Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants (35 or more weeks’ gestation) – Summary

Fetus and Newborn Committee, Canadian Paediatric Society (CPS)

Paediatr Child Health 2007;12(5):401-7
Reference No. FN07-02

Parent handout: Jaundice in newborns

Index of position statements from the Fetus and Newborn Committee

Content

• Abstract
• Background and epidemiology
  • Definitions of terms as used in this statement
• Methods of statement development
• Can severe hyperbilirubinemia be accurately predicted?
  • Timed TSB measurements
  • Blood group and Coombs testing
  • Glucose-6-phosphate dehydrogenase deficiency
  • Recommendations
• Who should have their bilirubin concentration measured, when and how?
  • Measurement of bilirubin
  • Measurement of conjugated bilirubin
  • Recommendations
• How can the risk of severe hyperbilirubinemia be reduced?
  • Primary prevention of severe hyperbilirubinemia
  • Breastfeeding support
  • Prevention of severe hyperbilirubinemia in infants with mild or moderate hyperbilirubinemia
  • Phototherapy
  • Interrupting breastfeeding
  • Intravenous immunoglobulin
  • Supplemental fluids
  • Recommendations
• How should severe hyperbilirubinemia be treated?
  • Phototherapy
  • Exchange transfusion
  • Recommendations
  • Fellow-up
  • Further investigations
  • Recommendations
• Conclusion
• Selected references

ABSTRACT

Hyperbilirubinemia is very common and usually benign in the term newborn infant and the late preterm infant at 35 and 36 completed weeks’ gestation. Critical hyperbilirubinemia is uncommon but has the potential for causing long-term neurological impairment. Early discharge of the healthy newborn infant, particularly those in whom breastfeeding may not be fully established, may be associated with delayed diagnosis of significant hyperbilirubinemia. Guidelines for the prediction, prevention, identification, monitoring and treatment of severe hyperbilirubinemia are presented.

For more information, please refer to the full text position statement at <http://www.cps.ca/English/statements/FN/fn07-02.htm>.

BACKGROUND AND EPIDEMIOLOGY

Definitions of terms as used in this statement

• Kernicterus – the pathological finding of deep-yellow staining of neurons and neuronal necrosis of the basal ganglia and brainstem nuclei.
• Acute bilirubin encephalopathy – a clinical syndrome, in the presence of severe hyperbilirubinemia, of lethargy, hypotonia and poor suck, which may progress to hypertonia (with opisthotonos and retrocollis) with a high-pitched cry and fever, and eventually to seizures and coma.
• Chronic bilirubin encephalopathy – the clinical sequelae of acute encephalopathy with athetoid cerebral palsy with or without seizures, developmental delay, hearing deficit, oculomotor disturbances, dental dysplasia and mental deficiency (1).
• Severe hyperbilirubinemia – a total serum bilirubin (TSB) concentration greater than 340 µmol/L at any time during the first 28 days of life.
• Critical hyperbilirubinemia – a TSB concentration greater than 425 µmol/L during the first 28 days.

The prevention, detection and management of jaundice in term and late preterm newborn infants remains a challenge (2-4). Sixty per cent of term newborns develop jaundice, and 2% exceed a TSB concentration of 340 µmol/L (5). The incidence of acute encephalopathy is much lower, recent data (6) suggesting an incidence of approximately one per 10,000 live births; the incidence of chronic encephalopathy has been estimated to be between one per 50,000 live births and one per 100,000 live births (6-9). Acute encephalopathy does not occur in full-term infants whose peak TSB concentration remains below 340 µmol/L and is very rare unless the peak TSB concentration exceeds 425 µmol/L; above this level, the risk for toxicity progressively increases (10). Two-thirds of patients with chronic encephalopathy had a recorded peak TSB concentration that exceeded 600 µmol/L (11).

Prevention of acute bilirubin encephalopathy requires appropriate clinical assessment, interpretation of TSB concentration and treatment, which must involve the entirety of the systems involved in the provision of health care and community support.

