|Year : 2016 | Volume
| Issue : 3 | Page : 486-492
|The effect of phototherapy on urinary calcium excretion in term neonates
Afshin Safaei Asl1, Marjaneh Zarkeshl2, Abtin Heidarzadeh3, Shohreh Maleknejad4, Kaveh Hagikhani5
1 Department of Pediatrics, Division of Nephrology, Guilan University of Medical Sciences, Rasht, Iran
2 Department of Pediatrics, Division of Neonatology, Guilan University of Medical Sciences, Rasht, Iran
3 Department of Epidemiology, Guilan University of Medical Sciences, Rasht, Iran
4 Department of Pediatrics, Division of Gastroenterology, Guilan University of Medical Sciences, Rasht, Iran
5 Department of Pediatrics, Guilan University of Medical Sciences, Rasht, Iran
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|Date of Web Publication||13-May-2016|
| Abstract|| |
Phototherapy is the most common, most effective, and least dangerous treatment method for neonatal hyperbilirubinemia and is the treatment of the first choice for neonatal icterus. Hypocalcemia is one of the lesser-known complications of phototherapy. Some studies have shown a relationship between increased urinary calcium excretion and phototherapy-induced hypocalcemia. We aimed to assess the effect of phototherapy on urinary calcium excretion in term neonates. This before-after study was performed on 80 term neonates having hyper- bilirubinemia referred to the 17thShahrivar Hospital, Rasht, Guilan Province, Northern Iran, over a one-year period from May 2013 to May 2014. Electrocardiography was performed to measure QTc in all neonates at admission and 48 h after phototherapy. Blood and urine samples were taken from all neonates before and 48 h after phototherapy. Phototherapy was performed using four lamps with similar wavelengths from a distance of 20 cm. The serum and urinary calcium and sodium levels and urinary creatinine level before and after phototherapy were measured and compared. Data were analyzed using SPSS software, version 16. The mean age of the study subjects was 7.01 ± 4.13 days. We did not find any significant difference between urinary calcium levels (P = 0.0001), urinary creatinine levels (P = 0.954), or the calcium/creatinine ratio (P = 0.086) before and after phototherapy. The neonates' mean ± standard deviation plasma as well as urinary sodium levels differed before and after phototherapy; the difference was not statistically significant (P = 0.658). Phototherapy might increase urinary calcium excretion although it does not cause hypocalcemia.
|How to cite this article:|
Asl AS, Zarkeshl M, Heidarzadeh A, Maleknejad S, Hagikhani K. The effect of phototherapy on urinary calcium excretion in term neonates. Saudi J Kidney Dis Transpl 2016;27:486-92
|How to cite this URL:|
Asl AS, Zarkeshl M, Heidarzadeh A, Maleknejad S, Hagikhani K. The effect of phototherapy on urinary calcium excretion in term neonates. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2021 Dec 8];27:486-92. Available from: https://www.sjkdt.org/text.asp?2016/27/3/486/182381
| Introduction|| |
Hyperbilirubinemia is a common and often benign condition in neonates and is seen in 60% of term neonates during the 1[st]week of birth and 80% of premature neonates. It is usually caused by the dermal accumulation of lipid-soluble, nonpolar unconjugated bilirubin pigments (indirect type).Although an anti- oxidant role for bilirubin is possible, high amounts of indirect unconjugated bilirubin are potentially neurotoxic. The most important complication of indirect hyperbilirubinemia is its role in creating neurological disorders which are typically caused by severe indirect hyperbilirubinemia.,
Phototherapy is a commonly used method for the treatment and prophylaxis of unconjugated hyperbilirubinemia. Phototherapy can decrease total bilirubin concentration in most neonates regardless of their maturity, degree of dermal pigmentation, and hemolysis. Considering pre- vious studies on the effect of phototherapy and that serious complications were not observed, it has been concluded that this treatment me- thod is relatively safe and can reduce the need for exchange transfusion in infants. Moreover, follow-up studies have reported no serious complications in neonates who had undergone phototherapy.
