Abstract
Objective: To investigate the structural basis of abnormal Doppler waveforms in the utero-placental circulations in cases of chronic fetal hypoxia.
Study design: Morphometric analysis was performed on placental samples from 58 pregnancies with abnormal Doppler waveforms in the uterine, placental and umbilical circulations at 32-34 weeks, and 10 pregnancies with normal waveforms.
Results: The volume of placental villi reduced from 350.5 cm3 in controls to 286.4 cm3 (P < 0.05) in the severest cases. The volume of the fetal capillaries reduced from 59.7 cm3 to 20.5 cm3 (P < 0.05). These reductions were associated with increased placental infarction. The myometrial segments of the spiral arteries were severely constricted, demonstrating failure of physiological conversion secondary to deficient trophoblast invasion.
Conclusion: The placental vascular bed is greatly reduced in cases of chronic fetal hypoxia. We propose impaired placental perfusion causes oxidative stress and regression of the fetal vasculature, leading to fetal growth retardation and distress.
Keywords: Placenta; Hypoxia; Doppler ultrasonography; Morphometry; Oxidative stressReferences
References.
Poon LC, Zaragoza E, Akolekar R, Anagnostopoulos E, Nicolaides KH.Maternal serum placental growth factor (P1GF) in small for gestational age pregnancy at ll(+0) to 13(+6) weeks of gestation. Prenat Diagn. 2008 Dec;28(12):l 110-5.
Botasheva T.L., Zamanskaya T.A., Orlov A.V., Norits S.N. Gradients of maternal and fetal blood flow at threat of premature delivery // XVII European Congress of Ultrasound in Medicine and Biology, Geneva, Switzerland, 25–28 sept. 2005 // European Journal Ultraschall in Med. – 2005. – Vol.109. – P.099.
Cetin I, Antonazzo P.The role of the placenta in intrauterine growth restriction (IUGR).Z Geburtshilfe Neonatol. 2009 Jun;213(3):84-8. Epub 2009 Jun 17.
Maulik D, Frances Evans J, Ragolia L.Fetal growth restriction: pathogenic mechanisms. Clin Obstet Gynecol. 2006 Jun;49(2):219-27. Review.
Kim YN, Lee DS, Jeong DH, Sung MS, Kim KT. The relationship of the level of circulating antiangiogenic factors to the clinical manifestations of preeclampsia. Prenat Diagn. 2009 May;29(5):464-70.
Rampello S, Frigerio L, Ricci E, Rota E, Lucianetti M, Parazzini F. Transabdominal uterine arteries Doppler at 12-14th and 20-24th week of gestation and pregnancy outcome: A prospective study. Eur J Obstet Gynecol Reprod Biol. 2009 Aug 26.
Stepan H, Jank A. Angiogenic factors and their role in pathogenesis and prediction of preeclampsia. Z Geburtshilfe Neonatol. 2009 Jun;213(3):101-5. Epub 2009 Jun 17. German.
Torry DS, Hinrichs M, Torry RJ.Determinants of placental vascularity.Am J Reprod Immunol. 2004 Apr;51(4):257-68. Review.
Wallner W, Sengenberger R, Strick R, Strissel PL, Meurer B, Beckmann MW, Schlembach D. Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction.Clin Sci (Lond). 2007 Jan;l 12(l):51-7.
Hung T-H, Skepper JN, Charnock-Jones DS, Burton GJ. Hypoxia/ reoxygenation. A potent inducer of apoptotic changes in the human placenta and possible etiological factor in preeclampsia. Circ Res 2002;90:1274-81.
Krauss T, Pauer HU, Augustin HG. Prospective analysis of placenta growth factor (P1GF) concentrations in the plasma of women with normal pregnancy and pregnancies complicated by preeclampsia. Hypertens Pregnancy. 2004;23(1):101-11.
Sattar N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? Br Med J. 2002; 325.
Redman CW, Sargent IL: Latest advances in understanding preeclampsia. Science 2005;308:1592-4.
Zygmynt M., Herr F., Munstedt K. et al. Angiogenesis and vasculogenesis in pregnancy. Obstst Gynecol 2003;110:3:10-18.
Roschinger W, Muntau AC, Duran M, Dorland L, Ijlst L, Wanders RJ, Roscher AA. Carnitine-acylcarnitine translocase deficiency: metabolic consequences of an impaired mitochondrial carnitine cycle. Clin Chim Acta 2000 Aug;298(l-2):55-68
Shingo Kajimura', Katsumi Aida, and Cunming Duan. Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. 2002 J. Endocrinol. 175, 3—18.
Regnault TR, Galan HL, Parker TA, Anthony RV. Placental development in normal and compromised pregnancies review. Placenta 2002;23(SupplA):1 19-29.
Machaalani R, Makris A, Thornton C, Hennessy A.Vascular endothelial growth factor receptor 1 (Fltl) and apoptosis in the preeclamptic placenta and effects of in vivo anti-hypertensive exposure.Hypertens Pregnancy. 2008;27(4):361-73.
Many A, Hubel CA, Fisher SJ, Roberts JM, Zhou Y. Invasive cytotrophoblasts manifest evidence of oxidative stress in preeclampsia. Am J Pathol 2000; 156:321-31.
Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA: Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004; 350:672-83.
Zhang EC, Burton GJ, Smith SK, Charnock-Jones DS. Placental vessel adaptation during gestation and to high altitude: changes in diameter and perivascular cell coverage. Placenta 2002;23:751-62.
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