Several factors that increase the risk of severe hyperbilirubinemia have been identified, including: visible jaundice at younger than 24 h of age, visible jaundice before discharge at any age, gestation less than 38 weeks, sibling with severe hyperbilirubinemia, visible bruising, cephalhematoma, male sex, maternal age older than 25 years of age, ethnic background (Asian or European), and exclusive and partial breastfeeding. These risk factors are all very common and are, thus, of limited usefulness for directing surveillance, investigation or therapy by themselves, but can be useful in combination with timed TSB analysis.

METHODS OF STATEMENT DEVELOPMENT

Literature searches were last updated in January 2007. The hierarchy of evidence from the Centre for Evidence-Based Medicine (Table 1) (12) was applied. The reference lists of recent publications were also examined (9).

CAN SEVERE HYPERBILIRUBINEMIA BE ACCURATELY PREDICTED?

Timed TSB measurements
Carefully timed TSB measurements can be used to predict the chances of developing severe hyperbilirubinemia. A study (13) in direct antiglobulin test (DAT)-negative term and late preterm infants demonstrated that a timed measurement of TSB concentration at discharge (between 18 h and three days of age) could predict a later TSB concentration greater than 300 µmol/L (evidence level 1b, Figure 1). Combining a timed TSB at less than 48 h of age with gestational age (14) improved the prediction of a subsequent TSB concentration greater than 342 µmol/L (evidence level 2b).

Blood group and Coombs testing
ABO isoimmunization may cause severe hyperbilirubinemia, most commonly in blood group A or B infants born to a mother of group O (15,16). It is therefore recommended to perform a DAT in infants who are clinically jaundiced, or in the high intermediate zone (Figure 1) of mothers who are group O.

The usual antenatal screen for a panel of red cell antibodies occasionally identifies more infrequent antibodies that increase the risk of hemolysis. Infants may require further testing, closer follow-up and earlier therapy; consultation with a paediatric hematologist or neonatologist is suggested.

Glucose-6-phosphate dehydrogenase deficiency
Newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency have an increased incidence of severe hyperbilirubinemia (evidence level 1b). Testing for G6PD deficiency is advised in boys and girls at increased risk (eg, children of Mediterranean , Middle Eastern, African [17] or Southeast Asian origin) (18,19). G6PD-deficient newborns require intervention at a lower TSB concentration (18); therefore, a test for G6PD deficiency should be considered in all infants with severe hyperbilirubinemia (evidence level 5) (18). Unfortunately, in many centres, it currently takes several days for a G6PD deficiency screening test result to become available. Because G6PD deficiency is a disease with life-long implications, its identification is still of value for the infant.

Recommendations

• All mothers should be tested for ABO and Rh (D) blood types and be screened for red cell antibodies during pregnancy (recommendation grade D [Table 2]).
• If the mother was not tested, cord blood from the infant should be sent for evaluation of the blood group and a DAT (Coombs test) (recommendation grade D).
• Blood group evaluation and a DAT should be performed in infants with early jaundice or in the high intermediate zone (Figure 1) of mothers of blood group O (recommendation grade B).
• Selected at-risk infants of Mediterranean , Middle Eastern, African or Southeast Asian origin should be screened for G6PD deficiency (recommendation grade D).
• A test for G6PD deficiency should be considered in all infants with severe hyperbilirubinemia (recommendation grade D).

WHO SHOULD HAVE THEIR BILIRUBIN CONCENTRATION  MEASUREd, WHEN AND HOW?

Clinical assessment of jaundice is inadequate for diagnosing hyperbilirubinemia, particularly in infants with darker skin colour; only 50% of babies with a TSB concentration greater than 128 µmol/L appear jaundiced. The peak TSB concentration usually occurs between three and five days of age, at which time the majority of babies have already been discharged from hospital. Therefore, it is clear that at the usual age of discharge, TSB concentrations in the high zone (Figure 1) cannot be reliably detected by visual inspection, especially in infants with darker skin colour.

It is therefore recommended that either TSB or transcutaneous bilirubin (TcB) concentration be measured in all infants between 24 h and 72 h of life; if the infant does not require immediate treatment, the results should be plotted on the predictive nomogram to determine the risk of progression to severe hyperbilirubinemia. The TSB (or TcB) and the predictive zone should be recorded, a copy given to the family at the time of discharge and follow-up arrangements should be made for infants who are at elevated risk of developing severe hyperbilirubinemia. 

