Donald School Journal of Ultrasound in Obstetrics and Gynecology

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VOLUME 16 , ISSUE 2 ( April-June, 2022 ) > List of Articles


Investigation of Cardiac Remodeling and Cardiac Function on Fetuses with Growth Restriction: A Review

Maria Papamichail, Panos Antsaklis, Lara Spalldi Barisic, Sanja Malinac Malojčić

Keywords : Cardiac morphology, Cardiac morphometry, Growth restriction

Citation Information : Papamichail M, Antsaklis P, Barisic LS, Malojčić SM. Investigation of Cardiac Remodeling and Cardiac Function on Fetuses with Growth Restriction: A Review. Donald School J Ultrasound Obstet Gynecol 2022; 16 (2):124-137.

DOI: 10.5005/jp-journals-10009-1928

License: CC BY-NC 4.0

Published Online: 05-07-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Fetal growth restriction (FGR) is defined as failure to reach full growth potential in utero and in clinical routine, it is translated as estimated fetal weight (EFW) below the 10th percentile, according to the growth charts. FGR affects 7–10% of pregnancies and it is responsible for the vast majority of perinatal mortality and morbidity. Moreover, FGR is considered as a risk factor for long-term infirmities such as motor skills disorders, cognitive, memory, and neuropsychological impairment, immune disorders, and metabolic syndrome. Importantly, there is an increasing pool of data, suggesting that individuals who as fetuses suffered from FGR, are at high risk for cardiovascular disease (CVD) in adulthood, namely hypertension, atherosclerosis, coronary artery disease, and stroke. Changes in cardiac function and cardiac morphology can be assessed prenatally and especially according to the severity of FGR.

