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Neonatal jaundice

The National Institute of Child Health and Human Development (NICHHD) study in the USA
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which compared phototherapy with no treatment, used exchange transfusion as an outcome. The
morbidity and mortality associated with exchange transfusions was also examined in the 190
subjects who received 331 exchange transfusions. The serum bilirubin levels at which exchange
transfusions were indicated ranged from 171 micromol/litre for high-risk low-birthweight babies to
342 micromol/litre for babies with birthweight > 2500 g. The mean reduction in serum bilirubin
was 139 ± 30 micromol/litre. Adverse effects related to exchange transfusions were transient
bradycardia in eight babies (4.2%) – six after receiving calcium – transient cyanosis in three
(1.6%), transient vasospasm in two (1.0%), vasospasm with thrombosis in two (1.0%) and apnoea
and/or bradycardia requiring treatment in seven babies (3.7%). Three babies died within 24 hours
(one within 6 hours) of exchange transfusion. [EL 1++]
Evidence summary

Most of the included RCTs were of poor quality, had small sample sizes and were conducted
more than 30 years ago. In one trial with EL 1−, no difference was observed in the mortality or
incidence of kernicterus between babies given DVET and those not given any treatment,
although this study did not specify the demographic characteristics or the criteria for diagnosing
kernicterus. Results from the second trial with EL 1+ suggest that, compared with simple
transfusion, DVET leads to fewer deaths and less kernicterus in the treatment of haemolytic
disease of the newborn. Another trial with EL 1− compared phototherapy with DVET for the
treatment of non-haemolytic hyperbilirubinaemia and showed better results with phototherapy.
However, DVET was carried out as a single procedure and was not followed by phototherapy,
as is the current clinical practice. The other trials showed no statistically significant differences
between DVET and SVET, albumin-enriched exchange transfusions or transfusion using frozen
erythrocytes diluted in plasma for the treatment of hyperbilirubinaemia.
Evidence on the adverse effects of exchange transfusions was collated from non-comparative
studies. The most common adverse effects were thrombocytopenia, hypocalcaemia, catheter
malfunction, hypotension, venous thrombosis, hypokalaemia and hypoglycaemia.

GDG translation from evidence
The GDG considered the potential adverse side effects of DVET when carried out by
experienced healthcare professionals and concluded that this procedure is relatively safe and
effective for babies at risk of kernicterus from severe hyperbilirubinaemia.

The GDG noted that a single study reported no difference between SVET and DVET but
considered this single study to be insufficient evidence to change current clinical practice. The
clinical rationale for using double volume rather single volume is to reduce the likelihood of
needing repeat transfusion.
No added benefit was found for albumin priming or for giving calcium with the exchange
transfusion, so the GDG considered that in the absence of evidence to support these practices
they should not be recommended.

Blood used for exchange transfusions should comply with the current guidance from the British
Committee for Standards in Haematology (www.bcshguidelines.com). The GDG noted that babies
whose parents object to the use of blood transfusions for religious or cultural reasons should be
treated with the same standard of care as all babies, with the best interests of the child paramount.
Local procedures should be in place to support communication with parents in this situation.
As stated in Section 3.2, acute bilirubin encephalopathy is a risk factor for kernicterus, and as such
the GDG concluded that there is no reason to change current clinical practice, which is to perform
an exchange transfusion in babies with signs of acute bilirubin encephalopathy (which include
opisthotonos and retrocollis). Babies with signs attributable to acute bilirubin encephalopathy
require exchange transfusion even if their bilirubin levels are controlled by phototherapy.
As bilirubin levels may not fall and may continue to rise, even after an exchange transfusion, it
is considered ‘best’ practice to estimate bilirubin levels within 2 hours to assess whether another
exchange transfusion is needed.

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