Vasculopathic and thrombophilic risk factors for spontaneous preterm birth

Background Mothers who give birth to preterm infants are at increased risk of mortality from coronary heart disease and stroke, but the biological pathways underlying these associations have not been explored. Methods We carried out a case-control study nested in a large (n=5337) prospective, multicentre cohort. All cohort women had an interview, examination and venipuncture at 24―26 weeks. Frozen plasma samples in spontaneous preterm births (n=207) and 444 term controls were analysed for plasma homocysteine, folate, cholesterol (total, low-density lipoprotein and high-density lipoprotein) and thrombin-antithrombin (TAT) complexes. DNA was extracted and analysed for seven gene polymorphisms involved in thrombophilia or folate or homocysteine metabolism. Fresh placentas were fixed, stained and blindly assessed for histologic evidence of infarction and decidual vasculopathy. Results High (above the median) plasma homocysteine and HDL cholesterol were significantly and independently associated with the risk of spontaneous preterm birth [adjusted odds ratios (OR)s=1.9 (95% 1.1-3.3) and 0.5 (0.3-0.9), respectively]. A higher proportion of women with high homocysteine concentrations had decidual vasculopathy [ ( 13.0 vs 6.8%; OR= 1.9 (1.1―3.5)], although the positive association between decidual vasculopathy and preterm birth did not achieve statistical significance [OR= 1.5 (0.9-2.7)]. No significant associations were observed with the DNA polymorphisms or with plasma TAT or folate levels. Conclusions Similar vasculopathic risk factors may underlie preterm birth and adult coronary heart disease and stroke.