Second‐ and third‐trimester serum levels of growth‐differentiation factor‐15 in prediction of pre‐eclampsia

Abstract

Objective Pre‐eclampsia (PE) is a significant contributor to adverse maternal and perinatal outcome; however, accurate prediction and early diagnosis of this condition remain a challenge. The aim of this study was to compare serum levels of growth‐differentiation factor‐15 (GDF‐15) at three different gestational ages between asymptomatic women who subsequently developed preterm or term PE and healthy controls. Methods This was a case–control study drawn from a prospective observational study on adverse pregnancy outcomes in women attending for their routine second‐ and third‐trimester hospital visits. Serum GDF‐15 was determined in 300 samples using a commercial GDF‐15 enzyme‐linked immunosorbent assay: 120 samples at 19–24 weeks of gestation, 120 samples at 30–34 weeks and 60 samples at 35–37 weeks. Multiple linear regression was applied to logarithmically transformed GDF‐15 control values to evaluate the influence of gestational age at blood sampling and maternal characteristics on GDF‐15 results. GDF‐15 multiples of the normal median (MoM) values, adjusted for gestational age and maternal characteristics, were compared between pregnancies that subsequently developed preterm or term PE and healthy controls. Results Values of GDF‐15 increased with gestational age. There were no significant differences in GDF‐15 MoM values between cases of preterm or term PE and normotensive pregnancies at 19–24 or 35–37 weeks of gestation. At 30–34 weeks, GDF‐15 MoM values were significantly increased in cases of preterm PE, but not in those who later developed term PE. Elevated GDF‐15 MoM values were associated significantly with a shorter interval between sampling at 30–34 weeks and delivery with PE (P = 0.005). Conclusion Serum GDF‐15 levels at 19–24 or 35–37 weeks of gestation are not predictive of preterm or term PE. At 30–34 weeks, GDF‐15 levels are higher in women who subsequently develop preterm PE; however, this difference is small and GDF‐15 is unlikely to be useful in clinical practice when used in isolation. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis

“…Pooled results with ten studies [24][25][26][27][28][29][30][31] showed that compared to controls of women with normal pregnancy at least matched for GA, women with preeclampsia had significantly higher circulating level of GDF-15 at the diagnosis of the disease (SMD: 0.66, 95 % CI: 0.16 to 1.17, p = 0.01, I 2 = 93 %; ▶Fig. 2a).…”

“…3b, p for subgroup difference > 0.05). Moreover, meta-analysis with three studies [26,31,32] also showed a higher level of GDF-15 was before the diagnosis in women who subsequently developed preeclampsia than those who did not (SMD:…”

“…Overall, nine reports including 498 women with preeclampsia and 2349 women with normal pregnancy contributed to the meta-analysis 24 25 26 27 28 29 30 31 32 . Because one report included three datasets from three independent cohorts and these datasets were included independently 30 , a total of 11 observational studies were included for the meta-analysis.…”

miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage

“…GDF15, as a member of the transforming growth factor (TGF)-β superfamily (Mullican et al 2017), is expressed at the undetectable level under normal physiological in most somatic tissues of human, but, in some pathological conditions, such as inflammation and cancer, its expression level is highly increased, and especially, it is abundantly expressed by the syncytiotrophoblast (STB) in placenta (Wischhusen et al 2020). Although the association of circulating level of GDF15 in the second and third trimester with the PE (Wertaschnigg et al 2020) or pregnancy-associated vomiting (Petry et al 2018) has been evaluated, however, the association of its circulating level in the first trimester with RM has not yet been reported. ITIH3 belongs to the ITIH gene family, and ITIHs play important roles in inflammation and carcinogenesis in humans (Hamm et al 2008), as well as in the maintenance of the uterine surface glycocalyx during placenta development in pig (Geisert et al 2003).…”

Clinical tools and biomarkers to predict preeclampsia

“…However, other recent works found increased serum GDF15 at 30-34 weeks in those destined to develop early onset preeclampsia, but no significant change at 35-37 weeks prior to preeclampsia at term. 64 The most important difference between these studies was the use of plasma in one, and serum in the other. Caution must be exercised when using different sample types for comparison or validation of biomarkers.…”