The influence of maternal Lewis, Secretor and ABO(H) blood groups on fetal growth restriction

Fetal growth restriction (FGR) is associated with thrombosis of the placenta and an increased risk of subsequent vascular disease in the mother and fetus. The products of interactions between ABO(H), Lewis and Secretor genes are also associated with thrombosis and vascular disease risk.

A prospective case-control study of mothers with a severe FGR pregnancy (cases, n = 128; controls, n = 288) was performed to determine whether FGR is associated with particular maternal blood groups.

No association with ABO(H) status was observed, but FGR was more common in maternal secretors (odds ratio [OR] 1.70, 95% confidence interval [CI] 1.08-2.69) and consequently in those mothers expressing Le(b) on their red cells (OR 1.80, 95% CI 1.15-2.83), with a reduced risk in non-secretors and those expressing Le(a). Given the association between blood groups and both activated protein C resistance (APCR) and von Willebrand factor (VWF) levels, post hoc pilot studies on first-trimester APCR and VWF antigen levels and blood group genotypes were performed. No relationship with Lewis or Secretor was observed. Despite this, lower first-trimester VWF levels were observed in pregnancies subsequently complicated by FGR.

This is the first study reporting a relationship between maternal Secretor/Lewis status and FGR. A link between blood groups and FGR is plausible, as both are associated with cardiovascular disease. We observed no relationship between Lewis/Secretor status and VWF or APCR, but this should be confirmed in a larger study. Thus, the mechanism whereby Secretor and/or Lewis influences FGR is unknown.