Serum Calcium Levels in Preterm and Term Neonates on Phototherapy

Introduction: In addition to known causes of hypocalcemia like, prematurity, Intrauterine growth retardation (IUGR), asphyxia, sepsis, infants of diabetic mothers (IDM), high phosphate formula, Magnesium deficiency, effect of phototherapy on serum calcium levels has caught attention of researchers from time to time. The objectives of this study were to evaluate serum calcium levels in relation to duration of phototherapy, single surface Vs double surface phototherapy in term and preterm neonates. Materials and Methods: This study was done in a neonatal ICU of a tertiary care hospital. Hundred preterm and term neonates > 72 hrs of age with weight appropriate for gestational age were selected. Serum calcium levels were measured at the onset and after 24 hrs and 48 hrs of phototherapy and results were analyzed in both the groups. Results: Hypocalcemia was more frequently observed in term group as compared to preterm group. Hypocalcemia occurred more frequently after 48 hrs of continuous phototherapy in both groups. Hypocalcemia was more common under DSPT as compared to SSPT in both groups. Conclusion: Hypocalcemia is a significant problem in neonates subjected to phototherapy.


Introduction
P athological hyperbilirubinemia with its neurotoxic complica ons is one of the reasons for admission of newborns to neonatal unit in addi on to sepsis, perinatal asphyxia, prematurity, respiratory distress syndrome and metabolic derangements 1 .Phototherapy is a convenient and inexpensive modality for the treatment of neonatal hyperbilirubinemia which has revolu onized the management of jaundice thereby decreasing the number of exchange transfusions dras cally 2 .It requires protec on of eyes to prevent re nal damage, covering genitalia to prevent chroma d changes, maintenance of adequate hydra on par cularly in preterm babies due to large surface area and euthermia.Decreased ac vity of glutathione reductase in red blood cells and subsequent haemolysis and preven ve role of vitamin B 2 was suggested by WuZL 3 .Green stools due to transient lactose intolerance and increased concentra on of bile salts and unconjugated bilirubin in the bowel is common under phototherapy 4 .
Hypocalcemia defi ned as total serum calcium level less than 8mg/dl in term and less than 7mg/dl in preterm babies is an important metabolic aberra on in neonatal period due to its ill eff ects on neurological and cardiac func ons 5 .Hypocalcemia may be asymptoma c par cularly early onset hypocalcemia or symptoma c in the form of ji eriness, lethargy, apnea, hypotonia, high pitched cry, stridor, irritability and seizures.Uninhibited eff ect of cor costeroids due to decreased synthesis of melatonin from pineal gland under phototherapy is thought to be responsible for hypocalcemia.

Results
All the 46 preterms and 54 term babies were appropriate for gesta onal age and more than 72 hrs of age.Majority of babies (preterm 78% and term 85%) were 72-96 hrs old at the ini a on of phototherapy.Gesta onal age was 34-37 weeks in 28 preterms and 30-34 weeks in 18 preterm babies thus all were more than 30 weeks of gesta on.Hypocalcemia was observed in 20 out of 46 preterms (43%) and 30 out of 54 term neonates (56%) a er 48 hrs of con nuous phototherapy.
At the end of 24 hrs four preterms (9%) developed hypocalcemia with number increasing to 20 (43%) at end of 48 hrs with a t value 9.786 and 11.443 respec vely which is more than table value of t at 95% confi dence level (t 0.05=2.000)which was sta s cally signifi cant.23 term babies (42%) developed hypocalcemia at the end of 24 hrs and number rose to 30 (56%) at the end of 48 hrs when three babies had serum calcium levels less than 7mg/dl.t value was 7.58 and 9.66 respec vely which was sta s cally signifi cant (Table 1).
Out of 24 preterms subjected to SSPT, none had hypocalcemia at end of 24 hrs while seven had hypocalcemia at the end of 48 hrs.t value was more than table value of t at 95% confi dence level (t 0.05 = 2.069).On the other hand under DSPT four preterms (18%) out of 22 had hypocalcemia at the end of 24 hrs and 13 (59%) had serum calcium level below 7mg/dl at 48 hrs, t value higher than table value of t at 95% confi dence level which is sta s cally signifi cant (Table 2).11 (33%) and 14 (42%) term babies developed hypocalcemia under SSPT at 24 and 48 hrs respec vely.Fall in serum calcium level is sta s cally signifi cant as t value is more than table value of t at 95% confi dence level (t 0.05= 2.02).Under DSPT 12 (57%) term babies had hypocalcemia at 24 hrs and 16 (76%) term babies developed hypocalcemia at 48 hrs.Two term neonates had serum calcium level below 7mg/dl at 48 hrs.Fall in serum calcium level is sta s cally signifi cant since t value is more than table value of t at 95% confi dence level (t.0.05 = 2.084) (Table 3).
Because of widespread use of phototherapy for treatment of neonatal hyperbilirubinemia, present study was conducted to study the eff ect of phototherapy, its dura on and single (SSPT) versus (vs) double surface phototherapy (DSPT) on serum calcium levels in term and preterm babies and its clinical implica ons if any.

