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VOLUME 1 , ISSUE 1 ( January-March, 2022 ) > List of Articles


Recent Advances in the Study of Fetal Brain Structure and Function

Asim Kurjak

Keywords : Antenatal neurodevelopment, Fetal neurodevelopment, KANET

Citation Information : Kurjak A. Recent Advances in the Study of Fetal Brain Structure and Function. 2022; 1 (1):81-93.

DOI: 10.5005/jp-journals-11005-0013

License: CC BY-NC 4.0

Published Online: 06-05-2022

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


Assessment of the fetal nervous system, both in the anatomical and functional way, has remained a part of the research project for several years. Advances in ultrasound techniques, especially the evolution of ultrasound techniques and particularly the introduction of 3D and 4D techniques, offered the chance to check fetal anatomy and activity in real-time and in extreme detail. How the brain of the fetus develops and matures both in utero and during extrauterine life is a very complex process that follows a selected behavioral pattern that undergoes changes and progresses reciprocal to every week of growth, mirroring its neurological integrity. If the stages that the neurological development goes through during in utero life may be recognized and standardized, then the doubtless abnormal neurobehaviors may be defined and prompt diagnosis of pathological conditions of the fetal nervous system may be possible. To this goal, a pioneer test was introduced by Kurjak; Kurjak antenatal neurodevelopmental test (KANET) uses 4D ultrasound to assess fetal behavior and movements in a way similar to postnatal neonatal neurological evaluation. Evidence from multicenter studies shows that the test has the potential to spot fetuses at risk for neurodevelopment impairment and it's applicable in everyday clinical practice.

