Haemolytic disease of the foetus and newborn due to anti‐M: A systematic review

BACKGROUND AND OBJECTIVES: Haemolytic disease of the foetus and newborn (HDFN) caused by anti-M antibodies is historically considered clinically insignificant. This systematic review aims to comprehensively evaluate the literature on anti-M-mediated HDFN, assessing its clinical spectrum, risk factors, management and outcomes. MATERIALS AND METHODS: A systematic search was conducted across PubMed, Chongqing VIP information Co., Ltd (CQVIP), Wanfang Data and China National Knowledge Infrastructure (CNKI) from database inception (PubMed 1966, CNKI 1979) to 30 April 2024. Studies published in English or Chinese, which reported diagnostic parameters, clinical management or quantifiable outcomes of anti-M-mediated HDFN, were included. Data on maternal history, serological results, interventions and perinatal outcomes were extracted and analysed. RESULTS: Among cases reported in the Chinese and English language literature included in this review, a marked geographical concentration was observed, primarily reflecting the inclusion of Chinese-language databases. Severe HDFN was significantly associated with multiparity, adverse pregnancy history and elevated antibody titres (p < 0.05). Notably, 65% (61/94) of neonates tested were direct antiglobulin test (DAT)-negative, and 50% (14/28) of anti-M samples exhibited stronger reactivity at 4°C/room temperature than at 37°C. Clinically, antenatal interventions were required in 20.3% (25/123) of pregnancies. Outcomes included total pregnancy loss in 11.4% (14/123) and persistent neonatal anaemia in 13.0% (14/108) of live births. CONCLUSION: Within the Chinese and English language literature, anti-M-mediated HDFN is shown to be a cause of severe perinatal morbidity and mortality, with a pronounced overrepresentation of severe cases in Asian populations. The findings highlight the necessity of dual-temperature serological testing and vigilant monitoring of at-risk pregnancies. The observed ethnic concentration warrants further investigation.