title: Maternal plasma fetuin-A concentration is lower in patients who subsequently developed preterm preeclampsia than in uncomplicated pregnancy: a longitudinal study.
abstract: Objective: Fetuin-A is a negative acute phase protein reactant that acts as a mediator for lipotoxicity, leading to insulin resistance. Intravascular inflammation and insulin resistance have been implicated in the mechanisms of disease responsible for preeclampsia (PE). Maternal plasma concentrations of fetuin-A at the time of diagnosis of preterm PE are lower than in control patients with a normal pregnancy outcome. However, it is unknown if the changes in maternal plasma fetuin-A concentrations precede the clinical diagnosis of the disease. We conducted a longitudinal study to determine whether patients who subsequently developed PE had a different profile of maternal plasma concentrations of fetuin-A as a function of gestational age (GA) than those with uncomplicated pregnancies. Methods: A longitudinal case-control study was performed and included 200 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered appropriate for gestational age (AGA) neonates (n = 160); and (2) patients who subsequently developed PE (n = 40). Longitudinal samples were collected at each prenatal visit and scheduled at 4-week intervals from the first or early second trimester until delivery. Plasma fetuin-A concentrations were determined by ELISA. Analysis was performed using mixed-effects models. Results: The profiles of maternal plasma concentrations of fetuin-A differ between PE and uncomplicated pregnancies. Forward analysis indicated that the rate of increase of plasma fetuin-A concentration in patients who subsequently developed PE was lower at the beginning of pregnancy (p = 0.001), yet increased faster mid-pregnancy (p = 0.0017) and reached the same concentration level as controls by 26 weeks. The rate of decrease was higher towards the end of pregnancy in patients with PE than in uncomplicated pregnancies (p = 0.002). The mean maternal plasma fetuin-A concentration was significantly lower in patients with preterm PE at the time of clinical diagnosis than in women with uncomplicated pregnancies (p < 0.05). In contrast, there were no significant differences in maternal plasma fetuin-A concentration in patients who developed PE at term. Conclusions: (1) The profile of maternal plasma concentrations of fetuin-A over time (GA) in patients who develop PE is different from that of normal pregnant women; (2) the rate of change of maternal plasma concentrations of fetuin-A is positive (increases over time) in the midtrimester of normal pregnancy, and negative (decreases over time) in patients who subsequently develop PE; (3) at the time of diagnosis, the maternal plasma fetuin-A concentration is lower in patients with preterm PE than in those with a normal pregnancy outcome; however, such differences were not demonstrable in patients with term PE.
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development , NIH, Bethesda, Maryland and Detroit, MI , USA .
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Korzeniewski
authors.forename: Alyse G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Jezid
authors.initials: J
authors.lastname: Miranda
authors.forename: Ahmed I
authors.initials: AI
authors.lastname: Ahmed
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Tinnakorn
keywords: hypertensive disorders in pregnancy; insulin resistance; intravascular inflammation; negative acute phase protein reactant; α2-Heremans–Schmid glycoprotein