Neonatal jaundice is a condition in which a newborn infant develops scleral and skin citrus due to an increase in serum bilirubin concentration [1]. Pathophysiological jaundice begins within the first week of life and reflects the capacity of the fetal liver enzyme system, increased bilirubin production due to hemolysis of fetal red blood cells, and a delay in bilirubin excretion [2]. Although physiological jaundice in newborns is mostly harmless and resolves on its own, the patient’s total bilirubin level must be closely observed and appropriately managed to avoid adverse outcomes such as kernicterus and acute bilirubin encephalopathy. Phototherapy is the most common treatment for neonatal jaundice. Phototherapy entails directing light of a particular range of wavelengths towards the body of the infant, commonly in the blue-green region of the range 460–490 nm [3]. This light photo-isomerizes biliverdin by photoisomerization and structural isomerization so that it can be conjugated in bile and urine without requiring conjugation by the liver. Phototherapy is very useful in reducing bilirubin levels and increasing the chance of developing extreme hyperbilirubinemia, which has the potential to trigger neurological problems [4].

Phototherapy may have side effects, including hypocalcemia. Hypocalcemia in neonates is anything less than 7 mg/dl calcium and can manifest with signs such as jitteriness, irritability, seizure activity, and poor feeding [5]. The exact causes of hypocalcemia due to phototherapy are not well understood but are believed to arise from the suppression of melatonin production by light, which in turn decreases parathyroid hormone (PTH) activity. PTH plays a vital role in calcium balance; thus, hypocalcemia may result from the suppression of PTH in photosynthetically treated neonates. Knowledge of the effect of phototherapy on serum calcium levels is important for several reasons [6]. First, even though phototherapy is lifesaving in the management of hyperbilirubinemia, hypocalcemia is inimical to the neurological and physiological well-being of neonates. Second, neonates are prone to develop calcium dyshomeostasis because the parathyroid glands are immature and calcium stores are normally low. Last but not least, this finding will help in early recognition of hypocalcemia to avoid complications and thus, safe practice of phototherapy. In any case, phototherapy is not without complications including hypocalcemia. Hypocalcemia in neonates occurs at a calcium level below 7 mg/dl and can cause signs such as irritability, seizures, and poor feeding [7]. The mechanism of hypocalcemia due to phototherapy has not been determined, but it is assumed to be due to the inhibition of melatonin secretion by light, which in turn inhibits the secretion of parathyroid hormone (PTH) [6]. PTH plays a significant role in calcium homeostasis; therefore, hypocalcemia may be secondary to PTH suppression in photosynthetically treated neonates. This study aimed to evaluate the effect of phototherapy on serum calcium levels in neonates with physiological jaundice. This study aimed to examine the prevalence and severity of hypocalcemia in neonates undergoing phototherapy and explore potential correlations with factors such as the duration of phototherapy, initial bilirubin levels, and gestational age.

This cross-sectional study was conducted in the Department of Pediatrics, with cooperation from the Department of Obstetrics and Gynecology, MNR Medical College and Hospital, Sangareddy, Telangana. Institutional Ethical approval was obtained for this study. Written consent was obtained from all parents of the children included in the study after explaining the nature of the study in vernacular language.

Inclusion criteria

1. Term neonates     (37     completed      weeks      to     41      weeks)      with unconjugated hyperbilirubinemia requiring phototherapy
2. Admitted to the neonatal care unit of our hospital
3. The parents voluntarily agreed to participate in the

Exclusion criteria

1. Preterm infants
2. Jaundice on day 1 of
3. Born to diabetic
4. APGAR less than 7 at 5 min of
5. The mother was placed on
6. Fed with Cow’s
7. Neonates requiring an exchange
8. The patient had jaundice for > 14
9. With sepsis

After obtaining written consent, neonates who fulfilled the inclusion criteria for the demographic profile of the mother and infant were recorded. Clinical examination of the infant was performed under natural light, and the infant was then subjected to laboratory investigations, including Baseline Investigations (Before Phototherapy): serum total bilirubin, serum total calcium, serum ionized calcium, and LFT. Serum bilirubin levels, and calcium levels at the initiation, 24 hrs, 48 hrs, and at the end of phototherapy.

