Detection of fetal hypoxia: a review of the literature


  • Ivona Plesa Department of Gynecology and Obstetrics, Clinical Hospital „Sveti Duh“, Zagreb
  • Marta Orlovic Department of Gynecology and Obstetrics, Clinical Hospital „Sveti Duh“, Zagreb
  • Ana Marija Krznaric Lovosevic Department of Gynecology and Obstetrics, Clinical Hospital „Sveti Duh“, Zagreb
  • Maja Brkic Department of Gynecology and Obstetrics, Clinical Hospital „Sveti Duh“, Zagreb
  • Kosjenka Dermit Department of Gynecology and Obstetrics, Clinical Hospital „Sveti Duh“, Zagreb
  • Tihana Galic Department of Gynecology and Obstetrics, Clinical Hospital „Sveti Duh“, Zagreb
  • Vladimir Blagaic Department of Gynecology and Obstetrics, Clinical Hospital „Sveti Duh“, Zagreb



chronic hypoxia, doppler indices, intrauterine growth restriction, placental insufficiency


Fetal hypoxia is a condition characterized by a reduced oxygen supply of fetal tissues. Although fetal hypoxia can be caused by many factors, it usually occurs due to progressive placental insufficiency and is associated with intrauterine growth restriction. In a state of fetal hypoxia, adaptation mechanisms are activated, and bloodstream centralization occurs, which is beneficial to the fetal brain (brain sparing effect), heart, and adrenal glands, while the periphery remains deprived of adequate amounts of oxygen. It is important to emphasize that diagnostic tools for measuring blood flow redistribution in favor of the fetal brain have been developed, and their bases are Doppler indices of the umbilical and middle cerebral arteries. Monitoring of the Doppler indices, particularly cerebroumbilical ratio, is the most important prenatal diagnostic tool for the prognosis of neurodevelopmental disorders. New findings are based on the fact that functional and structural brain damage occurs even in stable hemodynamic compensatory mechanisms, so the brain sparing effect is not considered to be an entirely physiological response. The consequences of fetal hypoxia and intrauterine growth restriction can be periventricular leukomalacia, intracranial bleeding, and a wide range of functional neurological damage. Therefore, research in modern perinatal medicine should be based on finding a new high-quality diagnostic tests or using a combination of the existing ones to allow early diagnosis of potentially endangered fetuses and define the time of delivery. This would prevent perinatal brain damage and its long-term effects on the health of children.


1. Đelmiš J, Orešković S. Fetalna medicina i opstetricija. Zagreb: Medicinska naklada; 2014.
2. Hutter D, Kingdom J, Jaeggi E. Causes and mechanisms of intrauterine hypoxia and its impact on the fetal cardiovascular system: a review. Int J Pediatr. 2010;2010:401323. doi: 10.1155/2010/401323.
3. Nicolaides K, Rizzo G, Hecher K, Xiamenes R. Doppler in Obstetrics. London: The fetal Medicine Fundation; 2002.
4. Miller J, Turan S, Baschat AA. Fetal growth restriction. Semin Perinatol. 2008;32(4):274-280. doi: 10.1053/j.semperi.2008.04.010.
5. Baschat AA. The fetal circulation and essential organs-a new twist to an old tale. Ultrasound Obstet Gynecol. 2006;27(4):349-354. doi: 10.1002/uog.2762.
6. Pardi G, Marconi AM, Cetin I. Placental-fetal interrelationship in IUGR fetuses--a review. Placenta. 2002;23 Suppl A:S136-141. doi: 10.1053/plac.2002.0802.
7. Baschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol. 2011;37(5):501-514. doi: 10.1002/uog.9008.
8. Ginosar Y. Anesthesia and the fetus. Hoboken: Wiley-Blackwell; 2013.
9. Rosenberg A. The IUGR newborn. Semin Perinatol. 2008;32(3):219-224. doi: 10.1053/j.semperi.2007.11.003.
10. Gerber S, Hohlfeld P, Viquerat F, Tolsa JF, Vial Y. Intrauterine growth restriction and absent or reverse end-diastolic blood flow in umbilical artery (Doppler class II or III): A retrospective study of short- and long-term fetal morbidity and mortality. Eur J Obstet Gynecol Reprod Biol. 2006;126(1):20-26. doi: 10.1016/j.ejogrb.2005.07.008.