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  1. Hobbins JC, Gumina DL, Zaretsky MV, et al. Size and shape of the four-chamber view of the fetal heart in fetuses with an estimated fetal weight less than the tenth centile. Am J Obstet Gynecol 2019;221(5):495.e1–495.e9. DOI: 10.1016/j.ajog.2019.06.008
  2. Cnattingius S, Haglund B, Kramer MS. Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study. BMJ 1998;316(7143):1483–1487. DOI: 10.1136/bmj.316.7143.1483
  3. Khalil AA, Morales-Rosello J, Elsadigg M, et al. The association between fetal Doppler and admission to neonatal unit at term. Am J Obstet Gynecol 2015;213(1):57.e1–57.e7. DOI: 10.1016/j.ajog.2014.10.013
  4. Eixarch E, Meler E, Iraola A, et al. Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 2008;32(7):894–899. DOI: 10.1002/uog.6249
  5. Cruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, et al. Fetal cardiovascular remodeling persists at 6 months of life in infants with intrauterine growth restriction. Ultrasound Obstet Gynecol 2016;48(3):349–356. DOI: 10.1002/uog.15767
  6. Barker DJ, Winter PD, Osmond C, et al. Weight in infancy and death from ischaemic heart disease. Lancet 1989;2(8663):577–580. DOI: 10.1016/s0140-6736(89)90710-1
  7. Crispi F, Miranda J, Gratacos E. Long-term cardiovascular consequences of fetal growth restriction: biology, clinical implications, and opportunities for prevention of adult disease. Am J Obstet Gynecol 2018;218(2S):S869–S879. DOI: 10.1016/j.ajog.2017.12.012
  8. Madden JV, Flatley CJ, Kumar S. Term small-for-gestational-age infants from low-risk women are at significantly greater risk of adverse neonatal outcomes. Am J Obstet Gynecol 2018;218(5):525.e1–252.e9. DOI: 10.1016/j.ajog.2018.02.008
  9. McEwen EC, Guthridge SL, He VY, et al. What birthweight percentile is associated with optimal perinatal mortality and childhood education outcomes? Am J Obstet Gynecol 2018;218(2S):S712–S724. DOI: 10.1016/j.ajog.2017.11.574
  10. Malhotra A, Allison BJ, Castillo-Melendez M, et al. Neonatal morbidities of fetal growth restriction: pathophysiology and impact. Front Endocrinol (Lausanne) 2019;10:55. DOI: 10.3389/fendo.2019.00055
  11. Grantz KL, Hediger ML, Liu D, et al. Fetal growth standards: the NICHD fetal growth study approach in context with INTERGROWTH-21st and the World Health Organization Multicentre Growth Reference Study. Am J Obstet Gynecol 2018;218(2S):S641–S655.e28. DOI: 10.1016/j.ajog.2017.11.593
  12. O'Dwyer V, Burke G, Unterscheider J, et al. Defining the residual risk of adverse perinatal outcome in growth-restricted fetuses with normal umbilical artery blood flow. Am J Obstet Gynecol 2014;211(4):420.e1–420.e5. DOI: 10.1016/j.ajog.2014.07.033
  13. McCowan LM, Figueras F, Anderson NH. Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. Am J Obstet Gynecol 2018;218(2S):S855–S868. DOI: 10.1016/j.ajog.2017.12.004
  14. Figueras F, Caradeux J, Crispi F, et al. Diagnosis and surveillance of late-onset fetal growth restriction. Am J Obstet Gynecol 2018;218:S790–802. DOI: 10.1016/j.ajog.2017.12.003
  15. Chauhan SP, Beydoun H, Chang E, et al. Prenatal detection of fetal growth restriction in newborns classified as small for gestational age: correlates and risk of neonatal morbidity. Am J Perinatol 2014;31(3):187–194. DOI: 10.1055/s-0033-1343771
  16. Mattioli KP, Sanderson M, Chauhan SP. Inadequate identification of small-for-gestational-age fetuses at an urban teaching hospital. Int J Gynaecol Obstet 2010;109(2):140–143. DOI: 10.1016/j.ijgo.2009.11.023
  17. Crispi F, Crovetto F, Gratacos E. Intrauterine growth restriction and later cardiovascular function. Early Hum Dev 2018;126:23–27. DOI: 10.1016/j.earlhumdev.2018.08.013
  18. Cruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, et al. A fetal cardiovascular score to predict infant hypertension and arterial remodeling in intrauterine growth restriction. Am J Obstet Gynecol 2014;210(6):552.e1–552.e22. DOI: 10.1016/j.ajog.2013.12.031
  19. Pérez-Cruz M, Cruz-Lemini M, Fernández MT, et al. Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler. Ultrasound Obstet Gynecol 2015;46(4):465–471. DOI: 10.1002/uog.14930
  20. Crispi F, Bijnens B, Figueras F, et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation 2010;121(22):2427–2436. DOI: 10.1161/CIRCULATIONAHA.110.937995
  21. Crispi F, Figueras F, Cruz-Lemini M, et al. Cardiovascular programming in children born small for gestational age and relationship with prenatal signs of severity. Am J Obstet Gynecol 2012;207(2):121.e1–121.e9. DOI: 10.1016/j.ajog.2012.05.011
  22. Opie LH, Commerford PJ, Gersh BJ, et al. Controversies in ventricular remodelling. Lancet 2006;367(9507):356–367. DOI: 10.1016/S0140-6736(06)68074-4