Some complications might occur during phototherapy. Animal studies have shown that retinal degeneration could occur after several days of extended phototherapy. However, the effect of intense light on the human neonates' eyes is still unknown. Phototherapy may increase body and room temperature. As a result, dehydration could occur during photo- therapy, especially by insensible water loss.,,
Bronze baby syndrome is phototherapy's other complication. In this syndrome, the neo- nate's serum, urine, and skin turn bronze seve- ral hours after the baby is put into the photo- therapy device. Other complications such as electric shock and burn can occur due to inade-quate protection.,
One of the less common complications of phototherapy is hypocalcemia. In animal studies, researchers have found that photo- therapy might reduce melatonin levels and as a result, decrease glucocorticoid secretion and cause hypocalcemia by increasing calcium (Ca) resorption.,,
In some studies, the mean urinary Ca excre- tion increased in several neonates after 48 h of phototherapy.,Urinary Ca excretion in the 1[st]week of life is directly dependent on the urinary sodium excretion as well as gestational age. Furthermore, glomerular filtration can affect Ca secretion by urinary excretion of cyclic 3',5'-adenosine mono-phosphate and potassium.,Whether hypocalcemia is the result of increased urinary Ca excretion is yet to be known and should be further studied.
In recent years, a limited number of studies have evaluated phototherapy as a risk factor for hypocalcemia.,,Hypocalcemia and its consequent seizures could have a negative im- pact on the central nervous system (CNS) and intensify the damage to CNS possibly affected by jaundice itself. Since the main cause of hypocalcemia is still controversial, evaluating the etiology of phototherapy-induced hypocal- cemia is also important. Moreover, to the best of our knowledge, there are few studies in this regard that have mostly focused on preterm neonates. Therefore, we aimed to assess the effect of phototherapy on urinary Ca excretion in term neonates.
| Patients and Methods|| |
This before-after study was performed on 80 term neonates suffering from hyperbilirubi- nemia referred to 17thShahrivar Hospital, Rasht, Guilan Province, Northern Iran, over a one-year period from May 2013 to May 2014. All stages of the study were explained to the parents and their written informed consent was obtained. This study was approved by the Ethics Committee of Guilan University of Medical Sciences.
We included neonates with a birth weight of >2500 g who were more than two days old, did not have a history of icterus during the 48 h after birth, had an indication for photo- therapy (serum bilirubin: 15-19 mg/dL), and were breastfed.
We excluded neonates who were on anti- biotic therapy or candidates for exchange transfusion, hemolytic anemia, asphyxia, res- piratory distress, sepsis, infants of diabetic mothers, and infants with a history of intra- venous therapy and admission at birth because of disease.
Electrocardiography was performed to mea- sure QTc in all neonates at admission and 48 h after phototherapy. Blood and urine samples were drawn from all neonates before and 48 h after phototherapy. Phototherapy was per- formed using four lamps with similar wave- lengths from a distance of 20 cm. The neo- nates were allowed to urinate from the time of admission to the beginning of phototherapy for 2 h to obtain urine samples. In case of no urination, phototherapy was not postponed, but the neonate was excluded from the study.
The serum and urinary Ca, sodium, and creat- inine levels before and after phototherapy were measured and compared. Urine samples were collected from urine bags. Hypercalciuria was defined as the Ca/creatinine ratio of more than 0.85.,
Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 16.0 soft- ware (SPSS Inc, Chicago, IL, USA). Wilcoxon and paired t-tests were used as appropriate.
| Results|| |
We assessed 80 neonates with a mean age of 7.01 ± 4.13 days (range: 3-26 days) diagnosed with nonphysiological hyperbilirubinemia. Most of the neonates were 2-5 days old. There were 46 boys (57.5%) and 34 girls (42.5%). The mean gestational age was 38.45 ± 0.54 weeks with a minimum and maximum gesta- tional age of 38 and 40 weeks. The mean weight of the infants was 3198.9 ± 373.2 g (range: 2500-4420 g).The mean ± standard deviation (SD) of total bilirubin level was 16.54 ± 0.92 mL/dL [Table 1].
