Fetal Abdominal Aorta: Doppler and Structural Evaluation of Endothelial Function in Intrauterine Growth Restriction and Controls

Abstract

Purpose The human aorta stores strain energy in the distended wall during systole through the extracellular matrix of the tunica media that could be influenced by blood pressure, flow, or increased peripheral resistance. In intrauterine growth restriction (IUGR) fetuses, the increased aorta intima media thickness (aIMT) could reflect a different extracellular matrix composition and, therefore, functionality. The aim of this study was to analyze the resistance to flow in the fetal descending aorta and its relation to aIMT and systolic and diastolic fetal abdominal aorta diameters in IUGR fetuses and controls.

Materials and Methods This is a prospective case control study of single pregnancies collected at a tertiary center for feto-maternal medicine in Northeast Italy. An IUGR group as cases and a group of fetuses appropriate for gestational age (AGA) as controls were included.

Results We found a greater PI of the fetal abdominal aorta in the IUGR group (1.82) than in the AGA group (1.21) (p < 0.05). The change between the systolic and diastolic fetal abdominal aorta diameters was significantly greater in IUGR fetuses (0.10 mm (IQR 0.07 – 0.28)) than in the AGA group (0.04 mm (0.03 – 0.05)) (p < 0.05). In the IUGR group aIMT was significantly correlated with peak systolic velocity (PSV) and systolic-diastolic aorta diameter change, while these two correlations were not found in the control group.

Conclusion The change between the systolic and diastolic fetal abdominal aorta diameters in IUGR cases during the early third trimester of pregnancy was significantly increased and aIMT in the IUGR group was significantly correlated to systolic-diastolic diameter change and PSV, probably reflecting aortic wall adaptation to blood flow changes in IUGR fetuses.

Zusammenfassung

Ziel Die Aorta speichert während der Systole Dehnungsenergie in der geblähten Wand durch die extrazelluläre Matrix der Tunica media, die durch Blutdruck, Strömung oder einen erhöhten peripheren Widerstand beeinflusst werden kann. Bei Feten mit intrauteriner Wachstumsretardierung (IUGR) kann eine erhöhte Intima-Media-Dicke der Aorta (aIMT) eine abweichende Zusammensetzung und Funktionalität der extrazellulären Matrix widerspiegeln. Das Ziel dieser Studie war es, den Strömungswiderstand in der fetalen absteigenden Aorta und dessen Beziehung zu aIMT und den systolischen und diastolischen Durchmessern der abdominalen Aorta bei IUGR-Feten und Kontrollen zu analysieren.

Material und Methoden Für diese prospektive Fall-Kontroll-Studie wurden einzelne Schwangerschaften in einem Tertiärzentrum für Feto-Maternale Medizin in Nordost-Italien gesammelt. Eine Fallgruppe mit IUGR wurde mit zeitgerecht entwickelten Feten („appropriate for gestational age“ AGA) als Kontrolle verglichen.

Ergebnisse Bei IUGR fanden (1.82) wir im Vergleich zu AGA (1.21) einen erhöhten PI in der fetalen abdominalen Aorta (p < 0,05). Die Änderung zwischen den systolischen und diastolischen Aorta-Durchmessern war bei IUGR-Feten mit 0,10 mm (IQR 0,07 – 0,28) signifikant höher als bei AGA-Feten mit 0,04 mm (0,03 – 0,05) (p < 0,05). In der IUGR-Gruppe zeigte sich eine signifikante Korrelation von aIMT zur maximalen systolischen Strömungsgeschwindigkeit (PSV) und zur Änderung der systolisch-diastolischen Aorta-Durchmesser, die bei den Kontrollen nicht auftrat.

Schlussfolgerung Die Änderung zwischen den systolischen und diastolischen Durchmessern der fetalen abdominalen Aorta war bei IUGR-Fällen im frühen dritten Schwangerschaftstrimenon signifikant erhöht. Die aIMT bei IUGR-Feten zeigte eine signifikante Korrelation zur Änderung der systolisch-diastolischen Durchmesser und zur PSV, was möglicherweise die Anpassung der Aorta-Wand an die Blutflussänderungen bei IUGR widerspiegelt

Key words

intrauterine growth restriction - fetal abdominal aorta - aorta diameter - doppler

