Longitudinal changes in maternal serum placental growth factor and soluble fms-like tyrosine kinase-1 in women at increased risk of pre-eclampsia.

OBJECTIVES: To investigate longitudinal changes in maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in pregnant women who develop pre-eclampsia (PE) or gestational hypertension (GH). METHODS: This was a prospective longitudinal study in women with singleton pregnancies identified by screening at 11 + 0 to 13 + 6 weeks' gestation as being at high-risk of PE. Blood samples were taken every 4 weeks until delivery. Values were compared in women who developed preterm PE (requiring delivery before 37 weeks' gestation), term PE or GH and those who remained normotensive. RESULTS: A total of 1069 samples were analyzed in 234 women, including 172 who remained normotensive, 18 who developed GH, 22 who developed preterm PE and 22 who developed term PE. In the preterm PE group, compared to the normotensive group, sFlt-1 levels were significantly higher from 15 weeks' gestation onward and the difference increased with gestational age (P < 0.001). In the preterm PE group, compared to the normotensive group, PlGF levels were significantly lower from 11 weeks' gestation onward and the difference increased significantly with gestational age (P < 0.001). Similarly, in the term PE and GH groups, PlGF levels were lower from 13 and 27 weeks onward, respectively, and the differences increased significantly with gestational age (P < 0.001 for both groups). In the preterm PE group, compared to the normotensive group, the sFlt-1/PlGF ratio was significantly higher from 11 weeks onward and the difference increased significantly with gestational age (P < 0.001). A random slope model provided a significantly better fit to the data than did a single-level model for sFlt-1 (likelihood ratio (LR) = 516; degrees of freedom (df) = 3; P < 0.001), PlGF (LR = 542; df = 3; P < 0.001) and the sFlt-1/PlGF ratio (LR = 468; df = 3; P < 0.001). CONCLUSION: Repeat measurements of the biochemical markers used in this study are likely to be better predictors of PE than are measurements at a single time point during pregnancy, as the differences between normotensive and hypertensive pregnancies increase with gestational age. In screening for preterm PE, maternal serum level of PlGF is a useful marker from the first trimester onward, while the level of sFlt-1 is likely to have a predictive value from the second trimester onward. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal changes in maternal corin and mid-regional proatrial natriuretic peptide in women at risk of pre-eclampsia.

OBJECTIVE: Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Yet, elevated maternal plasma atrial natriuretic peptide (ANP) and corin levels have been reported in pregnancies complicated by pre-eclampsia (PE). The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and mid-regional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop PE and gestational hypertension (GH). METHODS: This was a nested case-control study drawn from a larger prospective longitudinal study in singleton pregnancies identified as being at high risk for PE by screening at 11 + 0 to 13 + 6 weeks' gestation. Blood samples were taken every 4 weeks until delivery. Values were compared in pregnancies that developed preterm PE (requiring delivery before 37 weeks' gestation), term PE, GH and those that remained normotensive. RESULTS: A total of 471 samples were analyzed from 122 women, including 85 that remained normotensive, 12 that developed GH, 13 term PE and 12 preterm PE. In the normotensive group, log10 corin levels were associated with gestational age (P < 0.01), whereas log10 MR-PANP levels were not. In the preterm-PE group, compared with the normotensive group, corin was significantly lower until 20 weeks' gestation (P = 0.001). In the GH and term-PE groups, corin did not differ significantly from the normotensive group (P = 0.637 and P = 0.161, respectively). Compared with the normotensive group, MR-PANP levels were significantly higher in the pregnancies that developed preterm PE and GH (P = 0.046 and P = 0.019, respectively), but not term PE (P = 0.467). CONCLUSION: Maternal-plasma corin and MR-PANP could potentially be useful biomarkers for the prediction of preterm PE.

Longitudinal changes in maternal soluble endoglin and angiopoietin-2 in women at risk for pre-eclampsia.

OBJECTIVE: To investigate longitudinal changes in maternal plasma levels of soluble endoglin (sEng) and angiopoietin-2 (Ang-2) in pregnant women who develop pre-eclampsia (PE) and gestational hypertension (GH). METHODS: This was a nested case-control study drawn from a larger prospective longitudinal study in singleton pregnancies identified by screening at 11 + 0 to 13 + 6 weeks' gestation as being at high-risk for PE. Blood samples were taken every 4 weeks until delivery. Values were compared in women who developed preterm PE (requiring delivery before 37 weeks), term PE, GH and those who remained normotensive. RESULTS: A total of 471 samples were analyzed in 122 women, comprising 85 who remained normotensive, 12 who developed GH, 13 who developed term PE and 12 who developed preterm PE. In the normotensive group, there was an increase in log10 sEng levels with gestational age. In the preterm PE group, compared with the normotensive group, sEng was higher from 18 weeks onwards, and the difference increased significantly with gestational age (P < 0.001). In the GH and term PE groups, sEng did not differ significantly from that of the normotensive group (P = 0.583 and P = 0.890, respectively). The square root of Ang-2 decreased significantly with gestational age, but did not differ significantly among the different outcome groups (P = 0.571). CONCLUSION: Maternal plasma sEng, but not Ang-2, may be a useful mid- and late-gestation biomarker for the development of PE.

