REVIEW ARTICLE

https://doi.org/10.5005/jp-journals-10009-1970
Donald School Journal of Ultrasound in Obstetrics and Gynecology
Volume 17 | Issue 2 | Year 2023

KANET Test in Clinical Practice: Lessons Learned and Future Challenges

Panagiotis Antsaklis1, Asim Kurjak2

1Department of Obstetrics and Gynecology, Alexandra Maternity Hospital, Athens, Greece, Department of Fetal Maternal Medicine, National and Kapodistrian University of Athens (NKUA), Zografou, Greece

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

Corresponding Author: Panagiotis Antsaklis, Department of Obstetrics and Gynecology, Alexandra Maternity Hospital, Athens, Greece, Department of Fetal Maternal Medicine, National and Kapodistrian University of Athens (NKUA), Zografou, Greece, Phone: +30 2132162000, e-mail: panosant@gmail.com

Received on: 05 April 2023; Accepted on: 05 May 2023; Published on: 30 June 2023

ABSTRACT

Assessing fetal neurobehavior during pregnancy has been challenging due to limited evaluation methods. Conditions such as cerebral palsy, often misattributed to labor incidents, actually originate during fetal development. This highlights the poor understanding and diagnosis of neurological problems. Recent advancements, such as Kurjak’s antenatal neurodevelopmental test (KANET) test utilizing four-dimensional (4D) ultrasound technology, offer a way to study fetal neurobehavior in utero, define normal profiles, and identify abnormalities. Multicentric studies have demonstrated the utility of KANET, which has been standardized and successfully integrated into clinical practice for both high and low-risk cases, in understanding fetal neurology, particularly in uncertain cases like ventriculomegaly, providing comprehensive assessment and counseling for affected couples. KANET exhibits good sensitivity, specificity, predictive values, and acceptable variability among observers. With proper training and access to 4D ultrasound machines, ultrasound specialists can easily learn and apply KANET. This method has the potential to identify fetuses at risk for neurological impairment, enabling timely interventions, and improved outcomes through early diagnosis and appropriate follow-up.

How to cite this article: Antsaklis P, Kurjak A. KANET Test in Clinical Practice: Lessons Learned and Future Challenges. Donald School J Ultrasound Obstet Gynecol 2023;17(2):165–180.

Source of support: Nil

Conflict of interest: Dr Asim Kurjak is associated as Editorin- Chief of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of the Editor-in-Chief and his research group.

Dr Panagiotis Antsaklis1 is associated as Editor of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of the Editors and his research group.

Keywords: Cerebral palsy, Early diagnosis, Fetal neurology, Fetal neurological profile, Fetal assessment, Kurjak’s antenatal neurodevelopmental test

INTRODUCTION

Fetal behavior during in utero life is one of the most challenging fields in fetal medicine. The advances in ultrasound technology allow direct observation of the fetus in real time so that movements, expressions, and fetal reactions can be studied and monitored.1-3 Modern technology that has been introduced into clinical practice and particularly four-dimensional (4D) ultrasound technology, allows the assessment of fetal anatomy and fetal behavior at the same time, with explicit detail. Structured assessment of fetal anatomy and behavior has led to the understanding of the pattern and the steps that fetal neurological development goes through every week of gestational age.4 The human brain is a very complicated organ, both from an anatomic and functional point of view. The developmental process of the human brain starts early during in utero life and carries on for many months or even years after birth, being influenced by many genetic and epigenetic factors.4 The basic steps of neurodevelopment are demonstrated in Table 1. The fact that neurodevelopment is multifactorial and can be affected by many parameters makes it difficult to identify if disrupted at any time, exactly when did that happen, especially during in utero life. This is even more difficult for preterm infants, particularly for infants of extreme prematurity, which are very sensitive and prone to many incidents that can affect their neurodevelopment, without being able to identify when exactly the incident occurred, during in utero life, during labor or sometime after birth, and exactly how severely will it affect it, and when exactly will the problem be diagnosed, as it is mostly diagnosed after birth and sometimes long after birth.4-6 The main reason why almost all cases of neurological impairment are diagnosed after birth is that there is no standardized method of assessing the fetus neurologically in utero.6,7 Kurjak’s antenatal neurodevelopmental test (KANET) aims to fill in this gap in fetal medicine as the philosophy of this method is to change the way we examine the fetus and, with the assistance of 4D ultrasound perform a complete examination as we would do with a neonate.