Statistical analysis: All available data were gathered, refined, and uploaded to an MS Excel spreadsheet and analyzed using SPSS version 22 in Windows format. Continuous variables are represented as means, standard deviations, and percentages. Categorical variables were calculated using Pearson’s chi-square test to determine the p values. Statistical significance was set at p (<0.05) and was considered statistically significant.

A total of 100 cases of neonatal jaundice were included in the study, based on the inclusion and exclusion criteria. Of the 100 newborns included in this study, 42% were male (42%) and 58% were female. Figure 1 shows the incidence of hypocalcemia in this study. Higher incidence of hypocalcemia in females: More female babies (9) developed hypocalcemia (low calcium levels) than male babies (6). The results showed that the risk of phototherapy-induced hypocalcemia was similar between male (14.3%) and female (15.5%) neonates. Although more females in number developed hypocalcemia, this is likely because there were more females in the study overall. The percentage difference was small and not significant.

Figure 1: Incidence of hypocalcemia in the cases of the study

Table 1 compares total serum calcium levels before and after phototherapy in male and female neonates with physiological jaundice. Before phototherapy, all neonates (both males and females) had normal calcium levels (9-11 mg/dl). After phototherapy, some neonates in both groups developed hypocalcemia, five had mild hypocalcemia (7 - 8.9 mg/dl), and one had significant hypocalcemia (< 7 mg/dl). Females: 7 had mild hypocalcemia (7 - 8.9 mg/dl) and 2 had significant hypocalcemia (< 7 mg/dl). The mean value of calcium before phototherapy was 9.21 ± 1.01 for the cohort and the mean value of serum calcium after phototherapy was 8.44 ± 1.11. The p-values (0.023 for males and 0.019 for females) indicate a statistically significant change in calcium levels after phototherapy in both groups. This shows that phototherapy has a statistically significant effect on lowering serum calcium levels.

Table 1: Comparison of total serum calcium levels before and after phototherapy

Out of the total 100 cases, we found that post-phototherapy we found 73 babies (73%) had decreased serum calcium levels from their baseline value (Figure 2). Out of these 73 babies, 7 babies (9.59%) had <5% decrease in serum calcium levels, 41 babies (56.16%) had a 5.1- 10% decrease, 17 babies (23.29%) had a 10.1 – 15% decrease, rest of the 8 (10.96%) had >15% decrease in serum calcium compared to their baseline.

Figure 2: Percentage change in serum calcium levels from baseline values after phototherapy in the cohort

Table 2 shows the relationship between the duration of phototherapy and its impact on serum calcium levels in newborns with physiological jaundice. The number of neonates with hypocalcemia (both mild and significant) appears to increase with longer durations of phototherapy. The highest number of neonates with hypocalcemia is seen in the 24-48 hours group. Significant hypocalcemia (< 7 mg/dl) is only observed in the 24-48 hours and > 48 hours groups. The p-value of 0.04 for the > 48-hour group suggests that the change in calcium levels within this group before and after phototherapy is statistically significant.

Table 2: The association of serum calcium levels with duration of phototherapy

*Significant

In this study, we found that out of the 94 babies born between 37- 40 weeks gestational age, 6 had gestational age greater than 40 weeks depicted in Table 3. Among the 6 babies who were born at a gestational age of > 40 weeks, only 1 baby was Hypocalcemic and the remaining 14 hypocalcemic cases were from the gestational age 37 – 40 weeks. The gestational age had no co-relation with post-phototherapy calcium level with a p-value of 0.957 (not significant). Out of 66 newborns with a birth weight of 2.5-3.3kg, among them 9 newborns were found to be hypocalcemic <7mg/dl. 34 newborns had a birth weight of >3.3 kg, and 6 babies had hypocalcemia <7mg/dl. In this study, birth weight was not significantly correlated with serum calcium level with p p-value of 0.804 (not significant). Out of 38 babies who were put on single surface phototherapy (SSPT), hypocalcemia was found in 5 babies. Among 45 babies who were put on Double surface phototherapy (DSPT), hypocalcemia was documented in 6 babies. Among 17 babies who were put on (TSPT), hypocalcemia was reported in 4 babies. In this study, there was no correlation between the type of phototherapy and serum calcium level (p=0.587). The overall decrease in calcium levels was found to be present in 61% of all the neonates included in the study following phototherapy.

