Telephone , fax , e-mail moc. All rights reserved This article has been cited by other articles in PMC. OBJECTIVES: To determine whether hospitals had implemented these guidelines; to investigate how guideline-recommended care is organized; and to understand the factors influencing guideline implementation. There was heterogeneity in how hospitals organized services, but there was a notable trend toward hospital-based postdischarge care. The shift to hospital-based care runs counter to current health policy directions and highlights the lack of integration among health care sectors. Further analysis is needed to determine the impact that the guidelines and the differences in implementation have had on clinical outcomes and the utilization of health services.
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Depending on the level indicated in Figure 2 , treatment with phototherapy may also be indicated. DAT Direct antiglobulin test If the TSB concentration had not been measured earlier because of clinical jaundice, a TSB measurement should be obtained at the same time as the metabolic screening test to avoid an increase in the number of painful procedures and to minimize costs; alternatively, a TcB measurement should be obtained either at discharge or before 72 h of life.
The prediction of severe hyperbilirubinemia is more accurate if the gestational age at birth is included in the prediction model . Some of the most severely affected infants require therapy to be started before the time of the metabolic screen to prevent severe hyperbilirubinemia and its complications.
Sudden increases in TSB concentration may also occasionally occur after the first two to three days . This may occur particularly in association with excessive postnatal weight loss. Therefore, the institution of a program of universal screening complements, but does not replace, careful ongoing assessment of newborn infants beginning from the first hours of life and continuing through the first weeks.
Systems to ensure follow-up within the recommended intervals after hospital discharge must be in place so that an infant who develops severe hyperbilirubinemia can be identified and treated promptly.
This requires, for example, that an infant discharged from hospital in the first 24 h of life be reviewed within 24 h, any day of the week, by an individual with the training to recognize neonatal hyperbilirubinemia, obtain measurement of TSB or TcB without delay and refer the infant to a treatment facility if required. This individual may be from any medical or nursing discipline.
In addition to universal measurement, all newborns should be clinically assessed for jaundice repeatedly within the first 24 h, and again, at a minimum, 24 h to 48 h later. This should be performed by an individual competent in the assessment of the newborn who can, if necessary, immediately obtain a TSB or TcB measurement and arrange treatment for the infant, whether in hospital or after discharge.
Measurement of bilirubin It is possible to measure bilirubin concentration using capillary or venous blood samples or transcutaneously. There is no systematic difference between the results of capillary or venous samples  . Capillary sampling is the method used most often in Canada and in most studies, including those of Bhutani et al .
There are several limitations to TcB measurements  : they become unreliable after initiation of phototherapy  , and they may be unreliable with changes in skin colour and thickness . However, the results are more accurate at lower levels of bilirubin, and therefore, use of TcB as a screening device is reasonable . The available devices differ in accuracy; safe use of the device mandates knowledge of the accuracy of the particular device.
Measurement of free bilirubin Displacement of bilirubin from albumin-binding sites by certain toxic medications and additives has caused numerous cases of kernicterus in the past, mostly in the neonatal intensive care unit population . It is believed to be free bilirubin ie, not bound to albumin that crosses the blood-brain barrier and causes neuronal damage  - .
The clinical value of measurement of free bilirubin is currently uncertain and it is not readily available . Measurement of conjugated bilirubin Although early neonatal jaundice is generally due to unconjugated hyperbilirubinemia, in some situations the conjugated fraction may be elevated, such as in rhesus erythroblastosis, liver disease and cholestasis .
In infants placed on phototherapy, measurement of the conjugated fraction should be considered. However, previous reports   on the epidemiology of bilirubin toxicity use the TSB concentration as the standard, which remains the deciding value for phototherapy and other therapies.
If not required earlier because of clinical jaundice, a TSB measurement should be obtained at the same time as the metabolic screening test; alternatively, a TcB measurement should be obtained either at discharge or, if not yet discharged, at 72 h of life recommendation grade C. If the TSB concentration does not require immediate intervention, the results should be plotted on the predictive nomogram. The result of the TSB measurement, the time at which it was obtained and the zone should be recorded, and a copy should be given to the parents.
Follow-up of the infant should be individualized according to the risk assessment recommendation grade D. Any infant discharged before 24 h of life should be reviewed within 24 h by an individual with experience in the care of the newborn who has access to testing and treatment facilities recommendation grade D. There should be a systematic approach to the risk assessment of all infants before discharge and institution of follow-up care if the infant develops jaundice recommendation grade D.
All newborns who are visibly jaundiced in the first 24 h of life should have their bilirubin level determined recommendation grade D. Transcutaneous bilirubinometry is an acceptable method, either as a routine procedure or in infants with visible jaundice. TSB concentration may be estimated on either a capillary or a venous blood sample recommendation grade C. Infants with severe or prolonged hyperbilirubinemia should be further investigated, including measurement of the conjugated component of bilirubin recommendation grade C.
