INTRODUCTION:

Mankind has tried since its birth, methods and means to improve the man ,his ability and quality of life .He realized quite early that in order to do this ,he has to improve the man of tomorrow i.e. the “ child ” of the today and still better to improve sapling “the newborn”. The neonatal period is highly vulnerable time for an infant, who is completing many of the physiologic adjustments required for extrauterine existence. The high mortality and morbidity rates attest the fragility of life during this period .Major cause of death in newborn period are – prematurity, septicemia, birth asphyxia and congenital malformations . Neonatal hyperbillirubinemia is not major cause of neonatal mortality but its morbidity during neonatal period and subsequently , is sufficiently severe to make its early diagnosis and timely and adequate management ,an important aspect of Preventive Paediatrics. Neonatal hyperbillirubinemia is the visible manifestation of skin and sclera of elevated serum concentration of bilirubin . this is common and in most cases benign problem in neonates .This is observed during first week of life in in approximately 60 % of term neonates and 80% of preterm Neonates ^1,2.This yellow color usually results from the accumulation of unconjugated , non polar , lipid soluble bilirubin pigment in skin and sclera

Bilirubin is produced in reticuloendothelial system by biotransformation of heme, released from hemolysing Red Blood Cells which is brought to liver and conjugated there. So all prehepatic cuases in this pathway results in unconjugated hyperbillirubinaemia. Whereas hepatic and post hepatic cuases results in conjugated hyperbillirubinaemia.

The aim of therapy for neonatal hyperbillirubinaemia is to ensure that the serum billiubin is kept at a safety level and brain damage is prevented. For above aim various preventive and supportive measures like adequate feeding, aspiration of cephalhematoma, treatment of sepsis, phenobarbitone and clofibrate being used and various measures to reduce serum billirubin like Phototherpy, exchange blood transfusion, exposure to sunlight, various drugs like agar, cholestyramin, orotic acid, tin–mesoporphyrin, albumin infusion, surgical treatment etc. effective, but phototherapy is widely accepted as relatively safe and effective method for treatment of neonatal hyperbillirubinaemia. It reduces or blunts the rise of unconjugated bilirubin levels regardless of maturity, presence or absence of haemolysis^3,4Phototherapy results in production of photoproducts which are excreted in the bile and subsequently removed in stool. It uses blue light spectrum of 450-460nm wavelength and irradiance of 6-12µw/cm²/nm. Phototherapy reduces configurationally photo- isomerization, structural–isomerization and hepatic excretion of unconjugated hyperbillirubin into the intestinal lumen. Neonates receiving phototherapy have increased insensible water loss, redistribution of blood flow, watery diarrhoea, irritability, rise in temperature, retinal damage, bronze baby syndrome, gonadal toxicity, impaired maternal-infant interaction, hypocalcaemia, riboflavin deficiency, DNA strand breakage, chromosomal mutations damage, and in few studies even thrombocytopenia.^1,2,5,7 Thrombocytopenia as a side effect of phototherapy that has not been described in the standard textbooks although many authors did try to look into this particular side effect. Maurer et al^5,6 and Pishwa et al⁷· observed in their studies that neonates exposed to phototherapy had decreased platelet counts and increased platelet turnover. This study was done with an aim to find the incidence of thrombocytopenia in neonates with indirect hyperbilirubinaemia receiving phototherapy.

role and mechanism of action of phototherapy and its effect on platelets

The first report on the use of phototherapy for treatment of neonates with jaundice was published more than 20 years ago. Since then, phototherapy has been used extensively and, along with other factors, has contributed to a considerable decline in the need for exchange transfusion in the treatment of neonatal hyperbilirubinemia. However, in certain circumstances phototherapy may be used inappropriately, which causes important medical and psychosocial problems and increases the cost of health care. Inappropriate use of this treatment suggests that its action and therapeutic aims are not well understood.

Investigations:

The following criteria may help to identify infants who require investigation or treatment

* Clinically apparent jaundice in the first 24hours of life

* Increase in total serum bilirubin concentration of more than 85 µmol/L (5 mg/100 ml) per day.

* Total serum bilirubin concentration higher than 220 µmol/L (13 mg/100 ml) within the first 4 days of life in term infants.

* Direct serum bilirubin concentration higher than 34 µmol/L (2 mg/100 ml).

* Visible jaundice lasting more than 1 week in term infants or 2 weeks in premature infants.

