Fetal growth restriction - clinical manifestations through the perspective of pathophysiological changes

Capros Hristiana Capros 1 * , Voloceai Victoria 1, Cotelea Veronica 1, Mitriuc Diana 1, Pavlenco Angela 1
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1 Department of Obstetrics and gynecology, State Medical University "N. Testemitanu", Chisinau, Republic of Moldova
* Corresponding Author
J CLIN MED KAZ, Volume 21, Issue 1, pp. 21-25. https://doi.org/10.23950/jcmk/14130
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Author Contributions
Conceptualization, C. H.; methodology, C. H.; validation, C. H. and V. V and C. V. and M. D. and P. A.; formal analysis, C. H. and V. V and C. V. and M. D. and P. A.; investigation, C. H.; resources, C. H; data curation, C. H; writing – original draft preparation, C. H.; writing – review and editing, C. H. and V. V and C. V. and M. D. and P. A.; visualization, C. H. and V. V and C. V. and M. D. and P. A.; supervision, C. H. and V. V and C. V. and M. D. and P. A.; project administration, C. H; funding acquisition, C. H. All authors have read and agreed to the published version of the manuscript.


Intrauterine restriction of fetal growth is one of the most interestings and nowadays  intensively studied problems of modern obstetrics. Fetal growth restriction can lead to significant obstetric complications, as well as consequences after delivery. For the obstetricians the fetal growth means iatrogenic prematurity,  fetal distress, perinatal morbidity but also long term consequences as metabolic disease, cardiovascular pathology and Alzhaimer disease.  There was considerable controversy as to how fetal growth restriction should be defined and diagnosed. Biometric and biophysical tests have been proposed to diagnose growth restriction, but until recently there were no unanimously accepted standards for the diagnosis of this pathology. This definition was reached in 2021 by the FIGO publication. Under the condition of  intrauterine hypoxia adaptation mechanisms are activated. Understanding  the ongoing pathophysiological process of adaptation in a hypoxic media helps to better understand proposed diagnosis criteria and the classification.


Capros CH, Victoria V, Veronica C, Diana M, Angela P. Fetal growth restriction - clinical manifestations through the perspective of pathophysiological changes. J CLIN MED KAZ. 2024;21(1):21-5. https://doi.org/10.23950/jcmk/14130


  • ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol. 2013; 121(5): 1122-1133. https://doi.org/10.1097/01.AOG.0000429658.85846.f9. PMID: 23635765.
  • WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006; 450: 76-85. https://doi.org/10.1097/10.1111/j.1651-2227.2006.tb02378.x. PMID: 16817681.
  • Nardozza LM, Araujo Júnior E, Barbosa MM, Caetano AC, Lee DJ, Moron AF. Fetal growth restriction: current knowledge to the general Obs/Gyn. Arch Gynecol Obstet. 2012; 286(1):1-13. https://doi.org/10.1007/s00404-012-2330-6. Epub 2012 Apr 24. PMID: 22526452.
  • Damhuis SE, Ganzevoort W, Gordijn SJ. Abnormal Fetal Growth: Small for Gestational Age, Fetal Growth Restriction, Large for Gestational Age: Definitions and Epidemiology. Obstet Gynecol Clin North Am. 2021; 48(2): 267-279. https://doi.org/10.1016/j.ogc.2021.02.002. PMID: 33972065.
  • Malhotra A, Allison BJ, Castillo-Melendez M, Jenkin G, Polglase GR, Miller SL. Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact. Front Endocrinol (Lausanne). 2019; 10: 55. https://doi.org/10.3389/fendo.2019.00055. PMID: 30792696; PMCID: PMC6374308.
  • D'Agostin M, Di Sipio Morgia C, Vento G, Nobile S. Long-term implications of fetal growth restriction. World J Clin Cases. 2023; 11(13): 2855-2863. https://doi.org/10.12998/wjcc.v11.i13.2855. PMID: 37215406; PMCID: PMC10198075.
