A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction

Abstract

Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and ‘placental’ intrauterine growth restriction patients, which could be used in developing common diagnostic criteria for pregnant patients.

Systematic review of maternal Placental Growth Factor levels in late pregnancy as a predictor of adverse intrapartum and perinatal outcomes

“…Twenty-six studies (total participants, N = 42,609) were deemed to be eligible for final inclusion. Of these, 21 studies reported the relationship between PlGF and SGA or FGR infants with a participant total of N = 41,837 (10,13,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42), seven studies detailed the predictive value of PlGF for other adverse perinatal outcomes with a participant total of N = 13,401 (8,10,13,14,25,38,43) and three studies described the role of PlGF in distinguishing between placentally-mediated FGR and constitutionally SGA infants with a participant total of N = 841 (10,44,45). Table 1 and include the type of study, populations of recruited women, total number of participants, gestation at which PlGF was measured, type of PlGF assay, criteria for abnormal maternal PlGF levels if defined and specific outcomes investigated.…”

“…antenatal ultrasound (10,30,39,44,45), two recruited those at risk of either FGR or pre-eclampsia (27,43), and one study recruited women with abnormal uterine artery Dopplers (40). Two studies investigated specific populations -women with Type 1 Diabetes Mellitus (35) and those living at high altitude (28).…”

“…Although all the included studies collected PlGF samples >20 weeks gestation, eight studies collected samples exclusively in the third trimester (>30 weeks gestation) (8,13,14,25,26,31,32,44). The included studies used a variety of PlGF assay platforms from various manufacturers -R&D Systems ® (14,24,26,27,35,(38)(39)(40)(41)(42)44), Roche Diagnostics ® (13,25,28,29,31,32,34,36), Alere ® (8,10,30,43,45), PerkinElmer ® (37) and BRAHMS KRYPTOR ® (33). Only half of the included studies reported the definition of an abnormal PlGF criterion (10, 13, 14, 24, 25, 29-32, 38, 40, 43, 45); of these the majority used <5 th centile for gestational age as the defined threshold (10,13,25,(29)(30)(31)(32)45).…”

The role of interleukins in preeclampsia: A comprehensive review

“…It is also remarkable that no statistical association was found in studies that measured IL‐6 concentration in the first and second trimester of pregnancy. A newer study confirmed the elevated levels of IL‐6 both in early‐ and late‐onset PE, while Taylor et al did not observe a significant increase in the first and second trimester. Moreover, Rădulescu et al showed that although second‐trimester IL‐6 was significantly elevated, its diagnostic efficacy was not adequate (AUC: 0.568).…”

The role of disordered angiogenesis tissue markers (sflt-1, Plgf) in present day diagnosis of preeclampsia

“…It must be emphasized, however, that the sFlt-1 and PlGF angiogenesis -related disease markers also demonstrate irregularities in other conditions related to placental hypoperfusion and ischemia. The markers show similar variation profiles in intrauterine growth restriction syndromes (IUGR) [29], and in some cases of placental abruption [30].…”