Phototherapy should be used only in hospitals where appropriate monitoring of bilirubin levels and basic investigations are possible. The aim of phototherapy is to prevent potentially toxic bilirubin levels and to decrease the need for exchange transfusion. There are no absolute scientific facts on which to base a decision to initiate phototherapy. Clinical jaundice per se is not an indication for its use. The decision for therapy depends on such factors as the actual bilirubin level and its rate of increase, the weight and length of gestation at birth, the postnatal age and the presence of factors that influence bilirubin-albumin binding. An otherwise healthy newborn with nonhemolytic jaundice should not receive phototherapy unless bilirubin levels are greater than 255 µmol/L (15 mg/100 ml) and rising (Appendix I).

The hematocrit or hemoglobin level must be closely followed to detect significant late anemia (hemoglobin level less than 100 g/L by 6 weeks of age). Delaying initiation of phototherapy until bilirubin levels are greater than 200 µmol/L (12 mg/100 ml) by 24 hours after birth may significantly reduce the number of infants receiving phototherapy without increasing the need for exchange transfusion. In a collaborative trial of the National Institutes of Health (NIH), however, phototherapy did not significantly change the incidence of exchange transfusion in infants weighing more than 2.5 kg who had ABO incompatibility. The use of phototherapy in ABO incompatibility does not appear to increase the risk of late anemia if the hemoglobin level was greater than 150 g/L in the initial period of life. The continued use or initiation of phototherapy after an exchange transfusion for ABO incompatibility or Rh hemolytic disease of the newborn may decrease the total number of exchange transfusions that may be required.

Mechanism of action

The radiant energy emitted by light with wavelengths ranging from 400 to 500 nm is mostly responsible for the action of phototherapy. Exposure of a newborn with jaundice to visible light in this wavelength decreases the amount of serum unconjugated bilirubin, blanches the skin and increases excretion of unconjugated bilirubin in bile. Phototherapy acts on unconjugated bilirubin, to a depth of 2 mm from the epidermis, by freeing it from collagen and lipoproteins, to which it is bound in the interstitial space. The fall in bilirubin level is proportionately greater in the skin than in the serum. The effectiveness of phototherapy is related to the area of epidermis that is exposed.⁹ Phototherapy has not been shown to have any significant direct effect on hepatic function that explains the increased extraction of unconjugated bilirubin that is found in the bile during treatment.^10-12

The bilirubin molecule can undergo many photoreactions in vitro.¹³ The most effective wavelength at which this occurs corresponds closely to that at which bilirubin absorbs light maximally (460 nm). Initially it was thought that photo-oxidation of unconjugated bilirubin occurred and produced nontoxic degradation products excretable in bile and urine.^14-16 More recent evidence indicates that light of suitable wavelength causes isomerisation of the molecule without modifying its chemical constitution.^17,18 These changes make the bilirubin molecule more hydrophilic and directly excretable in bile. The isomers have been called "photobilirubins"; they have been recovered from the bile and serum of the congenitally jaundiced Gunn rat and of newborn infants receiving phototherapy. ^19-21 The process of isomerization is rapid but unstable, so that photobilirubins quickly revert to natural bilirubin in bile. During phototherapy. Phototherapy units consist of banks of fluorescent lights or lamps with tungsten-halogen bulbs. The most effective fluorescent lights are special blue lights, followed by blue lights and white lights. The radiant energy emitted in the blue spectrum is not related to the visible brightness of the light. It is measured with a photoradiometer, which registers all energy absorbed by its detector within a predetermined wavelength.²² The energy detected from the same light source varies between photoradiometers depending on the wavelength settings and the sensitivity of their detectors.²³ The energy emitted in the therapeutic wavelength varies with the age of the light bulbs. Regular blue fluorescent lights have a relatively rapid loss of emission in the blue spectrum, with an estimated life of 350 hours.²⁴ Special blue fluorescent lightsare said to maintain 80% of their initial energy emission in this spectrum for more than 3000 hours. Standard white fluorescent lights maintain a reasonably stable energy output in this spectrum for more than 2000 hours. Overheating of phototherapy units because of poor ventilation increases the rate of loss of effectiveness. This loss can be detected only by repeated photoradiometer measurements. The radiant energy can also be affected by the number of lights used.²³ Most phototherapy units have a bank of eight fluorescent lights. Intensive phototherapy with up to 15 lights has been reported in the literature²⁵ but is not recommended for routine clinical practice since it could deliver a supratherapeutic dose of radiant energy. The amount of radiant energy received (irradiance) is inversely proportional to the square of the distance from the light source to the infant. Standard free-standing phototherapy units should be 35 to 40 cm from the infant. Phototherapy with fluorescent lamps attached to the canopy of infant radiant warmers is therefore inefficient.²⁶ Lamps with tungsten-halogen bulbs, however, provide adequate phototherapy under such conditions.²⁷Altering the distance between the light and theinfant by 1 cm leads to a change of 3% in theirradiance from a phototherapy unit with fluorescentlight. A decrease inirradiance of up to 40% occurs when a standard phototherapy unit is placed at a 450 angle to thepatient (e.g. when an infant is being nursed underan infant warmer).The amount of irradiance reaching the epidermis may be reduced by various materials interposed between the light and the patient. The acrylic plastic shield commonly found in phototherapy units with fluorescent lights is required to block out ultraviolet and infrared rays.^28,29 The shield allows more than 90% of the radiant energy between 400 and 500 nm to pass through.

