The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

Abstract

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age, The Journal of Maternal-Fetal & Neonatal Medicine, 21:5, 279-287, DOI: 10.1080 AbstractIntroduction. An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate. Methods. This longitudinal case-control study included 402 singleton pregnancies in the following groups: (1) normal pregnancies with appropriate for gestational age (AGA) neonates (n ¼ 201); (2) patients who delivered an SGA neonate (n ¼ 145); and (3) patients who developed PE (n ¼ 56). Maternal plasma samples were obtained at the time of each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. In this study, we included two samples per patient: (1) first sample obtained between 6 and 15 weeks of gestation ('first trimester' sample), and (2) second sample obtained between 20 and 25 weeks of gestation ('second trimester' sample). Plasma concentrations of s-Eng, sVEGFR-1, and PlGF were determined by specific and sensitive immunoassays. Changes in the maternal plasma concentrations of these angiogenesis-related factors were compared among normal patients and those destined to develop PE or deliver an SGA neonate while adjusting for maternal age, nulliparity, and body mass index. General linear models and polytomous logistic regression models were used to relate the analyte concentrations, ratios, and product to the subsequent development of PE and SGA. Results.(1) An increase in the maternal plasma concentration of s-Eng between the first and second trimesters conferred risk for the development of preterm PE and SGA (OR 14.9, 95% CI 4.9-45.0 and OR 2.9, 95% CI 1.5-5.6, respectively).(2) An increase in the maternal plasma concentration of sVEGFR-1 between the first and second trimester conferred risk for the development of preterm PE (OR 3.9, 95% CI 1.2-12.6). (3) A subnormal increase in maternal plasma PlGF concentration between the first and the second trimester was a risk factor for the subsequent development of preterm and term PE (OR 4....

Prediction of the preeclampsia: a view of biochemical markers

“…In contrast, a large nested case-control study within a cohort of nearly 30,000 pregnant women in Norway showed that low sFlt1 in first trimester predicted early onset preeclampsia [41]. Kusanovic et al also had confirmed that low sFlt1 in first trimester predicting preterm (as well as term) preeclampsia [43] and Erez et al [42]. Although after adjusting for BMI, age and nulliparity, this significance had disappeared.…”

“…PIGF value is also low with pregnancy complications associated with a dysfunctional placenta (SGA, preeclampsia or both) [44]. Several studies have found that low PlGF concentrations in first trimester are also predictive factor for SGA, even in the absence of preeclampsia [40,42,47].…”

“…By the way this situation leads to a course of antagonizing the angiogenic factors such as PlGF. Some studies have found that low PlGF is a good predictive factor in first trimester for preeclampsia [39][40][41][42][43], while other studies showed no predictive value for PlGF in first trimester [44][45][46][47]. Most studies have found that low PlGF in the second trimester predicts later occurrence of preeclampsia [47][48][49][50][51][52][53][54].…”

“…When, s-Eng used as first trimester screening marker, it shows conflicting results [42]. The prediction rate for early onset PE was 77.8% at a false positive rate of 5% (61) when s-Eng is used with Doppler ultrasound and PlGF.…”

The role of an ‘anti-angiogenic state’ in complications of pregnancy

“…A third article demonstrates that the magnitude of change in the maternal plasma concentrations of anti-angiogenic and angiogenic factors is associated with the subsequent risk for the development of preterm and term preeclampsia as well as delivering an SGA neonate [56].…”