Association between maternal-fetal HLA-DR relationships and fetal growth

To determine whether maternal-fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight.

A cohort of 659 primigravid women were enrolled in this study in the prepartum period and their neonates were subsequently examined. Anthropometric, maternal cigarette smoking behavior, health, pregnancy, and delivery data were collected; serogenetic typing was conducted on maternal and cord bloods to determine maternal and neonatal HLA antigenic phenotypes. Women and their neonates were assigned to one of the four different types of maternal-fetal relationships existing at each of the HLA-A, B, DR, and DQ loci. Birthweights were treated quantitatively and qualitatively (neonates classified as growth-retarded or normal).

After controlling for other factors influencing birthweight (e.g., smoking, maternal body size), significantly lower birthweight trends (P < .01) were found when neonates expressed a single HLA-DR antigen and their mothers expressed a second HLA-DR antigen that was foreign (allogeneic) to their neonate.

Our findings supports the hypothesis that lack of maternal immune exposure to fetal HLA antigens is associated with a slowing of fetal growth. However, in this situation slowed fetal growth is most likely to occur when the fetus is potentially exposed to maternal HLA-DR alloantigens. We believe this sheds new light on immunologic events at the maternal-fetal interface influencing fetal growth. We present one possible explanation to account for this finding.