Interposition of another shield, as when the newborn is in a single-wall incubator, allows 80% of the energy to pass through.^28,30 Semicircular acrylic plastic heat shields, bubble-wrap sheets and cellophane sheets used to reduce insensible water loss further decrease the irradiance by 7% to 10% . The dose-response relation between the amount of radiant energy emitted in blue light and the proportionate fall in serum bilirubin level over 24 hours of treatment is nonlinear.^24,25,31,32 A saturation point exists (10 to 12 µW/cm2 pe/ nanometre); increases in energy emitted beyond that point will not increase the rate of fall of serum bilirubin levels. Theoretically, a unit consisting of four daylight and four special blue lights will deliver this amount of irradiance.³⁴ The minimal level of irradiance required to obtain a clinically significant fall in serum bilirubin levels (4 µW/cm2/ nanometre) is delivered by a unit with eight fluorescent white lights under optimal conditions.

Although often considered innocuous, phototherapy has potential side effects. More discriminating use, especially in term infants with jaundice who are otherwise healthy, may have significant financial and psychosocial benefit. Unnecessary use of phototherapy may prolong the infant's hospital stay. The use of phototherapy at home has been reported in recent literature from the United States³³ and is in part a response to economic pressures from third-party insurers. Although information is limited, such an approach may lead to overuse of phototherapy and may avoid the question of whether phototherapy is really necessary. If phototherapy at home becomes widespread, how will standards of care be maintained? A parallel support system or extension of the hospital program may be necessary. Only a small number of infants would likely meet the criteria for home treatment. We can better meet their socioeconomic responsibilities by following more specific criteria for the use of phototherapy in hospital. A healthy newborn with moderate jaundice can be followed on an outpatient basis by means of monitoring bilirubin levels until phototherapy is indicated or the problem is resolved if appropriate laboratory support and parental cooperation are available.

The use of phototherapy often generates anxiety in the parents. It may partially isolate the infant from them and reduce their involvement in its care. A reasonable approach to minimize such potential problems is for hospitals to use phototherapy in the mother's room, where she can continue to provide most of the care for her baby under adequate guidance and supervision. Phototherapy can be interrupted for routine care without its overall efficacy being affected. Jaundice in a breast-fed infant is not in itself an indication to interrupt breast-feeding. Although such infants tend to have higher bilirubin levels than do bottle-fed infants^34,35 the values rarely reach dangerous levels. Even when phototherapy is used, breast-feeding need only be interrupted if it becomes necessary to differentiate prolonged indirect hyperbilirubinemia from a pathological process. Our present knowledge of the mode of action, dosage, efficacy and side effects of phototherapy should permit the clinician to use it with confidence.

However, new knowledge regarding bilirubin deposition and toxicity does lead to certain additional questions.

* Is the bilirubin staining of brain tissue seen in premature infants with low bilirubin levels a variant of classic kernicterus, or is it passive staining with no clinical significance?

* Recent studies have shown that the bloodbrain barrier in experimental animals can be influenced by hyperosmolality and hypercarbia, which lead to increased entry of albumin-bound bilirubin into brain tissues^36-38. Is this bilirubin complex itself toxic? Is this a mechanism of production of kernicterus in clinical situations?

* Studies in evoked potentials in term infants with hyperbilirubinemia have shown that changes in the brain stem subside when bilirubin levels decrease either spontaneously or following exchange transfusion.^39,40

Are these signs of clinical toxic effects that have long-term significance? It may be necessary to modify our approach to the treatment of newborns with jaundice and to the indications for therapy in the light of future clinical and basic research.

