Double versus single intensive phototherapy with LEDs in treatment of neonatal hyperbilirubinemia.

OBJECTIVE: We investigate whether double phototherapy reduces total serum bilirubin concentration faster than single light during intensive phototherapy with high levels of irradiance using light-emitting diodes. STUDY DESIGN: Eighty-three infants with gestational age ⩾33 weeks and uncomplicated hyperbilirubinemia were randomized to either double (n=41) or single phototherapy (n=42) for 24 h. The mean irradiance was 64.8 µW cm-2 nm-1 from above and 39 µW cm-2 nm-1 from below. RESULTS: The percentage decreases of total serum bilirubin after 12 h of double vs single phototherapy were (mean (95% confidence interval (CI))) 39% (37 to 42) vs 30% (27 to 32), respectively (P<0.001). After 24 h, the decreases were 58% (56 to 61) vs 47% (44 to 50), respectively (P<0.001). The results were still significant after adjustment for confounding. The only side effect was loose stools. CONCLUSION: Even with intensive phototherapy increasing spectral power by increasing the irradiated body surface area, the efficacy of phototherapy is improved.

Effect of infants' position on serum bilirubin level during conventional phototherapy.

AIM: To compare the decrease in total serum bilirubin (TSB) concentration during conventional phototherapy in infants treated in supine position exclusively versus infants alternated between exposure in supine and prone position every third hour. Moreover, to survey current practice patterns in two Scandinavian countries as far as alternating exposure. METHODS: A total of 112 infants with non-haemolytic hyperbilirubinaemia, but otherwise healthy, and a gestational age > or =33 weeks were randomized to one of the treatment groups. All infants received phototherapy for 24 h. TSB was measured at start of phototherapy and after 12 and 24 h of treatment. Questionnaires about routines for position changes in infants during phototherapy were sent to all 41 neonatal departments in Denmark and Norway. RESULTS: No statistically significant differences in the decrease in TSB were observed between the two treatment groups: at 12 h of therapy, TSB decreased 32% in both groups and at 24 h 49% and 50%, respectively. In two-thirds of Danish and Norwegian departments, the infants were routinely turned during phototherapy, most often every third hours. CONCLUSION: The decrease in TSB was not significantly associated with positioning of the infant during conventional phototherapy. Alternating exposure is widely practiced in Scandinavia but is unnecessary.

Phototherapy with turquoise versus blue light.

Preterm jaundiced infants were treated by phototherapy with a new turquoise fluorescent lamp. This was more effective in reducing plasma total bilirubin in relation to light irradiance than the ubiquitously used blue fluorescent lamp.

Weekly oral vitamin K prophylaxis in Denmark.

AIM: To evaluate oral vitamin K prophylaxis at birth by giving 2 mg phytomenadione, followed by weekly oral vitamin K prophylaxis; 1 mg was administered by the parents until 3 mo of age. METHODS: A total of 507850 live babies were born in Denmark during the study period, November 1992 to June 2000. Of these infants, 78% and 22% received oral and intra-muscular prophylaxis, respectively; i.e. about 396000 neonates received oral prophylaxis at birth. Weekly oral prophylaxis was recommended for all infants as long as they were mainly breastfed. A survey of possible cases of vitamin K deficiency bleeding (VKDB) was carried out by repeated questionnaires to all Danish paediatric departments and by checking the National Patient Register. RESULTS: No cases of VKDB were revealed, i.e. the incidence was 0-0.9:100000 (95% CI). The questionnaires were used to evaluate compliance with the regimen. Parents of 274 infants participated. A dose of vitamin K was regarded as having been given if the infant received a drop of vitamin K or was mostly formula-fed that week, and the prophylaxis was regarded as completed if the infant had received at least 9 doses. Compliance was good, with 94% of the infants completing the course of prophylaxis. CONCLUSION: Weekly oral vitamin K supplementation during the first 3 mo of life was an efficient prophylaxis against VKBD. Parental compliance with the regimen was good.

A new transcutaneous bilirubinometer, BiliCheck, used in the neonatal intensive care unit and the maternity ward.