If the TSB concentration has not been measured earlier because of clinical jaundice, a TSB measurement should be obtained at the same time of the metabolic screening test to decrease pain and minimize costs; alternatively a TcB measurement should be obtained either at discharge or before 72 h of life (14).

Some of the most severely affected infants require therapy initiation before the time of the screen; sudden increases in TSB concentration may also occasionally occur after the first two to three days (20), particularly in association with excessive postnatal weight loss. Therefore, the institution of a program of universal screening does not replace the need for careful on-going assessment of newborn infants continuing throughout the first weeks of life. Systems to ensure follow-up within 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 within 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 newborn infants should be clinically assessed for jaundice repeatedly within the first 24 h and again, at a minimum of  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
Estimation of TSB using capillary blood sampling is acceptable (21,22). TcB measurements are also acceptable, however, there are several limitations to TcB measurements – they become unreliable after initiation of phototherapy and may also be unreliable with changes in skin colour and thickness. The results are more accurate at lower levels of bilirubin; therefore, the use of TcB as a screening device is reasonable. The available devices differ in accuracy; the safe use of TcB mandates knowledge of the accuracy of the individual device. The 95% CIs for TSB based on the TcB concentration range from approximately 37 µmol/L to 78 µmol/L (23,24). For example, if the 95% CI is 37 µmol/L, then a TcB concentration greater than 37 µmol/L below the intervention line (Figure 2) should be safe (eg, if the intervention at 24 h is at 170 µmol/L, then a TcB concentration of less than 133 µmol/L should be safe) (evidence level 1b).

Measurement of conjugated bilirubin
Early neonatal jaundice is generally due to unconjugated hyperbilirubinemia in infants placed on phototherapy; measurement of the conjugated fraction should be considered to detect the uncommon case of an infant with an elevation. However, previous reports on the epidemiology of bilirubin toxicity use the TSB concentration as the standard, which remains the deciding value for phototherapy or other therapies. An infant with persistent jaundice (longer than two weeks) and/or hepatosplenomegaly should have an estimation of conjugated bilirubin fraction. A total conjugated bilirubin concentration greater than 18 µmol/L or greater than 20% of the TSB concentration warrants further investigation (25).

Recommendations

• Either TSB or TcB concentration should be measured in all infants during the first 72 h of life. If not required earlier because of clinical jaundice, TSB should be obtained at the time of obtaining the metabolic screening test; alternatively, a TcB measurement should be obtained either at discharge or, if not yet discharged, before 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 results of the TSB measurement, the time at which it was obtained and the zone should be recorded, and a copy 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 newborn infants who are visibly jaundiced within the first 24 h of life should have a bilirubin level determined (recommendation grade D).
• Transcutaneous bilirubinometry is an acceptable method; the result should be summed with the 95% CI of the device to estimate the maximum probable TSB concentration (recommendation grade C).
• 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 the 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 higher risk for developing severe hyperbilirubinemia than formula-fed infants, the known risks of acute bilirubin encephalopathy are very small when weighed against the substantial known benefits of breastfeeding (26). Support of the breastfeeding mother by knowledgeable individuals increases the frequency and duration of breastfeeding, and providing such support is recommended (evidence level 5). Exclusively breastfed infants experience their maximum weight loss by day 3 and lose, on average, 6% to 8 % of their birth weight (26). Infants who lose more than 10% of their birth weight should be carefully evaluated by an individual with training and experience in support of breastfeeding mothers (26) (evidence level 5). Routine supplementation of breastfed infants with water or dextrose water does not prevent hyperbilirubinemia (evidence level 2b) (27).