Phototherapy has emerged as the most widely used form of therapy for the treatment and prophylaxis of neonatal unconjugated hyperbilirubinemia. In nearly all infants, phototherapy reduces or blunts the rise of serum bilirubin concentration regardless of maturity, presence or absence of hemolysis, or degree of skin pigmentation⁴¹. Phototherapy as a modality of treatment of jaundiced babies was first introduced by Cremer et al⁴² in 1958 after her chance observation of rapid clearance of aundice in neonates exposed to sunlight in the nursery. Since then phototherapy has been used extensively and, along with other factors has contributed to a considerable decline in the need for exchange transfusion in the treatment of neonatal hyperbilirubinemia^43,44,54. Phototherapy is an effective and relatively safe method for reducing indirect bilirubin levels, particularly when initiated before serum bilirubin increase to levels associated with kernicterus⁴⁵.Animal and human studies suggest that hyperbilirubinemia and phototherapy may lead to thrombocytopenia. Maurer et al found that rabbits exposed to phototherapy had decreased platelet counts and increased platelet turnover ^46,47. Zieve and assistants described the effects of high- intensity white light on human platelets in vitro. Platelets which had been briefly exposed to light following photosensitization by hematoporphyrin lost the ability to aggregate, and released potassium, acid phosphatise, serotonin, and adenosine triphosphate. Electron photomicrographs of these altered platelets showed depletion of cytoplasmic materials and smothered membrane contours as compared to controls ^48-50 Harold Maurer observed similar kinds of platelet abnormalities within a two hour period of exposure in the absence of hematoporphyrin preconditioning. Exposed platelets would not aggregate, were depleted of adenine nucleotides and glycogen and on electron photomicrographs showed loss of glycogen granules and organelles plus ill-defined external membranes⁴⁷. This information is of concern because of reports that broad spectrum blue fluorescent light can penetrate the dermis (and other tissues) to a degree that would permit photochemical reactions to occur in sub-dermal tissues, including the vascular bed.

Maurer and Fratkin⁴⁸ studied the effects of phototherapy on platelet count in low birth weight infants and on platelet production and life span in rabbits undergoing phototherapy continuously for 96 hours. Platelet life span was shortened to a mean of 4.2 days as compared to 6 days in controls receiving no phototherapy. Platelets also emerged from marrow earlier in these animals. Second, in low birth- weight infants, the effect of 96 hours of continuous daylight phototherapy on platelets showed that in 38.7% of babies’ platelet count fall below 150000 /mm³and the lowest count was 52000/ mm³. In a study, 20 babies out of 101 neonates developed thrombocytopenia, with no relationship birth weight, gestational age or postnatal age and the incidence and/ or severity of thrombocytopenia. Since the platelet count was normal before the between inclusion of patients, there was no need for a control group. The mechanism of action of light on platelets in vivo is unknown. The in vitro data suggests that photochemical reactions occur in the platelet membrane. Whether these reactions occur in vivo remains to be determined. Shortened platelet life span may be the result of sequestration of damaged platelets in the spleen ^51-54. In a study the effect of conventional phototherapy on platelet count was studied in 101 newborns with indirect hyperbilirubinemia, out of whom 50 patients (49.5%) had decreased levels of platelets; 20 (19.8%) of the latter had a platelet count of below 100000/mm3. Decreased platelet count was maximum during the first 24 hours of phototherapy. Ultraviolet light may increase plateled turnover and injury during phototherapy by and unknown mechanism⁵⁵

MATERIALS AND METHOD:

This prospective study was conducted in the Department of Pediatrics and Department of Pathology in Netaji Subhash Chandra Bose Medical College and associated Hospital, Jabalpur, Madhya Pradesh (India) between August 2009 and August 2010; in consecutively enrolled cohort of apparently healthy neonates, who developed indirect hyperbilirubinaemia and required phototherapy irrespective of gestational age and birth weight.

The indication of phototherapy was based on IAP-NNF guidelines 2006 on level II Neonatal care : American Academy of Pediatrics 2006.⁸ . Neonates having features suggestive of haemolysis, direct hyperbilirubinaemia, sepsis, anti-platelet drugs given to baby or mother, haemangioma, and other congenital anomalies were excluded. Neonates who developed features suggestive of sepsis during phototherapy were also excluded. Neonates who fulfilled the inclusion criteria were admitted to the hospital. After a detailed history, clinical examination and baseline investigations all babies were put on continuous phototherapy.

Platelet counts were performed and mean platelet count is taken as a comparator for thrombocytopenia in correlation with gestational age, weight, income, postnatal age and mode of delivery, at admission, 48 hours, 96 hours and before discontinuing phototherapy; by automated haematology analyzer and reconfirmed by microscopy. Thrombocytopenia was defined as platelet count < 150,000/ mm3. Mild, moderate and severe thrombocytopenia were defined as platelet counts between 100,000–150,000/mm3; 50,000– 100,000/mm3; < 50,000/mm3, respectively. Neonates showing a fall of platelet count were recorded. Neonates were then divided in two groups namely group A and group B showing the presence and absence of thrombocytopenia, respectively. Various factors like levels of serum bilirubin at the onset of phototherapy and subsequently, on days 1 and 2, duration as well as the type of phototherapy and epidemiological factors such as sex, birth weight, gestational age, neonatal age; maternal factors like maternal age and parity were studied and compared .