UNLABELLED: Transcutaneous bilirubin (TcB) was measured with a new bilirubinometer, BiliCheck, in 261 jaundiced infants in the neonatal intensive care unit (NICU) [gestational age (GA) 25-43 wk] (group 1) and in 227 healthy jaundiced term and near-term infants (GA 35-43 wk) (group 2). Imprecision of a single determination of TcB measured on the forehead [TcB(h)], expressed as 1 standard deviation, was 15-18 micromol l(-1). No statistically significant difference between intraoperator and interoperator imprecision was found. There was a good correlation between TcB(h) and total serum bilirubin (TSB) in both groups of infants, although TcB(h) was on average lower than TSB. In the NICU infants, TcB(h), other things being equal, was lower in males than in females, and decreased with increasing postnatal age, for the same TSB level. In the infants in both groups who had a GA > or = 35 wk, sick infants had a higher TcB(h) than healthy infants for the same TSB level. The differences were statistically significant, but small and of minor clinical significance. Blood haemoglobin concentration, GA and ethnic origin were not found to influence TcB(h), i.e. BiliCheck corrects sufficiently for these factors. In all 488 infants, TcB was measured at four different body sites. Measurements on the forehead and sternum [TcB(s)] correlated well with TSB, while measurements on the knee and foot correlated less well. In the NICU infants TcB(h) predicted TSB statistically significantly better than TcB(s), while in the healthy term and near-term infants TcB(h) and TcB(s) predicted TSB equally well. Therefore, the preferable body site for measurement of TcB under routine conditions is the forehead. By retrospective analysis of the data, a screening model is presented whereby TcB(h) can be used to screen infants who require phototherapy. We found that using screening limits for TcB(h), which are 70% of the currently used phototherapy limits for TSB, 80% of blood samples in healthy term and near-term infants, and 42% of NICU infants with GA > or = 32 wk, could be avoided. CONCLUSION: BiliCheck is suitable for screening both NICU and healthy newborn infants with jaundice, with regard to the need for phototherapy. The authors recommend using a TcB(h) limit which is 70% of the currently recommended TSB limits for phototherapy, to decide whether TSB needs to be measured.

Recurrence of kernicterus in term and near-term infants in Denmark.

UNLABELLED: Classical acute bilirubin encephalopathy (kernicterus) in term and near-term infants had not been seen in Denmark for at least 20 y until 1994. From 1994 to 1998. however, six cases were diagnosed. Aetiology of the hyperbilirubinaemia was known in two infants; spherocytosis and galactosaemia, most likely known in two infants; possible A-O blood type immunization, and unknown in two infants. However, one of these last-mentioned infants had a gestational age of only 36 wk. The maximum plasma total bilirubin concentrations were 531-745 micromol/L. The increase in the number of cases of kernicterus was considered to have been caused by: (i) a decreased awareness of the pathological signs, (ii) a change in the assessment of the risk of bilirubin encephalopathy, (iii) early discharge of the infants from the maternity ward, (iv) so-called breastfeeding-associated jaundice, (v) demonstration of bilirubin being an antioxidant, and (vi) difficulty in estimating the degree of jaundice in certain groups of immigrants. Accordingly, for prevention: (a) Attempt to change the healthcare workers' understanding of the risk of bilirubin encephalopathy, (b) give further instructions, both orally and in writing, to mothers before discharge from the maternity ward, (c) be more liberal in giving infant formula supplements, (d) conduct home visits by the community nurse at an earlier stage, (e) follow authorized guidelines for phototherapy and exchange transfusion, (f) lower plasma bilirubin concentration limits as an indication for phototherapy and exchange transfusion, (g) screen all term and near-term infants, and (h) measure the skin's yellow colour with a device that corrects for the skin's melanin content. CONCLUSIONS: Audit of the six cases presented indicates that measures are necessary in both the primary and secondary healthcare sectors if the risk of kemicterus is to be avoided. Screening may be considered, but in order to identify the problems it would first be reasonable to perform a larger prospective study in which audit is performed on all newborn infants, born at term and near-term, who develop a plasma bilirubin concentration above the exchange transfusion limit.

[Phototherapy of newborn infants]. / Lysbehandling af nyfødte børn.

The effect of light treatment on neonates with jaundice was discovered in 1958. Since then, many hundred thousand infants have been treated with light. The presumed mechanism of effect is photo-excitation of bilirubin extravascularly in the skin with the formation of bilirubin isomers which can be excreted in unconjugated form in the bile and photo-oxidation products which can be excreted in the urine. The quantitative relationships have only been partially elucidated. Blue light is the most effective. Green light causes lowering of bilirubin but, on the basis of present knowledge, there is no basis to recommend this as ye. Intermittent phototherapy has limited distribution. If intensive phototherapy is required, double light is effective. No long-term side effects of light treatment have been observed but, during treatment, side effects in the form of diarrhoea, drowsiness and transient exanthemata may occur.

Low reserve albumin for binding of bilirubin in neonates with deficiency of bilirubin excretion and bronze baby syndrome.

The plasma reserve albumin concentration for binding of bilirubin was found to be low in four newborn infants with deficiency of bilirubin excretion, of whom two had the bronze baby syndrome. Thus, the risk of bilirubin encephalopathy was increased. Also the ratio of binding fraction of albumin, i.e. unconjugated bilirubin plus reserve albumin, to total albumin was low. Possible causes of the low reserve albumin concentration and the ratio are discussed.