  • Mayow, J. Tractatus quinque medico-physici; Quorum primus agit De salnitro, et spiritu nitro-aereo; Secundus De respiratione; Tertius De respiratione foetus in utero, et ovo; Quartus De motu musculari, et spirtitibus animalibus; Ultimus De rhachide. E. Theatro Sheldonian, Oxonii. 1674
  • Capros H, Scoricova I, Mihalcean L. Intrauterine growth restriction: contemporary issues in diagnosis and management. The Moldovan Medical Journal. 2017; 60 (2): 26-31. ISSN 2537-6373.
  • Maršál K. Physiological adaptation of the growth-restricted fetus. Best Pract Res Clin Obstet Gynaecol. 2018; 49: 37-52. https://doi.org/10.1016/j.bpobgyn.2018.02.006. Epub 2018 Feb 24. PMID: 29753694.
  • Cahill LS, Hoggarth J, Lerch JP, Seed M, Macgowan CK, Sled JG. Fetal brain sparing in a mouse model of chronic maternal hypoxia. Journal of Cerebral Blood Flow & Metabolism. 2019; 39(6):1172-1184. https://doi.org/10.1177/0271678X17750324.
  • Uyan Hendem, Derya, Ocal, Fatma Doga, Oluklu, Deniz, et al. Evaluation of fetal middle adrenal artery Doppler and fetal adrenal gland size in pregnancies with fetal growth restriction: a case-control study. Journal of Perinatal Medicine. 2023; 51 (4): 492-499. https://doi.org/10.1515/jpm-2022-0270.
  • Garcia-Canadilla P, de Vries T, Gonzalez-Tendero A, Bonnin A, Gratacos E, Crispi F, et al. Structural coronary artery remodelling in the rabbit fetus as a result of intrauterine growth restriction. PLoS One. 2019; 14(6): e0218192. https://doi.org/10.1371/journal.pone.0218192. PMID: 31226127; PMCID: PMC6588274.
  • Norvilaitė K, Ramašauskaitė D, Bartkevičienė D, Šliachtenko A, Kurmanavičius J. Fetal Tibial Artery Doppler in Late IUGR Fetuses: A Longitudinal Study. J Clin Med. 2022; 12(1): 82. https://doi.org/10.3390/jcm12010082. PMID: 36614891; PMCID: PMC9821295.
  • Redline RW, Ravishankar S. Fetal vascular malperfusion, an update. APMIS. 2018; 126(7): 561-569. https://doi.org/10.1111/apm.12849. PMID: 30129125.
  • Chang EI, Wesolowski SR, Gilje EA, Baker PR 2nd, Reisz JA, D'Alessandro A, et al. Skeletal muscle amino acid uptake is lower and alanine production is greater in late gestation intrauterine growth-restricted fetal sheep hindlimb. Am J Physiol Regul Integr Comp Physiol. 2019 1; 317(5): R615-R629. https://doi.org/10.1152/ajpregu.00115.2019. Epub 2019 Sep 4. PMID: 31483682; PMCID: PMC6879841.
  • Boddy K, Dawes GS, Fisher R, Pinter S, Robinson JS. Foetal respiratory movements, electrocortical and cardiovascular responses to hypoxaemia and hypercapnia in sheep. J Physiol. 1974; 243(3): 599-618. https://doi.org/10.1113/jphysiol.1974.sp010768. PMID: 4475694; PMCID: PMC1330726.
  • Indications for Outpatient Antenatal Fetal Surveillance: ACOG Committee Opinion, Number 828. Obstet Gynecol. 2021; 137(6): e177-e197. https://doi.org/10.1097/AOG.0000000000004407. PMID: 34011892.
  • Capros H, Mihalcean L, Surguci M. Fetal growth restriction. New terminology and classification. Obstetrics and Gynaecology of Saint-Petersburg. 2020; 1(2): 6-10. ISSN: 2541-8491.