• References

• 1 Lausman A, Kingdom J, Gagnon R. et al. Intrauterine growth restriction: screening, diagnosis, and management. J Obstet Gynaecol Can 2013; 35: 741-757
• 2 Cosmi E, Visentin S, Fanelli T. et al. Aortic intima media thickness in fetuses and children with intrauterine growth restriction. Obstet Gynecol 2009; 114: 1109-1114
• 3 Swanson AM, David AL. Animal models of fetal growth restriction: Considerations for translational medicine. Placenta 2015; 36: 623-630
• 4 Londero AP, Orsaria M, Marzinotto S. et al. Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study. Histochem Cell Biol 2016; 146: 191-204
• 5 Mori A, Iwabuchi M, Makino T. Fetal haemodynamic changes in fetuses during fetal development evaluated by arterial pressure pulse and blood flow velocity waveforms. BJOG 2000; 107: 669-677
• 6 Skilton MR, Evans N, Griffiths KA. et al. Aortic wall thickness in newborns with intrauterine growth restriction. Lancet 2005; 365: 1484-1486
• 7 Mäkikallio K, Vuolteenaho O, Jouppila P. et al. Ultrasonographic and biochemical markers of human fetal cardiac dysfunction in placental insufficiency. Circulation 2002; 105: 2058-2063
• 8 Hecher K, Campbell S, Doyle P. et al. Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies. Circulation 1995; 91: 129-138
• 9 Greenwald SE. Ageing of the conduit arteries. J Pathol 2007; 211: 157-172
• 10 Cheng JK, Wagenseil JE. Extracellular matrix and the mechanics of large artery development. Biomech Model Mechanobiol 2012; 11: 1169-1186
• 11 Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev 2009; 89: 957-989
• 12 Gerrity RG, Cliff WJ. The aortic tunica media of the developing rat. I. Quantitative stereologic and biochemical analysis. Lab Invest 1975; 32: 585-600
• 13 Leung DY, Glagov S, Mathews MB. Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth. Correlation of cellular synthetic response with medial tension. Circ Res 1977; 41: 316-323
• 14 Bendeck MP, Keeley FW, Langille BL. Perinatal accumulation of arterial wall constituents: relation to hemodynamic changes at birth. Am J Physiol 1994; 267: H2268-H2279
• 15 Bendeck MP, Langille BL. Rapid accumulation of elastin and collagen in the aortas of sheep in the immediate perinatal period. Circ Res 1991; 69: 1165-1169
• 16 Cleary EG, Sandberg LB, Jackson DS. The changes in chemical composition during development of the bovine nuchal ligament. J Cell Biol 1967; 33: 469-479
• 17 Dubick MA, Rucker RB, Cross CE. et al. Elastin metabolism in rodent lung. Biochim Biophys Acta 1981; 672: 303-306
• 18 Keeley FW. The synthesis of soluble and insoluble elastin in chicken aorta as a function of development and age. Effect of a high cholesterol diet. Can J Biochem 1979; 57: 1273-1280
• 19 Shapiro SD, Endicott SK, Province MA. et al. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. J Clin Invest 1991; 87: 1828-1834
• 20 Visentin S, Lapolla A, Londero AP. et al. Adiponectin levels are reduced while markers of systemic inflammation and aortic remodelling are increased in intrauterine growth restricted mother-child couple. Biomed Res Int 2014; 2014: 401595
• 21 Hadlock FP, Harrist RB, Sharman RS. et al. Estimation of fetal weight with the use of head, body, and femur measurements–a prospective study. Am J Obstet Gynecol 1985; 151: 333-337
• 22 Visentin S, Londero AP, Bellamio B. et al. Fetal Endothelial Remodeling in Late-Onset Gestational Hypertension. Am J Hypertens 2016; 29: 273-279
• 23 Miyashita S, Murotsuki J, Muromoto J. et al. Measurement of internal diameter changes and pulse wave velocity in fetal descending aorta using the ultrasonic phased-tracking method in normal and growth-restricted fetuses. Ultrasound Med Biol 2015; 41: 1311-1319
• 24 Sugawara M, Niki K, Furuhata H. et al. Relationship between the pressure and diameter of the carotid artery in humans. Heart Vessels 2000; 15: 49-51
• 25 Visentin S, Londero AP, Grumolato F. et al. Timing of delivery and neonatal outcomes for small-for-gestational-age fetuses. J Ultrasound Med 2014; 33: 1721-1728
• 26 Weiner CP, Williamson RA. Evaluation of severe growth retardation using cordocentesis–hematologic and metabolic alterations by etiology. Obstet Gynecol 1989; 73: 225-229
• 27 Baschat AA, Gembruch U, Reiss I. et al. Neonatal nucleated red blood cell counts in growth-restricted fetuses: relationship to arterial and venous Doppler studies. Am J Obstet Gynecol 1999; 181: 190-195
• 28 Bernstein PS, Minior VK, Divon MY. Neonatal nucleated red blood cell counts in small-for-gestational age fetuses with abnormal umbilical artery Doppler studies. Am J Obstet Gynecol 1997; 177: 1079-1084
• 29 Makh DS, Harman CR, Baschat AA. Is Doppler prediction of anemia effective in the growth-restricted fetus?. Ultrasound Obstet Gynecol 2003; 22: 489-492
• 30 Rightmire DA, Nicolaides KH, Rodeck CH. et al. Fetal blood velocities in Rh isoimmunization: relationship to gestational age and to fetal hematocrit. Obstet Gynecol 1986; 68: 233-236
• 31 Gindes L, Matsui H, Achiron R. et al. Comparison of Ex-Vivo High-Resolution Episcopic Microscopy with in-Vivo Four-Dimensional High-Resolution Transvaginal Sonography of the First-Trimester Fetal Heart. Ultrasound Obstet Gynecol 2012; 39: 196-202