Maternal-Child Blood Group Discordance and Congenital Heart Disease Severity: An Immunological Risk Perspective from a Tertiary Hospital-Based Study

Background
Congenital heart disease (CHD) is the most prevalent congenital anomaly, with outcomes strongly influenced by disease complexity. Beyond genetic and environmental determinants, maternal-fetal immuno-haematological interactions may contribute to CHD risk and severity. ABO and Rh incompatibilities can trigger immune responses in utero, yet their role in CHD severity remains unclear. This study assessed associations between maternal-child blood groups, compatibility patterns, and CHD severity using the Risk Adjustment for Congenital Heart Surgery (RACHS) scoring system and cyanosis status.

Methods
A retrospective cohort of 900 non-syndromic singleton children with CHD (0-12 years) undergoing surgical correction and their mothers was analysed at a tertiary referral center. Maternal and child ABO/Rh blood groups and compatibility status were documented. CHD was categorised as simple (RACHS 1), moderate (RACHS 2), or complex (RACHS ≥3), and as cyanotic vs. acyanotic. Associations were tested using comparative statistics and ordinal regression with subgroup validation by age.

Results
Of 900 cases, 562 (62.4%) were acyanotic; RACHS distribution was 64 simple, 432 moderate, and 404 complex. Blood group B predominated in mothers (n=319, 35.4%) and children (n=316, 35.1%). ABO and Rh incompatibilities occurred in 257 (28.6%) and n=44 (4.9%) dyads, respectively. Maternal-child ABO discordance was significantly associated with moderate CHD (OR=3.31, 95% CI: 1.19-9.18; p=0.022), while Rh incompatibility showed a notable trend with cyanotic CHD (p=0.076) in children aged 1-5 years. Maternal blood groups B and AB were protective against CHD severity compared to O (OR=0.26-0.41, p <0.05). Child blood groups A, B, and AB also conferred protection against moderate and complex CHDs (OR=0.29-0.39, p <0.05). No significant association was observed for combined ABOxRh discordance.

Conclusion
This study provides the first evidence that maternal–child blood group relationships, particularly ABO incompatibility, may influence CHD severity. These findings warrant multicentric validation and exploration of underlying immunogenetic mechanisms.