Horm Metab Res 2023; 55(02): 114-123
DOI: 10.1055/a-1956-2961
Original Article: Endocrine Care

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

Lihong Wang
1   Department of Obstetrics and Gynecology, Baogang Hospital, Baotou, China
,
Qiuli Yang
1   Department of Obstetrics and Gynecology, Baogang Hospital, Baotou, China
› Author Affiliations

Abstract

Growth differentiation factor 15 (GDF-15) has been suggested as a potential biomarker of preeclampsia. However, previous studies evaluating circulating GDF-15 in women with preeclampsia showed inconsistent results. A meta-analysis was performed accordingly in this study. Observational studies comparing circulating GDF-15 between women with preeclampsia normal pregnancy were identified by search of electronic databases including PubMed, Embase, Web of Science, Wanfang, and CNKI. The Newcastle-Ottawa Scale (NOS) was used for assessing the quality of the studies. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results. Eleven observational studies including 498 women with preeclampsia and 2349 women with normal pregnancy contributed to the meta-analysis. Results showed that compared to controls of women with normal pregnancy at least matched for gestational ages, women with preeclampsia had significantly higher circulating GDF-15 at the diagnosis [standard mean difference (SMD): 0.66, 95% confidence interval (CI): 0.16 to 1.17, p=0.01, I2=93%]. Subgroup analysis showed consistent results in women with preterm and term preeclampsia in Asian and non-Asian women and in studies with different quality scores, which were not statistically significant between subgroups (p for subgroup difference>0.05). Moreover, a higher level of GDF-15 was also found before the diagnosis in women who subsequently developed preeclampsia than those who did not (SMD: 1.32, 95% CI: 0.45 to 2.18, p=0.003, I2=89%). In conclusion, a higher circulating GDF-15 is observed in women with preeclampsia even before the diagnosis of the disease.