Comparison between two preparations of human serum albumin in treatment of neonatal hyperbilirubinaemia.

Thirty-six newborn infants with normal birth weights and with uncomplicated hyperbilirubinaemia, treated with light, were studied. At onset of phototherapy the infants received intravenously 1 g human serum albumin (HSA) per kg body weight as a 9% solution. Two different preparations of HAS were used and compared. One of these, HSAI, contained sodium caprylate and N-acetyltryptophan, 5 mmol/l of each, as stabilizers. HSAII contained only caprylate, 5 mmol/l. Nineteen infants received HSAI and seventeen infants HSAII. The reserve albumin for binding of bilirubin, measured by the [14C] MADDS method, was low in both preparations in vitro. During the infusion, the serum concentrations of albumin and reserve albumin increased and the serum unconjugated bilirubin concentration decreased, resulting in a fall in the index of plasma bilirubin toxicity in all infants. After completion of the infusion, the serum concentrations of albumin and reserve albumin declined, and a slight rise in index occurred. The increase in the serum reserve albumin concentration was markedly higher during infusion of HSAII than of HSAI. It is concluded that infusion of both HSA preparations during phototherapy provides an immediate protection against bilirubin encephalopathy. HSAI is inferior to HSAII, probably due to its content of N-acetyltryptophan.

Albumin administration combined with phototherapy in treatment of hyperbilirubinaemia in low-birth-weight infants.

Fifty-nine jaundiced light treated newborn infants with low birth weight were studied. At onset of phototherapy 30 infants received 1 g human serum albumin per kg body weight as a 9% solution containing sodium caprylate and N-acetyltryptophan as stabilizers. 29 infants did not receive human serum albumin and served as controls. Blood samples were taken before initiation of the therapy and again 24 and 48 h thereafter, and the following determinations were made: Serum concentrations of unconjugated bilirubin, albumin, reserve albumin for binding of bilirubin by the [14C]-MADDS method, packed cell volume and pH. Before infusion of albumin it was found that the binding fraction of serum albumin, i.e. the sum of the serum concentrations of bilirubin-albumin and reserve albumin, constituted about half of the total serum albumin concentration. The other half was non-binding, in agreement with previous findings in neonates. The effect of albumin therapy was mainly an unexpected increase of the non-binding fraction of serum albumin, while the increase of the serum reserve albumin concentration was small and the concentration of bilirubin-albumin was not changed.

Bilirubin, reserve albumin for binding of bilirubin and pH in plasma during phototherapy (ordinary and double light) of term newborn infants.

Forty-five term newborn infants with uncomplicated hyperbilirubinaemia were treated continuously with phototherapy for 24 hours. Twenty-eight infants received double light treatment and 17 infants ordinary phototherapy. During both treatments a significant decrease in the serum unconjugated bilirubin concentration, a significant increase in the serum reserve albumin concentration for binding of bilirubin determined by the [14C] MADDS method, and a significant decrease in the index of serum bilirubin toxicity occurred. The changes in these parameters were significantly greater during the double light treatment than during the ordinary phototherapy. During the treatment the fall in index was constant. No significant change in plasma pH was seen. Thus, the study gives further evidence that the risk of bilirubin encephalopathy is reduced by phototherapy and that double light treatment is in the respect superior to ordinary phototherapy. Prior to phototherapy the molar ratio in serum of unconjugated bilirubin plus reserved albumin for binding of bilirubin to albumin was only 0.60, on average, and during the treatment the increase in the serum reserve albumin concentration was less than the decrease in the serum bilirubin concentration. This can be explained either by the presence in infant serum of an unknown ligand interfering competitively or allosterically in the binding of MADDS and bilirubin to albumin, or by the existence of a foetal albumin with a lower affinity for MADDS than adult albumin.

The relationship between serum bilirubin and reserve albumin for binding of bilirubin during phototherapy of preterm infants.

Thirty-four preterm newborn infants suffering from uncomplicated hyperbilirubinaemia were studied. The infants received ordinary phototherapy continuously during 48 hours. The serum unconjugated bilirubin concentration decreased significantly during the treatment, and a significant correlation between the changes in the serum bilirubin concentration and the changes in the serum reserve albumin concentration for binding of bilirubin measured by the [14C]MADDS method was found. The regression coefficients were -0.50 and -0.48 after 24 and 48 hours of treatment, respectively. Thus, it can be concluded that the risk of bilirubin encephalopathy is reduced by phototherapy in preterm infants.

Bilirubin-albumin binding affinity and serum albumin concentration during intensive phototherapy (blue double light) in jaundiced newborn infants.