Prevention of severe hyperbilirubinemia in infants with mild or moderate hyperbilirubinemia
Phototherapy
Phototherapy decreases the progression to severe hyperbilirubinemia in infants with moderate hyperbilirubinemia (evidence level 1a). Its effectiveness is related to the area of skin exposed and the intensity of the light at the skin at the relevant wavelengths (28). Intensity can be increased by using multiple phototherapy units (29) or moving the unit closer to the infant. Phototherapy causes minor increases in transepidermal skin water loss in full-term infants. Side effects include temperature instability, intestinal hypermotility, interference with maternal-infant interaction and, rarely, bronze discolouration of the skin. Phototherapy is perceived by parents as implying that their infant’s jaundice is a serious disease (30) (evidence level 2); reassurance of the parents is an important part of their care. Eye patches should be used to protect the developing retina (31).

Fluorescent light sources are most commonly used (32), but their intensity wanes over time; thus, a program of biomedical support for ensuring adequate light intensity is important. Fibre optic phototherapy systems have the advantage of allowing the baby to be breastfed without interruption of phototherapy and eye pads are not required, but the disadvantage is that the peak intensity is lower than in fluorescent systems. Halogen spotlights may also be used, but they must not be placed closer to the infant than the manufacturer’s recommendation.

Intensive phototherapy, as recommended by the present position statement summary, implies that a high intensity of light (greater than 30 µW/cm2/nm) is applied to the greatest possible surface area of the infant. In usual clinical situations, this will imply 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 approaching the exchange transfusion threshold, the addition of a fibre optic blanket under the infant can increase the surface area illuminated; the diaper should then be removed (or a phototherapy wavelength-transmitting diaper used instead). The guidelines for therapy (Figure 2) are based on limited direct evidence, but are thought to be the most appropriate currently available standard. Conventional phototherapy – a single bank of fluorescent lights placed above the incubator or bassinet of an infant nursed with a diaper in place – is less effective because both surface area and intensity are reduced; nevertheless, it will have some effect on TSB concentration.

Enteral feeding should be continued to replace missing fluid, supply energy and reduce enterohepatic reuptake of the bilirubin (33).

The recommendations for treatment are determined from Figure 2. These recommendations are as follows:

1. Intensive phototherapy for infants with severe hyperbilirubinemia or those at greatly elevated risk of developing severe hyperbilirubinemia.
2. In addition, there is an option for conventional phototherapy for those infants with moderately elevated risk and at TSB concentrations of 35 µmol/L to 50 µmol/L below the thresholds (Figure 2).

A useful tool is available on-line at <http://bilitool.org> for deciding whether intensive phototherapy would be recommended by these guidelines.

Interrupting breastfeeding
Interrupting breastfeeding as part of hyperbilirubinemia therapy is associated with an increase in the frequency of stopping breastfeeding by one month (evidence level 2b) (30). Contin-uing breastfeeding in jaundiced infants receiving photothe-rapy is not associated with adverse clinical outcomes (34).

Intravenous immunoglobulin
Intravenous immunoglobulin (IVIG) at a dose of either 500 mg/kg or 1 g/kg reduces bilirubin concentrations in newborns with immune hemolytic jaundice (35,36) and reduces the need for exchange transfusion (evidence level 1a). These studies only included infants at high risk of requiring an exchange transfusion. IVIG should therefore be given to infants with predicted severe disease based on antenatal investigation and to those with an elevated risk of progressing to exchange transfusion.

Supplemental fluids
Nondehydrated infants with severe jaundice appear to have a reduced risk of progressing to exchange transfusion if they receive extra fluids, either intravenous or orally (37,38) during intensive phototherapy (evidence level 1b). There is a concern that offering supplemental oral fluids may interfere with the eventual duration of breastfeeding (39,40) (evidence level 2b). The frequency of exchange transfusion in the studies supporting supplemental fluids, noted above, was very high (37). In breastfed infants, therefore, extra fluids are indicated for, but should be restricted to, those infants with an elevated risk of requiring exchange transfusion (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 (recommended grade B).
• Infants with a positive DAT who have predicted severe disease based on antenatal investigation or an elevated risk of progressing to exchange transfusion based on the postnatal progression of TSB concentration should receive IVIG at a dose of 1 g/kg (recommended grade A).
• A TSB concentration consistent with increased risk (Figure 1 and Table 3) should lead to enhanced surveillance for the 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 (recommended grade C).
• Intensive phototherapy should be given according to the guidelines shown in Figure 2 (recommended grade D).
• Conventional phototherapy is an option at TSB concentrations 35 µmol/L to 50 µmol/L, lower than the guidelines in Figure 2 (recommended grade D).
• Breastfeeding should be continued during phototherapy (recommended grade A).
• Supplemental fluids should be administered, orally or by intravenous infusion, in infants receiving phototherapy who are at elevated risk of progressing to exchange transfusion (recommended 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. 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 in the DAT-positive infant.