Table 1: Neurodevelopment—the basic steps4
Neurodevelopment Age
Primary neurulation (dorsal induction) 3–4 weeks antenatally
Prosencephalic cleavage (ventral induction) 5–6 weeks antenatally
Neuronal Proliferation
Cerebral 2–4 months antenatally
Cerebellar 2–10 months postnatally
Neuronal migration
Cerebral 3–5 months antenatally
Cerebellar 4–10 months antenatally
Neuronal differentiation
Axon outgrowth 3 months–birth
Dendric growth and synapse formation 6 months–1 year postnatally
Synaptic rearrangement Birth–years postnatally
Myelination Birth–years postnatally

FROM FETAL MOVEMENTS TO FETAL NEUROBEHAVIOR

Similarly, with neonates, fetal cerebral integrity is represented up to a point by its behavior.8,9 It has been shown that optimal fetal movements are excellent indicators of a fetal neurological condition,10-17 and this can be assessed and confirmed with relatively good sensitivity with the classical two-dimensional (2D) ultrasound.18-21

De Vries was one of the pioneers who worked on fetal movements and managed to describe and categorize them through gestational age according to each stage of fetal development:

Subgroups of These Movements are

  • Hand-to-head.

  • Hand-to-mouth.

  • Hand-near-mouth.

  • Hand-to-face.

  • Hand-near-face.

  • Hand-to-eye.

  • Hand-to-ear.

As the development of the fetal brain follows a very specific way of development, it has been suggested that the type of movements and the overall fetal behavior for each trimester could represent an expected or abnormal condition.21-24 Direct observation of the fetus with 4D ultrasound changed the way fetal behavior is assessed and allowed examination of details that could not be seen before, such as facial expressions and detailed finger movements.24-30

Many studies have applied 4D ultrasonography for the assessment of fetal behavior and have confirmed, first of all, that it is possible and which parameters can be indicative of underlying neurological pathology.31-34 4D ultrasound allows the examination of the fetus in a similar way that we would examine a neonate and develop the behavioral and developmental status of the fetus that corresponds to each period of in utero life in order to define which behavioral patterns are normal for each trimester and what could be abnormal.1-4,18-23,35 KANET was the first method that managed to assess the fetus neurologically by using 4D ultrasound in a similar way that we would assess a neonate postnatally.36-39

KURJAK ANTENATAL NEURODEVELOPMENTAL TEST (KANET)

Kurjak antenatal neurodevelopmental test (KANET) is a structured way of assessing fetal behavior with 4D ultrasound, in a similar way that a neonate is assessed after birth KANET aims to define normal fetal behavior for each stage of pregnancy and, on the other hand, to identify abnormal conditions that could be related to neurologic impairment.36,76 KANET has a general part that includes fetal GM and the general part that includes parameters modified by the neonatal assessment, the so-called Amiel-Tison Neurological Assessment at Term (ATNAT) signs.37,40 The following parameters are included 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).

A basis of KANET is the fact that continuity of fetal behavior exists after birth and that all movements which are present in neonates are also present in fetal life, with the exception of Moro’s reflex,41 which can be explained by the differences in gravity between in utero and postnatal life.6

KANET is a standardized method with adequate reproducibility and a learning curve (about 80 cases), which is very acceptable for medical staff with ultrasound knowledge.42,43,53 KANET must be applied during the 3rd trimester of pregnancy, mainly after 28 weeks. It should last around 15–20 minutes and ideally should be performed when the fetus is awake. If KANET cannot be completed, the test should be repeated in 30 minutes or the following day at a minimum period of 14–16 hours.