OBSERVATION:

Table no.1 - Correlation of platelet count with mode of birth (LSCS V/s NVD)

Mode of birth		PLT 1 a	PLT 2 b	PLT 3 c	P a/b	P b/c	P a/c
LSCS I	Mean	176.25	123-13		<0.05	NA	NA
	Std. Deviation	52.145	40.602
	N	16	16
NVD II	Mean	166.13	128.38	135.00	<0.05	>0.05	<0.05
	Std. Deviation	52.696	44.116	25.166
	N	80	80	4
P I/II		>0.05	>0.05	NA

Table no.2 - Correlation of platelet count with locality ( Rural V/s Urban)

Mode of birth		PLT 1 a	PLT 2 b	PLT 3 c	P a/b	P b/c	P a/c
RURAL I	Mean	162.35	125.60	122.54	<0.05	>0.05	>0.05
	Std. Deviation	49.440	44.257
	N	57	57	2
URBAN II	Mean	175.79	130.28	120.00	<0.05	>0.05	<0.05
	Std. Deviation
	N	39	39	2
P I/II		>0.05	>0.05	0.05

Table no.3 - Correlation of platelet count with gestational age ( Preterm V/s Term )

Gestational Age in weeks		PLT 1 a	PLT 2 b	PLT 3 c	P a/b	P b/c	P a/c
<37 I	Mean	168.44	126.66	136.67	<0.05	>0.05	>0.05
	Std. Deviation	53.668	46.801	30.551
	N	71	71	3
37- 42 II	Mean	166.04	129.88	130.00	<0.05	>0.05	<0.05
	Std. Deviation	49.917	32.489	0
	N	25	25	1
P I/II		>0.05	>0.05	>0.05

Table no.4 -Correlation of platelet count with birth weight

Birth weight in kg		PLT 1 a	PLT 2 b	PLT 3 c	P a/b	P b/c	P a/c
<2.5 I	Mean	162.42	119.90	120.00	<0.05	>0.05	<0.05
	Std. Deviation	46.812	35.171	14.142
	N	60	60	2
>2.5 II	Mean	166.13	128.38	135.00	<0.05	>0.05	<0.05
	Std. Deviation	52.696	44.116	25.166
	N	36	36	2
P I/II		>0.05	<0.05	>0.05

Table no.5. - Correlation of platelet count with positive Vs. negative Antenatal/ Perinatal history.

ANH		PLT 1	PLT 2	PLT 3	P a/b	P b/c	P a/c
N	Mean	158.80	119.03	170.00	<0.05	<0.05	>0.05
	Std. Deviation	49.292	35.324	0
	N	40	40	1
Y	Mean	174.25	133.55	123.33	<0.05	>0.05	<0.05
	Std. Deviation	54.138	47.722	11.547
	N	56	56	3
P I/II		>0.05	>0.05	<0.05

Table no.6- Correlation of family income with platelet count.

fci1		PLT 1	PLT 2	PLT 3	P a/b	P b/c	P a/c
<4380	Mean	167.97	125.11	123.33	<0.05	>0.05	<0.05
	Std. Deviation	54.102	43.965	11.547
	N	70	70	3
4380-6560	Mean	177.23	142.62	170.00	>0.05	<0.05	>0.05
	Std. Deviation	55.963	45.021	0
	N	13	13	1
>6560	Mean	157.54	125.23		<0.05	-	-
	Std. Deviation	40.261	38.423
	N	13	13
	P I/II	>0.05	>0.05	<0.05
	P I/III	>0.05	>0.05	#DIV/0!
	P II/III	>0.05	>0.05	#DIV/0!

Table no.7 - Correlation of platelet count with postnatal age

		PLT 1	PLT 2	PLT 3	P a/b	P b/c	P a/c
<1	Mean	177.57	124.68	130.00	<0.05	>0.05	<0.05
	Std. Deviation	53.286	43.321	0
	N	28	28	1
1-7	Mean	160.86	125.77	140.00	<0.05	>0.05	>0.05
	Std. Deviation	48.756	36.585	42.426
	N	56	56	2
7-14	Mean	164.67	122.89	130.00	<0.05	>0.05	<0.05
	Std. Deviation	51.517	33.183	0
	N	9	9	1
>14	Mean	216.00	200.00		>0.05	-	-
	Std. Deviation	101.134	121.244
	N	3	3
	P-1/2	>0.05	>0.05	>0.05
	P-1/3	>0.05	>0.05	-
	P-1/4	>0.05	>0.05	-
	P-2/3	>0.05	>0.05	>0.05
	P-2/4	>0.05	>0.05	-
	P-3/4	>0.05	>0.05	-

RESULT:

Out of 96 neonates included in study 67(69.8 percent) were male and 29(30.2 percent) were female. At the initiation of phototherapy 35 (36.5 percent) neonates were having platelet count below 150000/cumm while after 48 hours of phototherapy 76 (79.2 percent) neonates were having platelet count below 150000/ cumm. (thrombocytopenia).Majority of neonates had mild (58.2 percent) to moderate (20.8 percent) thrombocytopenia respectively during the first 48 hours of phototherapy.