Exchange transfusion
If phototherapy fails to control the rising bilirubin concentration, exchange transfusion is indicated to lower TSB concentration. Exchange transfusion should be considered when the TSB exceeds the thresholds on Figure 3 (despite adequate intensive phototherapy). 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 presents for medical care and is already above the exchange transfusion line, then immediate consultation with a referral centre is required. 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 may be avoided. Exchange transfusion is a procedure with substantial morbidity that should only be performed in centres with the appropriate expertise under the 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 (Figure 3) should have immediate intensive phototherapy, and should be referred for further investigation and preparation for exchange transfusion (recommendation category B).
• An infant with clinical signs of acute bilirubin encephalopathy should have an immediate exchange transfusion (recommendation category D).

Follow-up
Routine newborn surveillance, whether in hospital or after discharge, should include assessment of breastfeeding and jaundice every 24 h to 48 h until feeding is established (usually on the third or fourth day of life). All jaundiced infants, especially high-risk infants and those who are exclusively breastfed, should continue to be closely monitored until feeding and weight gain are established and the TSB concentration starts to fall. Community services should include breastfeeding support and access to TSB or TcB testing. Infants with isoimmunization are at risk for severe anemia after several weeks; it is suggested that a repeat hemoglobin measurement be performed after two weeks if it was low at discharge, and at four weeks if it was normal (evidence level 5). Infants requiring exchange transfusion or those who exhibit neurological abnormalities should be referred to regional multidisciplinary follow-up programs. Neurosensory hearing loss is of particular importance in infants with severe hyperbilirubinemia, and their hearing screen should include brainstem auditory evoked potentials.

Further investigations
The occurrence of severe hyperbilirubinemia mandates an investigation of the cause of hyperbilirubinemia. Investigations should include clinically pertinent history of the baby and the mother, family history, description of the labour and delivery, and the infant’s clinical course. A physical examination should be supplemented by laboratory investigations (conjugated and unconjugated bilirubin levels; direct Coombs test; hemoglobin and hematocrit levels, and complete blood cell count including differential count, blood smear and red cell morphology). Investigations for sepsis should be performed if warranted by the clinical situation.

Recommendations

• Adequate follow-up should be ensured for all infants who are jaundiced (recommendation grade D).
• Infants requiring intensive phototherapy should be investigated for determination of the cause of jaundice (recommendation grade C).

CONCLUSION

Severe hyperbilirubinemia in relatively healthy term or late preterm newborns (greater than 35 weeks’ gestation) continues to carry the potential for complications from acute bilirubin encephalopathy and chronic sequelae. Careful assessment of the risk factors involved, a systematic approach to the detection and follow-up of jaundice with the appropriate laboratory investigations, along with judicious phototherapy and exchange transfusion when indicated, are all essential to avoid these complications.  

ACKNOWLEDGEMENTS: The Canadian Paediatric Society’s Community Paediatrics Committee and The College of Family Physicians of Canada reviewed the full position statement.  