If the result of KANET is abnormal or borderline, the fetus should be followed up every 2 weeks. Special attention should be paid to facial movements and eye blinking—”the face is the mirror of the brain,” and also fetal movements should be noted (Figs 123456).40,42

Figs 1A and B: Typical fetal facial expressions and hand movements as seen during the performance of KANET and recorded

Figs 2A and B: Mouthing and yawning is an important parameter of KANET and a good sign of neurological development


Figs 3A to C: Mouthing and yawning is an important parameter of KANET and a good sign of neurological development

Figs 4A and B: Fetal hand and finger movements. Detailed movements are very indicative of the neurological maturation and very important parameter of KANET

Fig. 5: Normal KANET test at 34 weeks of gestation

Fig. 6: A complete KANET test—facial alterations mouthing, eye blinking, and hand movement

The minimum requirement of the ultrasound machine when applying KANET should be a frame rate of at least 24 volumes/second. KANET consists of eight parameters (Table 2). The results of KANET are divided into three groups: (1) abnormal when the score is 0–5; (2) borderline for a score of 6–13 and finally; (3) normal for a score of 14–20 (Table 3). Ideally, at least a 2-year follow-up should be available and documented for all fetuses to whom KANET has been applied in order to draw safe conclusions.

Table 2: The parameters of standardized KANET43
Sign score Sign score
Sign 0 1 2
Isolated head anteflexion
 Abrupt Small range (0–3 times of movements) Variable in full range, many alternation (>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) Fluency (>5 times of blinking)
Facial alteration (grimace or tongue expulsion)

or Mouth opening (yawning or mouth movement)
 Not present Not fluent (1–5 times of alteration) Fluency (>5 times of alteration)
Isolated leg movement
 Cramped Poor repertoire or small in range (0–5 times of movement) Variable in full range, many alternation (>5 times of movements)
Isolated hand movement

or Hand to face movements
 Cramped or abrupt Poor repertoire or small in range (0–5 times of movement) Variable in full range, many alternation (>5 times of movements)
Fingers movements
 Unilateral or bilateral clenched fist, (neurological thumb) Cramped invariable finger movements Smooth and complex, variable finger movements
Gestalt perception of GMs Definitely abnormal Normal Total score
Table 3: Kurjak’s antenatal neurodevelopmental test (KANET) scoring system43
Total score Interpretation
0–5 Abnormal
6–9 Borderline
10–16 Normal

The scoring system of KANET aims to divide cases into low-risk, borderline, and high-risk, in order to categorize the cases for clinical practice. For pathological cases with severe anatomical or chromosomal abnormalities, it has been confirmed that KANET can identify the degree of motoric disability, while in all cases, the prognostic value of the test has been verified postnatally and especially in high-risk cases, the prognostic value of KANET for neurological impairment has been confirmed.35,49-58

The success rate of KANET has been calculated to 91–95, and for specific parameters of KANET, the completion rate ranged from 88% for isolated eye blinking to 100% for mouth opening and isolated leg movement with an almost 100% negative predictive value. Interobserver agreement between two examiners for different components of the KANET test was assessed by calculation of κ values which were lowest for the facial expression (K = 0.68) and highest for the finger movements (K = 0.84), proving that the KANET test is a reliable method to be used in clinical practice, after appropriate training.

Evolution of KANET

First form of the KANET scoring system was applied by Andonotopo and Kurjak54 who aimed to assess whether facial expression and body movements could be of any diagnostic value regarding cerebral palsy in growth-restricted fetuses. And noticed decreased behavioral activity in the intrauterine growth restriction (IUGR) fetuses compared to the non-IUGR. This initiated the idea for the development of KANET which started by comparing neonates with neurological impairment and compared them with normal neonates and applied these differences in fetuses by 4D ultrasound, in order to detect these neurological problems prenatally. The first application of KANET was retrospective in low and high-risk cases. The abnormal KANET scores included four cases with alobar holoprosencephaly, one with severe hydrocephaly, one with thanatophoric dysplasia, and four cases with multiple severe structural abnormalities. This study (Table 4) initiated a cascade of other studies which followed.25,32

