Fetal MCA Doppler to time intrauterine transfusions in red cell alloimmunisation: A randomised trial

OBJECTIVES: Red cell alloimmunisation affects up to 0.6% of all live births, and can be successfully treated with intrauterine fetal blood transfusion. Fetal middle cerebral artery (MCA) Doppler peak systolic velocity (PSV) is a non-invasive test, to identify fetal anaemia and requiring intrauterine transfusion (IUT). Traditionally, timing of subsequent IUTs has involved estimating a fall in fetal haematocrit of 1% per day, or a fall in fetal haemoglobin of 0.3 g/dL per day. The aim of this pragmatic multi-centre randomised trial was to evaluate whether Doppler MCA-PSV in the fetus that has undergone one IUT for anaemia secondary to red cell alloimmunisation was non-inferior to timing IUT by timing based on predicting the fall in fetal haematocrit or fetal haemoglobin, without compromising infant haemoglobin at birth.

METHODS: We conducted an international, multi-centre randomised trial. Women with pregnancies complicated by fetal anaemia secondary to red cell alloimmunisation (due to any antibody alone or in combination) as indicated by the need to undergo a single IUT were eligible for inclusion. Women were randomised to the Timing of Transfusion by MCA-PSV Group (ultrasound determination of the fetal MCA-PSV, with a serial upward trend with values >1.5MoM considered indicative of the need for another IUT), or to the Timing of Transfusion by Prediction of the Fall in Fetal Haematocrit (Hct) Group (subsequent IUT's timed according an estimated fall in fetal Hct of 1% per day or fetal haemoglobin of 0.3 g/dL per day, to maintain the fetal haemoglobin between 7-10 g/dL). The primary study outcome was infant haemoglobin measured at birth. The trial was registered on the Australian and New Zealand Clinical Trials Register (ACTRN12608000643370).

RESULTS: We randomised 71 women (36 to the MCA-PSV Group; and 35 to the Fall in Fetal Hct. Group) from 13 centres in Australia, New Zealand, Canada, United Kingdom, Ireland, Belgium, and Argentina. The median gestational age at randomisation was 30.3 weeks, and the majority of women were Caucasian and non-smokers; 9.9% of women had Kell alloimmunisation, and 14% of fetuses were hydropic at their first IUT. There were no statistically significant differences between the two treatment groups with regards to mean haemoglobin at birth (MCA-PSV Group 103.6 ± 38.2 g/dL versus Fall in Fetal Hct Group 120.3 ± 31.4 g/dL; adjusted mean difference -15.6; 95% CI -32.4 to 1.3; p = 0.070)), or the number of IUTs performed after randomisation (MCA-PSV Group 1.75 (±1.79) versus Fall in Fetal Hct Group 1.80 (±1.32); adjusted relative risk aRR 0.88; 95% confidence interval (CI) 0.61 to 1.26; p = 0.474). There were no statistically significant differences between the two groups in the risk of adverse infant outcomes related to alloimmunisation, or procedure related complications.

CONCLUSIONS: Both Doppler MCA-PSV measurement and estimating the fall in fetal haematocrit or haemoglobin can be used to time second and subsequent IUTs.