SELECTED REFERENCES

1. Newman TB, Maisels MJ. Evaluation and treatment of jaundice in term newborns: A kinder, gentler approach. Pediatrics 1992;89:809-18.
2. American Academy of Pediatrics, Subcommittee on Neonatal Hyperbilirubinemia. Neonatal jaundice and kernicterus. Pediatrics 2001;108:763-5.
3. Penn AA, Enzmann DR, Hahn JS, Stevenson DF. Kernicterus in a full term infant. Pediatrics 1994;93:1003-6.
4. Maisels MJ, Newman TB. Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics 1995;96:730-3.
5. Stevenson DK, Fanaroff AA, Maisels MJ, et al. Prediction of hyper-bilirubinemia in near-term and term infants. Pediatrics 2001;108:31-9.
6. Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006;175:587-90.
7. Maisels MJ, Newman TB. Jaundice in full term and near term babies who leave the hospital within 36 hours: The pediatrician’s nemesis. Clin Perinatol 1998;25:295-302.
8. Ebbesen F. Recurrence of kernicterus in term and near-term infants in Denmark. Acta Paediatr 2000;89:1213-7.
9. American Academy of Pediatrics Subcommittee on Neonatal hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316. (Erratum in 2004;114:1138).
10. Harris MC, Bernbaum JC, Polin JR, Zimmerman R, Polin RA. Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia. Pediatrics 2001;107:1075-80.
11. Bhutani VK, Johnson LH, Maisels JM, et al. Kernicterus: Epidemiological strategies for its prevention through systems-based approaches. J Perinatol 2004;24:650-62.
12. Oxford Centre for Evidence-Based Medicine. <http://www.cebm.net/index.aspx?o=1047> (Version current at April 25, 2007 ).
13. Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant bilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103:6-14.
14. Newman TB, Liljestrand P, Escobar GJ. Combining clinical risk factors with serum bilirubin levels to predict hyperbilirubinemia in newborns. Arch Pediatr Adolesc Med 2005;159:113-9.
15. Newman TB. Easterling MJ, Goldman ES, Stevenson DK. Laboratory evaluations of jaundiced newborns. Frequency cost and yield. Am J Dis Child 1990;144:364-8. (Erratum in 1992;146:1420-1).
16. Sarici SU, Yurdakok M, Serdar MA, et al. An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility. Pediatrics 2002;109:e53.
17. Kaplan M, Herschel M, Hammerman C, Karrison T, Hoyer JD, Stevenson DK. Studies in hemolysis in glucose-6-phosphate dehydrogenase-deficient African American neonates. Clin Chim Acta 2006;365:177-82.
18. Meloni T, Forteleoni G, Dore A, Cutillo S. Neonatal hyperbilirubinaemia in heterozygous glucose-6-phosphate dehydrogenase deficient females. Br J Haematol 1983;53:241-6.
19. Kaplan M, Beutler E, Vreman HJ, et al. Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. Pediatrics 1999;104:68-74.
20. Watchko JF. Vigintiphobia revisited. Pediatrics 2005;115:1747-53.
21. Leslie GI, Philips JB III, Cassady G. Capillary and venous bilirubin values. Are they really different? Am J Dis Child 1987;141:1199-200.
22. Amato M, Huppi P, Markus D. Assessment of neonatal jaundice in low birth weight infants comparing transcutaneous, capillary and arterial bilirubin levels. Eur J Pediatr 1990;150:59-61.
23. Rubaltelli FF, Gourley GR, Loskamp N, et al. Transcutaneous bilirubin measurement: A multicenter evaluation of a new device. Pediatrics 2001;107:1264-71.
24. Maisels MJ, Ostrea EMJ, Touch S, et al. Evaluation of a new transcutaneous bilirubinometer. Pediatrics 2004;113:1628-35.
25. Powell JE, Keffler S, Kelly DA, Green A. Population screening for neonatal liver disease: Potential for a community-based programme. J Med Screen 2003;10:112-6.
26. Maisels MJ, Gifford K. Breast-feeding, weight loss, and jaundice. J Pediatr 1983;102:117-8.
27. Nicoll A, Ginsburg R, Tripp JH. Supplementary feeding and jaundice in newborns. Acta Pediatr Scand 1982;71:759-761.  
28. Seidman DS, Moise J, Ergaz Z, et al. A new blue light-emitting phototherapy device: A prospective randomized controlled study. J Pediatr 2000;136:771-4.
29. Sisson TR, Kendall N, Shaw E, Kechavarz-Oliai L. Phototherapy of jaundice in the newborn infant. II. Effect of various light intensities. J Pediatr 1972:81:35-8.
30. Kemper K, Forsyth B, McCarthy P. Jaundice, terminating breast-feeding, and the vulnerable child. Pediatrics 1989;84:773-8.
31. Messner KH, Maisels MJ, Leure-DuPree AE. Phototoxicity to the newborn primate retina. Invest Ophthalmol Vis Sci 1978;17:178-82.
32. Mills JF, Tudehope D. Fiberoptic therapy for neonatal jaundice. Cochrane Database Syst Rev 2001;(1):CD002060.
33. Brown AK, Kim MH, Wu PY, Bryla DA. Efficacy of phototherapy in prevention and management of neonatal hyperbilirubinemia. Pediatrics 1985;75:393-400.
34. Martinez JC, Maisels MJ, Otheguy L, et al. Hyperbilirubinemia in the breast-fed newborn: A controlled trial of four interventions. Pediatrics 1993;91:470-3.
35. Alcock GS, Liley H. Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates. Cochrane Database Syst Rev 2002;(3):CD003313.
36. Miqdad AM, Abdelbasit OB, Shaheed MM, Seidahmed MZ, Abomelha AM, Arcala OP. Intravenous immunoglobulin G (IVIG) therapy for significant hyperbilirubinemia in ABO hemolytic disease of the newborn. J Matern Fetal Neonatal Med 2004;16:163-6.
37. Mehta S, Kumar P, Narang A. A randomized controlled trial of fluid supplementation in term neonates with severe hyperbilirubinemia. J Pediatr 2005;147:781-5.
38. Boo NY, Lee HT. Randomized controlled trial of oral versus intravenous fluid supplementation on serum bilirubin level during phototherapy of term infants with severe hyperbilirubinaemia. J Paediatr Child Health 2002;38:151-5.
39. Casiday RE, Wright CM, Panter-Brick C, Parkinson KN. Do early infant feeding patterns relate to breast-feeding continuation and weight gain? Data from a longitudinal cohort study. Eur J Clin Nutr 2004;58:1290-6.
40. Horvath A, Koletzko B, Kalisz M, Szajewska H. The effect of supplemental fluids or feedings during the first days of life on the success and duration of breast-feeding: A systematic review of randomized controlled trials. Arch Pediatr Adolesc Med 2005;159:597-8.

