Continuous Phototherapy Research Articles

Oxygen consumption and resting energy expenditure during phototherapy in full term and preterm newborn infants

OBJECTIVESTo determine the effect of phototherapy on the oxygen consumption and resting energy expenditure of term and preterm newborn infants.METHODSA total of 202 infants (gestation 30–42 weeks; body weight 1270–4100...

Antioxidant defense systems in newborns undergoing phototherapy.

This paper was designed to investigate whether phototherapy is an oxidative stress in newborn infants undergoing phototherapy. A day-light continuous phototherapy was given to jaundiced 20 term and 16 preterm newborns for 72 hours. We measured serum vitamin E and the activities of red blood cell anti-oxidation enzymes (superoxide dismutase, catalase and glutathione peroxidase) before and after 72 h of phototherapy. Serum vitamin E levels were not different before and after 72 h of phototherapy in both preterm and term infants. In several studies, antioxidant enzyme activities have been shown to increase in response to oxidative stresses. In this study, however, the antioxidant enzyme activities in the hemolysate were similar before and at the end of the phototherapy in both preterm and full term. In conclusion, the results of our in vivo study do not confirm the thesis that phototherapy is an oxidative stress in newborn infants. Therefore, phototherapy would preferably seem to be safe and efficient method of treatment for all neonates presenting with hyperbilirubinemia.

Testicular changes in newborn rats exposed to phototherapy.

In this study we investigated the long-term effects of 72-h continuous phototherapy on the reproductive system of newborn rats. The animals' weight, fertilization rates, and number of newborn and histopathological changes in the gonads in a normal group not exposed to phototherapy and in the test animals were compared. At the age of 24 weeks there were no significant differences between the two groups, apart from the histology of the testicles of the male rats who were exposed to the phototherapy. The study group showed a significantly reduced diameter of the seminiferous tubules when compared to the controls (P < 0.001). It can be postulated that phototherapy may cause histological degenerative changes in the structure of the rat's testes, even though there were no changes in fertilization rates. Further studies are necessary to reveal the effects of phototherapy on humans and to determine the effects, if any, on fertility.

Sister chromatid exchange in Chinese newborn infants treated with phototherapy for more than five days.

The frequency of sister chromatid exchange (SCE) was determined in newborn infants given phototherapy for more than five days, then determined again one year later. There were 8 healthy newborn infants and 15 icterus infants; 8 of these were treated with phototherapy for more than 5 days and the other 7 were not. In the follow-up study, 6 treated infants were evaluated. The results revealed that there was an increase in mean SCE frequency of peripheral lymphocytes after phototherapy, which reversed itself one year after treatment discontinuation. Prolonged continuous phototherapy may be responsible for the increase observed in SCEs in Chinese newborn.

Cholestatic pruritus: effect of phototherapy on pruritus and excretion of bile acids in urine

Pruritus associated with hepatic cholestasis may cause significant morbidity and its correlation to retention of bile acids in skin is inconsistent. Available treatment modalities are only partially effective and can have several adverse effects. Phototherapy has recently been reported to improve cholestatic pruritus, but has not been evaluated previously in children, and its mechanism is still unclear. We report the outcome of multiple Daylite phototherapy treatments over two years in a seven-year-old child with chronic hepatic cholestasis that was resistant to other therapeutic modalities. Bile acid levels in urine were used as markers of effectiveness in parallel with clinical response. Night phototherapy alone increased the bile acids/creatinine ratio in urine from 1.54 +/- 0.04 mumol/mg at baseline to 2.07 +/- 0.29 mumol/mg. Continuous phototherapy combined with night diuresis raised the ratio further to 2.28 +/- 0.55 mumol/mg. Night diuresis alone had no effect. Continuous phototherapy combined with night diuresis raised the bile acids/creatinine ratio by 44% on the first day and by 61% on the second day, but declined to baseline on the third day of treatment. A marked clinical improvement was noted for one week following two days of phototherapy. This schedule has been repeatedly effective in improving pruritus for approximately one year and may be due to the ability of phototherapy to enhance excretion of bile acids and other possible pruritogens into urine.

Sister chromatid exchanges in peripheral lymphocytes in newborns treated with phototherapy and vitamin E.

