Background: About 85.3% of hemolytic disease of newborn (HDN) is caused by maternal-fetal ABO blood group incompatibility, however, there is currently no recommended 'best' therapy for ABO incompatibility during gestation.

Objectives: To systematically assess the safety and effectiveness of oral administration of Chinese herbal medicine (CMH) on preventing HDN due to ABO incompatibility.

Methods: The protocol of this review was registered on the PROSPERO website (No. CRD42016038637). Six databases were searched until April 2016. Randomised-controlled trials (RCTs) of CHM for maternal-fetal ABO incompatibility were included. The primary outcome was incidence rate of HDN. The risk of bias of the Cochrane Handbook was used to assess the methodological quality of included trials. Risk ratio (RR) and mean difference with a 95% confidence interval were used as effect measures. Meta-analysis was used by Revman 5.3 software if sufficient trials without obvious clinical or statistical heterogeneity were available.

Results: A total of 28 RCTs with 3413 women were included in the review (Fig 1). The majority of them have unclear or high risk of bias (Fig 2). The results found the HDN rate and the incidence of the icterus neonatorum of the newborn in herbal medicine group might be 70% lower than in usual care group (RR from 0.25 to 0.30, Fig 3-5); herbal medicine may increase twice numbers (RR from 2.15 to 3.14, Fig 6) of the women whose antibody titer lower than 1:64 after treatment compared to usual care; umbilical cord blood bilirubin in herbal medicine group would be 4umol/L less than usual care; and no difference of Apgar scores or weight of the newborn between groups.

Conclusions: This review found very low-quality evidence of CHM with function of clearing heat and draining dampness for maternal-fetal ABO incompatibility on preventing HDN (Table 1). No firm conclusion could be draw for the effectiveness or safety of CHM for this condition.