FETUS AND NEWBORN COMMITTEE
Members: Drs Khalid Aziz, Department of Pediatrics (Neonatology), Janeway Children’s Health and Rehabilitation Centre, St John’s, Newfoundland and Labrador (board representative 2000-2006); Keith J Barrington, Royal Victoria Hospital, Montreal, Quebec (chair); Joanne Embree, University of Manitoba, Winnipeg, Manitoba (board representative); Haresh Kirpalani, Children’s Hospital – Hamilton HSC, Hamilton, Ontario; Koravangattu Sankaran, Royal University Hospital, Saskatoon, Saskatchewan; Hilary Whyte, The Hospital for Sick Children, Toronto, Ontario (sabbatical 2006-2007); Robin Whyte, IWK Health Centre, Halifax, Nova Scotia
Liaisons: Drs Dan Farine, Mount Sinai Hospital, Toronto, Ontario (Society of Obstetricians and Gynaecologists of Canada); David Keegan, London, Ontario (College of Family Physicians of Canada, Maternity and Newborn Care Committee); Francine Lefebvre, Sainte-Justine UHC (Canadian Paediatric Society, Neonatal-Perinatal Medicine Section); Catherine McCourt, Ottawa, Ontario (Public Health Agency of Canada, Health Surveillance and Epidemiology); Ms Shahirose Premji, Hamilton Health Sciences Centre (Neonatal Nurses); Dr Alfonso Solimano, BC’s Children’s Hospital, Vancouver, British Columbia (Canadian Paediatric Society, Neonatal-Perinatal Medicine Section, 2002–2006); Dr Ann Stark, Texas Children’s Hospital, Houston, Texas, USA (American Academy of Pediatrics, Committee on Fetus and Newborn); Ms Amanda Symington, Hamilton Health Sciences Centre – McMaster Site, Hamilton, Ontario (Neonatal Nurses, 1999–2006)
Principal authors: Drs Keith Barrington, Royal Victoria Hospital, Montreal, Quebec; Koravangattu Sankaran, Royal University Hospital, Saskatoon, Saskatchewan

Posted June 2007