Donald School Journal of Ultrasound in Obstetrics and Gynecology
Volume 17 | Issue 1 | Year 2023

From Structure to Function of Fetal Brain: A Long Journey

Asim Kurjak1, Milan Stanojević2, Panos Antsaklis3, Edin Medjedović4, Sanja Tomasović5

1Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina

2Department of Obstetrics and Gynecology, School of Medicine, University of Zagreb, Zagreb, Croatia; Sveti Duh Hospital, Zagreb, Croatia

3Department of Obstetrics and Gynecology, University of Athens, Athens, Greece

4Clinic of Gynecology and Obstetrics, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

5Department of Neurology and Neurosurgery, Faculty of Medicine, Josip Juraj Strossmayer University, Osijek, Croatia

Corresponding Author: Asim Kurjak, Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina, Phone; +385 91 4512096, e-mail:

Received on: 30 December 2022; Accepted on: 25 January 2023; Published on: 14 April 2023


Understanding the structure and function of the fetal nervous system has been the dream of physicians for centuries. The pioneering efforts of Ian Donald in obstetric ultrasound (US) in the latter part of the 20th century have permitted this dream to become a reality. The initial contribution of obstetric US focused on normal and abnormal structures. Initially, anencephaly was described and followed by increasingly subtle central nervous system (CNS) abnormalities such as agenesis of the corpus callosum. The current and evolving challenge for investigators in obstetric US is to have similar success with the understanding of fetal neurological function. There are many functional neurological abnormalities, such as cerebral palsy (CP), whose causes are poorly understood. There are also an escalating number of results illustrating that a large presence of neurological problems, such as minimal cerebral dysfunction, schizophrenia, epilepsy, or autism, upshot at least in part from prenatal neurodevelopmental problems. Clinical and epidemiological studies have revealed that CP most often results from prenatal rather than perinatal or postnatal causes. Currently, although momentous advances in prenatal and perinatal care, there are no means to identify or expect the development of these disorders. Therefore, the development of diagnostic strategies to avoid and condense the saddle of perinatal brain damage has to turn into one of the most imperative tasks of contemporary perinatal medicine. The application of the new neurobehavioral test Kurjak’s antenatal neurobehavioral test (KANET) might improve our understanding of prenatal neurodevelopmental events and possibly antenatal detection of CP and other neurological diseases.

How to cite this article: Kurjak A, Stanojević M, Antsaklis P, et al. From Structure to Function of Fetal Brain: A Long Journey. Donald School J Ultrasound Obstet Gynecol 2023;17(1):11-35.

Source of support: Nil

Conflict of interest: Dr. Asim Kurjak, Dr. Milan Stanojević, Dr. Panos Antsaklis and Dr. Edin Medjedović are associated as the Editorial Board Members of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of these Editorial Board Members and their research group.

Keywords: Cerebral palsy, Kurjak’s antenatal neurobehavioral test, Prenatal neurology, Structure and function of fetal brain.

This paper has been previously published as a chapter of Asim Kurjak, Milan Stanojević, and Panagiotis Antsaklis. From structure to function: A long journey. In: Donald School Fetal Brain Functioning. Kurjak A., (ed.) Jaypee Brothers, New Delhi, 2022, pp 1–39. Since Donald School Journal of Ultrasound in Obstetrics and Gynecology (DSJUOG) is an educational journal, and more readers, have access to it, and since the publisher of both the book and journal is the same, the authors gave permission to publish their text in the journal.


For investigators in obstetric US, there is a current and growing challenge to have similar success with the understanding of fetal neurological function. In many functional neurological abnormalities like CP, the causes are poorly understood. There has also been noticed an escalating number of results which show that a large presence of neurological problems (like minimal cerebral dysfunction, schizophrenia, epilepsy, or autism), at least in part, come from prenatal neurodevelopmental problems. Clinical and epidemiological studies showed that CP most often results from prenatal rather than perinatal or postnatal causes.1

Although significant advances in prenatal and perinatal care are obvious, currently, there are no means to identify or expect the development of these disorders. Consequently, one of the most imperative tasks of contemporary perinatal medicine became the development of diagnostic strategies to avoid and condense the saddle of perinatal brain damage. Understanding of the prenatal neurodevelopmental events and possibly antenatal detection of CP and other neurological diseases might be improved by applying the new neurobehavioral test—KANET.

Structural Development of CNS

The generation of the neuroectoderm from ectoderm during the 3rd postconceptional week results in the formation of the neural plate. Thus, the neural epithelium of the embryo, which is a precursor of neurons and glia, is virtually the first part of an organism that acquires the separate identity from other cells.2

The formation of the neural plate is succeeded by the folding of its edges and the formation of a neural tube, whose further growth and reshaping results in the formation of structures of CNS. According to O’Rahilly and Muller, the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon) can be distinguished in the rostral portion of the unfused neural folds3 earlier than it is usually referred to, approximately at 22nd postconceptional day. In rapid succession, during the 4th postconceptional week, the forebrain components—diencephalon and telencephalon can be detected. Three embryonic zones, ventricular, intermediary, and marginal zone (seen from ventricular to the pial surface), are present in all parts of the neural tube, while the telencephalon contains two additional zones, subventricular and subplate zone,3 ventricular zone, and subventricular zone of telencephalon are the site of neurogenesis, and all the future neurons and glia are born in this structures.3 During migration towards the pial surface, they form other transitional zones before reaching their genetically predetermined final destinations.3 Those destinations are cortical plates or different nuclei in the brain stem, diencephalon, and basal forebrain.1 One of the transitional structures, a subplate zone that is a site for transient synapses and neuronal interactions, can play a major role in the developmental plasticity following perinatal brain damage.4 Early appearance of interneuronal connections, shown in Table 1, implicates a possibility of early functional development.3,4 However, these first synapses exist only temporarily and disappear due to the normal reorganization processes. Most embryonic zones, types of neurons and glia, and early synapses, which play a crucial role in certain periods of fetal brain development, eventually disappear, significantly changing the structure and function of the brain.4 Reorganization processes include apoptosis, the disappearance of redundant synapses, axonal retraction and transposition, and transformation of the neurotransmitters phenotype.4 Further details we have described elsewhere.5

Table 1: Dynamics of the most important progressive processes in the development of the human brain3,4
Beginning Most intensive activity Ending
Neurogenesis Early embryonic period (4th week) 8–12th week Approx 20 weeks
Migration Simultaneously with proliferation 18–24th week 38th week
Synaptogenesis 6–7th week–spinal cord
8th week–cortical plate
13–18th week, after 24th week, 8th month–2 years of postnatal life Puberty

Table 1 shows a significant overlap of neurogenesis, migration, and synaptogenesis in embryonic and fetal life. At the time of delivery, the development of the human brain is not completed. In an infant born at term, characteristic cellular layers can be observed in motor, somatosensory, visual, and auditory cortical areas.

While in a term, infant proliferation and migration are completed, synaptogenesis and neuronal differentiation continue very intensively.6 Brainstem demonstrates a high level of maturity, whereas all histogenetic processes actively persist in the cerebellum.7 Therefore, only subcortical formations and the primary cortical areas are well developed in a newborn. The associative cortex, which is barely visible in a newborn, is poorly developed in a 6-month-old infant. Postnatal formation of synapses in associative cortical areas, which intensifies between the 8th month and 2nd year of life, precedes the onset of first cognitive functions, such as speech.1,7 Following the 2nd year of age, many redundant synapses are eliminated.7 The elimination of synapses begins very rapidly and continues slowly until puberty, when the same number of synapses as seen in adults is reached.7

Functional Development of CNS

The first synapses appear in the spinal cord at 6–7 postconceptional weeks8 and in the cortical plate at 8 postconceptional weeks.9 This is the phase when the first electrical bustle and conduction of information take place. The earliest spontaneous fetal movements can be observed at 7.5 postconceptional weeks. These movements, which consist of slow flexion and extension of the fetal trunk accompanied by the inactive displacement of arms and legs and emerging in asymmetrical sequences, have been described as “vermicular.”10,11 They are substituted by various general movements (GMs) consisting of head, trunk, and limb movements, such as “rippling” seen at week 8, “twitching” and “strong twitching” at weeks 9 and 9.5, respectively, and “floating” “swimming,” and “jumping” at week 10.12 Almost simultaneously with the GMs, isolated limb movements emerge. At the same time with the beginning of spontaneous movements, at 7.5 postconceptional weeks, the initial motor reflex activity can be detected, permitting the hypothesis to be made of the existence of the first afferent-efferent circuits.8 Head tilting following perioral stimulation was noted at that time.8 The primary reflex movements are immense and signify a limited number of synapses in a reflex pathway.8 During the 8th week of gestation, these substantial reflex movements are replaced with local movements, possibly due to an increase in the number of axodendritic synapses.8 Hands become susceptible at 10.5 weeks, and lower limbs start to contribute to these reflexes at around week 14.12,13 The first sign of supraspinal control on fetal motor activity are GMs.10,11 Brainstem, which consists of the medulla oblongata, pons, and midbrain, begins to develop and mature in a caudal to rostral direction approximately at the 7 postconceptional weeks.7-9 As the medulla matures in advance of more rostral structures of the brainstem, reflexive movements of the head, body, and extremities, as well as breathing movements and heart rate alterations, appear in advance of other functions.13 The amount and incidence of movements have increased since the 10th week onwards.13 Fetuses are highly active, with the longest period between movements of only 5–6 minutes by 14–19 weeks.10-12 A total of 15 singular types of movement can be observed in the 15th week.10-12 We can see general body movements and isolated limb movements, retroflexion, anteflexion, and rotation of the head.13 Furthermore, face movements, such as mouthing, yawning, hiccups, sucking, and swallowing, can be included in an ample repertoire of fetal motor activity in this stage.14 However, during the first half of pregnancy, a dynamic pattern of neuronal production and migration, as well as the immature cerebral circuits, are considered too immature for cerebral involvement in motor behavior.4 Merely at the end of this period do a quantifiable number of synapses appear in the structures preceding the cerebral cortex, perhaps forming a substrate for the first cortical electric activity, noted at week 19.4 At the 20th week the spinothalamic tract is established and myelinated by 29 weeks of gestation while at 24–26 weeks the thalamocortical connections penetrate the cortical plate.15 At the 29th week, evoked potentials can be detected from the cortex, suggesting that the functional connection between the periphery and cortex operates from that time onwards.15 In the second half of pregnancy, particularly during the last 10 weeks, the number of GMs gradually decreases.16 This decrease was first explained as a result of the reduction in amniotic fluid volume; however, it is now believed to be a result of maturation processes in the brainstem.13 An increase in facial movements, as well as opening or closing of the jaw, swallowing, and chewing, can be observed simultaneously with the decline in the number of generalized movements.16 These activities can be seen mainly in periods of absence of GMs. This pattern is considered to be a manifestation of the normal neurological development of the fetus.16 However, alterations not only in the number of movements but also in their complexity are revealed to be the result of cerebral maturation processes.13 It is important to point out that subunits of the brainstem remain the main regulators of all fetal behavioral patterns until delivery.13 The study of prenatal behavior is still in its infancy despite medical reports from 100 years ago and >30 years of systematic research initiated by Prechtl.10,17-19 One of the most promising progress in the field of US was the new four-dimensional (4D) US technology. Its advance has been achieved in the last year, giving visualizations in almost real-time.20-23 In an extraordinary way, the availability of new diagnostic data raised our knowledge about intrauterine life, substantially modifying some earlier interpretations.24 With conventional two-dimensional US (2D US), first spontaneous fetal movements can be observed around the 8th gestational week, while the newly developed 4D US enables the visualization of fetal motility one week earlier (Table 2).25