Table 3: The association of serum calcium levels with various parameters

Neonatal jaundice is the leading cause of morbidity in newborns, frequently requiring hospitalization and readmission during the first week of life. Global surveys estimate that approximately 1.1 million newborns develop severe neonatal jaundice annually, with the majority residing in sub-Saharan Africa and South Asia [8]. Phototherapy is a widely accepted and safe method to manage neonatal jaundice effectively. Romagnoli et al. [9] were the first to report an association between phototherapy and hypocalcemia in newborns. This study found a significant proportion of neonates, particularly those undergoing longer durations of phototherapy (24-48 hours and >48 hours), experienced hypocalcemia. This aligns with previous research, demonstrating a potential link between phototherapy and hypocalcemia in neonates [10].

Calcium homeostasis during the neonatal period is a subject of significant interest. At birth, newborn blood contains more calcium than the calcium levels loaded into the mother's bloodstream. The blood calcium count declines continuously from newborn to day two or three. The plasma calcium measurements of full-term babies return to their normal range at around ten days of age. Researchers believe that phototherapy triggers the pineal gland's shutdown, which blocks melatonin release from the brain. The decrease prevents cortisol from controlling how the body uses bone calcium. The bone takes up more calcium as cortisol triggers both processes to lower circulating calcium amounts in the body. Hunter et al. supported this mechanism; furthermore, Eghbalian F et al. [11] demonstrated a direct relationship between the duration of phototherapy and the likelihood of hypocalcemia, strengthening the evidence for this phenomenon. In our study overall incidence of decreased calcium levels was in 61% of neonates out of which 15% were found to have hypocalcemia. The correlation of hypocalcemia with other confounding factors is depicted in Table 3. A similar study by Taheri P et al. [5] showed that 7% of the term neonates exhibited phototherapy-induced hypocalcemia. Similarly, Other studies in this field have reported hypocalcemia from 8.7% to 15% [12, 13]

In this study, we found that no hypocalcemia occurred when the duration of phototherapy was less than 24 hours however, between 24 – 48 hours 15.5% of cases exhibited hypocalcemia and the percentage increased to 40% in case of neonates with a duration of phototherapy greater than 48 hours. In a similar study, Jain et al. [14] observed that hypocalcemia was noted in 30% of neonates treated with 48 hours of phototherapy. In another study, Yadav et al. [15] noted a very high percentage of 66.6% of neonates with hypocalcemia following phototherapy and similar studies have found 22.6 to 90% of neonates with hypocalcemia following phototherapy [16-18]. Bahbah et al. [19] in Egypt found that 26% of neonates suffered from hypocalcemia following phototherapy. The effectiveness of phototherapy for neonatal jaundice is well recognized however, hypocalcemia must be recognized as a potential complication. The important determinant factors could be the severity of hyperbilirubinemia and the duration of phototherapy. Our study explains a significant effect of phototherapy on the calcium balance in a term neonate with jaundice, receiving phototherapy. Further studies are needed to elaborate on this aspect further, to suggest if calcium supplementation were to be given to neonates who receive phototherapy for neonatal jaundice.

Within the limitations of the current study, it is evident that there is a decrease in serum calcium levels after phototherapy. The important determinant factors were the duration of exposure and severity of hyperbilirubinemia. In this study, none of the babies developed symptoms of hypocalcemia, but the occurrence of symptoms is not always predictable regarding the decrease of serum calcium levels. Hence it is always advisable to monitor the serum calcium levels before and after phototherapy and supplement it as needed, especially if it is a sick baby, to prevent morbidity.

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