  1. Antsaklis P, Kurjak A, Izetbegovic S. Functional test for fetal brain: the role of KANET test. Donald School J Ultrasound Obstet Gynecol 2013;7(4):385–399. DOI: 10.5005/jp-journals-10009-1309
  2. Kurjak A, Carrera JM, Stanojevic M, et al. The role of 4D sonography in the neurological assessment of early human development. Ultrasound Rev Obstet Gynecol 2004;4(3):148–159.
  3. Salihagic-Kadic A, Kurjak A, Medic M, et al. New data about embryonic and fetal neurodevelopment and behaviour obtained by 3D and 4D sonography. J Perinat Med 2005;33(6):478–490. DOI: 10.1515/JPM.2005.086
  4. Stanojevic M, Zaputovic S, Bosnjak AP. Continuity between fetal and neonatal neurobehavior. Semin Fetal Neonatal Med 2012;17(6):324–329. DOI: 10.1016/j.siny.2012.06.006
  5. Haak P, Lenski M, Hidecker MJ, et al. Cerebral palsy and aging. Dev Med Child Neurol 2009;51 (Suppl 4):16–23. DOI: 10.1111/j.1469-8749.2009.03428.x
  6. Kurjak A, Antsaklis P, Stanojevic M, et al. Fetal behavior assessed by four-dimensional sonography. Donald School J Ultrasound Obstet Gynecol 2017;11(2):146–168. DOI: 10.5005/jp/books/13058_36
  7. Pomeroy SL, Voipe JJ. Development of the nervous system. In: Polin RA, Fox, WW, editors. Fetal and neonatal physiology. Philadelphia-London-Toronto-Montreal-Sydney-Tokyo: WB Saunders Company 1992;1491–1509.
  8. Kostovic I, Judas M, Petanjek Z, et al. Ontogenesis of goal directed behavior: anatomo-functional considerations. Int J Psychophysiol 1995;19(2):85–102. DOI: 10.1016/0167-8760(94)00081-o
  9. Schaher S. Determination and differentiation in the development of the nervous system. In: Kandel ER, Schwartz JH, editors. Principles of Neural Science. 2nd ed. New York: Elsevier Science Publishing 1985:730–732.
  10. Kostovic I. Prenatal development of nucleus basalis complex and related fibre system in man: a histochemical study. Neuroscience 1986;17(4):1047–1077. DOI: 10.1016/0306-4522(86)90077-1
  11. Kurjak A, Panos A, Milan S. Fetal neurology: past, present and future. Donald Sch J Ultrasound Obstet Gynecol 2015;9(1): 6–29. DOI: 10.5005/jp–journals–10009–1385
  12. Prechtl FHR. Ultrasound studies of human fetal behavior. Early Hum Dev 1985;12(2):91–98.
  13. lanniruberto A, Tajani E. Ultrasonographic study of fetal movements. Semin Perinatal 1981;5(2):175–181.
  14. Goto S, Kato TK. Early movements are useful for estimating the gestational weeks in the first trimester of pregnancy. Ultrasound Med Biol 1983;Suppl 2:577–582.
  15. Joseph R. Fetal brain and cognitive development. Dev Rev 2000;20(1):81–98.
  16. D‘Elia A, Pighetti M, Moccia G, et al. Spontaneous motor activity in the normal fetus. Early Human Dev 2001;65(2): 139–144. DOI: 10.1016/s0378-3782(01)00224-9
  17. Andonotopo W, Medic M, Salihagic-Kadic A, et al. The assessment of embryonic and fetal neurodevelopment in early pregnancy: comparison between 2D and 4D sonographic scanning. J Perinat Med 2005;33(5):406–414. DOI: 10.1515/JPM.2005.073
  18. Kurjak A, Stanojevic M, Andonotopo W, et al. Behavioral pattern continuity from prenatal to postnatal life—a study by four-dimensional (4D) ultrasonography. J Perinat Med 2004;32(4):346–353. DOI: 10.1515/JPM.2004.065
  19. Kurjak A, Andonotopo W, Hafner T, et al. Normal standards for fetal neurobehavioural developments—longitudinal quantification by four-dimensional sonography. J Perinat Med 2006;34(1):56–65. DOI: 10.1515/JPM.2006.007
  20. Einspieler C, Prechtl HF. Prechtl's assessment of general movements: a diagnostic tool for the functional assessment of the young nervous system. Ment Retard Dev Disabil Res Rev 2005;11(1):61–67. DOI: 10.1002/mrdd.20051
  21. Moster D, Wilcox AJ, Vollset SE, et al. Cerebral palsy among term and postterm births. JAMA 2010;304(9):976–982. DOI: 10.1001/jama.2010.1271
  22. de Vries JI, Visser GH, Prechtl HF. The emergence of fetal behaviour. I. Qualitative aspects. Early Hum Dev 1982;7(4): 301–322. DOI: 10.1016/0378-3782(82)90033-0
  23. Nijhuis JG. Fetal behaviour: developmental and perinatal aspects. Oxford, Oxford University Press; 1992. Chapter 9. p. 489–498.