Table 2: Developmental sequence of fetal behavioral patterns observed by 4D US in the first trimester of pregnancy25
Postconceptional weeks
Type of movements 7 8 9 10 11
GM + + + + +
Startle + + + +
Stretching + + + +
Isolated arm movement + + + +
Isolated leg movement + + + +
Head rotation + + +
Head anteflexion + + +
Head retroflexion + + +

General movements (GMs) are the first complex fetal movement patterns observable by 2D US; however, assessment by 4D US is a considerable improvement. They can be recognized from the 8–9th weeks of pregnancy (Fig. 1 showed by 4D US) and continue to be present until 16–20 weeks after birth.19

Fig. 1: Four-dimensional (4D) US imaging demonstrated the fetus at 13 weeks of gestation, showing a GM pattern.

According to Prechtl, “these are gross movements involving the whole body. They wax and wane in intensity, force, and speed, and they have a gradual beginning and end.”14,19 The majority of sequences of extension and flexion of the legs and arms are complex and may be better assessed with 4D US.25 In the literature, there is a range between the 8th and 12th weeks regarding the first appearance of limb movements.14,19,21,26 De Vries et al. found isolated arm and leg movements in the 8th week of gestation.14 With 4D US, limb movements were found at the 8–9th weeks.25 By 4D sonography, Kurjak et al. found that from 13 gestational weeks onwards, a “goal orientation” of hand movements appears, and a target point can be recognized for each hand movement.20 It was noticed that more limb joints were active and moved simultaneously, like extension or flexion in the arm and elbow or hip and knee. Simultaneously, the elevation of the hand, and extension of the elbow joint, with a slight change in direction and rotation, could have been seen.27 The isolated limb movements which were seen in the 9th week are followed by the appearance of the movements in the elbow joint at 10 weeks, changes in finger position in the 11th week, and easily recognizable clenching and unclenching of the fist at the 12–13th week. Finally, isolated finger movements, as well as an increase in the activity and strength of movements of the hand or finger, can be seen in the 13–14th week.27 Recent examination of fetuses in the last trimester of gestation, which were performed by 4D US, has discovered an even wider range of movements of hand and face than was formerly explained.20 It has also been confirmed that the fetal movement patterns in the second half of pregnancy are about equal to those monitored after birth. However, the list of movements in the newborn consists of some patterns that cannot be observed in the fetus, such as the Moro reflex.28 In addition, at around the 20th gestational week, the study of anencephalic fetuses presented clear evidence for the influence of supraspinal structures on motor behavior. In these fetuses, the number of movements was normal or even increased, but the complexity of the movement patterns was distorted radically, and movements were stereotyped and simplified.29

The eminence of fetal movement patterns is distorted in fetuses undergoing intrauterine growth restriction (IUGR). The activities become monotonous and slower, similar to cramps, and we can see that their variability in force and amplitude is reduced.30 These changes might designate the subsistence of brain lesions in growth-restricted and possibly hypoxic fetuses. Despite the premature postulations, the changes in the amplitude and complexity of movements in these fetuses do not show to be due to oligohydramnios. In cases of premature rupture of fetal membranes and a subsequently reduced volume of amniotic fluid, movements arise less frequently, but their complexity looks like that of movements achieved in the normal volume of amniotic fluid.17 Qualitative, including quantitative analysis of fetal movements, divulged the consistency of the fetal nervous system and can be applied for the recognition of different cerebral dysfunctions and probably neuromuscular ailments.29

The new technology, 4D US, when applied in the examination of fetal facial movements, revealed the existence of a full range of facial expressions, including grimacing, tongue expulsion, and eyelid movements (Fig. 2), similar to emotional expressions in adults.28,31 The possibility of studying such subtle movements could open a new area of investigation.32

Fig. 2: Three-dimensional/four-dimensional (3D/4D) US provides a clear depiction of dynamic changes in fetal facial expression allowing the study of fetal behavior during all trimesters of pregnancy

During the first trimester, it was noticed a tendency towards the increased frequency of general fetal movements with increasing gestational age (Fig. 3A). While at the beginning of the second trimester, the fetuses began to display a tendency towards the increased frequency of observed fetal facial expression up to the end of the second trimester. An oscillation and dispersion of the incidence of the facial expression, as seen in the polynomial regression of the isolated eye blinking diagram, is observable in Figure 3B.31

Figs 3A to C: Quantitative analysis of normal fetal behavior patterns using 4D US (A) GMs; (B) Isolated eye blinking31; (C) Hand-to-face movement

In the second trimester, the most frequent facial movement patterns were isolated eye blinking, grimacing, suckling, and swallowing, while yawning, mouthing, tongue expulsion, and smiling could be observed less frequently.26,31 The fetuses began to display decreasing or stagnant incidence of fetal facial expression during the third trimester. From the beginning of the second trimester to the end of the third trimester, all types of head movements and hand-to-body contact indicated a tendency to decrease frequency (Fig. 3C).31

In this period, the investigations of fetal facial expressions established that all mechanisms of the fetal yawning pattern, prolonged jaw opening followed by a quick closure and accompanied by head flexion and elevation of arms, can easily be documented by 4D US (Fig. 4).33

Fig. 4: Four-dimensional (4D) US image sequences of facial expression characterized by stereotyped yawning opening

If we compared fetal yawning in the third trimester with the yawning in the neonates during the 1st week of life, no differences in the frequencies of this reaction were found. It was noticed that the frequency of yawning steadily increased between the 15th and 24th week, then from the 24th to 26th week, a short plateau was observed, which was followed by a slight decrease towards the term.31 A gestational age-related tendency in the frequency of yawning could be assumed as the maturation of the brain stem and probably the gaining of control of more cranial structures over the yawning pattern. These results gave new data about the route of neurodevelopment of this fascinating but poorly implicit reflex.31 It still continues to be determined whether this is distorted in cases of neurodevelopmental disorders and whether such adaptations can give us an impending into the function of the fetal nervous system in high-risk pregnancies. To what possibility are the facial motoric patterns related to the function and integrity of the CNS also stays to be determined. However, the fact that even in the embryonic stage, the identical inductive forces that cause growth and restyling of the neural tube influence the development of facial structures, and many genetic disorders affecting the CNS are also described by dysmorphology and dysfunction of facial structures, underlining the value of these studies.2,31,32

Continuity of GMs from Prenatal to Postnatal Life

Postnatal studies of neonatal behavior have taught us that the assessment of behavior is a better predictor of neurodevelopment disability than neurological examinations.34 It is important to mention that postnatal observation of movement patterns was launched by Prechtl and coworkers. They have been observing spontaneous movements of the infant using video typing and “offline” analysis of quantity as well as the quality of the movement.18,35 They have shown that the assessment of GMs in high-risk newborns has significantly higher predictive value for later neurological development than neurological examination.34,36,37 Kurjak et al. performed a study by 4D US and were able to confirm their earlier findings made by 2D US that there is behavioral pattern continuity from prenatal to postnatal life.28 Assessment of neonatal behavior has been shown to be a better method for early detection of CP than neurological examination alone.38 It is speculated that intrauterine detection of encephalopathy would improve the outcome. Many fetal behavioral studies have been conducted; however, it is still uncertain whether the assessment of continuity from fetal to neonatal behavior could improve our ability of early detection of brain pathology. Early detection could possibly rise an opportunity to intervene and even prevent the expected damage.

Could Some Postnatal Signs of Neurological Disability be Used Prenatally?

The fact that US is a powerful tool in the assessment of fetal behavior has been proven by 4D US-enabled visual observation of the fetus, particularly in two especially important domains: fetal finger movements and facial expressions.20,39 This new technology is not only a tool of fetal observation but a very useful tool to evaluate the development of fetal CNS in normally developing fetuses and those at high risk. A basic understanding of fetal neurology includes1—defining of motor pathways involved,2 chronology of their maturation, and3 the direction of myelination.40,41 This information helps the clinician to better interpret fetal movements. The experience acquired with Amiel-Tison’s neurological assessment at term (ATNAT) helps us in the interpretation of fetal movements.42-44

The domain of fetal neurology is already too extensive, but the focus of interest is mainly the second trimester, despite the fact that spontaneous fetal mobility emerges and has already become differentiated at a very early age.45 This means that we will take into consideration the period of pregnancy from 20 to 40 weeks of gestation, including the end of the neuronal migration and the postmigratory phase corresponding to the development of the neocortex.4,46

As already mentioned, CP describes a group of disorders of the development of movement and posture, causing limitations in activity, which are attributed to nonprogressive disturbances occurring at the time of development of the fetal brain.47-54 Motor disorders that occur in patients with CP are often accompanied by disturbances of sensation, cognition, communication, perception, behavior, and/or with a seizure disorder.47-54 “Disturbances” is a term that refers to events or processes influencing in some way the expected pattern of brain maturation.44 Those events or processes are many, with consequences varying from very conspicuous to very subtle. We should always keep in mind what many neurologists emphasize—that morphology does not always correspond to neurological outcomes.42-44 The opposite view is the one from pediatricians and neurophysiologists. They are involved in long-term follow-up studies, and they are certainly not that optimistic. It would be wise to consider the long-run prognosis for each specific type of fetal brain damage and make appropriate decisions for conservative management.