Table 4: Application of KANET for the detection of neurological impairment
Author Year Study Study design Study population Indication No GA (weeks) Time (minutes) Result Summary
Kurjak et al.15 2008 Cohort Retrospective High risk Multiple 220 20–36 30 Positive Introduction of scoring system was proposed for antenatal assessment of fetal neurobehavior
Kurjak et al.28 2010 Multi-center Prospective High risk Multiple 288 20–38 30 Positive KANET appeared to be prognostic of identification of neurological impairment in utero. KANET also identified fetuses with severeanatomical anomalies, especially related to neurological damage
Miskovic et al.32 2010 Cohort Prospective High risk Multiple 226 20–36 30 Positive Correlation between ante-natal (KANET) & postnatal (ATNAT) results identified. KANET showed variations in the neurobehavior of fetuses from high- to low-risk cases
Talic et al.31 2011 Multi-center Cohort Prospective High risk Multiple 620 26–38 15–20 Positive KANET test had prognostic value in discriminating normal from borderline to pathological neurobehavior. Abnormal KANET scores were predictable of both intrauterine and postnatal death.
Talic et al.29 2011 Multi-center Cohort Prospective High risk Ventriculomegaly 240 32–36 10–15 Positive Statistically significant difference in KANET scores between normal pregnancies and pregnancies with ventriculomegaly. Cases with pathological result & majority of cases with borderline results were noted in cases with severe ventriculomegaly, especially when combined with other anomalies
Honemeyer et al.59 2011 Cohort Prospective Unselected Unselected 100 28–38 N/A Positive KANET result had a significant predictive value of a good postpartum neurological evaluation
Lebit et al.27 2011 Cohort Prospective Low risk Normal 2D examination 144 7–38 15–20 Positive A specific mode of in utero neurobehavior corresponding to each stage of pregnancy was noted.
Abo-Yaqoub et al.51 2012 Cohort Prospective High risk Multiple 80 20–38 15–20 Positive Significant difference in KANET scores was noted. All antenatally abnormal KANET scores had also an abnormal postnatal neurological assessment.
Vladareanu et al.60 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. Difference in fetal movements was identified between the 2 groups. For normal pregnancies → 93,4% of fetuses had normal score, for high-risk pregnancies → 78,5% of fetuses had a normal score.
Honemeyer et al.61 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 of fetal diurnal rhythm with the pregnancy risk.
Kurjak et al.64 2013 Cohort Prospective High and low-risk Multiple 869 28–38 20 Positive Statistical differences regarding the distribution of normal, abnormal, and borderline results of KANET between low-risk and high-risk groupsfound. Fetal behavior was significantly different between the normal group and the high-risk subgroups.
Predojevic et al.72 2014 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 in better diagnosis and consultation
Athanasiadis et al.73 2013 Cohort Prospective Unselected (high and low-risk) Multiple (IUGR, PET, GDM) 152 Second and third trimester N/A Positive The neurodevelopmental trimester score was statistically significant higher in the low-risk in comparison to that of high-risk group (p < 0.0004). The KANET results in the diabetes subgroup was higher when compared to that of the IUGR and the preeclampsia subgroup (p = 0.0001)
Neto et al.76 2014 Cohort Prospective High and low-risk Multiple 51 Third trimester 20 Positive Statistical significance between high- and low-risk cases. All abnormal results come from high-risk cases
Hanaoka et al.77 2015 Cohort Prospective Mixed (Asian and Caucasian) Multiple 167 Third trimester N/A Positive Differences in pattern movements in different racial groups, so that ethnicity should be considered when performing KANET

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

In a study with 288 high-risk pregnancies, seven abnormal cases were included and also 25 cases with borderline KANET scores. Additionally, there were also 11 cases with abnormal KANET, of which six fetuses died in utero and five were terminated. The seven remaining neonates with abnormal KANET were followed up postnatally at 10 weeks and from these neonates, three had confirmed pathological ATNAT score postpartum. These three cases included a neonate with arthrogryposis, a neonate with cerebellar vermian complete aplasia, and one case with a history of cerebral palsy in a previous pregnancy, confirming the positive predictive value of KANET. What was also important was the fact that in these cases the facial expressions were characteristically decreased.