  23. Crispi F, Sepúlveda-Martínez Á, Crovetto F, et al. Main patterns of fetal cardiac remodeling. Fetal Diagn Ther 2020;47(5):337–344. DOI: 10.1159/000506047
  24. DeVore GR, Jone PN, Satou G, et al. Aortic coarctation: a comprehensive analysis of shape, size, and contractility of the fetal heart. Fetal Diagn Ther 2020;47(5):429–439. DOI: 10.1159/000500022
  25. Gonzalez-Tendero A, Torre I, Garcia-Canadilla P, et al. Intrauterine growth restriction is associated with cardiac ultrastructural and gene expression changes related to the energetic metabolism in a rabbit model. Am J Physiol Circ Physiol 2013;305(12):H1752–H1760. DOI: 10.1152/ajpheart.00514.2013
  26. Eixarch E, Figueras F, Hernández-Andrade E, et al. An experimental model of fetal growth restriction based on selective ligature of uteroplacental vessels in the pregnant rabbit. Fetal Diagn Ther 2009;26(4):203–211. DOI: 10.1159/000264063
  27. Eixarch E, Hernandez-Andrade E, Crispi F, et al. Impact on fetal mortality and cardiovascular Doppler of selective ligature of uteroplacental vessels compared with undernutrition in a rabbit model of intrauterine growth restriction. Placenta 2011;32(4):304–309. DOI: 10.1016/j.placenta.2011.01.014
  28. Ding YX, Cui H. Integrated analysis of genome-wide DNA methylation and gene expression data provide a regulatory network in intrauterine growth restriction. Life Sci 2017;179:60–65. DOI: 10.1016/j.lfs.2017.04.020
  29. Barker DJ, Osmond C, Golding J, et al. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989;298(6673):564–547. DOI: 10.1136/bmj.298.6673.564
  30. Baschat AA, Gembruch U, Reiss I, et al. Demonstration of fetal coronary blood flow by Doppler ultrasound in relation to arterial and venous flow velocity waveforms and perinatal outcome—the ‘heart-sparing effect’. Ultrasound Obstet Gynecol 1997;9(3):162–172. DOI: 10.1046/j.1469-0705.1997.09030162.x
  31. Tsyvian P, Malkin K, Wladimiroff JW. Assessment of fetal left cardiac isovolumic relaxation time in appropriate and small-for-gestational-age fetuses. Ultrasound Med Biol 1995;21(6):739–743. DOI: 10.1016/0301-5629(95)00016-k
  32. Rodríguez-López M, Cruz-Lemini M, Valenzuela-Alcaraz B, et al. Descriptive analysis of different phenotypes of cardiac remodeling in fetal growth restriction. Ultrasound Obstet Gynecol 2017;50(2):207–214. DOI: 10.1002/uog.17365
  33. Patey O, Carvalho JS, Thilaganathan B. Perinatal changes in cardiac geometry and function in growth-restricted fetuses at term. Ultrasound Obstet Gynecol 2019;53(5):655–662. DOI: 10.1002/uog.19193
  34. Garcia-Canadilla P, Rudenick PA, Crispi F, et al. A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction. PLoS Comput Biol 2014;10(6):e1003667. DOI: 10.1371/journal.pcbi.1003667
  35. Rizzo G, Mattioli C, Mappa I, et al. Hemodynamic factors associated with fetal cardiac remodeling in late fetal growth restriction: a prospective study. J Perinat Med 2019;47(7):683–688. DOI: 10.1515/jpm-2019-0217
  36. Larsen LU, Petersen OB, Sloth E, et al. Color Doppler myocardial imaging demonstrates reduced diastolic tissue velocity in growth retarded fetuses with flow redistribution. Eur J Obstet Gynecol Reprod Biol 2011;155(2):140–145. DOI: 10.1016/j.ejogrb.2010.12.020
  37. Cruz-Martinez R, Figueras F, Hernandez-Andrade E, et al. Changes in myocardial performance index and aortic isthmus and ductus venosus Doppler in term, small-for-gestational age fetuses with normal umbilical artery pulsatility index. Ultrasound Obstet Gynecol 2011;38(4):400–405. DOI: 10.1002/uog.8976
  38. Ichizuka K, Matsuoka R, Hasegawa J, et al. The Tei index for evaluation of fetal myocardial performance in sick fetuses. Early Hum Dev 2005;81(3):273–279. DOI: 10.1016/j.earlhumdev.2004.07.003
  39. Fouron JC, Gosselin J, Amiel-Tison C, et al. Correlation between prenatal velocity waveforms in the aortic isthmus and neurodevelopmental outcome between the ages of 2 and 4 years. Am J Obstet Gynecol 2001;184(4):630–636. DOI: 10.1067/mob.2001.110696
  40. Fouron JC, Gosselin J, Raboisson MJ, et al. The relationship between an aortic isthmus blood flow velocity index and the postnatal neurodevelopmental status of fetuses with placental circulatory insufficiency. Am J Obstet Gynecol 2005;192(2):497–503. DOI: 10.1016/j.ajog.2004.08.026
  41. Chawengsettakul S, Russameecharoen K, Wanitpongpan P. Fetal cardiac function measured by myocardial performance index of small-for-gestational age fetuses. J Obstet Gynaecol Res 2015;41(2):222–228. DOI: 10.1111/jog.12508
  42. Bauer F, Jamal F, Douillet R, et al. Acute changes in load: effects of myocardial velocities measured by doppler tissue imaging. Arch Mal Coeur Vaiss 2001;94(11):1155–1160.
  43. Kaya B, Tayyar A, Açar DK, et al. Comparison of fetal cardiac functions between small-for-gestational age fetuses and late-onset growth-restricted fetuses. J Perinat Med 2019;47(8):879–884. DOI: 10.1515/jpm-2019-0206