Hopes have been headed towards magnetic resonance (MR), but in many cases, brain changes cannot be detected as early as the 1st year of life, like, for example, pathological gliosis, which causes secondary hypomyelination.

While examining the fetal head in 4D, the sonographer should examine bony structures and fetal cranial sutures. If they are folding over one another, it is considered to be a bad sign, as previously described by Amiel-Tison.42,44 The same sign should be searched for postnatally as a part of neurological examination.51

The majority of pediatricians believe that the main obstacle to early prediction of CP based on a functional observation of the fetus, such as visual observation by 4D US, is due to the “precompetent” stage of most of the motor behavior observed in utero.42,44 One of the possible signs detected could be high arched palate, described by Amiel-Tison, in the clinical assessment of the infant nervous system.42,44 What was believed undetectable became visible by 4D. Recently, the 3D “reverse face technique” has been described. This technique overcomes shadowing the fetal face by rotating the frontal facial image through 180° along the vertical axis so that the palate, nasal cavity, and orbits become visualized.52,53

Pooh and Ogura, in their early work, examined 65 normal fetuses in 3D/4D. The purpose of their study was to investigate the natural course of fetal hand and finger positioning.27 During the 9th week and at the beginning of the 10th week, fetal hands were placed in front of the chest, and no movements of wrists and fingers could be visualized. Active arm movements were seen from the middle of the 10th week.27 This study is very important since it shows that movements of fingers and thumbs begin in the early stage of human life, long before the maturation of the upper system. Therefore this motor activity depends on the lower system and not before 30–32 weeks switches to the upper control.

Amiel-Tison also described the so-called “neurologic thumb” squeezed in a fist. Clenched fingers can also be found by 4D US, as well as overlapping cerebral sutures.20,27

According to de Vries et al., head anteflexion becomes visible during the 10th and 11th gestational weeks.45 However, the activity of flexor muscles will depend on the upper system from the 34th week of gestation. The absence of active head flexion explored by the raise-to-sit maneuver is one of the major neurological signs at 40 weeks of gestation.42,43,51


Kurjak’s antenatal neurobehavioral test (KANET) is a new scoring system for the assessment of fetal neurobehavior, which is based on prenatal evaluation of the fetus by 3D/4D US.55 The test is a combination of several parameters consisting of fetal GMs and of postnatal ATNAT signs, which can be easily visualized prenatally by using 4D US, as described earlier.26,56 As mentioned before, the following parameters have been incorporated in the KANET test—isolated head anteflexion, overlapping cranial sutures, head circumference, isolated eye blinking, facial alterations, mouth opening (yawning or mouthing), isolated hand and leg movements and thumb position, and gestalt perception of GMs (overall perception of the body and limb movements with their qualitative assessment).

Several papers have shown that there is a continuity of behavior from pre- to postnatal life. It has been observed that all movements which are present in neonates are also present in fetal life, with the exception of Moro’s reflex, which cannot be demonstrated in fetuses.57 This is probably due to a different environment to which the fetus and neonate are exposed. The fetus lives in an environment of microgravity, while the newborn is exposed to full gravity, which creates certain obstacles for neurodevelopment in the first months of life.58-60 The parameters were chosen based on the developmental approach to the neurological assessment and on the theory of central pattern generators of GM emergence. They were the product of multicentric studies conducted for several years.26,31 KANET is a combination of assessments of fetal behavior, GMs, and three out of four signs which have been postnatally considered as symptoms of possible neurodevelopmental impairment (neurological thumb, overlapping sutures, and small head circumference).58,59

The KANET test has been standardized; it is reproducible and easily applied by fetal medicine specialists.58 The recommendation is to perform KANET in the third trimester of pregnancy, between 28 and 38 weeks. The optimal duration of the examination is between 15 and 20 minutes, and the fetus should be examined while awake. If the fetus is in the sleeping period, the assessment should be postponed for 30 minutes or for the following day, at a minimum period of 14–16 hours. In cases of grossly abnormal or borderline scores, the test should be repeated every 2 weeks until delivery. Special attention should be paid to facial movements and to eye blinking, which are prenatally very informative and important (”the face is the mirror of the brain”). The overall number of movements should be defined in very active or inactive fetuses and compared with normal values of previous studies (Figs 5 and 6).26-31

Figs 5A and B: (A) Normal KANET score at 34 weeks of pregnancy; (B) Normal KANET score at 32 weeks of pregnancy—the impact of the evolution of US technology on the quality of fetal assessment

Figs 6: Face grimacing

For the application of the KANET test, all examiners should have extensive hands-on education, both in low and high-risk pregnancies. Interobserver and intraobserver variability should be available. It is advisable to use 4D US machines with a frame rate of a minimum of 24 volumes/second. KANET consists of eight parameters (Table 3).58

A score range of 0–5 is characterized as abnormal, a score calculated from 6 to 13 is considered borderline, and a score range of 14–20 is normal (Table 4).1,22,58 After that, neonates should be followed up postnatally for neurological development for a 2-year period.

Table 3: Proposal for the new KANET assessment tool consisting of eight parameters58,74
Sign Score Sign score
0 1 2
Isolated head anteflexion
Abrupt Small range (0–3 times of movements) Variable in full range, many alterations (>3 times of movements)
Cranial sutures and head circumference
Overlapping of cranial sutures Normal cranial sutures with measurement of HC below or above the normal limit (−2 SD) according to GA Normal cranial sutures with normal measurement of HC according to GA
Isolated eye blinking
Not present Not fluent
(1–5 times of blinking)
(>5 times of blinking)
Facial alteration (grimace or tongue expulsion)
Not present Not fluent (1–5 times of alteration) Fluency (>5 times of alteration)
Or Mouth opening (Yawning or mouthing)
Cramped Poor repertoire or small in range (0–5 times of movement) Variable in full range, many alterations (>5 times of movements)
Isolated leg movement
Isolated hand movement
Cramped or abrupt Poor repertoire or small in range (0–5 times of movement) Variable in full range, many alterations (> 5 times of movements)
or Hand-to-face movements
Unilateral or bilateral clenched fist (neurological thumb) Cramped invariant finger movements Smooth and complex, variable finger movements
Fingers movement
Gestalt perception of GMs Definitely abnormal Borderline Normal total score

Stanojevic et al. “Osaka Consensus Statement” DSJUOG 2011; 5:4 pp. 317-329

Table 4: Interpreration of KANET scores58,74
Total score Interpretation
0–5 Abnormal
6–9 Borderline
10–16 Normal

Stanojevic et al. “Osaka Consensus Statement” DSJUOG 2011; 5:4 pp. 317-329

The test evaluates quantitative as well as qualitative aspects of fetal motor behavioral patterns. The parameters examined by this test are a combination of GMs and parameters adopted from ATNAT.60,61 It is believed that the criterion of quality and quantity of spontaneous GMs has excellent reliability in evaluating the integrity of fetal CNS.62,63 Furthermore, the continuity of behavioral patterns from the prenatal to the postnatal period has been proven.28,64,65 Both those facts support the choice of the parameters used in this test which make KANET theoretically appropriate for the assessment of fetal behavior. According to previous reports,29,30,66-69 KANET easily detects serious functional impairment associated with structural abnormalities. Studies have shown that the application of KANET in both low and high-risk populations has given good results. Especially in high-risk populations, KANET may provide useful information regarding the neurological outcome of these fetuses.70 KANET is the first test that is based on 4D US, with an original scoring system, and has been standardized. Therefore it can be implemented in everyday practice, overcoming the difficulties and covering the gaps in methods that were used in the past for the evaluation of fetal behavior.17,71,72 Studies show that KANET is easily applicable to most pregnancies. Furthermore, the learning curve is reasonable for physicians who already have training in obstetrical US. The actual duration of KANET ranges from 15 to 20 minutes.73 All of these shows strong evidence that it can be widely implemented in everyday clinical practice.74

Kurjak’s antenatal neurobehavioral test (KANET) has been introduced in training, and it has been calculated that the number of KANET tests needed to be performed by experienced US specialists in order to be familiar with assessing a fetus with 4D US in 20 minutes is 80.75 The success rate of the test ranges from 91 to 95%. Further study of each parameter revealed a success rate for the assessment of particular signs of 88% for isolated eye blinking and 100% for mouth opening and isolated leg movement.75 KANET has almost 100% negative predictive value, and interobserver variability was satisfactory, with the lowest being for the facial expression (K = 0.68) and the highest for the finger movements (K = 0.84).75

What have Studies about KANET Shown so Far?