From the observation table no. 1 to 7, it is observe that mean platelet count at the time of initiation of phototherapy was seen >150000/cumm, After 48 to 96 hrs. of phototherapy the mean platelet count fell down in all babies irrespective of antenatal or perinatal history, mode of delivery, birth weight, gestational age, postnatal age of newborn, locality and in babies with income group I and III ( less than 4380, more than 6560), usually was not associated with clinical bleed.

Epidemiological Characteristics

Of the total 96 neonates under study, there were 67 males and 29 were females. Sixty neonates were having weight < 2,500 g, 71 neonates were pre-term, and 25 were full-term neonates. Onset of jaundice was maximum between in first week of postnatal age. The epidemiological characteristics in the two groups are as shown in Table 1. There was no statistically significant difference in the incidence of thrombocytopenia based on sex , gestational age , birth weight, parity and age of onset of jaundice. thrombocytopenia was seen in 76 (79.2%) cases during the first 48 hours of phototherapy. There was a steady decline in the mean platelet count in the initial 48–96 hours after administration of phototherapy.

DISCUSSION:

Neonatal jaundice is a physiological process in which bilirubin is produced in the reticuloendothelial system by biotransformation of heme released from hemolysing red blood cells. The heme ring is oxidized in reticuloendothelial cells biliverdin by microsomal enzyme heme oxygenase. During this reaction carbon monoxide and iron are released. Biliverdin is then reduce to bilirubin by enzyme bilirubin reductase^56,57.

Physiological polycythemia and shorter life span of fetal RBC’s (90 days vs. 120 days in adults) results in release of 0.15g/kg of haemoglobin everyday because 1 ml/kg (approximately 1%) of blood hemolyse everyday 1 gm. of haemoglobin yields about 35 gms. of bilirubin so that in 3 kg. infant about 15 mg of bilirubin is produced daily from haemoglobin sources. Additional 1 mg./kg. bilirubin is produced from non haemoglobin sources viz. myoglobin cytochromes and catalases thus resulting in net daily load of about 20mg of bilirubin to the liver in a healthy term infants. Hepatic uptake, conjugation and excretion of bilirubin is limited due to transient deficiency of Y and Z-acceptor proteins and UDP glucuronyl transferase enzyme in newborn babies specially those born prematurely. Because of relative lack of hepatic conjugatory enzyme, hyperbilirubinemia is mostly limited to unconjugated fraction of bilirubin during early days of life.

Phototherapy is by and large safe but several immediate and late side effects are reported. The common side effects include passage of green stools because of transient lactose intolerance and irritant effect of photocatabolites causing increased colonic secretoty losses. Hyperthermia, irritability and dehydration due to increased insensible water loss may occur. Body weight and serum osmolality should be monitored. Infants under phototherapy should receive additional (20-40 ml/kg/24hours) feeds to safeguard against dehydration and hemoconcentration. Term babies receiving phototherapy should be advised to take breast feed every 2 hourly.

There is increased risk of opening up of ductus arteriosus in preterm babies receiving phototherapy. Recently, phototherapy has been shown to increase mean cerebral blood flow velocity especially in preterm (<32 weeks) babies, hypocalcemia may occur during phototherapy due to secretiion of melotinin from pineal gland. There is controversial evidence that photo-oxidant damage to red blood cells may cause hemolysis. In some infants platelet turnover may be increased resulting in lower mean platelet counts but bleeding does not occur. There is theoretical increased risk of developing malignancy of skin in later life. Paradoxically it has been shown that intermittent phototherapy causes more damage to intracellular DNA as compared to continuous exposure to light. There is experimental evidence to suggest that exposure to light may disturb the circadian rhythem of the sex harmones thus having potential implications regarding onset of puberty and disturbances in future sex behaviour.^58-60

Correlations of S. Bilirubin with various factors

In the present study Statistical analysis revealed that the fall in S. Bilirubin both total as well as indirect did not correlate significantly with the following factors:-

Locality–Rural Vs. Urban, Positive Vs. Negative Antenatal/ perinatal history, Gestational age Preterm Vs. Term, Birth weight <2.5kg Vs. ≥2.5kg, Family income (socioeconomic status), Mode of birth LSCS Vs. vaginally delivered baby and Postnatal age of the baby upto 28 days.