A study was undertaken to determine whether blue fluorescent light might affect the sister chromatid exchange (SCE) frequency of peripheral lymphocytes in icteric newborns undergoing continuous phototherapy treatment (72 h). Also, the potential preventive effect of vitamin E on SCE frequency was studied in a subgroup of 11 preterm and 9 fullterm newborns after daily administration of vitamin E (46.44 mumol/kg/d, im). The results revealed that only the preterm icteric newborns showed an increase in mean SCE frequency of peripheral lymphocytes after phototherapy (9%, p = 0.02), but in no case did the highest SCEs/cell ratio exceed the normal values. No correlation was found between the average SCE rate and birth weight, gestational age or bilirubin levels. Also, no difference in SCEs was observed between newborns treated or untreated with vitamin E.

Initial Response of Serum Bilirubin Levels to Phototherapy

We demonstrated the phenomenon of transiently increasing total serum bilirubin within 4 h of phototherapy. We attempted to resolve the mechanism of this phenomenon in 29 hyperbilirubinemic full-term newborn infants who received continuous phototherapy for 24 h. Our present study suggests that this phenomenon may in part be bilirubin load (photobilirubin, photoisomers) from skin and subcutaneous bilirubin and/or peripheral capillary wall bilirubin into the blood stream pool, rather than delayed clearance of bilirubin and photoisomers from the blood stream to bile or urine. Further study is needed to determine these bilirubin compounds for safe and more effective phototherapy.

Effect of phototherapy on plasma levels of GH, LH and FSH in the newborn

Plasma levels of GH, LH and FSH were measured in 74 three-day-old newborn infants with hyperbilirubinemia before and after exposure to continuous phototherapy (PhT) for 48 h. The results obtained were compared with data observed over the same period of time in 46 newborn infants belonging to the control group having homogeneous characteristics as far as form of delivery (spontaneous), gestation age, chronological age, sex, birth weight and basal blood glucose were concerned, except hyperbilirubinemia and necessity of PhT. Hyperbilirubinemic female newborn showed higher plasma GH concentrations in comparison with hyperbilirubinemic males and with controls. Forty-eight of continuous PhT significantly reduced GH levels which, however, appeared not to be substantially different from those of normal controls of the same age. Moreover, PhT determined a slight trend to increase in FSH of females, and did not modify the physiological decline of LH in both sexes during the first five days of life. The reduction of GH following PhT from abnormal to physiological concentrations may be due to the direct effect of light and/or to continuous light-related disorders of sleep. In conclusion, 48 h of continuous exposure to light (PhT) do not impair the newborn's pituitary functions here studied.

Osmotic fragility of erythrocytes in newborn infants treated by phototherapy.

In order to determine the in vivo effect of phototherapy on the erythrocytes' osmotic fragility, we have tested 10 preterm infants treated by continuous phototherapy, for jaundice of prematurity. Heparinized blood was obtained daily, starting before the initiation of phototherapy and ending 24 h after stopping the treatment. The osmotic fragility was tested in duplicate immediately, after 1 h incubation at 40 degrees C and after 24 h incubation at 4 degrees C in darkness. The erythrocytes of the preterm infant during and at the end of phototherapy showed a normal osmotic fragility pattern. Comparing the consecutive curves in each infant did not show any population of osmotically differing erythrocytes. Heating or cooling the erythrocytes did not alter these results. It is concluded that phototherapy does not increase the in vivo osmotic fragility of erythrocytes in newborn.

Phototherapy--a modified approach.

Continuous and intermittent (6 h-on and 6 h-off) phototherapy was given to the two closely matched groups of 18 and 22 newborns with hyperbilirubinemia, respectively. The percent fall of plasma bilirubin for each 24 h on first, second, third and fourth day of phototherapy was 7.55 percent (S.E. 3.18) 14.66 percent (S.E.2.26), 10.99 percent (S.E.2.97) and 14.55 percent (S.E.3.58) respectively in continuous phototherapy. The corresponding figures for intermittent phototherapy were 7.6 percent (S.E.3.94), 12.75 percent (S.E.1.53), 10.36 percent (S.E.2.51) and 13.39 percent (S.E.2.21). The differences were statistically insignificant (p>0.5). The total duration of photoexposure was 40.36 h (S.E.3.66) in the intermittent phototherapy group cs compared to 76 h (S.E.7.82) in the continuous phototherapy (p<0.001). In view of the concern which has been raised regarding the possible long term side effects of phototherapy, intermittent phototherapy offers an attractive therapeutic alternative by reducing the duration of light exposure to about half without decreasing the efficacy.

Effect of phototherapy on plasma 25(OH)-vitamin D in neonates.

