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Treatment

The use of IVIG in babies with haemolytic hyperbilirubinaemia is accompanied by significant
reduction in the need for exchange transfusion. This effect is greater in Rhesus haemolytic
disease (NNT = 2) than in ABO incompatibility (NNT = 5).
Riboflavin at a dose of 10 mg/kg body weight showed promising results in babies awaiting
exchange transfusion for haemolytic jaundice.

There was no evidence to support the use of metalloporphyrins, cholestyramine, albumin
infusions, agar, barbiturates, D-penicillamine, glycerin, charcoal, Pojark Manna, traditional
Chinese medicine, homeopathy or acupuncture.
Cost-effectiveness of other treatments

The clinical evidence suggests that babies with Rhesus and ABO haemolytic disease receiving
IVIG are less likely to require exchange transfusion, which is an expensive procedure with
associated morbidity and mortality. However, IVIG is also a relatively expensive therapeutic
intervention and there is a shortage of global supply. Therefore an economic evaluation was
undertaken to help guide GDG recommendations. Full details of this analysis can be found in
Appendix D. The analysis compared giving IVIG as an adjunct to phototherapy in babies with
Rhesus haemolytic disease and ABO haemolytic disease where serum bilirubin is continuing to
rise at more than 8.5 micromol/litre per hour against not giving IVIG to these babies.
In the base-case analysis, the NNT with IVIG to avoid an exchange transfusion was two for
babies with Rhesus haemolytic disease and five for babies with ABO haemolytic disease. The
model assumed a mortality rate of 2% for exchange transfusion for the base case but did not
consider other complications arising from an exchange transfusion or IVIG. This was partly
to simplify the analysis but also because any impact on quality-adjusted life years (QALYs)
would be small relative to the impact from assuming causation between exchange
transfusion and mortality. In the base-case analysis, IVIG appears to be a cost-effective
treatment for Rhesus haemolytic disease and ABO haemolytic disease, with incremental cost-
effectiveness ratios of £2,248 per QALY and £11,944 per QALY, respectively. However,
there is important uncertainty in the model, in particular in relation to the exact number
needed to treat with IVIG to avoid an exchange transfusion and the mortality attributable to
exchange transfusion. Therefore, to test the robustness of the base-case cost-effective finding,
a ‘worst-case’ sensitivity analysis was undertaken. This used the upper 95% confidence
interval for NNT (three for Rhesus disease and 13 for ABO disease) and a much lower 0.3%
mortality due to exchange transfusion. For Rhesus haemolytic disease this gave a cost per
QALY of £34,379, which is only just outside the upper bound of what NICE would accept as
cost-effective treatment. The incremental cost-effectiveness ratio for ABO haemolytic disease
in this ‘worst-case’ sensitivity analysis was £243,381 per QALY. These results suggest that
IVIG for Rhesus disease is likely to be cost-effective as it remains borderline cost-effective
even in a ‘worst-case’ scenario. However, the cost-effectiveness of IVIG in ABO disease is
less clear-cut and further research would be needed to more accurately establish its cost-
effectiveness in this population.
Overall GDG translation for other treatments

The evidence supports the current clinical practice of using IVIG alongside phototherapy in babies
with Rhesus and ABO haemolytic disease. This practice is also in line with recent guidance from
the Department of Health (www.dh.gov.uk/en/Publicationsandstatistics/Publications/Publications
PolicyAndGuidance/DH_085235). In these babies, IVIG has been shown to reduce the need for
exchange transfusion, a procedure which has associated morbidity and mortality. The GDG
agreed that concern over donor over-exposure, potential adverse effects and costs dictate that this
treatment should be reserved for cases with significant haemolysis evidenced by serum bilirubin
rising by > 8.5 micromol/litre per hour despite multiple phototherapy. While an economic
analysis suggested that IVIG was cost-effective, some uncertainty remains, especially for babies
with ABO haemolytic disease because of the higher number needed to treat to avoid an exchange
transfusion. Therefore, the GDG believes that further research could better inform cost-effective
practice. The GDG noted that babies whose parents object to the use of blood products for
religious or cultural reasons should be treated with the same standard of care as all babies, with

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