11. Jarvis S, Glinianaia SV, Torrioli M-G, Platt M-J, Miceli M, Jouk P-S. Cerebral palsy and intrauterine growth in single births: European collaborative study. Lancet. 362(9390):1106-1111. doi: 10.1016/S0140-6736(03)14466-2.
12. Hernandez-Andrade E, Figueroa-Diesel H, Jansson T, Rangel-Nava H, Gratacos E. Changes in regional fetal cerebral blood flow perfusion in relation to hemodynamic deterioration in severely growth-restricted fetuses. Ultrasound Obstet Gynecol. 2008;32(1):71-76. doi: 10.1002/uog.5377.
13. Jugovic D, Tumbri J, Medic M, Jukic MK, Kurjak A, Arbeille P. New Doppler index for prediction of perinatal brain damage in growth-restricted and hypoxic fetuses. Ultrasound Obstet Gynecol. 2007;30(3):303-311. doi: 10.1002/uog.4094.
14. Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol. 1980;136(6):787-795.
15. Manning FA. Fetal biophysical profile: a critical appraisal. Clin Obstet Gynecol. 2002;45(4):975-985.
16. Vintzileos AM, Gaffney SE, Salinger LM, Campbell WA, Nochimson DJ. The relationship between fetal biophysical profile and cord pH in patients undergoing cesarean section before the onset of labor. Obstet Gynecol. 1987;70(2):196-201.
17. Vintzileos AM, Fleming AD, Scorza WE, Wolf EJ, Balducci J, Campbell WA. Relationship between fetal biophysical activities and umbilical cord blood gas values. Am J Obstet Gynecol. 1991;165(3):707-713.
18. Giussani DA, Spencer JA, Moore PJ, Bennet L, Hanson MA. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. J Physiol. 1993;461:431-449.
19. Jensen A, Hanson MA. Circulatory responses to acute asphyxia in intact and chemodenervated fetal sheep near term. Reprod Fertil Dev. 1995;7(5):1351-1359.
20. Chamberlain PF, Manning FA, Morrison I, Harman CR, Lange IR. Ultrasound evaluation of amniotic fluid volume. I. The relationship of marginal and decreased amniotic fluid volumes to perinatal outcome. Am J Obstet Gynecol. 1984;150(3):245-249.
21. Alfirevic Z, Neilson JP. Doppler ultrasonography in high-risk pregnancies: Systematic review with meta-analysis. Am J Obstet Gynecol. 1995;172(5):1379-1387.
22. Giles WB, Trudinger BJ, Baird PJ. Fetal umbilical artery flow velocity waveforms and placental resistance: pathological correlation. Br J Obstet Gynaecol. 1985;92(1):31-38.
23. Starcevic M. Rani neurološki ishod novorođenčadi s intrauterinim zastojem u rastu [dissertation]. Zagreb: Sveučilište u Zagrebu, Medicinski fakultet; 2012.
24. Valcamonico A, Danti L, Frusca T, Soregaroli M, Zucca S, Abrami F. Absent end-diastolic velocity in umbilical artery: risk of neonatal morbidity and brain damage. Am J Obstet Gynecol. 1994;170(3):796-801.
25. Arbeille P. Fetal arterial Doppler-IUGR and hypoxia. Eur J Obstet Gynecol Reprod Biol. 1997;75(1):51-53.
26. Wladimiroff JW, Tonge HM, Stewart PA. Doppler ultrasound assessment of cerebral blood flow in the human fetus. Br J Obstet Gynaecol. 1986;93(5):471-475.
27. Dikshit S. Fresh look at the Doppler changes in pregnancies with placental-based complications. J Postgrad Med. 2011;57(2):138-140. doi: 10.4103/0022-3859.81880.
28. Picklesimer AH, Oepkes D, Moise KJ, Jr., Kush ML, Weiner CP, Harman CR. Determinants of the middle cerebral artery peak systolic velocity in the human fetus. Am J Obstet Gynecol. 2007;197(5):526.e1-4. doi: 10.1016/j.ajog.2007.04.002.