The mean serum Ca levels before and after phototherapy were 9.37 ± 0.86 and 9.25 ± 0.61 mg/dL, respectively (P = 0.171, paired t-test). The statistical difference between various para- meters before and after phototherapy was as follows: urinary Ca levels (P = 0.0001, Wilco- xon nonparametric test), urinary creatinine levels (P = 0.954), or Ca/Cr ratio (P = 0.086). The mean ± SD QTc intervals before and after phototherapy were 0.3955 ± 0.0456 mm and 0.3959 ± 0.53 mm, respectively (P = 0.083). According to the Kolmogorov-Smirnov test, the neonates' QTc was in the normal range before and after phototherapy [Table 2].
|Table 2. Comparison of the mean ± standard deviation of various laboratory parameters before and after phototherapy|
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The neonates' mean ± SD plasma sodium levels as well as urinary sodium levels differed significantly before and after phototherapy. However, the mean ± SD sodium excretion ratios had no significant difference before and after phototherapy (P = 0.658, [Table 2].
Basal serum creatinine at admission was tested and no significant difference was seen between the mean creatinine levels before and after phototherapy (P = 0.842).
The urinary Ca/Cr ratios before and after phototherapy did not differ significantly with respect to sex, age, gestational age, weight at birth, and total bilirubin levels [Table 3].
|Table 3. Comparison of mean ± standard deviation urinary calcium/creatinine ratios before and after phototherapy in the neonates according to sex, age, birth weight, gestational age, and total bilirubin levels (paired t-test).|
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The mean ± SD serum Ca levels differed significantly before and after phototherapy in girls, but the changes in serum Ca levels did not lead to hypocalcemia (P = 0.005). A signi- ficant decrease was seen in serum Ca levels before and after phototherapy in neonates who were ≥8 days old (P = 0.009) although the levels remained in the normal range. There was a significant difference between the serum Ca ratios before and after phototherapy in neonates with a total bilirubin level of 1-18 mg/dL (P = 0.037) although this difference did not cause hypocalcemia [Table 4].
We found a significant difference in the urinary Ca levels before and after photo- therapy in both boys (P = 0.001) and girls (P = 0.047), which indicates an increase in urinary Ca excretion. Urinary excretion ratios differed significantly before and after phototherapy in neonates who were 2-5 days (P = 0.028) and ≥8 (P = 0.014) days old [Table 5].
|Table 4. Comparison of mean ± standard deviation serum calcium levels before and after phototherapy in the neonates according to sex, age, birth weight, gestational age, and total bilirubin levels|
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|Table 5. Comparison of mean ± standard deviation urinary calcium levels before and after phototherapy|
in the neonates according to sex, age, birth weight, gestational age, and total bilirubin levels
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| Discussion|| |
The regulation of Ca homeostasis in the new- born period has been of considerable interest. At birth, the plasma Ca level in cord blood exceeds that in maternal blood. During the early days of life, the plasma Ca level pro- gressively decreases in normal infants so that by the second or third day of life, the level is lower than that found in older infants and children. In most normal full-term infants, the plasma Ca level returns to normal by 10 days of life. Phototherapy is an appropriate and safe measure to reduce indirect bilirubin level in newborns. Roming et al were the first to sug- gest the association of hypocalcemia in new- borns following phototherapy. Although pho- totherapy is one of the relatively safe and uncomplicated treatment methods for curing neonatal jaundice, it could have several side effects such as skin rash, loose stools, hyper- thermia, dehydration, DNA damage, chills, ophthalmic damage, nasal obstruction following eye coverage, and bronze baby syndrome.,One of the less frequent complications of phototherapy is hypocalcemia. The pathoge- nesis of phototherapy-induced hypocalcemia is still not fully understood.One study reported that Vitamin D does not have an important role in phototherapy-induced hypocalcemia because the administration of 25-hydroxy Vitamin D did not reduce the incidence of hypocalcemia in the studied premature neo- nates on phototherapy.
Hakanson et al found that white fluorescent light beam led to reduced serum Ca levels in newborn mice. This study showed that the re- duction of serum Ca levels was caused by the reduction of serum melatonin levels as a result of exposure of the pineal gland to photo- therapy. Moreover, they concluded that admi- nistering melatonin exogene could prevent hypocalcemia.In a study on the effect of using hats on phototherapy-induced hypocal- cemia in 120 newborns with icterus in Iran, the researchers found a significant difference in the amount of hypocalcemia in the group using hats compared with those receiving routine phototherapy (without hats). Head coverage in the occipital region was presented as a sui- table, safe, and inexpensive method for pre- venting phototherapy-induced hypocalcemia.The prevalence of phototherapy-induced hypocalcemia and hyper-calciuria varies in different studies. In a study on 63 term neo- nates weighing >2.5 kg who underwent photo- therapy for three days on average, a significant difference was found between the serum Ca concentration before (9.90 ± 0.93 mg/dL) and after (9.85 ± 1.23 mg/dL) phototherapy. The increased urinary Ca excretion observed in our study did not reduce the serum Ca levels, and we found no significant difference between se- rum Ca levels before and after phototherapy. However, our analysis was performed two days after phototherapy.