Thirty newborn infants with normal birth weights and uncomplicated hyperbilirubinaemia were studied. Twenty three of these were treated continuously for 24 h with intensive phototherapy (blue double light), and seven untreated infants served as controls. During the treatment the serum concentrations of total bilirubin and unbound bilirubin in diluted serum measured by the peroxidase method were markedly reduced. The binding affinity of bilirubin to its high affinity site on serum albumin was not affected. During the treatment a slight decrease of the serum albumin concentration occurred, and the possible causes of this observation are discussed.

Evaluation of the indications for early exchange transfusion in rhesus haemolytic disease during phototherapy.

The study material consisted of 251 newborn light-treated infants with rhesus haemolytic disease (RHD) caused by anti-D. 139 infants were treated with ordinary phototherapy (white single light) and 112 infants with intensive phototherapy (blue double light). An evaluation was made as to wheter the indications for early exchange transfusion which were devised for non light-treated infants with RHD were relevant, i.e. whether unnecessary early exchange transfusions are now being performed in light-treated infants. The study showed that the indications are still relevant to infants receiving ordinary phototherapy, whereas they were judged to be inappropriate for infants treated with intensive phototherapy.

Gut transit time and lactose malabsorption during phototherapy. I. A study using lactose-free human mature milk.

Sixty newborn infants with normal birth weight suffering from uncomplicated hyperbilirubinemia were studied. They were fed human mature milk from which lactose had been eliminated, whereafter either sucrose ("sucrose milk") or lactose ("lactose milk") was added. 30 infants received ordinary phototherapy and 30 intensive phototherapy (blue double light). 15 in each group had "sucrose milk" and 15 "lactose milk". There was no significant difference between the increase in blood glucose (delta BS) by lactose tolerance tests performed before phototherapy (LTT1) and by those performed during phototherapy (LTT11), neither in infants treated with ordinary nor with intensive phototherapy. All infants had normal delta BS-LTT11, except one receiving ordinary phototherapy. There was no significant difference in gut transit time between infants having "sucrose milk" and infants having "lactose milk", neither in those treated with ordinary nor with intensive phototherapy. Gut transit time was significantly shorter in infants treated with intensive phototherapy than in infants treated with ordinary phototherapy without there being any significant difference in delta BS-LTT11. The infant with flat LTT11 may have developed lactose malabsorption during the phototherapy. Thus, lactose malabsorption is not the usual cause of the reduced gut transit time during phototherapy and must be a rare complication in phototherapy.

Gut transit time and lactose malabsorption during phototherapy. II. A study using raw milk from the mothers of the infants.

Thirty newborn infants with normal birth weight suffering from uncomplicated hyperbilirubinemia were studied. 15 infants received ordinary phototherapy and 15 intensive phototherapy (blue double light). All infants received their mothers' milk or fresh milk from mothers of other newborn infants of the same age. All infants had normal lactose tolerance test during the phototherapy, except one infant receiving ordinary transit time was relatively long. The gut transit time was significantly shorter in the infants treated with intensive phototherapy than in those treated with ordinary phototherapy without there being any significant difference in the increase in blood glucose by lactose tolerance tests. It is concluded that lactose malabsorption is not the usual cause of the reduced gut transit time during phototherapy even if the infants receive their mothers' milk.

Late anaemia in infants with rhesus haemolytic disease treated with intensive phototherapy.

The purpose of the present study was to determine the incidence of late anaemia in infants with rhesus haemolytic disease (RHD) who had received intensive phototherapy. Sixty infants with RHD and with strongly positive direct Coombs' tests who had received intensive phototherapy (blue double light) were followed as out-patients with regard to development of late anaemia. Fifteen (25%) infants developed moderate anaemia and 5 (8%) severe anaemia, one of the latter requiring a blood transfusion. The incidence of late anaemia was equal in "non-exchanged" infants and those who required exchange transfusion. The former developed anaemia significantly earlier than the latter, and in both groups the declining Hb level caused a marked reticulocyte response which was equal in both groups. This response may explain the low incidence of anaemia in both the "non-exchanged" and "exchanged" infants. From the present study and previous investigations it can be concluded that phototherapy, especially intensive phototherapy, is of great value in the treatment of rhesus haemolytic disease.

Determination of serum bilirubin concentration during phototherapy of newborns and in vitro: results compared by the direct spectrometric method and the diazo method.

During direct illumination of a serum bilirubin solution the bilirubin concentration decreased markedly, both as determined by the direct spectrometric method and (even more so) by the diazo method. In contrast, I found the same values for serum bilirubin concentrations as determined by these two methods for serum from untreated, "single light", and "double light" treated full-term infants with neonatal hyperbilirubinemia without blood type immunization. The same was true for untreated and "single light" treated premature infants with this disease. Furthermore, no difference was found in the above-mentioned relationship between "single light" treated infants with the same disease, and untreated infants with neonatal hyperbilirubinemia without immunization, all born at term. This is important, because the direct spectrometric method is simpler and requires less serum than does the diazo method.