One of the first studies which used a preliminary form of the KANET scoring system was that by Andonotopo et al. in 2006. They aimed to assess the fetal facial expression and quality of body movements and examine if they are of diagnostic value for brain impairment in fetuses with growth restriction. In that prospective study of 50 pregnancies with IUGR fetuses in the third trimester of pregnancy, there has been noted a tendency for less behavioral activity in IUGR than in normal fetuses.30 Future investigation of the use of 4D US for quantitative and qualitative assessment of fetal behavior as possible indicators of the neurological condition in IUGR fetuses was encouraged by the results of this study (Figs 7 to 10).30

Figs 7A to I: Hand and finger movement

Fig. 8: Kurjak’s antenatal neurobehavioral test (KANET)—facial alterations mouthing, eye blinking, and hand movement

Fig. 9: Tongue expulsion and mouthing

Fig. 10: Smiling

In 2008, the Zagreb group was the first to introduce the KANET for the assessment of the neurological status of the fetus, aiming to the detection of the fetal brain and neurodevelopmental alterations due to in utero brain impairment.76,77 In order to develop the new scoring system, they identified severely brain-damaged neonates and neonates with good neurological conditions and then compared the neonatal findings with corresponding findings in utero76,77 In the group of 100 low-risk pregnancies, they retrospectively applied KANET. After delivery, postnatal neurological assessment (ATNAT) was performed, and all neonates assessed as normal reached a score between 14 and 20, assumed to be the score of optimal neurological development.76,77 A new scoring system was applied in the group of 120 high-risk pregnancies in which, based on postnatal neurological findings, three subgroups of newborns were identified—normal, mildly or moderately abnormal, and abnormal. Based on this, a neurological scoring system has been proposed.76,77 All normal fetuses reached a score from 14 to 20. A total of 10 fetuses who were postnatally described as mildly or moderately abnormal achieved a prenatal score of 5–13, while another ten fetuses postnatally assigned as neurologically abnormal had a prenatal score of 0–5.76,77 Among this group, four had alobar holoprosencephaly; one had severe hypertensive hydrocephaly, one had thanatophoric dysplasia, and four fetuses had multiple malformations.76,77 This study inspired a large series of multicenter studies (Table 5) that used the KANET in order to assess the usefulness of this promising new scoring system for the assessment of neurological status in fetuses and the recognition of signs of early brain impairment in utero.76,77

Table 5: List of studies that have applied KANET test to different populations
Author Year Study Study design Study population Indication No GA (weeks) Time (minutes) Result Summary
Kurjak et al.76,77 2008 Cohort Retrospective High-risk Multiple 220 20–36 30 Positive A new scoring system was proposed for the antenatal assessment of the fetal neurological status
Kurjak et al.78 2010 Multicenter Prospective High-risk Multiple 288 20–38 30 Positive KANET appeared to be prognostic of antenatal detection of serious neurological fetal problems. KANET also identified fetuses with severe structural abnormalities, especially associated with brain impairment
Miskovic et al.79 2010 Cohort Prospective High-risk Multiple 226 20–36 30 Positive A correlation between antenatal (KANET) and postnatal (ATNAT) results were found. KANET showed differences in fetal behavior between high and low-risk pregnancies
Talic et al.80 2011 Multicenter
Prospective High-risk Multiple 620 26–38 15–20 Positive KANET test had a prognostic value in discriminating normal from borderline and abnormal fetal behavior, in normal and in high-risk cases. Abnormal KANET scores were predictable in both intrauterine and postnatal death.
Talic et al.81 2011 Multicenter
Prospective High-risk Ventriculomegaly 240 32–36 10–15 Positive A statistically significant difference was identified in KANET scores between normal pregnancies and pregnancies with ventriculomegaly. Abnormal KANET scores and most of the borderline scores were noted in fetuses with severe ventriculomegaly, especially associated with additional abnormalities
Honemeyer et al.82 2011 Cohort Prospective Unselected Unselected 100 28–38 N/A Positive Normal prenatal KANET scores had a significant predictive value of a normal postnatal neurological evaluation
Lebit et al.83 2011 Cohort Prospective Low-risk Normal 2D examination 144 7–38 15–20 Positive A specific pattern of fetal neurobehavior corresponding to each trimester of pregnancy was identified
Abo-Yaqoub et al.84 2012 Cohort Prospective High-risk Multiple 80 20–38 15–20 Positive A significant difference in KANET scores was noted. All antenatally abnormal KANET scores also had an abnormal postnatal neurological assessment.
Vladareanu et al.85 2012 Cohort Prospective High-risk Multiple 196 24–38 N/A Positive Most fetuses with normal KANET → low-risk, those with borderline → IUGR fetuses with increased MCA RI, and most fetuses with abnormal KANET → threatened PTD with PPROM. The difference in fetal movements was identified between the two groups. For normal pregnancies → 93.4% of fetuses achieved a normal score, and for high-risk pregnancies → 78,5% of fetuses had a normal score.
Honemeyer et al.86 2012 Cohort Prospective High and low-risk Multiple 56 28–38 30 max Positive Introduction of the average KANET score → combination of the mean value of KANET scores throughout pregnancy. Revealed a relationship between fetal diurnal rhythm the pregnancy risk.
Kurjak et al.87 2013 Cohort Prospective High and low-risk Multiple 869 28–38 20 Positive Statistically significant differences in the distribution of normal, abnormal, and borderline KANET scores between low-risk and high-risk groups were found. Fetal behavior was significantly different between the normal group and the high-risk subgroups
Predojevic et al.88 2013 Case study Prospective High-risk IUGR 5 31-39 30 Positive KANET could recognize pathologic and borderline behavior in IUGR fetuses with or without blood flow redistribution. Combined assessment of hemodynamic and motoric parameters could enable better diagnosis and consultation
Athanasiadis et al.89 2013 Cohort Prospective Unselected (high and low-risk) Multiple (IUGR, PET, GDM) 152 2nd and 3rd trimester N/A Positive The neurodevelopmental score was statistically significantly higher in the low-risk group compared to the high-risk group (p < 0.0004). The diabetes subgroup score was statistically significantly higher compared to the IUGR and the pre-eclampsia subgroup (p = 0.0001)

GDM, gestational diabetes mellitus; IUGR, intrauterine growth restriction; KANET, Kurjak’s antenatal neurological test; MCA, middle cerebral artery; No., number of patients; PTD, preterm delivery; PPROM, preterm premature rupture of membranes; PET, pre-eclampsia

The first application of KANET was on growth-restricted fetuses,30 where mainly facial expressions and body movements were studied. A decreased behavioral activity in the IUGR fetuses compared to normal growth cases was noticed.30 The study that followed was the first with complete neurologic postnatal assessment for all studied fetuses. According to the used criteria, neonates were divided into three groups - 1. normal, 2. mildly or moderately abnormal, and 3. abnormal (30). Based on these groups, it was decided to form the first KANET scoring system, which was as follows—14–20 (normal), 5–13 (mildly or moderately abnormal), and 0–5 (abnormal). All the following studies were designed based on this scoring system.74,76,77

The first study, which included a large number of high-risk pregnancies, identified 32 fetuses at neurological risk—seven cases with abnormal scores were identified and 25 with a borderline KANET score.78 There were also 11 cases that either died in utero or had a termination of pregnancy, and all of these cases had an abnormal KANET score.78 The seven remaining neonates with abnormal KANET were followed up postnatally at 10 weeks of neonatal life, and three had confirmed pathological ATNAT scores.78 These three cases included a neonate with arthrogryposis, a neonate with cerebellar vermian complete aplasia, and one case with a history of CP in a previous pregnancy.78 Among the parameters that KANET uses, facial expressions appeared to be most pathological—the fetal faces, due to lack of expressions on 4D US, were characterized by the authors as “masks.”78 The remaining four pathological KANET cases had a normal postnatal assessment. However, these four cases had complications of pregnancy.78 There was one case with ventriculomegaly, one case with pre-eclampsia, one case with maternal thrombophilia, and one case with oligohydramnios.78 From 25 cases diagnosed with borderline KANET results, 22 neonates showed a borderline ATNAT score and were followed up.78 The three remaining cases showed normal ATNAT results. There was an interesting paper that studied a case of a fetus with prenatally diagnosed acrania. The authors studied fetal behavior and managed to document how it altered from 20 weeks of gestation onwards.78 It was noticed that as the pregnancy progressed and the control center of motoric activity shifted from the lower to the upper part, the KANET score decreased respectively, suggesting that neurological damage in later pregnancy is possible.78

A study with 226 cases, including different study populations, identified three cases with pathological KANET scores.79 All three cases had chromosomal abnormalities, and all three of them postnatally also had an abnormal ATNAT score.79 Scores from antenatal KANET and postnatal ATNAT were compared between low and high-risk groups, and they showed differences between them for eight out of the 10 parameters—these included—head anteflexion, eye blinking, facial expressions—grimacing, tongue expulsion, mouth movements such as yawning, jawing, swallowing—isolated hand movements, hand to face movements, fist and finger movements, and GMs.79

The comparison of the two tests revealed a correlation between them and proved that the neonatal exam (ATNAT) was a satisfactory confirmation of the prenatal US examination (KANET), stating that KANET could offer useful information about the neurological status of the fetus and can be applied in clinical practice.79

One of the largest studies regarding KANET105 included 620 cases of both low and high-risk populations (100 low-risk and 520 high-risk cases), and it showed differences in the scores between the two groups.80 The study showed interesting results that most abnormal cases were noted from pregnancies with a previous history of CP (23.8%) and that most borderline scores were noted in cases with possible chorioamnionitis (56.4%).80 There were parameters of KANET that were more notably different between the two groups—overlapping cranial sutures, head circumference, isolated eye blinking, facial expressions, mouth movements, isolated hand movements, isolated leg movements, hand-to-face movements, finger movements, and GMs.80 This study confirmed the relationship of pathological KANET with increased risk of perinatal mortality and neurological impairment and showed that the results could be confirmed and are reproducible postnatally.80

A very interesting study that tried to shed some light on the clinical dilemmas caused by the prenatal diagnosis of ventriculomegaly compared fetuses with ventriculomegaly81 with apparently low-risk fetuses (normal CNS appearance on US examination). A significant difference was noted between the two groups, with the KANET score decreasing as the degree of ventriculomegaly increased.81 For isolated cases of mild or moderate ventriculomegaly, no pathological KANET scores were noted, and postnatal evaluation confirmed the prenatal KANET, offering valuable information for the complete assessment of these fetuses and better counseling regarding their prognosis.81