Longitudinal changes in maternal hemodynamics in a population at risk for pre-eclampsia.

OBJECTIVE: To investigate longitudinal changes in maternal hemodynamics from the first trimester onward in women who develop pre-eclampsia (PE) or gestational hypertension (GH). METHODS: This was a prospective longitudinal study of singleton pregnancies identified by screening at 11 + 0 to 13 + 6 weeks' gestation as being at high risk for PE. Measurements of augmentation index (AIx), pulsed wave velocity (PWV) and aortic systolic blood pressure (SBPao) were taken every 4 weeks until delivery. Values were compared between women who developed preterm PE requiring delivery before 37 weeks, term PE or GH, and those who remained normotensive. RESULTS: A total of 1198 observations were recorded in 245 women, including 181 who were normotensive, 22 with preterm PE, 22 with term PE and 20 with GH. In the normotensive group, there was a U-shaped relationship between AIx and gestational age with a trough at 25 weeks' gestation, whereas changes in levels of PWV or SBPao were minimal, with a mild increase from 25 and 30 weeks' gestation onward, respectively. In the GH and preterm PE groups, compared to the normotensive group, SBPao was higher and the difference did not change significantly with gestational age. In the term PE group, SBPao did not differ significantly from that in the normotensive group. In the preterm PE group compared to the normotensive group, PWV and AIx were significantly higher from 16-17 weeks' gestation onward and the difference increased with gestational age in both cases. In the term PE and GH groups, PWV and AIx did not differ significantly from normal. CONCLUSION: This study describes temporal changes in AIx, PWV and SBPao in normotensive pregnant women and in women who develop PE or GH.

Longitudinal changes in uterine artery Doppler and blood pressure and risk of pre-eclampsia.

OBJECTIVE: To investigate longitudinal changes in the uterine artery mean pulsatility index (UtA-PI) and mean arterial pressure (MAP) in women who develop pre-eclampsia (PE) and gestational hypertension (GH). METHODS: This was a prospective longitudinal study of singleton pregnancies identified by screening at 11 + 0 to 13 + 6 weeks' gestation as being at high risk for PE. Measurements of UtA-PI and MAP were taken every 4 weeks until delivery and were compared in women who developed preterm PE, requiring delivery before 37 weeks, term PE and GH with those in women who remained normotensive. RESULTS: In the normal outcome group, UtA-PI decreased with gestational age and MAP decreased between 12 and 24 weeks and then increased. In the preterm PE group, as compared to the normal group, UtA-PI and MAP were higher from early pregnancy onward and the difference for both increased with gestational age. In the term PE group, UtA-PI was significantly increased only from 33 weeks onward and MAP was increased from 12 weeks onward but the difference from normal did not increase with gestation. In GH, UtA-PI did not differ significantly from normal but MAP was higher from 12 weeks onward. CONCLUSION: The study describes temporal changes in UtA-PI and MAP in normal pregnancies and in women who develop PE and GH.

Maternal hemodynamics at 11-13 weeks of gestation and preterm birth.

OBJECTIVE: Women who experience preterm birth (PTB) are at increased risk of cardiovascular morbidity and mortality in the subsequent decades. Individuals with cardiovascular disorders have increased central aortic systolic blood pressure (SBP(Ao)) and arterial stiffness, assessed by pulse wave velocity (PWV) and augmentation index (AIx). The aim of this screening study was to evaluate SBP(Ao), PWV and AIx at 11-13 weeks' gestation in women who delivered preterm. METHODS: This was a prospective study in singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation. Maternal history and characteristics were recorded, and PWV, AIx and SBP(Ao) were measured. We compared these parameters in women who had spontaneous (n = 244) or iatrogenic (n = 110) PTB before 37 weeks' gestation and before 34 weeks with those in women who had term delivery (n = 7489). RESULTS: Compared with women who had term delivery, women who had iatrogenic PTB had significantly higher AIx (1.08 (interquartile range (IQR), 0.91-1.27) multiples of the median (MoM), vs. 1.00 (IQR, 0.86-1.16) MoM) and SBP(Ao) (1.06 (IQR, 0.98-1.15) MoM vs. 1.00 (IQR, 0.93-1.07) MoM). However, there was no significant difference in AIx, PWV or SBP(Ao) between those who had spontaneous PTB and those who had term delivery. These findings were similar for those who had PTB at < 34 and < 37 weeks' gestation. CONCLUSION: Women who had iatrogenic PTB, but not those who had spontaneous PTB, have increased SBP(Ao) and arterial stiffness that is apparent from as early as the first trimester of pregnancy.