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Placental pathology, first-trimester biomarkers and adverse pregnancy outcomes

Journal of Perinatology volume 34, pages 186–191 (2014)Cite this article

Subjects

Abstract

Objective:

We investigated the relationship between placental pathological findings in pregnancies with adverse pregnancy outcomes and first-trimester serum analytes and uterine artery Doppler results.

Study design:

This is a secondary analysis of a prospective study of first-trimester screening for adverse pregnancy outcomes, including preterm birth (PTB (delivery<37 weeks)), pre-eclampsia (PE), gestational hypertension, and small for gestational age (SGA) infants (birth weight <10th percentile). We compared the mean levels of serum analytes (pregnancy-associated plasma protein A (PAPP-A), placental protein 13 (PP13), a-disintegrin and metalloproteinase 12 (ADAM12), placental growth factor (PLGF)) and uterine artery Doppler pulsatility index (UADPI) obtained between 11 and 14 weeks gestation in cases with adverse outcomes and abnormal placental histology to a control group without adverse outcome or abnormal placental pathology. Placental findings were classified as: lesions of maternal under perfusion, lesions causing reduced placental reserve, infections/inflammatory lesions, and fetal vascular lesions.

Result:

Among 193 cases, lesions of maternal under perfusion were seen in 50 cases (25.9%), lesions causing reduced placental reserve in 63 cases (32.8%), infection/inflammation in 65 cases (34.2%) and fetal vascular lesions in 23 cases (11.9%). There were 123 pregnancies with no adverse pregnancy outcome or placental lesion used as controls. Pregnancies with PE had a significant association with lesions of maternal under perfusion (P=0.005) and placental infection/inflammation (P=0.003). Significant differences were seen in mean levels of PAPP-A, ADAM12 and PLGF in cases with PE, PTB and SGA with specific placental histological findings when compared with controls. UADPI was not significantly different between the cases with adverse pregnancy outcomes and abnormal histology.

Conclusion:

Our findings provide evidence linking placental pathology with suboptimal secretion of analytes in the first trimester in pregnancies with adverse outcomes, especially PE.

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References

  1. Cowans NJ, Stamatopoulou A, Khalil A, Spencer K . PP13 as a marker of pre-eclampsia: a two platform comparison study. Placenta 2011; 32 (Suppl): S37–S41.

    Article  CAS  Google Scholar 

  2. Wortelboer EJ, Koster MP, Cuckle HS, Stoutenbeek PH, Schielen PC, Visser GH . First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia. BJOG 2010; 117 (11): 1384–1389.

    Article  CAS  Google Scholar 

  3. Romero R, Kusanovic JP, Than NG, Erez O, Gotsch F, Espinoza J et al. First-trimester maternal serum PP13 in the risk assessment for preeclampsia. Am J Obstet Gynecol 2008; 199: 122e1–122e11.

    Article  Google Scholar 

  4. Chafetz I, Kuhnreich I, Sammar M, Tal Y, Gibor Y, Meiri H et al. First-trimester placental protein 13 screening for preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol 2007; 197 (35): e1–e7.

    Google Scholar 

  5. Spencer K, Cowans NJ, Chefetz I, Tal J, Meiri H . First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol 2007; 29: 128–134.

    Article  CAS  Google Scholar 

  6. Spencer K, Cowans NJ, Nicolaides KH . Low levels of maternal serum PAPP-A in the first trimester and the risk of pre-eclampsia. Prenat Diagn 2008; 28: 7–10.

    Article  Google Scholar 

  7. Sekizawa A, Purwosunu Y, Yoshimura S, Nakamura M, Shimizu H, Okai T et al. PP13 mRNA expression in trophoblasts from preeclamptic placentas. Reprod Sci 2009; 16: 408–413.

    Article  CAS  Google Scholar 

  8. Goetzinger KR, Cahill AG, Kemna J, Odibo L, Macones GA, Odibo AO . First-trimester prediction of preterm birth using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics. Prenat Diagn 2012; 32 (10): 1002–1007.

    Article  CAS  Google Scholar 

  9. Akolekar R, Zaragoza E, Poon LC, Pepes S, Nicolaides KH . Maternal serum placental growth factor at 11+0 to 13+6 weeks of gestation in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol 2008; 32: 732–739.

    Article  CAS  Google Scholar 

  10. Crispi F, Llurba E, Dominguez C, Martin-Gallan P, Cabero L, Gratacos E . Predictive value of angiogenic factors and uterine artery Doppler for early- versus late-onset pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet Gynecol 2008; 31: 303–309.