A recent study with a complete follow-up82 postnatally up to 3 months of life, having complete postnatal documentation in all cases, showed that a normal KANET score is very reassuring of a good neonatal outcome, confirming the consistency of prenatal and postnatal assessment.82 It was a great challenge to understand the evolution of fetal movements by 4D US throughout pregnancy and how these movements reflect the development and integrity of the fetal nervous system. It was shown that during the 1st weeks of pregnancy, the development of the frequency and the complexity of fetal movements is more important, while during the second trimester, the variation of fetal movements develops, with more detailed movements (facial expressions and eye blinking) appearing at the end of this trimester.83 Finally, at the end of the third trimester, the number of fetal movements declines as a result of the increase of fetal rest periods due to fetal cerebral maturation, and this is something that most pregnant women notice near term.67-71

Abo-Yaqoub et al.84 aimed to study how practical it is to apply 4D US for the assessment of fetal neurobehavior and also how useful it is for the prediction of neurological impairment.84 Their results showed an agreement between prenatal scores with postnatal assessment. The parameters that were significantly different between the two groups were—isolated head anteflexion, isolated eye blinking, facial expressions, mouth movements, isolated hand movements, hand-to-face movements, finger movements, and GMs.84 The difference was not statistically significant regarding isolated leg movements and cranial sutures.84

Vladareanu et al.85 noted that the majority of normal KANET scores derived from low-risk populations that they studied, while the majority of cases with borderline or pathological KANET scores derived from the high-risk groups and in some cases were related to abnormal values of Doppler studies in IUGR fetuses.85 The authors concluded that KANET could be useful for the detection of neurological impairment, which could become obvious during the antenatal or postnatal period.85

The average KANET score was introduced for fetuses who had more than one assessment in order to have a complete picture of the behavior of these fetuses.86 The average KANET score was derived from the mean calculation of KANET scores for each fetus throughout pregnancy since these fetuses had more than one KANET assessment.86 What was new from this study was the association of the KANET score with fetal diurnal rhythm.86 For the high-risk group, 89% of the borderline scores were recorded at times that the mothers characterized as active periods, compared with 33.3%, respectively, in the low-risk pregnancies.86

Another important goal was to compare all parameters of KANET between high and low-risk pregnancies and observe differences in fetal behavior between them; for pathological KANET score, five out of eight parameters were significantly different: isolated head anteflexion, cranial sutures, and head circumference isolated hand movement or hand to face movements, isolated leg movement, and fingers movements.87-89 Further results showed that only high-risk patients had abnormal scores (8.5%); while comparing high and low-risk groups, it was noticed that 80.6% of high-risk patients had borderline results while 85.3% of low-risk patients were normal, both being statistically significant.87,89 For abnormal KANET results (score between 0 and 5), some were related to pregnancy complications (pre-eclampsia, threatened preterm labor, and drug abuse), and some were related to the fetal condition (trisomy 13, 18, and 21 and IUGR).87-89

Other studies confirmed the feasibility of neurodevelopment assessment by 4D US and showed further evidence that the KANET test is useful in the early identification of fetuses prone to neurological impairment.90,91

When comparing Caucasian to Asian populations in order to check for ethnic differences, the total KANET score was normal in both populations, but there was a difference noted in total KANET scores between these two populations.92 When individual KANET parameters were compared, significant differences were observed in four fetal movements—isolated head anteflexion, isolated eye blinking, facial alteration or mouth opening, and isolated leg movement.92 No significant differences were noted in the four other parameters—cranial suture and head circumference, isolated hand movement or hand-to-face movements, fingers movements, and gestalt of GMs, showing that ethnicity is a parameter that should be considered when evaluating fetal behavior, especially during the assessment of fetal facial expressions.92 The authors concluded that although there was a difference in the total KANET score between Asian and Caucasian populations, all the scores in both groups were within the normal range, proving that ethnical differences in fetal behavior do not affect the total KANET score, but close follow-up should be continued in some borderline cases.92

Unpublished data from Greece collected from 655 singleton pregnancies showed that KANET is a method that is feasible in everyday clinical practice, with a success rate of 95% and a very low negative predictive value. There were cases where KANET could not be completed. The reason for that was severe oligohydramnios, fibroid uterus (difficult imaging), very increased body mass index, and a case that, due to vasovagal reaction-supine hypotensive syndrome, US examination could not be completed. From the 655 cases, 1,712 KANET were performed from only two operators, and the interobserver variability was calculated, showing adequate results for all parameters, with the lowest being for facial alterations (K-value = 0.68) and the highest for finger movements (K-value = 0.84). This study was primarily designed to compare the neurological status of pregnancies complicated by diabetes compared to low-risk pregnancies, and it did show that there was a difference between the fetal neurobehavior of these two groups, with the diabetic pregnancies having lower scores.93

Figures 11 to 13 illustrate important parameters of KANET depicted by high-definition (HD) 4D US.

Figs 11A to C: Mouthing as part of the assessment of fetal neurobehavior (HD 4D US)

Fig. 12: Parameters of KANET test—mouthing, yawning, and hand movements (HD 4D US)

Fig. 13: Facial expression and grimacing (HD 4D US)

Interpretation of KANET Test Research

Assessment of fetal neurobehavior and detection of fetal neurological impairment in utero is one of the greatest challenges in perinatal medicine. KANET is the first method that applied 4D US for the assessment of the fetus in the same way that a neonate is assessed neurologically after birth by neonatologists. It appears to be a powerful diagnostic method for the detection of neurological impairment and for the assessment of fetal neurobehavior, conditions that were not accessible with the traditional prenatal diagnostic methods which were used so far.57 Studies have proved the validity of this method,28,29,74 proved that it could be applied in everyday clinical practice, especially for high-risk cases, showed how and by whom it should be performed, what is the value of the result of KANET, and how it should be managed. It is very difficult to make a diagnosis of neurological impairment prenatally, and usually, all these diagnoses are made postnatally, even months or years after delivery. Moreover, neurological conditions, such as CP, are not adequately understood, and they are falsely attributed to incidents during labor, although it has been proven that the majority of CP cases originate sometime during in utero life and are not related to intrapartum events. All these things lead to delayed diagnosis of neurological conditions. The later a neurological impairment is diagnosed, the less is possibility of an effective intervention. In order to increase a possibility of an effective intervention or even treatment, it would be extremely challenging to have a timely diagnosis of such conditions. KANET offers the possibility to detect prenatally fetuses at risk for neurological problems, offering a possibility of even an in utero intervention or at least an early postpartum intervention.74 The earliest physiotherapy is commenced, and intervention programs are applied in neonates that are born prematurely or with neurological problems, the better the neurodevelopmental outcome of these neonates, with the cognitive benefits persisting into preschool age. KANET appears to be able to offer this advantage of early identification of these fetuses with neurological problems so that they could be put under treatment as early as possible, aiming for a better outcome.76,77,94,95

Even more, the explicitly detailed pictures obtained by the new US machines but also the advanced techniques of molecular genetics, many times bring us, as US specialists, across findings (anatomical and chromosomal) of uncertain clinical significance and prognosis, especially regarding the neurological integrity of the fetus.96,97 A method like KANET offers a more comprehensive diagnostic approach to such dilemmas, and hopefully, in the near future, with more data, we could form a complete neurosonobehavioral assessment of the fetus and complete counseling of these couples.98

Many centers for the assessment of fetal neurobehavior of not only high-risk pregnancies but also low-risk pregnancies have introduced KANET in everyday clinical practice.

Studies show that the sensitivity and specificity of the test are satisfactory, as are the positive and negative predictive values and the inter and intraobserver variability of this method. The KANET has been introduced into systematical training, and US specialists have already been certified to perform this examination. Hopefully, the application of KANET on larger populations, both high and low risk, will give more knowledge regarding the early detection of fetuses at risk for neurological impairment in order to allow accurate diagnosis prenatally and, as a consequence, a prompt intervention that could possibly improve the outcome of some of these neonates.


The data of fetal prenatal neurological testing from nine centers by nine investigators from seven countries, which were performed from May 2010 to April 2020, with the number of 25–1,344 fetuses from singleton pregnancies, are presented.99 Altogether, there were 3,709 fetuses, of whom 1,573 (42.4%) completed the pregnancy, of which 1,556 were eligible for postnatal follow-up, while in 2,136 were mostly low-risk pregnancies for 2,094 the data were missing while in 42, the pregnancies were still ongoing (Table 6). From the group of 3,709 fetuses, 3,206 (86.5%) had normal, 379 (10.2%) borderline, and 124 (3.3%) abnormal KANET scores, respectively, while in those after completed pregnancy, 153 (9.7%) had borderline and 52 (3.3%) had abnormal KANET scores (Tables 6 and 7).

Table 6: The results of the KANET+ test from nine centers—the date of the introduction of KANET, the number of patients investigated, the total number of borderline and abnormal scores, the number with postnatal follow-up, the number of borderline and abnormal cases in all fetuses and those postnatally followed up99
Name of the investigator/country Introduction of KANET+ Number of fetuses All fetuses Postnatal follow-up
KANET+ scores Number of children KANET+ scores
Borderline Abnormal Borderline Abnormal
Lara Spalldi Barisic, Croatia* May 2010 1,344 98 (7.3%) 52 (3.9%) 482 (35.9%) 36 (7.5%) 19 (3.9%)
Panos Antsaklis, Greece19 January 2012 1,180 105 (8.9%) 40 (3.4%) 520 (44.1%) 47 (9.0%) 19 (3.7%)
Raul Moreira Neto, Brazil17 November 2014 631 115 (18.2%) 19 (3.0%) 212 (33.6%) 39 (18.2%) 6 (3.0%)
Suada Tinjić
Tuzla B&H18
May 2015 141 38 (27.0%) 5 (3.5%) 60 (42.6%) 16 (27.0%) 2 (3.5%)
Sonal Panchal, India33 October 2015 160 3 (1.9%) 0 145 (90.6%) 3 (1.9%) 0
Dorota Bomba Opon, Poland18 July 2017 63 6 (9.5%) 3 (4.8%) 26 (41.3%) 2 (9.5%) 1 (4.8%)
Gigi Selvan, India* July 2018 64 0 1 (1.6%) 35 (54.7%) 0 1 (1.6%)
Sertac Esin, Turkey18 February 2019 25 4 (16.0%) 1 (4.0%) 17 (68.0%) 3 (16.0%) 1 (4.0%)
Edin Medjedovic, B&H* July 2019 101 10 (9.9%) 3 (3.0) 76 (75.2%) 7 (9.2%) 3 (3.9%)
Total May 2010–July 2019 3,709 379 (10.2%) 124 (3.3%) 1573 (42.4%) 153 (9.7%) 52 (3.3%)