In accordance with the observations of the present study were, the findings of Tan et. al. the nature and dose response relationship of phototherapy for neonatal hyperbilirubinemia too did not revealed any significant correlation with various factors mentioned above²⁵. In another study advances in the diagnosis and treatment of hyperbilirubinemia by Yao et. al too endorsed the observations of the present study⁵⁹. Another research work on phototherapy effects and complications by KJ et. Al reported a significant fall in s. bilirubin after 24 hours of phototherapy⁶¹. A study by Susan et. al showed that continouos phototherapy causes more rapid decline in s. bilirubin than intermittent phototherapy⁵⁹. In an another reareach work on phototherapy Lawrence et. al suggested that phototherapy reduces bound fraction of s. bilirubin⁵⁷.

Keeping with the scientific reasons in the text books the observations of the present as well as other studies possibly explains the insignificant correlations between the s. bilirubin levels and the associated variants discussed above^57,58.

Correlation of Platelet count with various factors:

After 48 to 96 hrs. of phototherapy the platelet count fell down in all babies irrespective of antenatal or perinatal history, mode of delivery, birth weight, gestational age , postnatal age of newborn, locality and in babies with income group I and III (less than 4380, more than 6560). In accordance with present study M. D. Paulette et. al reported a fall in platelet count was observed after phototherapy⁶². a study by Maurer et. al showed that phototherapy increases rate of platelet turnover and when bone marrow compensation is inadequate platelet count falls down. Similar were the statements made by Zieve et. al that phototherapy causes alteration of platelet morphology and thus causes destruction of platelet(1966)^49,50. Maurer and HM Haggins also suggested that platelet injury caused by phototherapy and resulting into thrombocytopenia⁴⁷. They also showed phototherapy causes decreased platelet production and life span (1976)⁴⁶.In contrast to the present study Sakha et. al hypothesizes that phototherapy increase the release of platelet from bone marrow with sufficient platelet storage and so then causes increase in platelet count in peripheral blood.

CONCLUSION:

To conclude, this study establishes an association of phototherapy as a cause of thrombocytopenia in hyperbilirubinaemic neonates. Though the incidence of thrombocytopenia is substantial, yet it is clinically insignificant. This study helps the practitioner to be aware of this association and avoid unnecessary investigations, as thrombocytopenia was transient.

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8. 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. Erratum in: Pediatrics 2004; 114:1138.

9. Rubaltelli FF, Zanardo V, Granati B: Effect of various phototherapy regimens on bilirubin decrement. Pediatrics 1978; 61: 838-841.

10. Hegyi T, Brantley V, Hiatt IM: The effects of shielding the hepatic area on the clinical response to phototherapy. Eur. Pediatr 1981; 137: 303-305

11. Tan KL, Jacob E, Chua KS et al: Phototherapy and neonatal liver function. Biol Neonate 1979; 36: 128-132

12. Lund HT, Jacobsen J: Influence of phototherapy on the biliary excretion pattern in newborn infants with hyperbilirubinemia. J Pediatr 1974; 85: 262-267

13. Ostrow JD: Mechanisms of bilirubin photodegradation. Sernin Henmatol 1972; 9: 113-125

14. Silverberg D, Johnson L: Photodegradation products of bilirubin in myelinating cerebellum cultures. Birth Defects

15. Diamond IF: Studies on the neurotoxicity of bilirubin and distribution of its derivatives. Ibid: 124

16. Thaler M: Toxic effects of bilirubin and its photo-decomposition products. Ibid: 128

17. Cohen AN, Ostrow JD: New concepts in phototherapy: photoisomerization of bilirubin IX alpha and potential toxic effects of light. Pediatrics 1980; 65: 740-750

18. McDonagh AF, Lightner DA: Bilirubin, jaundice and phototherapy. Pediatrics 1985; 75: 443-455

19. Costarino AJ, Ennever JF, Baumgart S et al: Bilirubin photoisomerization in premature neonates under low and high-dose phototherapy. Ibid: 519-522

20. Onishi S, Isobe K, Itoh S et al: Demonstration of geometric isomer of bilirubin IX alpha in the serum of a hyperbilirubinemic newborn infant and the mechanism of jaundice phototherapy. Biochem J 1980; 190: 533-536

21. Lamola AA, Blumberg WE, McClead K et al: Photoisomerized bilirubin in blood from infants receiving phototherapy. Proc Natl Acad Sci USA 1981; 78: 1882-1886

