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Three Part Question

In [a full term healthy breastfed baby with physiological jaundice], above what [level of serum bilirubin] is [intervention in the form of phototherapy indicated to prevent neurological impairment]?

Clinical Scenario

You are the paediatrician called in to see a seven day old breast fed term baby, brought back to the hospital looking jaundiced. The total serum bilirubin level is 330 mumol/l, unconjugated 300 mumol/l and conjugated 30 mumol/l. Investigations ruled out haemolysis and sepsis. You wonder whether this baby should be treated with phototherapy.

Search Strategy

Medline via PubMed using MeSH terms: "Hyperbilirubinemia OR Jaundice, Neonatal AND Phototherapy" limit to Newborn: birth-1 month, English, Clinical Trial, Human
111 references out of which only 2 relevant studies compared treatment and non-treatment groups with serum bilirubin levels more than 300mmol/l

Search Outcome

2 relevant studies compared treatment and non-treatment groups with serum bilirubin levels more than 300mmol/l

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lewis et al 1982 UK	40 babies with SBR>250 mumol/l randomized into 1. Early group (20): phototherapy given when serum bilirubin level >250 mumol/l 2 Late group (20): phototherapy given when serum bilirubin level >320 mumol/l	RCT	1.Number of babies requiring phototherapy	All 20 in early group and only 3 in late group received phototherapy	Small study group 9 babies had other pathologies which might have aggravated physiological jaundice (polycythemia, cephalhaematoma, poor fluid intake and minor skin sepsis) No conclusion regarding the critical bilirubin level above which treatment should be initiated
			Maximum SBR (mumol/l)	Early group-265 (250-370)
			Time from entry to SBR<250 mumol/l (hours)	Early group-18 (12-84)
			Age when SBR fell <250 mumol/l (days)	Early group-5(3-8)
Martinez et al 1993 USA	126 full term breast fed babies with SBR>290 mumol/l included. Phototherapy was commenced when SBR exceeded 342 mumol/l. Babies were assigned at random to one of four interventions Group 1. continue breast feeding and observe (25 babies) Group 2. discontinue breast feeding, substitute formula (26 babies) Group 3. discontinue breast feeding, substitute formula + phototherapy (38 babies) Group 4. continue breast feeding + phototherapy (36 babies)	RCT	Treatment failure (if SBR reached 342 mumol/l)	Group 1- 6 (24%),Group 2-5 (19%),Group 3-1 (3%),Group 4-5 (14%)	Follow up period not mentioned No long term follow up to detect any neurological sequelae No conclusion regarding the critical bilirubin level above which treatment should be initiated
			Proportion of babies whose SBR fell to below 231 mumol/l by 48 hours after the intervention	Group 1- 0 (0%),Group 2-5 (19%),Group 3-15 (45%),Group 4-17 (42%)
			Comparison of fall in SBR 48 hours after intervention, between the groups	1 vs 2 p= 0.145,1 vs 3 p< 0.0001, 1 vs 4 p<.0.0001, 2 vs 3 p= 0.0010, 2 vs 4 p= 0.0134, 3 vs 4 p= 0.160, p<0.0083 is significant at the 0.05 level

Comment(s)

The management of the jaundiced, otherwise healthy term newborn without risk factors for hemolysis has been an issue of long standing controversy.Very high levels of serum bilirubin may be toxic to the central nervous system and may cause neurological impairment.1 On the other hand, phototherapy can separate mother from baby and is physiologically stressful.2 It is not known at what bilirubin concentration or under what circumstances significant risk of brain damage occurs or when the risk of damage exceeds the risk of treatment. Lewis et al reported no significant rise in the peak serum bilirubin levels when the threshold value for treatment was increased from 250 to 320 mumol/l.2 Martinez et al found that 76% - 80% of babies did not require phototherapy when the threshold value was 342 mumol/l and suggested discussing treatment options with the parents.3 The above two studies concluded that serum bilirubin level falls spontaneously without any intervention in most of the healthy term breast fed newborns with physiological jaundice. Both studies found faster rate of fall in serum bilirubin levels with phototherapy, but the clinical relevance of this is not clear. The American Academy of Paediatrics Practice guidelines recommend phototherapy at a serum bilirubin level of >20 mg/dL (340 mumol/L).1 However the total experience analyzed in setting these guidelines involved a relatively limited number of healthy term infants with high bilirubin levels. Also, these guidelines are based on evidence only where appropriate data exist but on consensus in areas where data are lacking. To our knowledge, there are no such guidelines in the United Kingdom and in most of the hospitals the assigned arbitrary value is 300 mumol/L. The evidence to assign a critical level of serum bilirubin above which phototherapy is indicated in these babies lacks the support of large randomized controlled clinical trials. The consequences of neurological impairment from not treating very high levels of serum bilirubin are far more devastating than the possible side effects of phototherapy. This may be the ethical reason preventing a proper prospective randomized controlled trial.

Clinical Bottom Line

• The critical serum bilirubin level above which physiological jaundice should be treated is uncertain. • Phototherapy may be initiated at serum bilirubin levels of 340 mumol/L (as per the AAP guidelines) until more evidence is available.

References

1. Lewis HM, Campbell RH, Hambleton G. Use or abuse of phototherapy for physiological jaundice of newborn infants. Lancet Lancet 1982;2(8295):408-10.
2. Martinez JC, Maisels MJ, Otheguy L, Garcia H, Savorani M, Mogni B, Martinez JC Jr. Hyperbilirubinemia in the breast-fed newborn: a controlled trial of four interventions. Pediatrics Pediatrics 1993;91(2):470-3