By studying the case of a fetus with acrania after 20 weeks of gestation it was shown that as the pregnancy progressed and the control center of motoric activity shifted from the lower to the upper part the KANET score was becoming abnormal, proving that neurological damage can occur at any stage of pregnancy.49 In a study where three abnormal cases were identified all of them were confirmed postnatally as they had a chromosomal abnormality.53

Through these initial studies, it was confirmed that the neonatal exam (ATNAT) showed similar results to the prenatal examination (KANET), confirming the value of KANET. KANET was also applied to high-risk cases such as threatened preterm delivery with or without preterm rupture of membranes (PPROM), previous history of cerebral palsy (CP), pregnancy hypertension, preeclampsia, gestational diabetes, IUGR, polyhydramnios, Rhesus alloimmunization, placental abruption, and maternal fever >39°C.53

It was shown a difference in these cases compared to normal cases with more characteristics than those with a previous history of CP (23.8%) while interestingly notable differences were also documented in the group of maternal fever, possibly attributed to chorioamnionitis (56.4%). The conclusion of this study was that an abnormal KANET score is related to an increased risk of both intrauterine and neonatal mortality, but also with an increased risk of neurological impairment. It was also concluded that KANET has a good predictive value both for normal and abnormal conditions which can be confirmed postnatally. The good prognostic value of a normal KANET was confirmed in a study with 100 cases and a neonatal follow-up of up to 3 months.59

In an attempt to extend this fetal monitoring, Lebit et al.27 started observing fetal behavior from 7 weeks up to 38 weeks and noticed that during the first weeks of pregnancy, the number of fetal movements increases as does their complexity. During the second trimester, the fetal motoric activity increases in number and variety, as specific movements develop (facial grimacing and eye blinking) from the second half of the second trimester. As fetal movements decrease during the final weeks of pregnancy, this is due to fetal cerebral maturation, and KANET aims to reflect the different levels of maturation during in utero life.25-27 Comparing low-risk with high-risk fetuses for neurological problems (ventriculomegaly) by application of KANET, significant differences were shown between the two groups, while the wider the degree of ventriculomegaly, or the presence of other anomalies the lower the KANET score.55

An important finding of this study was that for cases of mild ventriculomegaly with no other findings, KANET was normal and that was confirmed postnatally, revealing the additional importance of KANET, for the counseling of pregnancies where an anatomical fining is evident, but the significance of this finding for the neurodevelopment of this neonate is inadequate.

By comparing two groups (low- and high-risk for neurological impairment) significant differences in their KANET scores were noted and in all cases with abnormal KANET score was abnormal also postnatally there was some degree of neurological impairment, while when the KANET score was normal or even borderline the neurological outcome postnatally was also normal. 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. Regarding isolated leg movements and cranial sutures, the difference was not significant.51

Vladareanu et al.60 applied KANET both in high- and low-risk fetuses finding that the higher percentage of normal KANET scores belonged to the low-risk group (93.4 vs 75.8%). The majority of cases with borderline scores belonged to the IUGR group with abnormal findings in the middle cerebral artery (MCA) Doppler while the majority of cases with pathological KANET scores belonged to cases of threatened preterm labor with PPROM. Borderline and abnormal scores were dominant in high-risk pregnancies. There was a reduction of both the number and duration of GMs in the IUGR group with a reduction both in the number and the quality of fetal movements. Honemeyer et al.61 in their study did not identify any abnormal KANET scores, but most borderline scores were noticed within the high-risk pregnancies. This was the first study that introduced the average KANET score, which was derived from the scores of each fetus during pregnancy. Only one fetus had a borderline average KANET score, and this fetus who belonged to the high-risk group, was the only one out of 56 pregnancies who had an abnormal early neurological outcome. When the authors compared all 18 borderline KANET scores with fetal diurnal rhythm based on maternal observation, they noticed that 89% of the borderline scores of the at-risk group were recorded at times that the mothers characterized them as active periods, compared with 33.3% in the low-risk pregnancies concluding that fetal diurnal rhythm and pregnancy risk status should be taken under consideration. Kurjak et al.62 noticed differences in fetal behavior in the low-risk group and the following subgroups of fetuses: IUGR, gestational diabetes mellitus, threatened preterm birth, antepartum hemorrhage, maternal fever, sibling with cerebral palsy, and polyhydramnios showing the usefulness of KANET in early identification of fetuses prone to neurological impairment.