B & H, Bosnia and Herzegovina; +KANET, Kurjak antenatal neurodevelopmental test; *unpublished data

Table 7: The data on KANET scores from low and high-risk pregnancies shown as normal, borderline, and abnormal, comparing abnormal and borderline score prevalence depending on the pregnancy risk99
Name of the investigator Risk of the pregnancy KANET score Total number
Normal Borderline Abnormal
Lara Spalldi Barisic, N* = 1,344 Low 1,017 31 0 1,048
High 177 67 52 296
Panos Antsaklis, N = 1,180 Low 772 23 0 795
High 263 82 40 385
Raul Moreira Neto, N = 631 Low 348 58 0 406
High 149 57 19 225
Suada Tinjic, N = 141 Low 96 33 0 129
High 2 5 5 12
Sonal Panchal, N = 160 High 157 3 0 160
Dorota Bomba Opon, N = 63 Low 30 0 0 30
High 24 6 3 33
Gigi Selvan, N = 64 Low 30 0 0 30
High 33 0 1 34
Serac Esin, N = 25 High 20 4 1 25
Edin Medjedovic, N = 101 Low 64 0 0 64
High 24 10 3 37
Subtotal low risk 2,357 (94.2%) 145 (5.8%) 0 2,502 (67.5%)
Subtotal high risk 849 (70.3%) 234 (19.4%) 124 (10.3%) 1,207 (32.5%)
Total 3,206 (86.5%) 379 (10.2%) 124 (3.3%) 3,709
χ2 = 457.36; df+ = 2; p < 0.01

&Kurjak antenatal neurodevelopmental test; *N = total number of pregnancies; +df = degrees of freedom

The inter-rater reliability was substantial for low-risk pregnancies and moderate for high-risk pregnancies. There were 2,502 (67.5%) fetuses from low-risk pregnancies and 1,207 (32.5%) fetuses from high-risk pregnancies (Table 7). Compared to the fetuses from low-risk pregnancies, fetuses from high-risk pregnancies had higher frequencies of borderline and abnormal KANET scores, which was statistically significant. We could speculate that a hostile intrauterine environment is adversely affecting fetal neurobehavior, which can be detected by the KANET test. The dropout rate in the investigation was high (47.6%), respectively, which is a severe constraint of the investigation. Most of the dropouts were from low-risk pregnancies with low rates of borderline or abnormal KANET scores and a high probability of normal postnatal development.

Out of 1556 fetuses who were born after KANET testing, the distribution based on age is presented in Table 3. Most of the children were older than 3 years (819 out of 1,556 or 52.6%). Most of the infants were developing normally (1530 or 98.3%), eight (0.5%) had slight and moderate developmental delay, while 18 (1.2%) had severe developmental delay. The severe and moderate developmental delay could develop more frequently in the group of infants who, as fetuses, had abnormal KANET scores, which are presented in Table 8, which was statistically significant.

Table 8: Postnatal follow-up of infants who, as fetuses, had borderline and abnormal KANET scores from low and high-risk pregnancies, including termination of pregnancy and postnatal death99
Name of the investigator (N*) KANET score (N*) Postnatal developmental delay (N*) Comment
No Slight Moderate Severe
Lara Spalldi Barisic N = 482 Borderline N = 36 33 0 0 2 One IUD+
Abnormal N = 19 15 0 0 4 All severe congenital malformations
Panos Antsaklis N = 520 Borderline N = 47 45 0 0 1 1 IUD+
Abnormal N = 19 7 0 0 1++ Five died Six terminated
Raul Moreira Neto, N = 212 Borderline N = 39 39 0 0 0
Abnormal N = 6 3 0 0 3 One case of trisomy 13, 18, and 21
Suada Tinjic, N = 60 Borderline N = 16 16 0 0 0
Abnormal N = 2 1 1 0 0 IUGR** one with slight developmental delay
Sonal Panchal, N = 145 Borderline N = 3 0 0 2 1
Abnormal N = 0 0 0 0 0
Dorota Bomba Opon N = 26 Borderline N = 2 2 0 0 0
Abnormal N = 1 0 0 0 1 One with severe delay Kagami Ogata syndrome
Gigi Selvan, N = 35 Borderline N = 0 0 0 0 0
Abnormal N = 1 0 0 1 0 IUGR**
Serac Esin, N = 17 Borderline N = 3 3 0 0 0
Abnormal N = 1 0 0 0 1 Trisomy 18, died in the first day of life
Edin Medjedovic, N = 76 Borderline N = 7 7 0 0 0
Abnormal N = 3 3 0 0 3 Two severe congenital malformations and one IUGR**
Subtotal normal KANET 1351 (86.8%) 1,348 (99.8) 0 2 (0.1%) 1 (0.1%) One with severe delay Kagami Ogata syndrome
Subtotal borderline KANET 153 (9.8%) 145 (94.8%) 0 2 (1.3%) 4 (2.6%) Two IUD (1.3%)
Subtotal abnormal KANET 52 (3.3%) 26 (50.0%) 1 (1.9%) 1 (1.9%) 13 (25.0%) 11 terminated or died (21.2%)
Total 1,556 (100.0%) 1,519 (97.6%) 1 (0.1%) 5 (0.3%) 18 (1.2%) 13 (0.8%)
χ2 = 315.28; df+++ = 6; p < 0.01

&Kurjak antenatal neurodevelopmental test; +++df = degrees of freedom; +IUD, intrauterine death; **IUGR, intrauterine growth restriction; *N, number of infants; ++one infant with CP (with a previous case of cerebral palsy in the family)

Most of the infants with abnormal KANET scores were from high-risk pregnancies; they had severe congenital malformations, often IUGR, and had more chance to die in utero. To investigate the validity of the KANET test for the prediction of developmental delay and CP, we made predictive value calculations from sensitivity, specificity, and prevalence for all age-groups with developmental delay and only for the age-group above 2 years for the CP and severe developmental delay. The calculations showed that the KANET test has low sensitivity for the detection of CP and lower sensitivity for the detection of slight, moderate, and severe developmental delay than for only severe developmental delay. Specificity was rather high for the detection of CP; it was lower for the detection of developmental delay. In concordance, the positive predictive value and the false positive rate were high. The negative predictive value was high, and the false-negative rate was low. If the KANET score is normal, then there is a huge probability of normal postnatal development, with a very small chance that it is false negative, meaning that the probability of abnormal postnatal development is low if KANET is normal. There is a problem with the interpretation of abnormal and borderline KANET scores, which appears to have very low sensitivity and positive predictive value and a high false-positive rate. This means that based on the borderline or abnormal KANET score, one can not predict the neurodevelopmental outcome; although there is a higher tendency of developmental disorders to occur in infants with abnormal KANET scores from high-risk pregnancies, however, it can not be concluded concerning the type and severity of the disorder, especially not CP. As it has been pointed out many times in the papers published up to now by our team, the most important aim of the KANET introduction was to early predict the development of CP in order to intervene early enough to decrease possible consequences of the condition on individual, family, societal and public health level. We were aware that early diagnosis of CP was and is not easy, even postnatally. There is a rule saying that making the diagnosis of CP is inversely proportional to age, undermining confidence in diagnosing CP early. Possible barriers in early postnatal diagnosis could be:100-109

Another important recurrent discussion lasting for decades on CP is when the earliest diagnosis of CP could be made to avoid the development of deformities connected with the disease.100-109 For many years since the 1970s, it has been accepted that it is almost impossible to make the diagnosis of CP in infancy and that the acceptable age for the diagnosis is between 3 and 5 years.100-109 It has been claimed that in a well-developed healthcare system, the diagnosis of CP could be made in one in five children at the age of 6 months and in more than half of the cases after the 1st year of life.107 There is a belief that CP is neurologically silent in the first few months of age and almost impossible to be diagnosed. This was the reason for the development of the concept of GMs by Prechtl, which enabled the detection of neurological impairment by the recording of GMs by a camera and assessing them offline. The assessment was time-consuming and not practical or clinically applicable for everyday clinical practice. However, in the recently published guidelines for the early diagnosis (by the age of 5 months in high-risk infants) of CP, the following criteria have been mentioned:100-109

Mentioned criteria are aimed at high-risk infants, while infants with CP who do not have newborn detectable risks, and are seemingly healthy at birth, are less likely to be followed up, and there is a need for identifying these infants and administering best practice tools in order not to miss the diagnosis of CP, which is nowadays in low-risk population very often overlooked and missed.100-109 For such term and high-risk preterm infants automated computer-assisted/smartphone GMs assessment tool is under development,109 which will make a time-consuming assessment of GMs more practical, standardized, and clinically applicable.

We are aware of the weaknesses of our study: nine investigators included a high dropout rate, heterogeneity of the investigation group in terms of nationality and race, and inhomogeneous groups of pregnant women in terms of risk of pregnancy, social status, age, parity, and many other characteristics. Although KANET was standardized and was advised to be used in everyday clinical practice, it would be much better if all those weaknesses could have been avoided.59,88

The main weakness of the investigation is the postnatal follow-up of infants, which was dependent on local circumstances, and the information for infants who had developmental delays has been obtained from the parents and available medical charts. Such an approach may cause some children with developmental delay may have been missed without the awareness of the investigator(s). That is why the results of the study should be taken with due caution.

Based on the results of the study, we can conclude that if the KANET score is normal, then there is a high probability that the development of the infant will be normal, with a very low probability that the child with developmental delay would have been missed. However, if the KANET score is borderline and especially if abnormal in high-risk pregnancies, the postnatal development of the child may appear abnormal. Due to a high false-positive rate in those fetuses, thorough postnatal prospective neurodevelopmental follow-up, especially in high-risk infants with a positive family history of CP, should be advised.100-109 To make an early diagnosis of CP in high-risk cases, the protocol proposed by Novak et al. should be followed,107 while for low-risk infants with abnormal KANET scores, the protocol should be individualized and follow-up established on a case-by-case basis. The future development of fetal neurology should be multidisciplinary, with special emphasis on scrutinized postnatal follow-up of infants who had abnormal and borderline KANET scores and were born from high-risk pregnancies.