Publication History

Received: 30 August 2022

Accepted after revision: 21 September 2022

Article published online:
21 November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Erez O, Romero R, Jung E. et al. Preeclampsia and eclampsia: the conceptual evolution of a syndrome. Am J Obstet Gynecol 2022; 226: S786-S803
  • 2 Rana S, Lemoine E, Granger JP. et al. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 2019; 124: 1094-1112
  • 3 Miller EC, Wilczek A, Bello NA. et al. Pregnancy, preeclampsia and maternal aging: from epidemiology to functional genomics. Ageing Res Rev 2022; 73: 101535
  • 4 Fishel Bartal M, Sibai BM. Eclampsia in the 21st century. Am J Obstet Gynecol 2022; 226: S1237-S1253
  • 5 Executive summary: Workshop on preeclampsia, January 25-26, 2021, cosponsored by the Society for Maternal-Fetal Medicine and the Preeclampsia Foundation Am J Obstet Gynecol 2021; 225: B2-B7
  • 6 Backes CH, Markham K, Moorehead P. et al. Maternal preeclampsia and neonatal outcomes. J Pregnancy 2011; 214365
  • 7 Ukah UV, De Silva DA, Payne B. et al. Prediction of adverse maternal outcomes from pre-eclampsia and other hypertensive disorders of pregnancy: A systematic review. Pregnancy Hypertens 2018; 11: 115-123
  • 8 Wu P, Haththotuwa R, Kwok CS. et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2017; 10: e003497
  • 9 Yao M, Xiao Y, Yang Z. et al. Identification of biomarkers for preeclampsia based on metabolomics. Clin Epidemiol 2022; 14: 337-360
  • 10 Jung E, Romero R, Yeo L. et al. The etiology of preeclampsia. Am J Obstet Gynecol 2022; 226: S844-S866
  • 11 MacDonald TM, Walker SP, Hannan NJ. et al. Clinical tools and biomarkers to predict preeclampsia. EBioMedicine 2022; 75: 103780
  • 12 Nirupama R, Divyashree S, Janhavi P. et al. Preeclampsia: pathophysiology and management. J Gynecol Obstet Hum Reprod 2021; 50: 101975
  • 13 Qu H, Khalil RA. Vascular mechanisms and molecular targets in hypertensive pregnancy and preeclampsia. Am J Physiol Heart Circ Physiol 2020; 319: H661-H681
  • 14 Desmedt S, Desmedt V, De Vos L. et al. Growth differentiation factor 15: A novel biomarker with high clinical potential. Crit Rev Clin Lab Sci 2019; 56: 333-350
  • 15 Wischhusen J, Melero I, Fridman WH. Growth/differentiation factor-15 (GDF-15): from biomarker to novel targetable immune checkpoint. Front Immunol 2020; 11: 951
  • 16 Eddy AC, Trask AJ. Growth differentiation factor-15 and its role in diabetes and cardiovascular disease. Cytokine Growth Factor Rev 2021; 57: 11-18
  • 17 Wollert KC, Kempf T, Wallentin L. Growth differentiation factor 15 as a biomarker in cardiovascular disease. Clin Chem 2017; 63: 140-151
  • 18 Wang D, Day EA, Townsend LK. et al. GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease. Nat Rev Endocrinol 2021; 17: 592-607
  • 19 Lockhart SM, Saudek V, O’Rahilly S. GDF15: A hormone conveying somatic distress to the brain. Endocr Rev 2020; 41: bnaa007
  • 20 Andersson-Hall U, Svedin P, Mallard C. et al. Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy. PLoS One 2021; 16: e0248980
  • 21 Tong S, Marjono B, Brown DA. et al. Serum concentrations of macrophage inhibitory cytokine 1 (MIC 1) as a predictor of miscarriage. Lancet 2004; 363: 129-130
  • 22 Tong S, Ngian GL, Onwude JL. et al. Diagnostic accuracy of maternal serum macrophage inhibitory cytokine-1 and pregnancy-associated plasma protein-A at 6-10 weeks of gestation to predict miscarriage. Obstet Gynecol 2012; 119: 1000-1008
  • 23 Yakut K, Ocal DF, Ozturk FH. et al. Is GDF-15 level associated with gestational diabetes mellitus and adverse perinatal outcomes?. Taiwan J Obstet Gynecol 2021; 60: 221-224
  • 24 Marjono AB, Brown DA, Horton KE. et al. Macrophage inhibitory cytokine-1 in gestational tissues and maternal serum in normal and pre-eclamptic pregnancy. Placenta 2003; 24: 100-106
  • 25 Sugulle M, Dechend R, Herse F. et al. Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus. Hypertension 2009; 54: 106-112
  • 26 Chen Q, Wang Y, Zhao M. et al. Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases. Cytokine 2016; 83: 226-230
  • 27 Shi J, Chen ZQ. Determination and clinical significance of plasma growth differentiation factor 15 in hypertensive disorders complicating pregnancy. Chin J Family Plan Gynecol 2017; 9: 48-51
  • 28 Temel Yuksel I, Mathyk BA, Aslan Cetin B. et al. Maternal levels of growth differentiation factor-15 in patients with preeclampsia. Hypertens Pregnancy 2018; 37: 192-196
  • 29 Ma ZQ, Han Q. Combined diagnostic efficacy of GSTM1, PIGF, and GDF-15 for hypertensive disorders in pregnancy. Int J Lab Med 2019; 40: 2063-2165
  • 30 Cruickshank T, MacDonald TM, Walker SP. et al. Circulating growth differentiation factor 15 is increased preceding preeclampsia diagnosis: implications as a disease biomarker. J Am Heart Assoc 2020; 10: e020302
  • 31 Wertaschnigg D, Rolnik DL, Nie G. et al. Second- and third-trimester serum levels of growth-differentiation factor-15 in prediction of pre-eclampsia. Ultrasound Obstet Gynecol 2020; 56: 879-884
  • 32 Tahaa A, Abd Raboub I, Abd Halim H. The value of maternal serum levels of growth differentiation factor-15 as a predictor of preeclampsia. Sci J Al-Azhar Med Faculty Girls 2021; 5: 204-210
  • 33 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71
  • 34 Page MJ, Moher D, Bossuyt PM. et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160
  • 35 Higgins J, Thomas J, Chandler J. et al. Cochrane handbook for systematic reviews of interventions version 6.2. The Cochrane Collaboration. 2021 www.training.cochrane.org/handbook
  • 36 ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002 Obstet Gynecol 2002; 99: 159-167
  • 37 Wells GA, Shea B, O’Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2010 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
  • 38 Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration. 2011 www.cochranehandbook.org
  • 39 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
  • 40 Egger M, Davey Smith G, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
  • 41 Moore AG, Brown DA, Fairlie WD. et al. The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J Clin Endocrinol Metab 2000; 85: 4781-4788
  • 42 Li H, Dakour J, Guilbert LJ. et al. PL74, a novel member of the transforming growth factor-beta superfamily, is overexpressed in preeclampsia and causes apoptosis in trophoblast cells. J Clin Endocrinol Metab 2005; 90: 3045-3053
  • 43 Kiyokoba R, Uchiumi T, Yagi M. et al. Mitochondrial dysfunction-induced high hCG associated with development of fetal growth restriction and pre-eclampsia with fetal growth restriction. Sci Rep 2022; 12: 4056
  • 44 Zuo Q, Zou Y, Huang S. et al. Aspirin reduces sFlt-1-mediated apoptosis of trophoblast cells in preeclampsia. Mol Hum Reprod 2021; 27: gaaa089
  • 45 Arkoumani M, Papadopoulou-Marketou N. et al. The clinical impact of growth differentiation factor-15 in heart disease: A 2019 update. Crit Rev Clin Lab Sci 2020; 57: 114-125
  • 46 Tenorio MB, Ferreira RC, Moura FA. et al. Cross-talk between oxidative stress and inflammation in preeclampsia. Oxid Med Cell Longev 2019; 2019: 8238727
  • 47 Smith TA, Kirkpatrick DR, Kovilam O. et al. Immunomodulatory role of vitamin D in the pathogenesis of preeclampsia. Expert Rev Clin Immunol 2015; 11: 1055-1063
  • 48 Li E, Chen P, Lu J. et al. Serum growth differentiation factor 15 is closely associated with metabolic abnormalities in Chinese pregnant women. J Diabetes Investig 2021; 12: 1501-1507
  • 49 Tang M, Luo M, Lu W. et al. Serum growth differentiation factor 15 is associated with glucose metabolism in the third trimester in Chinese pregnant women. Diabetes Res Clin Pract 2019; 156: 107823