Athanasiades et al. also confirmed differences in fetal neurobehavior between high- and low-risk women with those with diabetes having statistically significantly higher KANET scores compared to the IUGR and the preeclampsia subgroup (p = 0.0001).73

Neto examined KANET high-risk cases and noticed that for KANET score 0, the parameters that were significantly different were the following: isolated head anteflexion, cranial sutures, and head circumference, isolated hand movement or hand-to-face movements, isolated leg movement and fingers movements. What was also important was the confirmation of the positive predictive value of KANET as all pathological KANET derived from high-risk cases, and none from low to that was confirmed postnatally.78

Hanaoka et al. performed a study where they tried to assess the differences in ethnic background on the KANET. What they noticed even in normal scores was a difference between the two populations (Japanese vs Croatian fetuses) and particularly a difference for four of the parameters (isolated head anteflexion, isolated eye blinking, facial alteration or mouth opening, and isolated leg movement). These differences did not affect the final score of KANET, however, ethnical differences are something that should be taken under consideration when assessing a fetus.77

Kurjak Antenatal Neurodevelopmental Test (KANET): The Importance of Prompt Detection of Neurological Problems

Most neurological problems are detected postnatally or at a time when the problem is very severe-obvious, that is at a time when not much can be done from a therapeutic point of view. The possibility of detecting such a problem earlier or even at the very initial stages, could offer the possibility of an earlier intervention, which could be more effective. KANET is a method that has such potential and could detect these high-risk fetuses, offer them an appropriate follow-up, and when possible an early diagnosis and as a result an early intervention. For physiotherapy, it is well known that the earlier it is initiated the better the outcome. A recent Cochrane meta-analysis shows that for preterm infants the earlier the intervention the better the outcome on cognitive and motor outcomes during infancy, with the cognitive benefits persisting into preschool age. Whether this could be applied in fetal life or early neonatal life, is still an area of interest, but KANET offers the opportunity to detect these fetuses and initiate further studies. Systematic family home programs for preterm infants for the first year of life showed selective long-term benefits, with caregivers experiencing fewer anxiety symptoms and lower odds of an anxiety disorder and preschoolers showing fewer internalizing behavior problems. The therapies and interventions in cases of neurological impairment are limited, but the timely application of these interventions has better results, so the earlier you have a diagnosis the indeed you can apply earlier these treatments to the correct group of people, and this is an area where definitely KANET can be a pioneer.74,75

Application of KANET in Clinical Practice

Kurjak antenatal neurodevelopmental test (KANET) has introduced into clinical practice about 10 years ago, aiming to the detection of problems that were inaccessible by any other method until now, such as fetal brain impairment and neurodevelopmental behavioral problems.41 More studies are needed and some studies are currently in progress.

The studies that we have until now confirm that KANET is a useful method for assessing fetal neurobehavior and that it has the capacity to detect fetuses with severe neurological problems.26,48,50 Application of KANET and its introduction into clinical practice is feasible, as a method it has been standardized and its positive predictive value has been confirmed, having as a future goal to make KANET part of the guidelines for a complete fetal neuro sonography and neurobehavior assessment.63 KANET offers the opportunity to systematically assess fetal neurobehavior, collect data on prenatal and postnatal findings, and long-term follow-up, in both high and low-risk cases, so that hopefully in a few years will have a complete evaluation of fetal neurological status and combine them even with anatomical findings, the significance of which may not be easily understood and explained.

CONCLUSION

Fetal neurology, as it is valid for postnatal neurology, is a field of great interest. Especially fetal neurobehavior during in utero life, due to the limited methods that we have to assess the fetus, has been a great challenge in the area of fetal and perinatal medicine. Neurological disorders, even severe ones, such as cerebral palsy, are almost always diagnosed after delivery, and many times 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. These facts prove that neurological problems are poorly understood and as such difficult to diagnose. In order to diagnose an abnormal condition, we should be able to define normal fetal neurobehavior, something that until recently had not been achieved. KANET with the application of 4D ultrasound technology offers the opportunity to study fetal neurobehavior in utero in the same way that a neonate is assessed postnatally, define the normal fetal neurological profile, and detect abnormal conditions. The usefulness of KANET has been proven by multicentric studies, as a method it has been standardized and it has been introduced into clinical practice with very good results and responses. Its importance has been documented for high-risk cases but it also shows benefits for low-risk cases. KANET has come to fill in the gap in fetal neurology and complete fetal assessment, especially in cases where there is a finding of uncertain significance and consequences on the neurological integrity of the fetus, like for example in cases of ventriculomegaly. In these cases it could offer the possibility of a more complete assessment of the fetus and therefore a more comprehensive counselling of the couples with an affected fetus. KANET has been introduced into clinical practice, has good sensitivity and specificity, has adequate positive and negative predictive value, and also inter and intraobserver variability and can be easily learned by ultrasound specialists with adequate knowledge of ultrasound and with access to 4D ultrasound machines. KANET is a method that could offer the possibility of detecting fetuses at risk for neurological impairment, and offer them appropriate follow-up, early diagnosis, and the opportunity for a timely intervention, which could lead to a better outcome.