1. Salihagic-Kadic A, Kurjak A, Medic M, et al. New data about embryonic and fetal neurodevelopment and behavior obtained by 3D and 4D sonography. J Perinat Med 2005;33(6):478–490. DOI: 10.1515/JPM.2005.086

2. Pomeroy SL, Voipe JJ. Development of the nervous system In.: Polin RA, Fox, WW (eds). Fetal and neonatal physiology. Philadelphia-London-Toronto-Montreal-Sydney-Tokyo: WB Saunders Copmany 1992;1491–1509.

3. O’Rahilly R, Muller F. Minireview: summary of the initial development of the human nervous system. Teratology 1999;60(1):39–41. DOI: 10.1002/(SICI)1096-9926(199907)60:1<39::AID-TERA11>3.0.CO;2-I

4. 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

5. Kurjak A, Stanojević M, Antsaklis P. From structure to function: a long Journey. In: Kurjak A, ed. Fetal Brain Functioning. New Delhi: Jaypee Brothers 2022:1–39.

6. Schaher S. Determination and differentiation in the development of the nervous system. In: Kandel ER, Schwartz JH, eds. Principles of Neural Science 2nd ed. New York: Elsevier Science Publishing 1985:730–732.

7. Kostovic I. Prenatal development of nucleus basalis complex and related fiber systems in man: a histochemical study. Neuroscience 1986;17(4):1047–1077. DOI: 10.1016/0306-4522(86)90077-1

8. Okado N. Onset of synapse formation in the human spinal cord. J Comp Neurol 1981;201(2):211–219. DOI: 10.1002/cne.902010206

9. Kostovic I. Zentralnervensystem. In: Hinrichsen KV, ed. Humanembryologie. Berlin: Springer-Verlag, 1990:381–448.

10. Prechtl HF. Ultrasound studies of human fetal behaviour. Early Hum Dev 1985;2(2):91–98. DOI: 10.1016/0378-3782(85)90173-2

11. Ianniruberto A, Tajani E. Ultrasonographic study of fetal movements. Semin Perinatol 1981;5(2):175–181. PMID: 7323822.

12. Goto S, Kato TK. Early movements are useful for estimating the gestational weeks in the first trimester of pregnancy. In: Levski RA, Morley P, eds. Ultrasound ’82. Oxford: Pergamon Press, 1983:577–582.

13. Joseph R. Fetal brain behavior and cognitive development. Dev Rev 1999;20(1):81–98. DOI: 10.1006/drev.1999.0486

14. 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

15. Kostovic I, Rakic P. Development of prestriate visual projections in the monkey and human fetal cerebrum revealed by transient cholinesterase staining. J Neurosci 1984;4(1):25–42. DOI: 10.1523/JNEUROSCI.04-01-00025.1984

16. D’Elia A, Pighetti M, Moccia G, et al. Spontaneous motor activity in normal fetuses. Early Hum Dev 2001;65(2):139–147. DOI: 10.1016/s0378-3782(01)00224-9

17. Prechtl HF, Einspieler C. Is neurological assessment of the fetus possible? Eur J Obstet Gynecol Reprod Biol 1997;75(1):81–84. DOI: 10.1016/s0301-2115(97)00197-8

18. Roodenburg PJ, Wladimiroff JW, van Es A, et al. Classification and quantitative aspects of fetal movements during the second half of normal pregnancy. Early Hum Dev 1991:25(1):19–35. DOI: 10.1016/0378-3782(91)90203-f

19. Prechtl HF. Qualitative changes of spontaneous movements in fetus and preterm infant are a marker of neurological dysfunction. Early Hum Dev 1990;23(3):151–158. DOI: 10.1016/0378-3782(90)90011-7

20. Kurjak A, Azumendi G, Vecek N, et al. Fetal hand movements and facial expression in normal pregnancy studied by four-dimensional sonography. J Perinat Med 2003:31(6):496–508. DOI: 10.1515/JPM.2003.076

21. Andonotopo W, Stanojevic M, Kurjak A, et al. Assessment of fetal behavior and general movements by four-dimensional sonography. Ultrasound Rev Obstet Gynecol 2004:4(2):103–114. DOI: 10.1080/14722240400016895

22. Kurjak A, Stanojevic M, Azumendi G, et al. The potential of four-dimensional (4D) ultrasonography in the assessment of fetal awareness. J Perinat Med 2005;33(1):46–53. DOI: 10.1515/JPM.2005.008

23. Kurjak A, Pooh RK, Carrera JM, et al. Structural and functional early human development assessed by three-dimensional (3D) and four dimensional (4D) sonography. Fertil Steril 2005;84(5):1285–1299. DOI: 10.1016/j.fertnstert.2005.03.084

24. Kurjak A, Miskovic B, Andonotopo W, et al. How useful is 3D and 4D ultrasound in perinatal medicine. J Perinat Med 2007;35(1):10–27. DOI: 10.1515/JPM.2007.002

25. 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

26. 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. PMID: 16158470.

27. Pooh RK, Ogura T. Normal and abnormal fetal hand positioning and movement in early pregnancy detected by three- and four-dimensional ultrasound. Ultrasound Rev Obset Gynecol 2004:4(1):46–51. DOI: 10.3109/14722240410001700249

28. 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

29. Andonotopo W, Kurjak A, Kosuta MI. Behavior of anencephalic fetus studied by 4D sonography. J Matern Fetal Neonatal Med 2005:17(2):165–168. DOI: 10.1080/14767050400028717

30. Andonopo 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

31. 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

32. Kurjak A, Azumendi G, Andonotopo W, et al. Three- and four-dimensional ultrasonography for the structural and functional evaluation of the fetal face. Am J Obstet Gynecol 2007;196(1):16–28. DOI: 10.1016/j.ajog.2006.06.090

33. Walusinski O, Kurjak A, Andonotopo W, et al. Fetal yawning assessed by 3D and 4D sonography. Ultrasound Rev Obstet Gynecol 2005;5(3):210–217. DOI: 10.3109/14722240500284070

34. 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.

35. Einspieler C, Prechtl HF, Ferrari F, et al. The qualitative assessment of general movements in preterm, term and young infants-review of the methodology. Early Hum Dev 1997;50(1):47–60. DOI: 10.1016/s0378-3782(97)00092-3

36. Cioni G, Prechtl HFR, Ferrari F, et al. Which better predicts later outcome in full term infants: quality of general movements or neurological examination? Early Hum Dev 1997;50(1):71–85. DOI: 10.1016/s0378-3782(97)00094-7

37. Ferrari F, Cioni G, Einspieler C, et al. Cramped synchronized general movements in preterm infants as an early marker for cerebral palsy. Arch Pediatr Adolesc Med 2002;156(5):460–467. DOI: 10.1001/archpedi.156.5.460

38. Prechtl HFR. 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

39. Kurjak A, Jackson D (eds.) An atlas of Three- and Four-Dimensional Sonography in Obstetrics and Gynecology. Taylor & Francis Group: London, 2004.

40. Sarnat HB. Anatomic and physiologic correlates of neurologic development in prematurity. In: Sarnat HB (ed.) Topics in neonatal neurology. New York: Grune and Stratton, 1984:1–24.

41. Sarnat HB. Functions of the corticospinal and corticobulbar tracts in the human newborns. J Pediatr Neurol 2003;1(1):3–8.

42. Amiel-Tison C. Update of the Amiel-Tison Neurological assessment for the term neonate or at 40 weeks corrected age. Pediatr Neurol 2002;27(3):196–212. DOI: 10.1016/s0887-8994(02)00436-8

43. Amiel-Tison C. Clinical assessment of the infant nervous system. In: Levente MI, Chervenak FA and Whittle M (eds.) Fetal and Neonatal Neurology and Neurosurgery. 3rd ed. Churchill Livingstone: London, 2001:99–120.

44. Salisbury AL, Duncan Fallone M, Lester B. Neurobehavioral assessment from fetus to infant: the NICU network neurobehavioral scale and the fetal neurobehavioral coding system. Ment Retard Dev Disabil Res Rev 2005;11(1):14–20. DOI: 10.1002/mrdd.20058

45. de Vries JIP, Visser GHA, Prechtl HFR. Fetal motility in the first half of pregnancy. In: Prechtl HFR (ed.) Continuity of neural functions from prenatal to postnatal life. Clin Dev Med 94 Oxford, Blackwell, 1984:46–63.

46. Kostović I, Seress L, Mrzljak L, et al. Early onset of synapse formation in the human hippocampus: a correlation with Nissl-Golgi architectonics in 15- and 16.5-week-old fetuses. Neuroscience 1989;30(1):105–116. DOI: 10.1016/0306-4522(89)90357-6

47. Mutch L, Alberman E, Hagberg B, et al. Cerebral palsy epidemiology: where are we now and where are we going? Dev Med Child Neurol 1992;34(6):547–551. DOI: 10.1111/j.1469-8749.1992.tb11479.x

48. Bax M, Goldstein M, Rosenbaum P, et al. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol 2005;47(8):571–576. DOI: 10.1017/s001216220500112x

49. Sankar C, Mundkur N. Cerebral palsy-definition, classification, etiology and early diagnosis. Indian J Pediatr 2005;72(10):865–868. DOI: 10.1007/BF02731117

50. Shapiro BK. Cerebral palsy: a reconceptualization of the spectrum. J Pediatr 2004;145(2 Suppl):S3–S7. DOI: 10.1016/j.jpeds.2004.05.014

51. Amiel-Tison C, Gosselin J, Infante-Rivard C. Head growth and cranial assessment at neurological examination in infancy. Dev Med Child Neurol 2002;44(9):643–648. DOI: 10.1017/s0012162201002699

52. Pooh RK, Pooh K, Nakagawa Y, et al. Clinical application of three-dimensional ultrasound in fetal brain assessment. Croat Med J. 2000;41:245–251. PMID: 10962041.