How can the risk of severe hyperbilirubinemia be reduced? Primary prevention of severe hyperbilirubinemia Breastfeeding support Although breastfed infants are at a higher risk for developing severe hyperbilirubinemia than are formula-fed infants, the known risks of acute bilirubin encephalopathy are very small when weighed against the substantial known benefits of breastfeeding  . Support of the breastfeeding mother by knowledgeable individuals increases the frequency and duration of breastfeeding.
It is difficult to find reliable evidence that the risk of severe jaundice can be minimized by a program of breastfeeding support, but other aspects of breastfeeding difficulty can be reduced by such programs, and providing such support is reasonable evidence level 5 .
Routine supplementation of breastfed infants with water or dextrose water does not appear to prevent hyperbilirubinemia evidence level 2b . Prevention of severe hyperbilirubinemia in infants with hemolysis Phenobarbitone Phenobarbitone, studied as a means of preventing severe hyperbilirubinemia in infants with G6PD deficiency  , did not improve clinically important outcomes evidence level 1b.
Tin-mesoporphyrin Synthetic analogues of heme oxygenase, such as tin-mesoporphyrin SnMP , strongly inhibit its activity and suppress the production of bilirubin. In a study  with historical controls in infants with G6PD deficiency, SnMP eliminated the need for phototherapy and appeared to prevent severe hyperbilirubinemia.
However, prospective RCTs have as yet failed to demonstrate a clinically important benefit evidence level 1b , and the compounds are not commercially available  .
Prevention of severe hyperbilirubinemia in infants with mild or moderate hyperbilirubinemia Phototherapy Phototherapy can be used both to prevent severe hyperbilirubinemia in infants with a moderately elevated TSB concentration and as initial therapy in those with severe hyperbilirubinemia.
The energy from light induces a conformational change in the bilirubin molecule, making it water soluble; light in the blue-green part of the spectrum is most effective.
The effectiveness of phototherapy is related to the area of skin exposed and the intensity of the light at the skin at the relevant wavelengths  - . More intense phototherapy can be achieved using multiple phototherapy units  or simply moving the unit closer to the infant. Although phototherapy increases water loss from transepidermal skin, this is not a clinically important issue in full-term infants who are drinking well.
Side effects of phototherapy include temperature instability, intestinal hypermotility, diarrhea, interference with maternal-infant interaction and, rarely, bronze discolouration of the skin . Reassurance of the parents that appropriate intervention and follow-up will prevent any consequences of hyperbilirubinemia is an important part of the care of these infants.
Eye patches should be used to protect the developing retina because animal studies demonstrate a potential risk . Phototherapy decreases the progression to severe hyperbilirubinemia in infants with moderate hyperbilirubinemia evidence level 1a . Some infants with jaundice are dehydrated, and rehydration will usually lead to a prompt fall in the TSB concentration; enteral feeding should be continued because it will replace missing fluid, supply energy and reduce enterohepatic reuptake of the bilirubin .
In general, fluorescent light is most commonly used  ; the intensity of light produced by fluorescent tubes wanes over time. A program of biomedical support for ensuring adequate light intensity is important to assure effective therapy. Fibre optic phototherapy systems were introduced in the late s; the advantages are that the baby can be breastfed without interruption of phototherapy and eye pads are not required, but the disadvantage is that the peak intensity is less than that of fluorescent systems.
In usual clinical situations, this will require two phototherapy units, or special high-intensity fluorescent tubes, placed approximately 10 cm from the infant, who can be nursed in a bassinet. Usually the diaper can be left in place. In infants whose TSB concentration is approaching the exchange transfusion threshold, the addition of a fibre optic blanket under the infant can increase the surface area illuminated, and the diaper should then be removed or a phototherapy wavelength-transmitting diaper used instead.
Conventional phototherapy — a single bank of fluorescent lights placed above the incubator of an infant nursed with a diaper in place — is, of course, less effective because both surface area and intensity are reduced; nevertheless, it will have an effect on TSB concentration.
The recommendations for treatment are determined from Figure 2. These recommendations are as follows: Intensive phototherapy for infants with severe hyperbilirubinemia or those at greatly elevated risk of developing severe hyperbilirubinemia.
A useful online tool is available for deciding whether intensive phototherapy would be recommended by these guidelines . Continued breastfeeding in jaundiced infants receiving phototherapy is not associated with adverse clinical outcomes, although an observational study  showed a slower response to phototherapy in the first 24 h in exclusively breastfed infants compared with those who received supplementation bilirubin decreases of The duration of phototherapy did not differ between the groups, and no other clinically important outcomes were affected.
