Relative risk of haemolytic diseases of the foetus and newborn based on maternal alloantibody specificity: systematic review and meta-analysis

Haemolytic Disease of the Foetus and Newborn (HDFN) is a common cause of foetal morbidity involving the incompatibility of alloimmunised maternal erythrocyte IgG antibodies and foetal erythrocytes causing haemolysis in the neonate. HDFN severity will depend upon the maternal erythrocyte antibody specificity and the antibody titre strength of the antibody. The primary aim of this review is to determine what is the relative risk of neonatal hyperbilirubinaemia and anaemia when comparing different erythrocyte antibody specificities present in pregnant mothers known to cause haemolytic disease of the foetus and newborn? To obtain appropriate papers to be used in this study, Scopus, Pubmed and Embase databases employed using the search dates from January 1st 2012 until August 31st 2022 using a range of keywords. Meta-analysis was conducted on these papers using Openmeta analyst software using binomial random effects proportion-based analysis employing the Arcsine transformed proportion metric with a maximum likelihood random effects method. Upon analysis of included studies maternal anti-D had the greatest risk of causing neonatal anaemia of 34.9% (95% CI [0.195 – 0.522], p<0.001), followed by anti-c with a relative risk of 26.2% (95% CI [0.120 – 0.435], p<0.001) and with anti-Kell with a relative risk of 15.4% (95% CI [0.041 – 0.321], p<0.001). Maternal anti-c appears to have the highest relative risk of hyperbilirubinaemia with 65.2% (95% CI [0.412 – 0.857], p<0.001), anti-D with a relative risk of 55.5% (95% CI [0.291 – 0.804], p<0.001) and then anti-Kell with a relative risk of 30.0% (95% CI [0.049 – 0.648], p=0.001).