Materials and Methods
Study comprised of 100 inborn and out born newborns admi ed in NICU of Sri Guru Ram Das Ins tute of Medical Sciences and Research for treatment of hyperbilirubinemia.46 were preterms and 54 were term babies.They were subjected to single or double surface phototherapy depending upon serum bilirubin values.Phototherapy was given according to the American Academy of Pediatrics Subcommi ee on hyperbilirubinemia guidelines in neonates 35 or more weeks of gesta on 8 .In neonates <35 weeks gesta on phototherapy was started when total serum bilirubin was 0.75% of birth weight in grams.Cut off values were 7-9mg/dl in 1000-1500 grams, 10-12 mg/dl in 1500-2000 grams,13-15 mg/ dl in 2000-2500 grams birth weight 9 .Single surface phototherapy was used for serum bilirubin level in the range 50-60% and double surface phototherapy for serum bilirubin level in the range of 60-70% of recommended value for exchange transfusion for diff erent birth weights 10 .Babies with IUGR, IDM, prolonged and diffi cult labor, respiratory distress and those receiving cow's milk were excluded from study.Phototherapy units with four blue and two white lights with a wavelength of 420-480nm and irradiance of 6-12μw/cm 2 /nm were used placed at a distance of 45cm from skin surface.Serum calcium was measured at the onset and then at 24 and 48 hrs of phototherapy by OCPC method.In addi on to CBC and blood group, serum bilirubin was es mated by Jendrassik and Grof method.Data was compiled and sta s cally analyzed with student's t test.t value was calculated and compared with table value for given degree of freedom and level of signifi cance calculated for 95% confi dence limit.T = ¯d (n)½ S = [Σd 2 .-n(d¯) 2 / (n-1) ]½ ¯d =Σd/n and interpreted following t table.Symptoma c hypocalcemia was more common in preterm group than term group.Ji eriness was the commonest symptoms observed in 7 (35%) preterms and 3 (10%) term babies followed by lethargy in 2 (10%) preterms and 1 (4%) term baby.Symptoms like irritability, poor feeding and convulsions were not encountered in the present study (Table 5).

Discussion
Forty six preterm >30 weeks of gesta on and 54 term babies were enrolled for the present study.All the babies were more than 72 hrs of life to avoid eff ect of early onset hypocalcemia.Sethi et al (1993) 12 and Eghbalian F et al (2002) 14 excluded newborns with icterus in fi rst 24 hrs of life.Sethi et al (1993) 12 and Karamifer H et al (2002) 13 selected preterms more than 31 weeks whereas Eghbalian et al (2002) 14 included only term neonates.
All the term and preterm neonates in the present study were appropriate for gesta onal age.Same was the case in the studies done by Romagnoli et al (1979)  16 , Sethi el al (1993) 12 and Jain BK et al (1998) 15 .
Hypocalcemia was more commonly encountered in term neonates 30 (56%) as compared to preterm neonates 20 (43%).Hypocalcemia was related to dura on of phototherapy in both groups.It was detected in 4 (9%) and 20 (44%) preterm babies at 24 hrs and 48 hrs of phototherapy respec vely.In term group hypocalcemia was detected in 23 (42%) and 30 (56%) babies at the end of 24 hrs and 48 hrs of phototherapy respec vely.Hypocalcemia was more commonly observed under DSPT as compared to SSPT in both groups.In preterm group, hypocalcemia occurred in 13 (59%) neonates under DSPT as compared to 7 (29%) under SSPT.In term group, hypocalcemia occurred in 16 (76%) newborns under DSPT.versus 14 (42%) under SSPT.Higher incidence of hypocalcemia in term group was probably a ributed to higher cut off value of serum calcium level of 8mg/dl as compared to 7mg/dl in preterm babies.Much higher incidence of hypocalcemia was observed by Sethi et al 12 and lowest incidence was reported by Karamifer H et al 13 .Hypocalcemia was reported more frequently in preterm babies as compared to term babies, percentage being 90%, 55% and 22.6% in preterm group & 75%, 30% and 87% in term group by Sethi et al (1993) 12 Jain BK et al (1998) 15 Karamifer H et al (2002) 13 .Romagnoli et al (1979) 16 only studied preterm group and observed hypocalcemia in 52.3% babies.
The diff eren al eff ect of single versus double surface phototherapy has not been studied by other workers.In present study symptoma c hypocalcemia was observed more frequently under DSPT as out of seven preterm having ji eriness six were under DSPT and two preterms had lethargy that too under DSPT.Jain BK et al 15 and Sethi et al 12 reported higher incidence of symptoma c hypocalcemia in preterm group (55% and 50% respec vely) as compared to term group (30% and 15%respecively).Symptoma c hypocalcemia has not been reported by Karamifer H et al (2002) 13 .Ji eriness was observed in 90% and 64% and irritability in 40% and 27% by Sethi et al 12 and Jain BK et al 15 respec vely in preterm group.In term neonates ji eriness was observed in all babies by Sethi et al 12 followed by irritability in 33%.Ji eriness, lethargy & irritability was no ced in 50%, 33% and 50% of hypocalcemic term babies by Jain BK et al. 15 In present study symptoms occurred only in term neonates under DSPT.

Conclusion
Thus hypocalcemia is a signifi cant problem in neonates subjected to phototherapy which is a commonly used modality of treatment for neonatal hyperbilirubinemia hence there is need for closed monitoring of serum calcium levels and prophylac c calcium supplementa on in neonates subjected to phototherapy.

Table 1 :
Serum calcium levels a er 24 hrs and 48 hrs of phototherapy

Table 2 :
Eff ect of SSPT Vs DSPT on serum calcium level in preterm babies.

Table 3 :
Eff ect of SSPT vs DSPT on serum calcium level in term babies.

Table 4 :
Comparison of hypocalcemia in Preterm & term neonates under SSPT and DSPT.

Table 5 :
Signs and symptoms of hypocalcemia.