53. Campbell S, Lees C, Moscoso G, et al. Ultrasound antenatal diagnosis of cleft palate by a new technique: the 3D “reverse face” view. Ultrasound Obstet Gynecol 2005;25(1):12–18. DOI: 10.1002/uog.1819

54. DiPietro JA. Neurobehavioral assessment before birth. Ment Retard Dev Disabil Res Rev 2005;11(1):4–13. DOI: 10.1002/mrdd.20047

55. Yigiter AB, Kavak ZN. Normal standards of fetal behavior assessed by four-dimensional sonography. J Matern Fetal Neonatal Med 2006;19(11):707–721. DOI: 10.1080/14767050600924129

56. Gosselin J, Gahagan S, Amiel-Tison C. The Amiel-Tison neurological assessment at term: conceptual and methodological continuity in the course of follow-up. Ment Retard Dev Disabil Res Rev 2005;11(1):34–51. DOI: 10.1002/mrdd.20049

57. Rees S, Harding R. Brain development during fetal life: influences of the intra-uterine environment. Neurosci Lett 2004;361(1–3):111–114. DOI: 10.1016/j.neulet.2004.02.002

58. 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. DOI: 10.3109/14722240400017075

59. Eidelman AI. The living fetus e dilemmas in treatment at the edge of viability. In: Blazer S, Zimmer EZ, editors. The embryo: scientific discovery and medical ethics. Basel: Karger; 2005:351e70.

60. 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

61. 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

62. 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

63. 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

64. Almli CR, Ball RH, Wheeler ME. Human fetal and neonatal movement patterns: gender difference and fetal-to-neonatal continuity. Dev Psychobiol 2001;38(4):252–273. DOI: 10.1002/dev.1019

65. DiPietro JA, Bronstein MH, Costigan KA, et al. What does fetal movement predict about behavior during the first two years of life? Dev Phych 2002;40(4):358–371. DOI: 10.1002/dev.10025

66. DiPetro JA, Hodson DM, Costigan KA, et al. Fetal antecedents of infant temperament. Child Dev 1996;67(5):2568–2583. DOI: 10.2307/1131641

67. DiPietro JA, Costigan KA, Pressman EK. Fetal state concordance predicts infant state regulation. Early Hum Dev 2002;68(1):1–13. DOI: 10.1016/s0378-3782(02)00006-3

68. Thoman EB, Denenberg VH, Sievel J, et al. State organization in neonate: developmental inconsistency indicates risk for developmental dysfunction. Neuropediatrics 1981;12(1):45–54. DOI: 10.1055/s-2008-1059638

69. St James-Roberts I, Menon-Johansson P. Predicting infant crying from fetal movement data: an exploratory study. Early Hum Dev 1999;54(1):55–62. DOI: 10.1016/s0378-3782(98)00084-x

70. de Vries JI, Visser GH, Prechtl HF. The emergence of fetal behaviour. II. Quantitative aspects. Early Hum Dev 1985;12(2):99–120. DOI: 10.1016/0378-3782(85)90174-4

71. de Vries JI, Visser GH, Prechtl HF. The emergence of fetal behaviour. III. Individual differences and consistencies. Early Hum Dev 1988;16(1):85–103. DOI: 10.1016/0378-3782(88)90089-8

72. Nijhuis JG, ed. Fetal Behaviour: Developmental and Perinatal aspects. Oxford, Oxford University Press: 1992

73. Kurjak A, Antsaklis P, Stanojevic M, et al. Fetal behavior assessed by four-dimensional sonography. Donald Sch J Ultrasound Obstet Gynecol 2017;11(2):146–168. DOI: 10.5005/jp-journals-10009-1516

74. Stanojevic M, Talic A, Miskovic B, et al. An attempt to standardize Kurjak’s Antenatal Neurodevelopmental Test: Osaka consensus statement. Donald Sch J Ultrasound Obstet Gynecol 2011;5(4):317–329. DOI: 10.5005/jp-journals-10009-1209

75. Kurjak A, Antsaklis P. 4D in functional studies of the fetus. Donald Sch J Ultrasound Obstet Gynecol 2019;13(1):23–33. DOI: 10.5005/jp-journals-10009-1582

76. Kurjak A, Tikvica A, Stanojevic M, et al. The assessment of fetal neurobehavior by three-dimensional and four-dimensional ultrasound. J Matern Fetal Neonatal Med 2008;21(10):675–684. DOI: 10.1080/14767050802212166

77. Kurjak A, Miskovic B, Stanojevic M, et al. New scoring system for fetal neurobehavior assessed by three- and four-dimensional sonography. J Perinat Med 2008;36(1):73–81. DOI: 10.1515/JPM.2008.007

78. Kurjak A, Luetic AT. Fetal neurobehavior assessed by three-dimensional/four dimensional sonography. Zdrav Vestn 2010;79(11):790–799.

79. 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

80. 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

81. Talic A, Kurjak A, Stanojevic M, et al. The assessment of fetal brain function in fetuses with ventriculomegaly: the role of the KANET test. J Matern Fetal Neonatal Med 2012;25(8):1267–1272. DOI: 10.3109/14767058.2011.634463

82. Honemeyer U, Kurjak A. The use of KANET test to assess fetal CNS function. First 100 cases. 10th World Congress of Perinatal Medicine 8-11 November 2011. Uruguay. Poster presentation P209

83. Lebit DF, Vladareanu PD. The role of 4D ultrasound in the assessment of fetal behaviour. Maedica (Buchar) 2011;6(2):120–127. PMID: 22205894.

84. 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

85. Vladareanu R, Lebit D, Constantinescu S. Ultrasound assessment of fetal neurobehaviour in high-risk pregnancies. Donald Sch J Ultrasound Obstet Gynecol 2012;6(2):132–147. DOI: 10.5005/jp-journals-10009-1235

86. 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

87. Kurjak A, Talic A, Honemeyer U, et al. 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

88. Predojević M, Talić A, Stanojević M, et al. 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

89. 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

90. Neto RM, Kurjak A. Recent results of the clinical application of KANET test. Donald Sch J Ultrasound Obstet Gynecol 2015;9(20):420–425. DOI: 10.5005/jp-journals-10009-1429

91. Neto RM. KANET in Brazil: first experience. Donald Sch J Ultrasound ObstetGynecol 2015;9(1):1–5. DOI: 10.5005/jp-journals-10009-1384

92. 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

93. 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

94. Pooh RK, Pooh K. Assessment of fetal central nervous system. Donald Sch J Ultrasound Obstet Gynecol 2013;7(4):369–384. DOI: 10.5005/jp-journals-10009-1308

95. Kurjak A, Ahmed B, Abo-Yaquab S, et al. An attempt to introduce neurological test for fetus based on 3D and 4D sonography. Donald Sch J Ultrasound Obstet Gynecol 2008;2(4):29–44. DOI: 10.5005/jp-journals-10009-1076

96. Kuno A, Akiyama M, Yamashiro C, et al. Three-dimensional sonographic assessment of fetal behavior in the early second trimester of pregnancy. J Ultrasound Med 2001;20(12):1271–1275. DOI: 10.7863/jum.2001.20.12.1271

97. Koyanagi T, Horimoto N, Maeda H, et al. Abnormal behavioral patterns in the human fetus at term: correlation with lesion sites in the central nervous system after birth. J Child Neurol 1993;8(1):19–26. DOI: 10.1177/088307389300800103

98. 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

99. Stanojevic M, Antsaklis P, Panchal S, et al. A critical appraisal of Kurjak antenatal neurodevelopmental test: five years of wide clinical used. Donald Sch J Ultrasound Obstet Gynecol 2021;14(4):304–310. DOI: 10.5005/jp-journals-10009-1669

100. Hepper PG. Fetal behavior: why so skeptical? Ultrasound Obstet Gynecol 1996:8:145–148.

101. Greenwood C, Newman S, Impey L, et al. Cerebral palsy and clinical negligence litigation: a cohort study. BJOG 2003;110(1):6–11. DOI: 10.1046/j.1471-0528.2003.02095.x

102. Strijbis EM, Oudman I, van Essen P, et al. Cerebral palsy and the application of the international criteria for acute intrapartum hypoxia. Obstet Gynecol 2006;107(6):1357–1365. DOI: 10.1097/01.AOG.0000220544.21316.80

103. de Vries JI, Fong BF. Changes in fetal motility as a result of congenital disorders: an overview. Ultrasound Obstet Gynecol 2007;29(5):590–599. DOI: 10.1002/uog.3917

104. de Vries JI, Fong BF. Normal fetal motility: an overview. Ultrasound Obstet Gynecol 2006;27(6):701–711. DOI: 10.1002/uog.2740

105. Rosier-van Dunné FM, van Wezel-Meijler G, Bakker MP, et al. General movements in the perinatal period and its relation to echogenicity changes in the brain. Early Hum Dev 2010;86(2):83–86. DOI: 10.1016/j.earlhumdev.2010.01.023

106. Velde A, Morgan C, Novak I, et al. Early diagnosis and classification of cerebral palsy: an historical perspective and barriers to an early diagnosis. J Clin Med 2019;8(10):1599. DOI: 10.3390/jcm8101599

107. Novak I, Morgan C, Adde L, et al. Early, accurate diagnosis and early intervention in cerebral palsy: advances in diagnosis and treatment. JAMA Pediatr 2017;171:897–900. DOI: 10.1001/jamapediatrics.2017.1689

108. Romeo DM, Cioni M, Palermo F, et al. Neurological assessment in infants discharged from a neonatal intensive care unit. Eur J Paediatr Neurol 2013;17:192–198. DOI: 10.1016/j.ejpn.2012.09.006

109. Kwong AK, Eeles AL, Olsen JE, et al. The Baby Moves smartphone app for general movements assessment: engagement amongst extremely preterm and term-born infants in a state-wide geographical study. J Paediatr Child Health 2019;55(5):548–554. DOI: 10.1111/jpc.14240

© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.