Z Geburtshilfe Neonatol 2016; 220(04): 166-172
DOI: 10.1055/s-0042-104801
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Einflussfaktoren auf die placental growth factor (PlGF) und soluble fms-like tyrosine kinase-1 (sFlt-1) Konzentration im Rahmen des Erst-Trimester-Screenings

Influences on Placental Growth Factor (PlGF) and Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Concentration Levels at the Time of First Trimester Screening
J. von See
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
,
V. Limperger
2   Institut für Klinische Chemie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
,
U. Pecks
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
,
C. Eckmann-Scholz
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
› Author Affiliations
Further Information

Publication History

eingereicht 19 September 2015

Publication Date:
02 May 2016 (online)

Zusammenfassung

Einleitung: Bei einer manifesten Präeklampsie sind die Angiogenesefaktoren soluble fms-like tyrosine kinase-1 (sFlt-1) erhöht und placental growth factor (PlGF) erniedrigt. Dies kann bereits im ersten Trimenon für PLGF signifikant sein.

Material und Methodik: Es liegt eine retrospektive Studie mit 161 Schwangeren aus dem Erst-Trimester-Screening (ETS)vor, bei denen ergänzend sFlt-1 und PlGF mit dem Roche Elecsys® aus mütterlichem Serum gemessen wurden.

Ergebnisse: Für sFlt-1 ergab sich ein Mittelwert in Höhe von 1 247,11±545,84 pg/ml und für PlGF von 47,00±22,62 pg/ml. Sowohl zwischen sFlt-1 und PAPP-A MoM (rS=0,681, p<0,001) als auch zwischen PlGF und PAPP-A MoM (rS=0,465, p<0,001) besteht ein positiv gerichteter Zusammenhang. sFlt-1 korreliert negativ mit dem mütterlichen BMI zum Zeitpunkt des ETS (rS=−0,225, p=0,005) und ist bei Übergewichtigen gegenüber Normalgewichtigen signifikant erniedrigt (p=0,003). Zwischen PlGF und der Scheitel-Steiß-Länge besteht eine positive Korrelation (rS=0,27, p<0,001), ein inverser Zusammenhang liegt zwischen PlGF und dem jeweils niedrigeren Pulsatility index der Aa. uterinae vor (rS=−0,235; p=0,012). Bei Patientinnen mit einem präexistenten Diabetes mellitus sind sFlt-1 und PlGF (p<0,05) signifikant erniedrigt. Raucherinnen zeigen signifikant erhöhte PlGF-Spiegel (p<0,001).

Schlussfolgerung: sFlt-1 und PlGF unterliegen während des ersten Trimenon diversen Einflussfaktoren, die bei der Interpretation der Messwerte Berücksichtigung finden müssen. Zur Validierung der vorliegenden Erkenntnisse sind neben vergangenen Studien weitere prospektive Studien erforderlich. Ziel sollte die Etablierung von MoM-Werten für sFlt-1 und PlGF sein, um die Angiogenesefaktoren als objektivierte, aussagekräftige Screeningparameter verwenden zu können.

Abstract

Introduction: The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are significantly altered in preeclampsia with elevated sFlt-1 levels and low PlGF in the continuation of pregnancies. Furthermore, patients with preeclampsia reveal significantly low PlGF levels in the first trimester.

Material and Method: We performed a retrospective study including 161 patients during the first trimester screening between 11+0 and 13+6 weeks of gestation. In addition, we analyzed sFlt-1 und PlGF in maternal serum with a Roche Elecsys® System.

Results: The mean values for sFlt-1 were 1 247,11±545,84 pg/ml and 47,00±22,62 pg/ml for PlGF. There is a positive correlation between sFlt-1 and PAPP-A MoM (rS=0,681, p<0,001), and PlGF and PAPP-A MoM (rS=0,465, p<0,001), respectively. There was a negative correlation between sFlt-1 and maternal body mass index (rS=−0,225, p=0,005). Overweight patients had significantly lower sFlt-1 values than patients with normal weight (p=0,003). PlGF and the crown-rump-length of the fetus showed a positive correlation (rS=0,27, p<0,001), whereas PlGF and the Pulsatility Index of the uterine arteries were negative correlated (rS=−0,235; p=0,012). Patients with a preexistent diabetes mellitus had significantly low sFlt-1 und PlGF (p<0,05) values. Smokers had significantly elevated PlGF-values (p<0,001).

Conclusion: sFlt-1 and PlGF are influenced by various factors during the first trimester of pregnancy which can be relevant for correct interpretation. Further prospective studies may be necessary to validate our results. The aim should be to establish sFlt-1 and PlGF MoM values to allow for integration into a screening for preeclampsia in the first trimester.