REFERENCES

1. 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

2. 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

3. Joseph R. Fetal brain and cognitive development. Dev Rev 1999;20:81–98. DOI: 10.1006/drev.1999.0486

4. 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

5. Eidelman AI. The living fetus - dilemmas in treatment at the edge of viability. In: Blazer S Zimmer EZ (eds): The embryo: scientific discovery and medical ethics. Karger, Basel, 2005:351–370.

6. 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

7. Haak P, Lenski M, Hidecker MJ et al. Cerebral palsy and aging. Dev Med Child Neurol 2009;51Suppl 4(0 4):16–23. DOI: 10.1111/j.1469-8749.2009.03428.x

8. 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

9. Salihagic-Kadic A, Kurjak A, Medić 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

10. 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

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

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

13. DiPietro JA, Hodgson DM, Costigan KA, et al. Fetal antecedents of infant temperament. Child Dev 1996;67(5):2568–2583.

14. 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

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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Nijhuis JG. Fetal Behaviour: Developmental and Perinatal Aspects. Oxford: Oxford University Press; 1992.

23. Prechtl HF. State of the art of a new functional assessment of the young nervous system. An early predictor of cerebral palsy. Early Hum Dev 1997;50(1):1–11. DOI: 10.1016/s0378-3782(97)00088-1

24. Kurjak A, Luetic AT. Fetal neurobehavior assessed by three-dimensional/four dimentional sonography. Zdrav Vestn 2010;79(11):790–799. DOI: 10.1080/14767050802212166

25. Salihagic-Kadic A, Medic M, Kurjak A, et al. 4D sonography in the assessment of fetal functional neurodevelopment and behavioural paterns. Ultrasound Rev Obstet Gynecol 2005;5:1–15. DOI: 10.3109/14767058.2010.534830

26. Kurjak A, Pooh R, Tikvica A, et al. Assesment of fetal neurobehavior by 3D/4D ultrasound. Fetal Neurol 2009:222–250. DOI: 10.5005/jp/books/10305_7

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

28. Merz E, Abramowicz JS. 3D/4D ultrasound in prenatal diagnosis: is it time for routine use? Clin Obstet Gynecol 2012;55(1):336–351. DOI: 10.1097/GRF.0b013e3182446ef7

29. Kurjak A, Vecek N, Hafner T, et al. Prenatal diagnosis: what does four-dimensional ultrasound add? J Perinat Med 2002;30(1):57–62. DOI: 10.1515/JPM.2002.008

30. Kurjak A, Vecek N, Kupesic S, et al. Four-dimensional ultrasound: how much does it improve perinatal practice? In: Carrera JM, Chervenak FA, Kurjak A, eds. Controversies in perinatal medicine, studies on the fetus as a patient. Parthenon Publishing: New York; 2003;222.

31. 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):103–108. DOI: 10.1080/14722240400016895

32. Kurjak A, Carrera J, Medic M, et al. The antenatal development of fetal behavioral patterns assessed by four-dimensional sonography. J Matern Fetal Neonatal Med 2005;17(6):401–416. DOI: 10.1080/14767050400029657

33. 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

34. 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

35. Morokuma S, Fukushima K, Yumoto Y, et al. Simplified ultrasound screening for fetal brain function based on behavioral pattern. Early Hum Dev 2007;83(3):177–181. DOI: 10.1016/j.earlhumdev.2006.05.012

36. 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

37. 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

38. Amiel-Tison C, Gosselin J, Kurjak A. Neurosonography in the second half of fetal life: a neonatologist’s point of view. J Perinat Med 2006;34(6):437–446. DOI: 10.1515/JPM.2006.088

39. Tomasovic S, Predojevic M. 4D Ultrasound - medical devices for recent advances on the etiology of cerebral palsy. Acta Inform Med 2011;19(4):228–234. DOI: 10.5455/aim.2011.19.228-234

40. 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.