There were no clinically important differences in outcomes. Intravenous immunoglobulin Intravenous immunoglobulin IVIG reduces bilirubin concentrations in newborns with rhesus hemolytic disease and other immune hemolytic jaundice.
It acts as a completive inhibitor for those antibodies that cause red cell destruction, release hemoglobin and cause jaundice . The entry criteria for each of these studies differed, making exact treatment indications difficult to determine. It appears reasonable to initiate this treatment in infants with predicted severe disease based on antenatal investigation and in those with an elevated risk of needing exchange transfusion based on the postnatal progression of TSB concentration.
SnMP SnMP, studied for preventing the progression of moderate hyperbilirubinemia  , showed no evidence of reduction in clinically important outcomes evidence level 1a.
Oral fluids appear to be as effective as intravenous fluids  during intensive phototherapy evidence level 1b. There is observational evidence that offering supplemental oral fluids may interfere with the eventual duration of breastfeeding  evidence level 2b , but such studies were not performed in the context of brief supplementation in the setting of neonatal jaundice, and a systematic review of intervention studies found no reliable evidence .
The frequency of exchange transfusion in the infants in the study noted above was very high  ; the same absolute risk reduction from extra fluids will not be seen in a population with a much lower likelihood of requiring exchange. Therefore, in breastfed infants, extra fluids are indicated for, but should be restricted to, infants with an elevated risk of requiring exchange transfusion evidence level 1b.
Agar Oral agar to prevent enterohepatic reuptake of bilirubin is not supported by the available evidence  -  evidence level 1b. Recommendations A program for breastfeeding support should be instituted in every facility where babies are delivered recommendation grade D.
Routine supplementation of breastfed infants with water or dextrose water is not recommended recommendation grade B. A TSB concentration consistent with increased risk Figure 1 and Table 4 should lead to enhanced surveillance for development of severe hyperbilirubinemia, with follow-up within 24 h to 48 h, either in hospital or in the community, and repeat estimation of TSB or TcB concentration in most circumstances recommendation grade C.
Intensive phototherapy should be given according to the guidelines shown in Figure 2 recommendation grade D. Breastfeeding should be continued during phototherapy recommendation grade A. Supplemental fluids should be administered, orally or by intravenous infusion, in infants receiving phototherapy who are at an elevated risk of progressing to exchange transfusion recommendation grade A.
How should severe hyperbilirubinemia be treated? Phototherapy An infant who presents with severe hyperbilirubinemia, or who progresses to severe hyperbilirubinemia despite initial treatment, should receive immediate intensive phototherapy. The bilirubin concentration should be checked within 2 h to 6 h of initiation of treatment to confirm response.
Consideration of further therapy should commence and preparations for exchange transfusion may be indicated. Supplemental fluids are indicated, and IVIG should be given if not already commenced for the infant with isoimmunization.
Exchange transfusion If phototherapy fails to control the rising bilirubin concentrations, exchange transfusion is indicated to lower TSB concentrations. Because blood collected after an exchange transfusion is of no value for investigating many of the rarer causes of severe hyperbilirubinemia, these investigations should be considered before performing the exchange transfusion. Appropriate amounts of blood should be taken and stored for tests such as those for red cell fragility, enzyme deficiency G6PD or pyruvate kinase deficiency and metabolic disorders, as well as for hemoglobin electrophoresis and chromosome analysis.
Preparation of blood for exchange transfusion may take several hours, during which time intensive phototherapy, supplemental fluids and IVIG in case of isoimmunization should be used. If an infant whose TSB concentration is already above the exchange transfusion line presents for medical care, then repeat measurement of the TSB concentration just before performance of the exchange is reasonable, as long as therapy is not thereby delayed.
In this way, some exchange transfusions, with their attendant risks, may be avoided. Exchange transfusion is a procedure with substantial morbidity that should only be performed in centres with the appropriate expertise under supervision of an experienced neonatologist.
An infant with clinical signs of acute bilirubin encephalopathy should have an immediate exchange transfusion evidence level 4. Recommendations Infants with a TSB concentration above the thresholds shown on Figure 3 should have immediate intensive phototherapy, and should be referred for further investigation and preparation for exchange transfusion recommendation grade B. An infant with clinical signs of acute bilirubin encephalopathy should have an immediate exchange transfusion recommendation grade D.
For a full-size downloadable version of this graph. Reproduced and adapted with permission from Pediatrics ;
Hyperbilirubinemia in the Newborn
What is hyperbilirubinemia in a newborn? Bilirubin is made by the breakdown of red blood cells. It can build up in their blood, tissues, and fluids. Bilirubin has a color. Jaundice may first appear when your baby is born. Or it may also show up any time after birth. What causes hyperbilirubinemia in a newborn?
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