The possibility that phototherapy may increase plasma levels of 25(OH)-vitamin D was assessed by measuring levels before and after 48 h continuous phototherapy using a standard phototherapy unit (Vickers, Basingstoke , England). There was no significant increase in plasma 25(OH)-vitamin D after 48 h phototherapy and it is concluded that such treatment does not stimulate photobiosynthesis of vitamin D.

Effect of jaundice phototherapy on intestinal mucosal bilirubin concentration and lactase activity in the congenitally jaundiced Gunn Rat.

The effect of phototherapy on intestinal mucosal bilirubin concentration and lactase activity in the Gunn rat was studied. Ten groups of six or seven animals each were studied. Heterozygous (Jj) and homozygous (jj) animals were given 24, 48, or 72 hr of continuous phototherapy, and Jj and jj animals were given 24- and 48-hr sham control treatments. Phototherapy reduced serum bilirubin concentration by 53% at 24 hr, 59% at 48 hr and 68% at 72 hr. The mucosal concentration of bilirubin appeared to parallel the declining serum concentration and was lower in treated than in control jj animals. The jejunal and ileal lactase activity, expressed per mg protein, was not depressed by phototherapy. The lactase activity of jejunum and of ileum of treated jj as compared to treated Jj and control jj at 24 and 48 hr and as compared to treated Jj at 72 hr was never reduced; i.e., jejunal lactase activity in jj treated for 72 hr was 15.1 +/- 4.2 (-x +/- S.D.) units/g protein as compared to 16.2 +/- 4.2 for Jj treated for 72 hr and 12.0 +/- 4.2 for jj 48-hr control animals. The ratio of lactase to sucrase activity demonstrated a significant increase in lactase activity relative to sucrase in all animals treated for 48 or 72 hr. This latter effect is potentially due to alteration in the circadian rhythm while under constant irradiance. These data convincingly demonstrate that the Gunn rat does not develop lactase deficiency consequent to phototherapy.

Bilirubin dynamics in the Gunn rat. Dose response of intermittent and continuous phototherapy.

Jaundiced Gunn rats underwent continuous and intermittent phototherapy with white and blue lights. Irradiances ranged from 0.088 to 1.4 mW/cm2 in the blue (415-465 nm) wavelengths. Changes in serum bilirubin concentration were analyzed by a single exponential model. Dose-response curves for 10 days of phototherapy indicated similar logarithmic relationships between light dose and serum bilirubin decline for intermittent and continuous blue light and continuous white light phototherapy. The dose-response curve for intermittent white light showed a low slope and correlation coefficient.

Intracellular deoxyribonucleic acid-modifying activity of intermittent phototherapy

Phototherapy is capable of damaging the genetic material of eukaryotic and prokaryotic cells at fluences considerably less than that received by irradiated infants. It has been suggested that intermittent phototherapy, with varying on-off cycles, may offer theoretical advantages since the total light dosage received by the exposed infant is reduced. The present study was undertaken to determine the effect of intermittent phototherapy on the genetic material of human cells in tissue culture. Intermittent illumination produced more DNA damage than a similar light dosage administered continuously. These results suggest that intermittent phototherapy regimens may prove more deleterious to irradiated infants than continuous phototherapy.

Effect of Various Phototherapy Regimens on Bilirubin Decrement

Continuous phototherapy in full-term newborns was found to be more effective than intermittent illumination. Treatment efficacy was also related to age and the initial bilirubin level of the infants. In fact, the reported data indicate an increased therapeutic effect in newborns affected with nonhemolytic hyperbilirubinemia who had an initial bilirubin level greater than 15 mg/dl as compared to neonates with an initial bilirubin level less than 15 mg/dl. The light treatment was also more effective in infants older than 3 days, possibly because of an increased ligandin and conjugating capacity. Shielding the hepatic area during illumination significantly decreases the efficiency of this treatment, suggesting that the liver could also be a phototherapeutic action site.

Effect of intermittent phototherapy on bilirubin dynamics in Gunn rats.

To determine whether continuous phototherapy is necessary to control neonatal jaundice, groups of jaundiced (Gunn) rats were exposed to four blue light regimens: continuous light, 30 min light/30 min dark, 6 min light/6 min dark, and 6 min light/18 min dark. An exponential decrease in serum bilirubin concentration (SBC) was found with all regimens. A logarithmic dose response curve was obtained with a 50% light dose exhibiting 75% efficacy, and a 25% light dose exhibiting 59% efficacy compared to continuous phototherapy. The time constants of the decrease in serum bilirubin concentration also varied logarithmically with doses with continuous therapy having a time constant of 1.4 days, and 6 min light/18 min dark therapy having a time constant of 3 days.

