Maternal soluble fms-like tyrosine kinase-1, placental growth factor, plasminogen activator inhibitor-2, and folate concentrations and early fetal size: The Generation R study

Objective: Fetal growth is dependent on adequate development of the placenta. Impaired angiogenesis and vasculogenesis in early pregnancy compromises placental and embryonic development. The proteins soluble fms-like tyrosine kinase (sFlt)-1, placental growth factor (PlGF), and plasminogen activator inhibitor (PAI)-2, and the B vitamin folate are determinants of placental development. This study aims to identify associations between these maternal biomarkers and early fetal size. Study Design: From a prospective birth cohort study in The Netherlands, 1491 pregnant women were selected for this study. At a mean gestational age (GA) of 12.4 weeks (SD 0.8) maternal venous blood samples were obtained to determine the concentrations of sFlt-1, PlGF, PAI-2, and folate. Early fetal size was assessed with measurement of the crown-to-rump length (CRL) at a mean of 12.4 weeks' GA (SD 0.8). Analyses were performed using multivariable linear regression analyses with the biomarkers (continuous, quintiles) as regressors and CRL as main outcome measure. Results: Linear trend analysis showed positive associations between maternal sFlt-1 (P <.001), PlGF (P =.042), PAI-2 (P <.001), and folate (P =.039) and CRL. These associations were independent of GA, maternal age, height, body mass index, ethnicity, fetal sex, parity, educational level, smoking, and folic acid supplement use (folate not adjusted). Conclusion: sFlt-1, PlGF, PAI-2, and folate are positively associated with first-trimester fetal size.

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