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ObjectiveTo analyze the clinical manifestation of hemolytic disease of the newborn (HDN) due to anti-M and Rhesus system.MethodsClinical information was collected and analyzed for three cases with HDN due to anti-M and 64 with Rhesus hemolytic disease, who were admitted to Department of Neonatology, Beijing Children's Hospital Affiliated to Capital Medical University from February 2011 to January 2015, as well as another 28 cases of HDN due to anti-M with complete information retrieved from literature in Wanfang and China National Knowledge lnfrastructure (CNKI) Database from 1992 to 2014.Chi-square test was performed for statistical analysis.ResultsTwo out of the 64 Rh hemolytic babies gave up therapy due to kernicterus and another two out of the 31 MN hemolytic babies, obtained from literature, died 24 h after birth because of anemia or edema, while the rest survived. Although more babies were the first child of the family in HDN due to anti-M than those of Rh hemolytic disease [26%(8/31) vs 9%(6/64),χ2=4.487, P=0.034], but lower incidence of jaundice [81%(25/31) vs 98%(63/64),χ2=9.686,P=0.002], less proportion of presentation of jaundice within 24 h after birth [29% (9/31) vs 64%(41/64),χ2=10.279,P=0.001] and lower positive rate of direct antiglobulin test [39%(12/31) vs 100%(64/64), Fisher exact test,P=0.000] were shown in HDN due to anti-M. No significant difference was found in the incidences of hyperbilirubinemia [58%(18/31) vs 66%(42/64),χ2=0.513], severe hyperbilirubinemia [23%(7/31) vs 36%(23/64),χ2=1.724], anemia [81%(25/31) vs 89%(57/64),χ2=1.253] and severe anemia [29%(9/31) vs 34%(22/64),χ2=0.271] between HDN due to anti-M and Rh hemolytic babies (allP>0.05).ConclusionsHDN due to anti-M and Rhesus hemolytic disease can cause severe pathological jaundice and/or anemia in newborns. Indirect antiglobulin test should be offered when direct antiglobulin test is negative which is helpful in the diagnosis of HDN due to anti-M.