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You are a neonatal junior doctor looking after the special care nursery. You process a capillary blood sample taken on the morning blood round by someone who has now gone home, and find the haematocrit to be high at 69%. You go back to the baby and find the child to be term, of low birth weight, and admitted to the special care nursery because of low Apgars the previous day. He has not been feeding too well, but the neonatal nurses are not otherwise concerned. He is normal on examination, and his venous haematocrit comes back at 68%. Does this baby need a partial plasma exchange transfusion (PPET)?
Structured clinical question
In an asymptomatic neonate with an incidental finding of raised venous haematocrit [patient], does treatment with a partial plasma exchange transfusion [intervention] reduce adverse neurological outcome [outcome]?
Search strategy and outcome
Using the Cochrane Controlled Trials Register—“Polycythaemia”. Verified using Medline—“polycythamia”, “neonate”, AND “RCT filter”. Six papers identified, of which one irrelevant and one of insufficient quality. See table 2.
The research papers all use hyperviscosity rather than polycythaemia as the basis for their studies. The test for this is not routinely available, and so in the clinical setting, polycythaemia is used as a marker for hyperviscosity. Hyperviscosity is the increased internal friction of blood. It varies according to the flow rate; it is in the capillaries, where the flow rate is low, that the hyperviscosity is thought to contribute to reduced tissue perfusion. Red cell concentration (haematocrit) contributes significantly to viscosity; Bada et al found a consistent correlation between the two (r = 0.5, p < 0.001).
Neonatal polycythaemia is associated with adverse neurological outcome. All papers in the table included a control group of non-polycythaemic or non-hyperviscous infants. The group of infants in the Black et al study showed a significant overall risk of mild developmental delay; this risk was greater than the modest treatment effect, compared with infants controlled for gestational age, birth weight, but not for perinatal risk factors (see table 2A).
The Bada et al study matched the control group for gestational age, birth weight, and perinatal risk factors of fetal distress or asphyxia, pre-eclampsia, and maternal diabetes. Regression analysis was performed to determine the effects of these risk factors on outcome. The risk of adverse neurological outcome was more strongly predicted by perinatal risk factors than the presence of hyperviscosity.
It is notable that there was no abnormal neurology in the infants studied at eight months follow up by van der Elst et al, which may be a result of the type of patients included, the small numbers of patients, or the relatively short follow up period. The subjects of the Black et al study included some who were neurologically normal at 1 year, but had developed signs by 2 years of age. However, the relatively low follow up rate (65% for those randomised, 51% for control infants) makes the findings tentative at best. Similarly, although the Goldberg et al study has 80% follow up of the 20 patients, only 6/10 of the observation group were studied, in contrast to 10/10 of the treatment group.
It is important to assess whether these patients are comparable to the clinical scenario. Only the van der Elst patients were selected on clinical grounds (“appearing polycythaemic”), the other patients being selected by a screening process. The other factor that makes the van der Elst et al group of patients comparable in particular to this scenario is that the infants included those who had “minor signs”, defined as lethargy, irritability, peripheral cyanosis, vomiting, and poor feeding.
CLINICAL BOTTOM LINE
Polycythaemia is a risk factor for later neurological abnormality.
Partial plasma exchange transfusion has no clear long term benefit in asymptomatic polycythaemia or hyperviscosity, though evidence either way is weak and inconsistent.
Citation Study group Study type (level of evidence) Outcome Key results Comments
Bada et al (1992) 28 neonates screening cord blood haematocrit, and found to have both arterial haematocrit 63% with hyperviscosity, and asymptomatic Randomised to PPET or symptomatic care RCT (level 1b) Mental development index/IQ Mean score in treated group 85 v observed 88; difference -3 (95% CI -19 to +13) Mean 27.5 mth follow up, assessors blind to neonatal course 71% follow up rate Mental retardation rate Higher borderline retardation rate in treated group (66% v 45%; ARR = 0.21 (95% CI -0.21 to 0.63) Black et al (1985) 93 neonates selected by: admission to nursery at 4–6 h of age, screened by heel prick testing, and found to have both venous polycythaemia (HCT 65%) and hyperviscosity, includes symptomatic and asymptomatic Randomised to PPET or symptomatic care RCT (level 1b) Mental delay rate Reduced by PPET (18% v 13%); "not significant" (numbers not given) 2 years follow up 65% follow up rate Includes 2 deaths in observed group, one of head trauma and one of hepatitis Motor delay rate Reduced by PPET (19% v 35%); "not significant" (numbers not given) Neurological diagnosis rate Reduced by PPET (25% v 55%); p<0.05 Goldberg et al (1982) 20 neonates, selected by: screening heel prick on all babies, result 68%, and hyperviscous on venous blood, excludes neurologically symptomatic Randomised to PPET or symptomatic care RCT (level 1b) Bayley mental development index Mean difference 2.6 (95% CI -16 to 21) 8 months 80% Bayley psychomotor development index (control score 112) Abnormal neurological findings Mean difference -0.8 (95% CI -13 to 15) (control score 108) Abnormal postural reflexes 1/6 of treatment group, 5/10 observed group, NNT = 3 (95% CI -10 to 1) 6/10 in treatment group, 0/6 in observed group, NNT = 2 (95% CI 1 to 3) van der Elst et al (1980) 49 neonates selected by: appearance of polycythaemia, central haematocrit 65%, and no symptoms, or mildly symptomatic* Randomised to PPET or symptomatic care RCT (level 1b) Developmental score "No difference" 8 months follow up Neurological examination "No difference" (normal in all) 86% follow up one death (NEC) in treatment group
*"Minor signs" defined as lethargy, tremulousness, irritability, peripheral cyanosis, vomiting, and poor feeding.