First-Trimester and Second-Trimester Maternal Serum Biomarkers as Predictors of Placental Abruption

OBJECTIVE: We hypothesized that the origins of abruption may extend to the stages of placental implantation; however, there are no reliable markers to predict its development. Based on this hypothesis, we sought to evaluate whether first-trimester and second-trimester serum analytes predict placental abruption. METHODS: We performed a secondary analysis of data of 35,307 women (250 abruption cases) enrolled in the First and Second Trimester Evaluation of Risk cohort (1999–2003), a multicenter, prospective cohort study. Percentiles (based on multiples of the median) of first-trimester (pregnancy-associated plasma protein A and total and free β-hCG) and second-trimester (maternal serum alpha-fetoprotein, unconjugated estriol, and inhibin-A) serum analytes were examined in relation to abruption. Associations are based on risk ratio (RR) and 95% confidence interval (CI). RESULTS: Women with an abnormally low pregnancy-associated plasma protein A (fifth percentile or less) were at increased risk of abruption compared with those without abruption (9.6% compared with 5.3%; RR 1.9, 95% CI, 1.2–2.8). Maternal serum alpha-fetoprotein 95th percentile or greater was more common among abruption (9.6%) than nonabruption (5.1%) pregnancies (RR 1.9, 95% CI 1.3–3.0). Inhibin-A fifth percentile or less (8.0% compared with 5.1%; RR 1.8, 95% CI 1.1–2.9), and 95th percentile or greater (9.6% compared with 5.0%; RR 2.0, 95% CI 1.3–3.1) were associated with abruption. Women with all three abnormal pregnancy-associated plasma protein A, maternal serum alpha-fetoprotein, and inhibin-A analytes were at 8.8-fold (95% CI 2.3–34.3) risk of abruption. No associations were seen with other analytes. CONCLUSION: These data provide support for our hypothesis that the origins of placental abruption may extend to the early stages of pregnancy.