41. Stanojevic M, Kurjak A, Salihagić-Kadić A, et al. Neurobehavioral continuity from fetus to neonate. J Perinat Med 2011;39(2):171–177. DOI: 10.1515/jpm.2011.004

42. Kurjak A, Andonotopo W, Hafner T, et al. Normal standards for fetal neurobehavioral developments–longitudinal quantification by four-dimensional sonography. J Perinat Med 2006;34(1):56–65. DOI: 10.1515/JPM.2006.007

43. Stanojevic M, Talic A, Miskovic B, et al. An attempt to standardize Kurjak’s antenatal neurodevelopmental test: Osaka Consensus Statement. Donald School J Ultrasound Obstet Gynecol 2011;5(4):317–329.

44. Pooh RK, Pooh K, Fetal VM. Donald School J Ultrasound Obstet Cochrane Database of Systematic Reviews 2015, Issue 11. Art. No.: Gynecol 2007;1:40–46.

45. Kurjak A, Ahmed B, Abo-Yaquab S, et al. An attempt to introduce neurological test for fetus based on 3D and 4D sonography. Donald School J Ultrasound Obstet Gynecol 2008;2(4):29–34. DOI: 10.5005/jp-journals-10009-1076

46. 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

47. 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

48. 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

49. 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

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

51. 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

52. 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

53. 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

54. Andonotopo W, Kurjak A. The assessment of fetal behavior of growth restricted fetuses by 4D sonography. J Perinat Med 2006;34(6):471–478. DOI: 10.1515/JPM.2006.092

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

56. Horimoto N, Koyanagi T, Maeda H, et al. Can brain impairment be detected by in utero behavioural patterns? Arch Dis Child 1993;69(1 Spec No):3–8. DOI: 10.1136/adc.69.1_spec_no.3

57. 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

58. Nijhuis JG, Prechtl HF, Martin CB Jr, et al. Are there behavioural states in the human fetus? Early Hum Dev 1982;6(2):177–195. DOI: 10.1016/0378-3782(82)90106-2

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

60. Vladareanu R, Lebit D, Constantinescu S. Ultrasound assessment of fetal neurobehavior in high-risk pregnancies. Donald School J Ultrasound Obstet Gynecol; 2012;6:132–147. DOI: 10.5005/jp-journals-10009-1235

61. 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

62. 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

63. Kurjak A, Predojevic M, Salihagic-Kadic A. Fetal brain function: lessons learned and future challenges of 4D sonography. Donald School J Ultrasound Obstet Gynecol 2010;5(2):85–92. DOI: 10.5005/jp-journals-10009-1182

64. Greenwood C, Newman S, Impey L, et al. Cerebral palsy and clinical negligence litigation: a cohort study. BJOG 2003;110(1):6–11.

65. 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

66. 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

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

68. 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

69. Hata T, Kanenishi K, Akiyama M, et al. Real-time 3-D sonographic observation of fetal facial expression. J Obstet Gynaecol Res 2005;31(4):337–340. DOI: 10.1111/j.1447-0756.2005.00298.x

70. Kozuma S, Baba K, Okai T, et al. Dynamic observation of the fetal face by three-dimensional ultrasound. Ultrasound Obstet Gynecol 1999;13(4):283–284.

71. 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

72. 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

73. 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

74. Stanojevic M, Antsaklis P, Salihadic-Kadic A et al. Is Kurjak antenatal neurodevelopmental test ready for routine clinical application? Bucharest Consensus Statement. Donald School J Ultrasound Obstet Gynecol 2015;9(3):260–265. DOI: 10.5005/jp-journals-10009-1412

75. Spencer-Smith MM, Spittle AJ, Doyle LW, et al. Long-term benefits of home-based preventive care for preterm infants: a randomized trial. Pediatrics 2012;130(6):1094–1101. DOI: 10.1542/peds.2012-0426

76. Neto RM, Kurjak A. Recent results of the clinical application of KANET test. Donald School J Ultrasound Obstet Gynecol 2015;9(4):420–425.

77. Hanaoka U, Hata T, Kanenishi 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

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

________________________
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), 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 (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.