Longitudinal trends in fetoplacental biochemical markers, uterine artery pulsatility index and maternal blood pressure during the first trimester of pregnancy

Abstract

To assess trends in levels of biochemical markers, uterine artery (UtA) pulsatility index (PI) and maternal blood pressure changes over time and study their relationships in uncomplicated first-trimester pregnancies. The study population comprised 86 women with singleton pregnancies. In each woman, a blood sample was collected at 6-7, 8-9, 10-11 and 12-13 weeks' gestation. At the same visit blood pressure was measured and ultrasound examination was performed to measure the crown-rump length and Doppler flow velocity waveform patterns of both UtAs. Serum concentrations of pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG), A disintegrin and metalloprotease domain-containing protein-12 (ADAM-12), placental protein-13 (PP-13) and placental growth factor (PlGF) levels were measured in thawed specimens using an automated time-resolved fluorescence assay. Summary curves were created to describe normal ranges and trends over time. The data were analyzed with a linear mixed model with the log-transformed marker values as dependent variables. This allowed for flexible modeling of patterns over time. Sixty-eight pregnancies had an uneventful outcome, with the birth of an appropriate-for-gestational-age (AGA) infant. In these pregnancies serum PAPP-A, ADAM-12, PP-13 and PlGF levels increased with gestational age. The UtA-PI decreased and the mean arterial blood pressure remained constant. There were no significant correlations between maternal age, birth-weight percentile, gender and blood pressure and any of the biochemical markers. The serum markers were highly correlated with each other except for β-hCG. A negative correlation was found between most biomarkers and UtA-PI, especially from 10 weeks onwards. Serum concentrations of ADAM-12 and PP-13 were lower in a small-for-gestational-age (SGA) subgroup born at term (n = 6), the former statistically significantly (P = 0.031), the latter non-significantly (P = 0.054), whereas UtA-PI was significantly higher (P = 0.02). Biomarker concentrations in 12 women delivering a large-for-gestational age infant did not differ from those delivering AGA neonates. There is a relationship between biochemical markers of early placentation and downstream resistance to flow in the UtAs in low-risk uncomplicated pregnancies, indicating differences in placentation. In a small series of SGA infants born at term we could demonstrate differences as compared to normal pregnancies, with potential value for screening.