  24. Prechtl HF. State of the art of a new functional assessment of the young nervous system. An early predictor of cerebral palsy. Early Hum Dev 1997;50(1):1–11. DOI: 10.1016/s0378-3782(97)00088-1
  25. Kurjak A, Luetic AT. Fetal neurobehavior assessed by three dimensional/four dimensional sonography. Zdrav Vestn 2010;79(11):790–799.
  26. Kurjak A, Vecek N, Kupesic S, et al. Four dimensional ultrasound: how much does it improve perinatal practice? In: Carrera JM, Chervenak FA, Kurjak A, editors. Controversies in perinatal medicine, studies on the fetus as a patient. New York: A CRC press company, Parthenon Publishing; 2003. p 222.
  27. Kurjak A, Ahmed B, Abo-Yaquab S, et al. An attempt to introduce neurological test for fetus based on 3D and 4D sonography. Donald School J Ultrasound Obstet Gynecol 2008;2(4):29–44. DOI: 10.5005/jp–journals–10009–1076
  28. Kurjak A, Azumendi G, Vecek N, et al. Fetal hand movements and facial expression in normal pregnancy studied by fourdimensional sonography. J Perinat Med 2003;31(6):496. DOI: 10.1515/JPM.2003.076
  29. Patrick J, Campbell K, Carmichael L, et al. Patterns of gross fetal body movements over 24-hours observation intervals during the last 10 weeks of pregnancy. Am J Obstet Gynecol 1982;142(4):363–371. DOI: 10.1016/s0002-9378(16)32375-4
  30. Vasung L, Lepage C, Radoš M, et al. Quantitative and qualitative analysis of transient fetal compartments during prenatal human brain development. Front Neuroanat 2016;10:11. DOI: 10.3389/fnana.2016.00011
  31. Hadders-Algra. The neuronal group selection theory: a framework to explain variation in normal motor development. Dev Med Child Neurol 2000;42(8):566–572. DOI: 10.1017/s0012162200001067
  32. Vladareanu R, Lebit D, Constantinescu S. Ultrasound assessment of fetal neurobehavior in high-risk pregnancies. Donald School J Ultrasound Obstet Gynecol 2012;6(2):132–147. DOI: 10.5005/jp-journals-10009-1235
  33. Nijhuis JG. Fetal behavior. Neurobiol Aging 2003;24 (Suppl 1): S41–46. DOI: 10.1016/s0197-4580(03)00054-x
  34. Arabin B, Bos R, Rijlaarsdam R, et al. The onset of inter-human contacts: longitudinal ultrasound observations in early twin pregnancies. Ultrasound Obstet Gynecol 1996;8(3):166–173. DOI: 10.1046/j.1469-0705.1996.08030166.x
  35. Kurjak A, Lausin I, Azumendi G. Assessment of fetal behavior by 3D and 4D sonography; in Hata T, Kurjak A, Kozuma S (Eds): Current Topics on Fetal 3D/4D Ultrasound Bentham Science Publishers 2009:234–265. (
  36. Hata T, Kanenishi K, Sasaki M. Four-dimensional sonographic assessment of fetal movement in the late first trimester. Int J Gynecol Obstet 2010;109(3):190–193. DOI: 10.1016/j.ijgo.2009.12.020
  37. Kurjak A, Spalldi Barisic L, Stanojevic M, et al. Are we ready to investigate cognitive function of fetal brain? The role of advanced four dimensional sonography. Donald School J Ultrasound Obstet Gynecol 2016;10(2):116–124. DOI: 10.5005/jp-journals-10009-1453
  38. Stanojevic M, Kurjak A. Continuity from fetal to neonatal behavior: lessons learned and future challenges. Donald School J Ultrasound Obstet Gynecol 2011;5(2):107–118. DOI: 10.5005/jp-journals-10009-1185.
  39. Hadders-Algra. General movements: a window for early identification of children at high risk for developmental disorders. J Pediatr 2004;145(2 Suppl):S12–S18. DOI: 10.1016/j.jpeds.2004.05.017
  40. Seme-Ciglenečki P. Predictive value of assessment of general movements for neurological development of high-risk preterm infants: comparative study. Croat Med J 2003;44(6):721–727.
  41. Kurjak A, Stanojevic M, Andonotopo W, et al. Fetal behavior assessed in all three trimesters of normal pregnancy by four-dimensional ultrasonography. Croat Med J 2005;46(5):772–780.
  42. Stanojevic M, Talic A, Miskovic B, et al. An attempt to standardize Kurjak's antenatal neurodevelopmental test: Osaka consensus statement. Donald School J Ultrasound Obstet Gynecol 2011;5(4):317–329. DOI: 10.5005/jp-journals-10009-1209
  43. Sekulić SR, Lukac DD, Naumović NM. The fetus cannot exercise like an astronaut: gravity loading is necessary for the physiological development during second half of pregnancy. Med Hypotheses 2005;64(2):221–228. DOI: 10.1016/j.mehy.2004.08.012