29. Figueroa-Diesel H, Hernandez-Andrade E, Acosta-Rojas R, Cabero L, Gratacos E. Doppler changes in the main fetal brain arteries at different stages of hemodynamic adaptation in severe intrauterine growth restriction. Ultrasound Obstet Gynecol. 2007;30(3):297-302. doi: 10.1002/uog.4084.
30. Bekedam DJ, Visser GH, van der Zee AG, Snijders RJ, Poelmann-Weesjes G. Abnormal velocity waveforms of the umbilical artery in growth retarded fetuses: relationship to antepartum late heart rate decelerations and outcome. Early Hum Dev. 1990;24(1):79-89.
31. Turan OM, Turan S, Gungor S, Berg C, Moyano D, Gembruch U. Progression of Doppler abnormalities in intrauterine growth restriction. Ultrasound Obstet Gynecol. 2008;32(2):160-167. doi: 10.1002/uog.5386.
32. Salihagić A, Georgescus M, Perrotin F. Daily Doppler assessment of the fetal hemodynamic response to chronic hypoxia: a five case report. Prenat Neonat Med. 2000;5:35-41.
33. Groenenberg IA, Baerts W, Hop WC, Wladimiroff JW. Relationship between fetal cardiac and extra-cardiac Doppler flow velocity waveforms and neonatal outcome in intrauterine growth retardation. Early Hum Dev. 1991;26(3):185-192.
34. Rizzo G, Arduini D, Romanini C, Mancuso S. Doppler echocardiographic assessment of time to peak velocity in the aorta and pulmonary artery of small for gestational age fetuses. Br J Obstet Gynaecol. 1990;97(7):603-607.
35. Beeby AR, Dunlop W, Hunter S. Evidence of redistribution of cardiac output in asymmetrical growth retardation. Br J Obstet Gynaecol. 1989;96(12):1453-1454.
36. Rizzo G, Arduini D. Fetal cardiac function in intrauterine growth retardation. Am J Obstet Gynecol. 1991;165(4 Pt 1):876-882.
37. Edelstone DI, Rudolph AM, Heymann MA. Effects of hypoxemia and decreasing umbilical flow liver and ductus venosus blood flows in fetal lambs. Am J Physiol. 1980;238(5):H656-663.
38. Reuss ML, Rudolph AM. Distribution and recirculation of umbilical and systemic venous blood flow in fetal lambs during hypoxia. J Dev Physiol. 1980;2(1-2):71-84.
39. Reuss ML, Rudolph AM, Dae MW. Phasic blood flow patterns in the superior and inferior venae cavae and umbilical vein of fetal sheep. Am J Obstet Gynecol. 1983;145(1):70-78.
40. Kiserud T, Crowe C, Hanson M. Ductus venosus agenesis prevents transmission of central venous pulsations to the umbilical vein in fetal sheep. Ultrasound Obstet Gynecol. 1998;11(3):190-194.
41. Rizzo G, Arduini D, Romanini C. Inferior vena cava flow velocity waveforms in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol. 1992;166(4):1271-1280.
42. Hecher K, Hackeloer BJ. Cardiotocogram compared to Doppler investigation of the fetal circulation in the premature growth-retarded fetus: longitudinal observations. Ultrasound Obstet Gynecol. 1997;9(3):152-161.
43. Gudmundsson S, Tulzer G, Huhta JC, Marsal K. Venous Doppler in the fetus with absent end-diastolic flow in the umbilical artery. Ultrasound Obstet Gynecol. 1996;7(4):262-267.
44. Rizzo G, Capponi A, Soregaroli M, Arduini D, Romanini C. Umbilical vein pulsations and acid-base status at cordocentesis in growth-retarded fetuses with absent end-diastolic velocity in umbilical artery. Biol Neonate. 1995;68(3):163-168.
45. Capponi A, Rizzo G, De Angelis C, Arduini D, Romanini C. Atrial natriuretic peptide levels in fetal blood in relation to inferior vena cava velocity waveforms. Obstet Gynecol. 1997;89(2):242-247.
46. Hecher K, Campbell S, Doyle P, Harrington K, Nicolaides K. Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies. Circulation. 1995;91(1):129-138.
47. Sinkovskaya E, Klassen A, Abuhamad A. A novel systematic approach to the evaluation of the fetal venous system. Semin Fetal Neonatal Med. 2013;18(5):269-278. doi: 10.1016/j.siny.2013.05.009.