  • Unterscheider J, O'Donoghue K, Malone FD. Guidelines on fetal growth restriction: a comparison of recent national publications. Am J Perinatol. 2015; 32(4): 307-16. https://doi.org/10.1055/s-0034-1387927. Epub 2014 Sep 13. PMID: 25217738.
  • Royal College of Obstetricians and Gynaecologists. The Investigation and Management of the Small-for-Gestational-Age Fetus. RCOG Green-top Guideline No. 31.
  • Vayssière C, Sentilhes L, Ego A, Bernard C, Cambourieu D, Flamant C et al. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians. Eur J Obstet Gynecol Reprod Biol. 2015; 193: 10-8. https://doi.org/10.1016/j.ejogrb.2015.06.021. Epub 2015 Jul 2. PMID: 26207980.
  • Lausman A, Kingdom J; Maternal fetal medicine committee. Intrauterine growth restriction: screening, diagnosis, and management. J Obstet Gynaecol Can. 2013; 35(8): 741-748. English, French. https://doi.org/10.1016/S1701-2163(15)30865-3. PMID: 24007710.
  • Salomon LJ, Alfirevic Z, Da Silva Costa F, Deter RL, Figueras F, Ghi T et al. ISUOG Practice Guidelines: ultrasound assessment of fetal biometry and growth. Ultrasound Obstet Gynecol. 2019; 53(6): 715-723. https://doi.org/10.1002/uog.20272. PMID: 31169958.
  • Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016; 48(3): 333-9. https://doi.org/10.1002/uog.15884. PMID: 26909664.
  • Melamed N, Baschat A, Yinon Y, Athanasiadis A, Mecacci F, Figueras F, et al. FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynaecol Obstet. 2021; 152 (51): 3-57. https://doi.org/10.1002/ijgo.13522. PMID: 33740264; PMCID: PMC8252743.
  • Lees CC, Romero R, Stampalija T, Dall'Asta A, DeVore GA, Prefumo F, et al. Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach. Am J Obstet Gynecol. 2022; 226(3): 366-378. https://doi.org/10.1016/j.ajog.2021.11.1357. Epub 2022 Jan 10. PMID: 35026129; PMCID: PMC9125563.
  • Lawin-O'Brien AR, Dall'Asta A, Knight C, Sankaran S, Scala C, Khalil A, et al. Short-term outcome of periviable small-for-gestational-age babies: is our counseling up to date? Ultrasound Obstet Gynecol. 2016; 48(5): 636-641. https://doi.org/10.1002/uog.15973. PMID: 27854384.
  • Visser GH, Nicholson WK, Barnea ER, Ramasauskaite D, Nassar AH; FIGO Safe Motherhood, Newborn Health Committee. FIGO position paper on reference charts for fetal growth and size at birth: Which one to use? Int J Gynaecol Obstet. 2021; 152(2): 148-151. https://doi.org/10.1002/ijgo.13500. Epub 2020 Dec 29. PMID: 33247958.
  • Morris RK, Malin G, Robson SC, Kleijnen J, Zamora J, Khan KS. Fetal umbilical artery Doppler to predict compromise of fetal/neonatal wellbeing in a high-risk population: systematic review and bivariate meta-analysis. Ultrasound Obstet Gynecol. 2011; 37(2): 135-42. https://doi.org/10.1002/uog.7767. Epub 2011 Jan 12. PMID: 20922778.
  • Baschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol. 2011; 37(5): 501-14. https://doi.org/10.1002/uog.9008. PMID: 21520312.
  • Crispi F, Miranda J, Gratacós E. Long-term cardiovascular consequences of fetal growth restriction: biology, clinical implications, and opportunities for prevention of adult disease. Am J Obstet Gynecol. 2018 Feb; 218 (2S): 869-879. https://doi.org/10.1016/j.ajog.2017.12.012. PMID: 29422215.