  44. Meigal AY. Synergistic action of gravity and temperature on the motor system within the lifespan: a “Baby Astronaut” hypothesis. Med Hypotheses 2013;80(3):275–283. DOI: 10.1016/j.mehy.2012.12.004
  45. Palmer FB. Strategies for the early diagnosis of cerebral palsy. J Pediatr 2004;145(Suppl 2):S8-S11. DOI: 10.1016/j.jpeds.2004.05.016
  46. Stanojevic M, Antsaklis P, Salihagic-Kadic A, et al. Is Kurjak antenatal neurodevelopmental test ready for routine clinical application? Bucharest Consensus Statement. Donald School J Ultrasound Obstet Gynecol 2015;9(3):260–265. DOI: 10.5005/jp-journals-10009-1412
  47. Andonotopo W, Kurjak A. The assessment of fetal behavior of growth restricted fetuses by 4D sonography. J Perinat Med 2006;34(6):471–478. DOI: 10.1515/JPM.2006.092
  48. Kurjak A, Abo-Yaqoub S, Stanojevic M, et al. The potential of 4D sonography in the assessment of fetal neurobehavior–multicentric study in high-risk pregnancies. J Perinat Med 2010;38(1):77–82. DOI: 10.1515/jpm.2010.012. PMID: 20047526.
  49. Miskovic B, Vasilj O, Stanojevic M, et al. 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
  50. Talic A, Kurjak A, Ahmed B, et al. The potential of 4D sonography in the assessment of fetal behavior in high-risk pregnancies. J Matern Fetal Neonatal Med 2011;24(7):948–954. DOI: 10.3109/14767058.2010.534830
  51. Honemeyer U, Kurjak A. The use of KANET test to assess fetal CNS function. First 100 cases. 10th World Congress of Perinatal Med 2011;8–11.
  52. Talic A, Kurjak A, Stanojevic M, et al. The assessment of fetal brain function in fetuses with ventrikulomegaly: the role of the KANET test. J Matern Fetal Neonatal Med 2012;25(8): 1267–1272. DOI: 10.3109/14767058.2011.634463
  53. Abo-Yaqoub S, Kurjak A, Mohammed AB, et al. The role of 4-D ultrasonography in prenatal assessment of fetal neurobehaviour and prediction of neurological outcome. J Matern Fetal Neonatal Med 2012;25(3):231–236. DOI: 10.3109/14767058.2011.568552
  54. Honemeyer U, Talic A, Therwat A, et al. The clinical value of KANET in studying fetal neurobehavior in normal and at-risk pregnancies. J Perinat Med 2013;41(2):187–197. DOI: 10.1515/jpm-2011-0251
  55. Kurjak A, Talic A, Honemeyer U, et al. Zalud I Comparison between antenatal neurodevelopmental test and fetal Doppler in the assessment of fetal well being. J Perinat Med 2013;41(1):107–114. DOI: 10.1515/jpm-2012-0018
  56. Athanasiadis AP, Mikos T, Tambakoudis GP, et al. Neurodevelopmental fetal assessment using KANET scoring system in low and high risk pregnancies. J Matern Fetal Neonatal Med 2013;26(4):363–368. DOI: 10.3109/14767058.2012.695824
  57. Neto RM. KANET in Brazil: first experience. Donald School J Ultrasound Obstet Gynecol 2015;9(1):1–5. DOI: 10.5005/jp-journals-10009-1384
  58. Hanaoka U, Hata T, Kananishi K, et al. Does ethnicity have an effect on fetal behavior? A comparison of Asian and Caucasian populations. J Perinat Med 2016;44(2):217–221. DOI: 10.1515/jpm-2015-0036
  59. Hata T, Kanenishi K, Mori N, et al. Prediction of postnatal developmental disabilities using the antenatal fetal neurodevelopmental test: KANET assessment. J Perinat Med 2018;47(1):77–81. DOI: 10.1515/jpm-2018-0169
  60. Kurjak A, Spalldi Barišić L, Stanojević M, et al. Multi-center results on the clinical use of KANET. J Perinat Med 2019;47(9):897–909. DOI: 10.1515/jpm-2019-0281. PMID: 31677378.
  61. Tan KH, Smyth RM, Wei X. Fetal vibroacoustic stimulation for facilitation of tests of fetal wellbeing. Cochrane Database Syst Rev 2013;(12):CD002963. DOI: 10.1002/14651858.CD002963.pub2
  62. Antsaklis P, Porovic S, Daskalakis G, et al. 4D assessment of fetal brain function in diabetic patients. J Perinat Med 2017;45(6):711–715. DOI: 10.1515/jpm-2016-0394
  63. Spencer-Smith MM, Spittle AJ, Doyle LW, et al. Long-term benefits of homebased preventive care for preterm infants: a randomized trial. Pediatrics 2012;130(6):1094–1101. DOI: 10.1542/peds.2012-0426
  64. Salihagić Kadić A, Kurjak A. Cognitive functions of the fetus. Ultraschall in der Medizin 2018;39(2):181–189 DOI: 10.1055/s-0043-123469
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