    Article  CAS  Google Scholar 

  11. Goetzinger KR, Zhong Y, Cahill AG, Odibo L, Macones GA, Odibo AO . Efficiency of first-trimester uterine artery Doppler, a-disintegrin and metalloprotease 12, pregnancy-associated plasma protein A, and maternal characteristics in the prediction of preeclampsia. J Ultrasound Med 2013; 32: 1593–1600.

    Article  Google Scholar 

  12. Costa SL, Proctor L, Dodd JM, Toal M, Okun N, Johnson JA et al. Screening for placental insufficiency in high-risk pregnancies: is earlier better? Placenta 2008; 29: 1034–1040.

    Article  CAS  Google Scholar 

  13. Cindrova-Davies T, Spasic-Boskovic O, Jauniaux E, Charnock-Jones DS, Burton GJ . Nuclear factor-kappa B, p38, and stress-activated protein kinase mitogen-activated protein kinase signaling pathways regulate proinflammatory cytokines and apoptosis in human placental explants in response to oxidative stress: effects of antioxidant vitamins. Am J Pathol 2007; 170: 1511–1520.

    Article  CAS  Google Scholar 

  14. Hung TH, Charnock-Jones DS, Skepper JN, Burton GJ . Secretion of tumor necrosis factor-alpha from human placental tissues induced by hypoxia-reoxygenation causes endothelial cell activation in vitro: a potential mediator of the inflammatory response in preeclampsia. Am J Pathol 2004; 164: 1049–1061.

    Article  CAS  Google Scholar 

  15. Tjoa ML, Cindrova-Davies T, Spasic-Boskovic O, Bianchi DW, Burton GJ . Trophoblastic oxidative stress and the release of cell-free feto-placental DNA. Am J Pathol 2006; 169: 400–404.

    Article  CAS  Google Scholar 

  16. Moldenhauer JS, Stanek J, Warshak C, Khoury J, SIBAI B . The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. Am J Obstet Gynecol 2003; 189: 1173–1177.

    Article  Google Scholar 

  17. Egbor M, Ansari T, Morris N, Green CJ, Sibbons PD . Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG 2006; 113: 580–589.

    Article  CAS  Google Scholar 

  18. Melchiorre K, Wormald B, Leslie K, Bhide A, Thilaganathan B . First-trimester uterine artery Doppler indices in term and preterm pre-eclampsia. Ultrasound Obstet Gynecol 2008; 32: 133–137.

    Article  CAS  Google Scholar 

  19. Odibo AO, Zhong Y, Longtine M, Tuuli M, Odibo L, Cahill AG et al. First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction. Placenta 2011; 32 (4): 333–338.

    Article  CAS  Google Scholar 

  20. American College of Obstetricians and Gynecologists. Diagnosis and Management of Preeclampsia and Eclampsia. ACOG Practice Bulletin No. 33. ACOG: Washington, DC, USA, 2002.

  21. Report of the National High Blood Pressure Education Program Working Group. Report on high blood pressure in pregnancy. Am J Obstet Gynecol 2000; 183: S1–S22.

    Article  Google Scholar 

  22. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan MA . United States national reference for fetal growth. Obstet Gynecol 1996; 87: 163–168.

    Article  CAS  Google Scholar 

  23. Tsiartas P, Kacerovsky M, Musilova I, Hornychova H, Cobo T, Sävman K et al. The association between histological chorioamnionitis, funisitis and neonatal outcome in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med 2013; 26: 1332–1336.

    Article  Google Scholar 

  24. Odibo AO, Zhong Y, Goetzinger KR, Odibo L, Bick JL, Bower CR et al. First-trimester placental protein 13, PAPP-A, uterine artery Doppler and maternal characteristics in the prediction of pre-eclampsia. Placenta 2011; 32 (8): 598–602.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Ultrasound and Genetic and Fetal Care Center, Washington University School of Medicine, St Louis, MO, USA

    A O Odibo, A Spitalnik & L Odibo

  2. Department of Pathology and Immunology, Washington University School Of Medicine, St Louis, MO, USA

    K R Patel & P Huettner

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  1. A O Odibo
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  2. K R Patel
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  3. A Spitalnik
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  4. L Odibo
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Correspondence to A O Odibo.

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The authors declare no conflict of interest.

Additional information

A poster presentation at the 33rd annual meeting of the Society of Maternal and Fetal Medicine, February, 2013, San Francisco, USA.

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Odibo, A., Patel, K., Spitalnik, A. et al. Placental pathology, first-trimester biomarkers and adverse pregnancy outcomes. J Perinatol 34, 186–191 (2014). https://doi.org/10.1038/jp.2013.176

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