CONTROLLED TRIAL OF INTERMITTENT PHOTOTHERAPY IN THE TREATMENT OF JAUNDICE OF THE PREMATURE INFANT

Because of the potential hazards of phototherapy, we have explored the feasibility of reducing total light dosage without impairing effectiveness. We have compared intermittent and continuous phototherapy in treating nonhemolytic “physiological” hyperbilirubinemia. Premature infants (n=76) weighing between 1200-2400 gm whose serum bilirubin concentration (SBC) exceeded 8 mg/dl within the first 3 days of life were included in the study. Patients were randomly assigned to one of four treatment groups: (a) continuous light (control, n=26), (b) 15 minutes light on, 15 minutes light off (n=16), (c) 15 min. on, 30 min. off (n=17),(d) 15 min. on, 60 min. off (n=17). Phototherapy was discontinued when the S.B.C. was 8 mg/dl or lets on two consecutive measurements. The total light dosage received by the study groups was (b) 49%, (c) 42%, (d) 28% of the exposure of control (a) infants. There was no statistically significant difference between the study groups and the control in the duration of phototherapy, the peak S.B.C. arid the time from the start of therapy to the peak value. There were no significant differences in the number of infants in each group whose peak S.B.C. exceeded 10 mg/dl and 12 mg/dl. Thus, intermittent phototherapy with the described time schedules (resulting in a reduction of total light dosage of up to 72%) is as effective as continuous phototherapy in the treatment of hyperbilirubinemia in the premature infant.

Long-term effect of phototherapy on visual function

Computer-averaged electroretinogram records were used to examine scotopic retinal functioning of a group of 4-year-old children who were treated for neonatal hyperbilirubinemia by exposure to at least 42 consecutive hours of continuous phototherapy. Dark adaptation functions of the children were similar to those previously found for control subjects, suggesting that no permanent damage to rod function had been incurred during exposure. Statistical analysis showed no significant differences in the final electroretinographic amplitudes of light-treated and control subjects. Ophthalmologic and neurologic examinations were also negative.

The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin.

The role of high serum and tissue levels of unconjegated bilirubin in the pathogenesis of the impaired urinary concentrating ability was investigated in homozygous (jj) Gunn rats with the congenital absence of hepatic glucuronyl transferase. Continuous phototherapy with blue fluorescent lights at a wave length of 460 nm or oral cholestyramine feeding or both reduced serum levels of unconjugated hilirubin to levels consistently below 3.0 mg/100 ml for several weeks in both weanling and adult jj Gunn rats. The renal concentrating defect was already present in weanling jj Gunn rats by 21 days of age. In treated weanling jj animals, maximum concentrating ability and the concentration of urea and nonurea solutes in the papilla and medulla, determined after 24 h of fluid deprivation, were normal when compared to unaffected heterozygous (Jj) littermates. Solute-free water reabsorption which is reduced in jaundiced jj Gunn rats was restored to normal in treated weanling jj rats. The tissue concentration of unconjugated bilirubin was reduced throughout the papilla and inner and outer medulla in the treated jj rats in comparison with untreated jj littermates. The defect in urinary concentrating ability was only partially reversible and sometimes irreversible in adult jj rats, probably because of permanent renal parenchymal damage occurring secondary to massive crystalline deposits in the papilla and medulla. It is concluded that unconjugated bilirubin is directly involved in the pathogenesis of the concentrating defect in jaundiced jj Gunn rats.

Effect of phototherapy in preterm infants on growth in the neonatal period

A total of 120 preterm infants were randomly divided at 24 hr of age into three groups: Group I, controls; Group II, continuous phototherapy for 5 days; and Group III, intermittent phototherapy (12 hr on and 12 hr off) for 5 days. At the end of week 1 80% of the control group regained and surpassed their birth weight as opposed to 44 and 57.6% in the continuous and intermittent phototherapy groups, respectively. In weeks 2 and 3 both phototherapy groups had greater weight gain than the control group. Similar but less marked differences were observed in body lenth and head circumference in the three groups. Data suggest decreased growth during phototherapy with subsequent catch-up in growth during weeks 2 and 3. Differences were less marked between infants on intermittent (rather than continuous) phototherapy and controls. Increased metabolic demands and decreased intestinal absorption during phototherapy may be two of the factors responsible for the observed differences in growth in the three groups.