In another study in Iran on 153 term and pre- term neonates, the researchers found that 22 (14.3%) neonates had hypocalcemia and that the incidence of hypocalcemia was conside- rably higher in preterm neonates (22.6% vs. 8.7%). In our study, all neonates were term and weighed over 2500 g and we found no significant relationship between urinary Ca, weight, and gestational age. Moreover, no sig- nificant difference was found between urinary creatinine levels before and after phototherapy as well as urinary Ca/Cr ratio before and after phototherapy and gestational age and weight. However, since we did not include preterm neonates, this lack of significance cannot be generalized to preterm neonates.Consistent with our study, Eghbalian et al found no sig- nificant relationship between phototherapy and the incidence and severity of hypocalcemia.
We studied the corrected QT in the neonates' electrocardiograms. Since increased QTc is re- lated to the reduction of ionized Ca levels,its change could indirectly show alterations in ionized Ca levels. We found no significant dif- ference between the amount of corrected QT before and after phototherapy which further confirms the obtained result regarding the in- considerable change in serum Ca levels before and after phototherapy. We did not assess al- bumin levels which are influential in ionized Ca levels because the aim of sampling in this study was to assess total Ca levels in which evaluating albumin levels was not important and would increase costs.
During phototherapy, the amount of insen- sible water loss from the skin and lungs increases. This increase is especially important in neonates weighing below 2000 g. If this water loss is not compensated by frequent feeding, dehydration (a known complication of phototherapy) occurs. Dehydration is evident in laboratory findings as increased serum electrolyte levels and plasma osmolality.,,
We found a significant increase in plasma sodium levels after phototherapy. This increase could indicate relative dehydration during pho- totherapy. We did not evaluate plasma osmo- lality. If increased sodium levels after photo- therapy could be attributed to dehydration, educating the mothers regarding the impor- tance of frequent feeding is highly important. Our results regarding the serum sodium levels before and after phototherapy are consistent with a previous study on new-born mice.
Tan and Jacob divided full-term neonates with hyperbilirubinemia into three groups undergoing phototherapy with different inten- sities and compared serum osmolality and se- rum electrolyte levels including serum sodium levels, before and after phototherapy. They found no significant difference between the three groups with respect to the studied va- riables before and after phototherapy.Their results were not consistent with ours. More- over, we did not find any case of symptomatic hypocalcemia which was in line with another studyand different from the findings of one other studythat showed one neonate with apnea induced by hypocalcemia.
Jain et al reported decreased Ca levels in 55% of preterm and 30% of term neonates. The considerable point in their study was that 63.6% of the preterm neonates with hypo- calcemia experienced jitteriness and 27.3% experienced irritability as compared to 50% and 16.7% in term neonates, respectively. Considering the high rate of symptomatic hypocalcemia, Ca prophylaxis was advised for neonates undergoing phototherapy.
In our study on 80 neonates, the effect of phototherapy on increased urinary Ca excre- tion was confirmed. However, since the diffe- rence between serum Ca levels before and after phototherapy was not statistically signi- ficant and since we did not observe any case of hypocalcemia based on electrocardiogram changes (as increased corrected QT) and clinical signs (apnea, seizure, irritability, jitte- riness, etc.), we do not suggest Ca prophylaxis before and during phototherapy. Moreover, considering the lack of increase in the sodium excretion fraction, we can state that the in- creased urinary Ca excretion is not related to renal dysfunction and other reasons should be investigated for this phenomenon.
On the basis of this study, phototherapy could increase urinary Ca excretion although it cannot cause hypocalcemia. Therefore, we do not advise Ca prophylaxis before and during phototherapy in term neonates. Further com- plimentary studies with larger sample sizes and on preterm, low birth weight and very low birth weight infants are suggested.
Conflict of interest: None.
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Afshin Safaei Asl
Department of Pediatrics, Division of Nephrology, Guilan University of Medical Sciences, Rasht
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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