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  • Literatur

  • 1 Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365: 785-799
  • 2 Levine RJ, Maynard SE, Qian C et al. Circulating angiogenic factors and the risk of preeclampsia. The New England journal of medicine 2004; 350: 672-683
  • 3 Maynard SE, Min JY, Merchan J et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. The Journal of clinical investigation 2003; 111: 649-658
  • 4 Schiettecatte J, Russcher H, Anckaert E et al. Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia. Clinical biochemistry 2010; 43: 768-770
  • 5 Verlohren S, Herraiz I, Lapaire O et al. New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension 2014; 63: 346-352
  • 6 Verlohren S, Galindo A, Schlembach D et al. An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. American journal of obstetrics and gynecology. 2010; 202: 161.e161-161.e111
  • 7 Akolekar R, de Cruz J, Foidart JM et al. Maternal plasma soluble fms-like tyrosine kinase-1 and free vascular endothelial growth factor at 11 to 13 weeks of gestation in preeclampsia. Prenatal diagnosis 2010; 30: 191-197
  • 8 Myers JE, Kenny LC, McCowan LM et al. Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study. BJOG : an international journal of obstetrics and gynaecology 2013; 120: 1215-1223
  • 9 Schneuer FJ, Nassar N, Guilbert C et al. First trimester screening of serum soluble fms-like tyrosine kinase-1 and placental growth factor predicting hypertensive disorders of pregnancy. Pregnancy hypertension 2013; 3: 215-221
  • 10 Crovetto F, Figueras F, Triunfo S et al. First trimester screening for early and late preeclampsia based on maternal characteristics, biophysical parameters, and angiogenic factors. Prenatal diagnosis 2015; 35: 183-191
  • 11 Thadhani R, Mutter WP, Wolf M et al. First trimester placental growth factor and soluble fms-like tyrosine kinase 1 and risk for preeclampsia. The Journal of clinical endocrinology and metabolism 2004; 89: 770-775
  • 12 WHO . Obesity: preventing and managing the global epidemic. World Health Organization technical report series. 2000; 894 i-xii 1-253
  • 13 Akolekar R, Zaragoza E, Poon LC et al. Maternal serum placental growth factor at 11+0 to 13+6 weeks of gestation in the prediction of pre-eclampsia. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2008; 32: 732-739
  • 14 Parra-Cordero M, Rodrigo R, Barja P et al. Prediction of early and late pre-eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2013; 41: 538-544
  • 15 Zera CA, Seely EW, Wilkins-Haug LE et al. The association of body mass index with serum angiogenic markers in normal and abnormal pregnancies. American journal of obstetrics and gynecology 2014;
  • 16 Tsiakkas A, Duvdevani N, Wright A et al. Serum soluble fms-like tyrosine kinase-1 in the three trimesters of pregnancy: effects of maternal characteristics and medical history. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2015; 45: 584-590
  • 17 Tsiakkas A, Duvdevani N, Wright A et al. Serum placental growth factor in the three trimesters of pregnancy: effects of maternal characteristics and medical history. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2015; 45: 591-598
  • 18 Akolekar R, Syngelaki A, Sarquis R et al. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks. Prenatal diagnosis 2011; 31: 66-74
  • 19 Pecks U, Caspers R, Schiessl B et al. The evaluation of the oxidative state of low-density lipoproteins in intrauterine growth restriction and preeclampsia. Hypertension in pregnancy : official journal of the International Society for the Study of Hypertension in Pregnancy 2012; 31: 156-165
  • 20 Han CS, Herrin MA, Pitruzzello MC et al. Glucose and metformin modulate human first trimester trophoblast function: a model and potential therapy for diabetes-associated uteroplacental insufficiency. American journal of reproductive immunology (New York, NY: 1989) 2015; 73: 362-371
  • 21 Cawyer CR, Horvat D, Leonard D et al. Hyperglycemia impairs cytotrophoblast function via stress signaling. American journal of obstetrics and gynecology 2014; 211: 541.e541-548.e541
  • 22 Levine R, Lam C, Qian C et al. Circulating angiogenic factors in smokers and non-smokers during normal pregnancy. American journal of obstetrics and gynecology 2005; 193: S75
  • 23 Pandya P, Wright D, Syngelaki A et al. Maternal serum placental growth factor in prospective screening for aneuploidies at 8-13 weeks' gestation. Fetal diagnosis and therapy 2012; 31: 87-93
  • 24 Kosinski P, Samaha RB, Bomba-Opon DA et al. Reference values for placental growth factor (PlGF) concentration and uterine artery doppler pulsatility index (PI) at 11-13(+6) weeks of gestation in the Polish population. Ginekologia polska 2014; 85: 488-493
  • 25 Conde-Agudelo A, Althabe F, Belizan JM et al. Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review. American journal of obstetrics and gynecology 1999; 181: 1026-1035