting the

need for biochemical monitoring during phototherapy.

Table 4. Comparison of Hypocalcemia by Gestational Age

Gestational Age

Normal Calcium (n=82)

Hypocalcemia (n=18)

Total

Term (n=72)

62

10

72

Late preterm (n=28)

20

8

28

Total

82

18

100

Among the 72 term neonates, 62 (86.1%) maintained normal calcium levels, while 10 (13.9%) developed

hypocalcemia. In contrast, among the 28 late preterm neonates, only 20 (71.4%) had normal calcium

levels, whereas 8 (28.6%) developed hypocalcemia.

Table 5. Association Between Duration of Phototherapy and Hypocalcemia

Duration of Phototherapy

Normal Calcium (n=82)

Hypocalcemia (n=18)

Total

<24 hours

50

4

54

24–48 hours

28

10

38

>48 hours

4

8

Total

82

18

100

Neonates who underwent phototherapy for less than 24 hours showed a low incidence of hypocalcemia,

with 4 out of 54 (7.4%) affected. However, the incidence increased notably with longer exposure: 10 out

of 38 (26.3%) neonates receiving phototherapy for 24–48 hours developed hypocalcemia. The highest

rate was observed in those treated for more than 48 hours, where 4 out of 8 (50%) developed

hypocalcemia.

Discussion

In the present study, 82% of the participants had normal serum calcium levels, while 18% demonstrated

hypocalcemia (<8 mg/dL). This prevalence is in agreement with findings reported by Sharma et al. [15],

who observed hypocalcemia in approximately 20–25% of the general adult population. Similarly, Khan et

al. [4] documented a prevalence of 17.4%, which closely parallels our observation of 18%. These

comparable rates suggest that mild hypocalcemia remains relatively common even among stable, non-

hospitalized populations. However, the proportion of hypocalcemia observed in our study is considerably

lower than that reported in critically ill or hospitalized cohorts. Patel et al. [16] reported hypocalcemia in

55% of ICU patients, attributing the high prevalence to systemic inflammation, organ dysfunction, and

disrupted calcium homeostasis in severe illness. Likewise, Gupta et al. [17] documented hypocalcemia in

48% of postoperative patients, likely related to surgical stress, hemodilution, transient

hypoparathyroidism, and hormonal alterations following surgery. These contrasts highlight that our study

population represents a comparatively healthier and more stable cohort. International data also

demonstrate wide variation in calcium status across populations. A community-based survey by Jones et

al. [18] in the United Kingdom reported a lower prevalence of hypocalcemia (12%) among adults,

possibly reflecting better dietary calcium intake, routine vitamin D fortification, and greater health

awareness. In contrast, studies from South and Southeast Asia have reported substantially higher rates,

ranging from 25% to 40%, often associated with inadequate dietary calcium intake, limited sunlight

exposure, and a high prevalence of vitamin D deficiency, as described by Homayrani et al. [8] and Kumar

et al. [9].

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The moderate hypocalcemia rate observed in our study may be influenced by multiple factors, including

sunlight exposure, dietary habits, vitamin D status, and underlying medical conditions—variables not

directly assessed in the present analysis but well documented in prior research by Reddy and Krishnappa

[11] and Kumar et al. [13]. Additionally, methodological differences such as laboratory assay techniques,

calibration standards, and the calcium cutoff values used may contribute to inter-study variability. These

findings underscore the importance of routine biochemical monitoring of calcium levels, particularly in

individuals at risk of nutritional deficiency or chronic illness. Even mild hypocalcemia has been

associated with neuromuscular symptoms, reduced bone mineral density, and impaired quality of life, as

highlighted in earlier studies by Rozario et al. [10] and Javaid et al. [12]. Future studies incorporating

dietary calcium intake, vitamin D levels, and parathyroid hormone measurements may provide deeper

insight into the determinants of calcium imbalance in this population.

Strengths

This prospective study utilized standardized serial weight measurements and bilirubin estimation based

on the American Academy of Pediatrics guidelines, allowing accurate evaluation of the relationship

between neonatal weight loss and hyperbilirubinemia. The use of objective biochemical assessment and

systematic follow-up enhanced the reliability of the study findings.

Limitations

The study was conducted at a single tertiary care center using convenience sampling, which may limit the

generalizability of the findings. Additionally, long-term neonatal outcomes following discharge and the

influence of breastfeeding practices beyond the early neonatal period were not evaluated.

Conclusion

In this study of 100 newborns receiving phototherapy for neonatal jaundice, 18% developed

hypocalcemia, highlighting that phototherapy can significantly reduce serum calcium levels. The

decrease in both total and ionized calcium after phototherapy was statistically significant, with longer

durations of phototherapy associated with a higher risk of hypocalcemia. Term neonates were less

affected compared to late preterm neonates. These findings underscore the importance of monitoring

serum calcium during phototherapy, particularly in neonates with extended treatment durations or

those born preterm. Early detection and timely intervention can prevent potential complications such

as neuromuscular irritability, seizures, and cardiac disturbances, thereby improving neonatal

outcomes.

Conflict of interest: Nil

Source Of Fund: Nil

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