  44. Crispi F, Bijnens B, Sepulveda-Swatson E, et al. Postsystolic shortening by myocardial deformation imaging as a sign of cardiac adaptation to pressure overload in fetal growth restriction. Circ Cardiovasc Imaging 2014;7(5):781–787. DOI: 10.1161/CIRCIMAGING.113.001490
  45. Voigt JU, Lindenmeier G, Exner B, et al. Incidence and characteristics of segmental postsystolic longitudinal shortening in normal, acutely ischemic, and scarred myocardium. J Am Soc Echocardiogr 2003;16(5):415–423. DOI: 10.1016/s0894-7317(03)00111-1
  46. Carlhäll C, Wranne B, Jurkevicius R. Is left ventricular postsystolic long-axis shortening a marker for severity of hypertensive heart disease? Am J Cardiol 2003;91(12):1490–1493, A8. DOI: 10.1016/s0002-9149(03)00407-7
  47. Weidemann F, Broscheit JA, Bijnens B, et al. How to distinguish between ischemic and nonischemic postsystolic thickening: a strain rate imaging study. Ultrasound Med Biol 2006;32(1):53–59. DOI: 10.1016/j.ultrasmedbio.2005.09.003
  48. Melchiorre K, Sutherland GR, Baltabaeva A, et al. Maternal cardiac dysfunction and remodeling in women with preeclampsia at term. Hypertension 2011;57(1):85–93. DOI: 10.1161/HYPERTENSIONAHA.110.162321
  49. Claus P, Weidemann F, Dommke C, et al. Mechanisms of postsystolic thickening in ischemic myocardium: mathematical modelling and comparison with experimental ischemic substrates. Ultrasound Med Biol 2007;33(12):1963–1970. DOI: 10.1016/j.ultrasmedbio.2007.06.003
  50. van Oostrum NHM, van der Woude DAA, Clur SB, et al. Right ventricular dysfunction identified by abnormal strain values precedes evident growth restriction in small for gestational age fetuses. Prenat Diagn 2020;40(12):1525–1531. DOI: 10.1002/pd.5805
  51. DeVore GR, Gumina DL, Hobbins JC. Assessment of ventricular contractility in fetuses with an estimated fetal weight less than the tenth centile. Am J Obstet Gynecol 2019;221(5):498.e1–498.e22. DOI: 10.1016/j.ajog.2019.05.042
  52. Henry A, Alphonse J, Tynan D, et al. Fetal myocardial performance index in assessment and management of small-for-gestational-age fetus: a cohort and nested case-control study. Ultrasound Obstet Gynecol 2018;51(2):225–235. DOI: 10.1002/uog.17476
  53. Graupner O, Ried C, Wildner NK, et al. Myocardial deformation analysis in late-onset small-for-gestational-age and growth-restricted fetuses using two-dimensional speckle tracking echocardiography: a prospective cohort study. J Perinat Med 2022;50(3):305–312. DOI: 10.1515/jpm-2021-0162
  54. Doust JA, Pietrzak E, Dobson AJ, et al. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ 2005;330(7492):625–639. DOI: 10.1136/bmj.330.7492.625
  55. Perez-Cruz M, Crispi F, Fernández MT, et al. Cord blood biomarkers of cardiac dysfunction and damage in term growth-restricted fetuses classified by severity criteria. Fetal Diagn Ther 2018;44(4):271–276. DOI: 10.1159/000484315
  56. Girsen A, Ala-Kopsala M, Mäkikallio K, et al. Cardiovascular hemodynamics and umbilical artery N-terminal peptide of proB-type natriuretic peptide in human fetuses with growth restriction. Ultrasound Obstet Gynecol 2007;29(3):296–303. DOI: 10.1002/uog.3934
  57. Crispi F, Hernandez-Andrade E, Pelsers MM, et al. Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses. Am J Obstet Gynecol 2008;199(3):254.e1–254.e8. DOI: 10.1016/j.ajog.2008.06.056
  58. Stergiotou I, Crispi F, Valenzuela-Alcaraz B, et al. Patterns of maternal vascular remodeling and responsiveness in early- versus late-onset preeclampsia. Am J Obstet Gynecol 2013;209(6):558.e1–558.e14. DOI: 10.1016/j.ajog.2013.07.030
  59. Sehgal A, Doctor T, Menahem S. Cardiac function and arterial biophysical properties in small for gestational age infants: postnatal manifestations of fetal programming. J Pediatr 2013;163(5):1296–1300. DOI: 10.1016/j.jpeds.2013.06.030
  60. Raitakari OT, Juonala M, Rönnemaa T, et al. Cohort profile: the cardiovascular risk in Young Finns study. Int J Epidemiol 2008;37(6):1220–1226. DOI: 10.1093/ije/dym225
  61. Alsaied T, Omar K, James JF, et al. Fetal origins of adult cardiac disease: a novel approach to prevent fetal growth restriction induced cardiac dysfunction using insulin like growth factor. Pediatr Res 2017;81(6):919–925. DOI: 10.1038/pr.2017.18
  62. Vickers MH, Gluckman PD, Coveny AH, et al. Neonatal leptin treatment reverses developmental programming. Endocrinology 2005;146(10):4211–4216. DOI: 10.1210/en.2005-0581
  63. Rodriguez-Lopez M, Osorio L, Acosta-Rojas R, et al. Influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction. Pediatr Res 2016;79(1-2):100–106. DOI: 10.1038/pr.2015.182
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