Human leukocyte antigen matching and fetal loss: results of a 10 year prospective study

The role that maternal and fetal human leukocyte antigen (HLA) genes playin pregnancy is unknown, but it has been suggested that fetuses whose HLAalleles do not differ from maternal alleles (i.e. histocompatible fetuses)are more likely to be aborted than fetuses with HLA alleles that differfrom maternal alleles (i.e. histoincompatible fetuses). To elucidate therole of HLA compatibility in pregnancy, we tested the hypothesis thatcouples who match for HLA alleles or haplotypes would have reducedfertility because only these couples could produce histocompatible fetuses.We conducted a 10 year prospective study of HLA matching and pregnancyoutcome in 111 Hutterite couples, providing information on 251 pregnancies.A logistic regression analysis was performed to determine the effects ofHLA matching at HLA regions and loci on pregnancy outcome (fetal lossversus delivery). Significantly increased fetal loss rates were observedamong couples matching for the entire 16-locus haplotype (P = 0.002). Amongthe individual loci, loss rates were increased among couples matching forHLA-B (P = 0.019), HLA-C (P = 0.033) and the complement component, C4 (P =0.043). We interpret these results as evidence that matching for the entire16-locus haplotype and/or alleles at an HLA-B-linked locus conferssignificant risk for fetal loss.