48. Arbeille P, Maulik D, Fignon A, Stale H, Berson M, Bodard S. Assessment of the fetal PO2 changes by cerebral and umbilical Doppler on lamb fetuses during acute hypoxia. Ultrasound Med Biol. 1995;21(7):861-870.
49. Harrington K, Thompson MO, Carpenter RG, Nguyen M, Campbell S. Doppler fetal circulation in pregnancies complicated by pre-eclampsia or delivery of a small for gestational age baby: 2. Longitudinal analysis. Br J Obstet Gynaecol. 1999;106(5):453-466.
50. Gramellini D, Folli MC, Raboni S, Vadora E, Merialdi A. Cerebral-umbilical Doppler ratio as a predictor of adverse perinatal outcome. Obstet Gynecol. 1992;79(3):416-420.
51. Salihagic-Kadic A, Medic M, Jugovic D, Kos M, Latin V, Kusan Jukic M. Fetal cerebrovascular response to chronic hypoxia--implications for the prevention of brain damage. J Matern Fetal Neonatal Med. 2006;19(7):387-396. doi: 10.1080/14767050600637861.
52. Degani S. Evaluation of fetal cerebrovascular circulation and brain development: the role of ultrasound and Doppler. Semin Perinatol. 2009;33(4):259-269. doi: 10.1053/j.semperi.2009.04.004.
53. Figueras F, Oros D, Cruz-Martinez R, Padilla N, Hernandez-Andrade E, Botet F. Neurobehavior in term, small-for-gestational age infants with normal placental function. Pediatrics. 2009;124(5):e934-941. doi: 10.1542/peds.2008-3346.
54. Starcevic M, Predojevic M, Butorac D, Tumbri J, Konjevoda P, Kadic AS. Early functional and morphological brain disturbances in late-onset intrauterine growth restriction. Early Hum Dev. 2016;93:33-38. doi: 10.1016/j.earlhumdev.2015.12.001.
55. Miskovic B, Vasilj O, Stanojevic M, Ivankovic D, Kerner M, Tikvica A. The comparison of fetal behavior in high risk and normal pregnancies assessed by four dimensional ultrasound. J Matern Fetal Neonatal Med. 2010;23(12):1461-1467. doi: 10.3109/14767051003678200.
56. Kurjak A, Antsaklis P, Stanojevic M, Vladareanu R, Vladareanu S, Neto RM. Multicentric studies of the fetal neurobehavior by KANET test. J Perinat Med. 2017;45(6):717-727. doi: 10.1515/jpm-2016-0409.
57. Predojevic M, Talic A, Stanojevic M, Kurjak A, Salihagic Kadic A. Assessment of motoric and hemodynamic parameters in growth restricted fetuses - case study. J Matern Fetal Neonatal Med. 2014;27(3):247-251. doi: 10.3109/14767058.2013.807241.
58. Bain E, Middleton P, Crowther CA. Different magnesium sulphate regimens for neuroprotection of the fetus for women at risk of preterm birth. Cochrane Database Syst Rev. 2012(2):CD009302. doi: 10.1002/14651858.CD009302.pub2.
59. Reynolds A, Slattery S, Byrne S, Neary E, Mullers S, Kent E. Timing of administration of antenatal magnesium sulfate and umbilical cord blood magnesium levels in preterm babies. J Matern Fetal Neonatal Med. 2017;13:1-6. doi: 10.1080/14767058.2017.1398724.
60. Brookfield KF, Elkomy M, Su F, Drover DR, Carvalho B. Optimization of Maternal Magnesium Sulfate Administration for Fetal Neuroprotection: Application of a Prospectively Constructed Pharmacokinetic Model to the BEAM Cohort. J Clin Pharmacol. 2017;57(11):1419-1424. doi: 10.1002/jcph.941.
61. Crowther CA, Middleton PF, Voysey M, Askie L, Duley L, Pryde PG. Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis. PLoS Med. 2017;14(10):e1002398. doi: 10.1371/journal.pmed.1002398.




How to Cite

Plesa, I., Orlovic, M., Krznaric Lovosevic, A. M., Brkic, M., Dermit, K., Galic, T., & Blagaic, V. (2017). Detection of fetal hypoxia: a review of the literature. BioMedicine and Surgery, 1(3), 125–132.