22. Behrman RE, Brown AK, Currie MR et al: Preliminary report of the committee on phototherapy in the newborn infant. J Pediatr 1974; 84: 135-147

23. Hammerman C, Eidelman Al, Lee KS et al: Comparative measurements of phototherapy. A practical guide. Pediatrics 1981; 67: 368-372

24. Sisson TR, Kendall N, Shaw E et al: Phototherapy ofjaundice in the newborn infant: 2. Effect of various light intensities. J Pediatr 1972; 81: 35-38

25. Tan KL: The pattern of bilirubin response to phototherapy for neonatal hyperbilirubinemia. Pediatr Res 1982; 16: 670-674

26. Bonta BW, Warshaw JB: Importance of radiant flux in the treatment of hyperbilirubinemia: failure of overhead phototherapy units in intensive care units. Pediatrics 1976; 57:502-505

27. Warshaw JB, Gagliardi J, Patel A: A comparison of fluorescent and non-fluorescent light sources for phototherapy. Pediatrics 1980; 65: 795-798

28. Wu PYK, Berdahl M: Irradiance in incubators under phototherapy lamps. J Pediatr 1974; 84: 754-755

29. Elder PL: Comment: Hazard of ultraviolet radiation from fluorescent lamps to infant during phototherapy. Ibid: 145

30. Yasunaga S, Kean EH: The effect of Plexiglas incubatorson phototherapy. J Pediatr 1972; 81: 89-90

31. Tan KL: The nature of the dose-response relationship of phototherapy for neonatal hyperbilirubinemia. J Pediatr1977; 90: 448-452

32. Mims LC, Estrada M, Gooden DS et al: Phototherapy for neonatal hyperbilirubinemia -A dose: response relationship. J Pediatr 1973; 83: 658-662

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36. Levine RL, Fredericks WR, Rapaport SI: Entry of bilirubin into the brain due to opening of the blood-brain barrier. Pediatrics 1982; 69: 255-259

37. Bratlid D, Cashore WJ, Oh W: Effect of serum hyperosmolality on opening of blood-brain barrier for bilirubin in rat brain. Pediatrics 1983; 71: 909-912

38. Idem: Effect of acidosis on bilirubin deposition in rat brain. Pediatrics 1984; 73: 431-434

39. Perlman M, Fainmesser P, Sohmer H et al: Auditory nerve-brain stem evoked responses in hyperbilirubinemic neonates. Pediatrics 1983; 72: 658-664

40. Nwaesei CJ, Van Aerde J, Boyden M et al: Changes in auditory brain stem responses in hyperbilirubinemic infants before and after . Pediatrics 1984; 74: 800-803

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43. Govil Y. C., Mishra P.K., Malik G.K., Kaul R : Current concepts in the mechanism of phototherapy. Indian J. Ped. 51:49-52, 1984.

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45. Richard E., Behram M.D. et al, In : Nelson essentials of paediatrics. Fetal and neonatal medicin. 192-195; 1994.

46. Maurer H.M., Fratkin M.M., Mc Williams NB., Kirkpatric B., Draper D., Haggins JC., and Hunteer CR: Effects of phototherapy on platelet count in low birth weight infants and on platelet production and life span in rabbits. Pediatrics 57: 506, 1976.

47. Murer H.M., Haggins JC., and Still WJ: Platelet injury during phototherapy. Am. J. Hematol. 1:89, 1976.

48. Luccy JF. Ferriro M. Hewitt Y : prevention of hyperbilirubinemia of prematurity by phototherapy Pediatrics: 41: 1047, 1968.

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50. Zieve PD., Solomon HM.: The effect of hematoporphyrin and light on human platelets: III, Release of Potassium and acid phosphatise. J. Cell physio : 681-6, 1966.

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52. Sussib TRC., Slaven B., Hamilton P: The effect of broad and narrow spectrum fluorescent light on blood constituents. Birth Defects. 1976, Vol. 12.

53. Rubaltelli FF., Allegri G., Costa C., De Antoni A : Urinary excretion of tryptophan metabolites during phototherapy. J Pediat. 85 : 865, 1974.

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58. Levine RL, Fredericks WR and Rapport SI. Entry of bilirubin into the brain due to opening of blood brain barrier. Pediatrics 1982,69 :

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62. M.D. Paulette Mehta a (Gainsville, Fla. USA), M.D. Rohitkumar Vasa b and M.D. Lois Neumannb (New York University School of Medicine, Department of Pediatrics. New York, N.Y. USA), M.D. Margaret Karpatkinb

Received on 05.02.2015 Modified on 22.03.2015

Asian J. Research Chem 8(4): April 2015; Page 221-230

DOI: 10.5958/0974-4150.2015.00039.5