The intrauterine fetal growth restriction (IUGR) is associated with an increased risk of perinatal mortality and morbidity and long term health consequences for survivors . The timely postnatal identification of newborns with IUGR and placental insufficiency may allow for early stratification of newborns and individually identify risk of disease in the postnatal period. Physiological feto-placental development correlates with a stage-specific disappearance of CD15+ placental endothelial progenitors (CD15+ pEPCs) in the placental resistance vessels . Our previous studies showed the involvement of CD15+ placental endothelial progenitors of resistance vessels in the processes of feto-placental growth and angioadaptation in conditions of placental insufficiency and fetal hypoxia [3,4]. The aim of the study was to evaluate CD15+ pEPCs as a diagnostic marker associated with placental insufficiency in pregnancies with IUGR and small for getational age (SGA) fetuses.
Materials and methods
A cross-sectional study of clinically normal (n-44) and pathological placentas (n-98) of 37-42 weeks of pregnancy associated with appropriate for gestational age (AGA, n-29), SGA (n-15), IUGR (n-38) fetuses, fetal death (IUFD) with IUGR (n-14) and sudden intrauterine fetal death (SIUD, n-46) was performed. Immunohistochemical expression of CD15+ pEPCs in resistance placental vessels was compared to clinical and morphological groups and prenatal Doppler characteristics. A relative amount of feto-placental resistance vessels containing CD15+ pEPCs was determined. Intensity and intravascular expression of CD15+ pEPCs was assessed using the Immunoreactive Score (IRS).
Expression of the feto-placental CD15+ pEPC in normal pregnancy with AGA fetus was noted in 9,4±2,2% of resistance vessels (IRS 0,9±0,6); SGA fetus with normal Doppler in 8,2±4,2% (IRS 0,7±0,6); SGA without Doppler study in 21,3±15,7% (IRS 4,3±1,5); IUGR without Doppler study in 28,7±14,3% (IRS 4,7±2,6); IUGR with pathological umbilical artery (UA) Doppler in 37,6±11,3% (IRS 5,8±2,2); IUFD with IUGR in 73,8±19,7% (IRS 10,9±1,4); SIUD in 69,24±19,7% (IRS 11,2±0,8).
We have shown that prenatally identified group of IUGR pregnancies with pathological UA Doppler's was accompanied by chronic placental insufficiency with feto-placental malperfusion and significant increase of CD15+ pEPCs in resistance placental vessels. The degree of CD15 expression correlated with severity of antenatal placental insufficiency. Placentas from pregnancies with SGA with normal Doppler characteristics did not show significant differences in the number of CD15+ pEPCs in resistance vessels compared with the normal pregnancies with AGA fetus. We recommend the use of CD15 Immunscore as an additional method for examination of placental tissue to identify newborns with placental insufficiency and IUGR.
- Beune I.M., Pels A., Gordijn S.J., Ganzevoort W. Definitions of fetal growth restriction in existing literature over time. Ultrasound Obstet Gynecol. 2018. doi: 10.1002/uog.19189. [Epub ahead of print].
- Seidmann L., Suhan T., Unger R., Gerein V., Kirkpatrick C.J. Transient CD15- positive endothelial phenotype in the human placenta correlates with physiological and pathological fetoplacental immaturity. Eur J Obstet Gynecol Reprod Biol. 2014; 180:172-9.
- Seidmann L., Suhan T., Kamyshanskiy Y., Nevmerzhitskaya A., Gerein V., Kirkpatrick C.J. CD15 - a new marker of pathological villous immaturity of the term placenta. Placenta. 2014; 35(11): 925-31.
- Seidmann L., Kamyshanskiy Y., Martin S.Z., Fruth A, Roth W. Immaturity for gestational age of microvasculature and placental barrier in term placentas with high weight. Eur J Obstet Gynecol Reprod Biol. 2017; 15:134-140.