REVIEW ARTICLE


https://doi.org/10.5005/jp-journals-10009-1952
Donald School Journal of Ultrasound in Obstetrics and Gynecology
Volume 17 | Issue 1 | Year 2023

Kurjak Antenatal Neurodevelopmental Test in Fetal Congenital Heart Defects: A Comparison of Antenatal and Postnatal Tests


Sertaç Esin1, Nilay C Balci2, Deniz A Ince3, Emre Gunakan4, Ozden Turan5, ─░lknur E Dogan6, Birgul Varan7, Latife A Karakas8, Meltem Aksu9, Ilkay Erdogan10, Niyazi K Tokel11, Ayse Ecevit12

1,8Division of Perinatology, Department of Obstetrics and Gynecology, Başkent University Faculty of Medicine, Başkent University, Ankara, Turkey

2Department of Physiotherapy and Rehabilitation, Ondokuz Mayıs University Faculty of Health Sciences, Samsun Ondokuz Mayıs University (OMU), Samsun, Turkey

3,9,12Division of Pediatric Neonatology, Department of Pediatrics, Başkent University Faculty of Medicine, Başkent University, Ankara, Turkey

4Department of Physiotherapy and Rehabilitation, Başkent University Faculty of Health Sciences, Başkent University, Ankara, Turkey

5,7,10,11Division of Pediatric Cardiology, Department of Pediatrics, Başkent University Faculty of Medicine, Başkent University, Ankara, Central Turkey

6Department of Physical Medicine and Rehabilitation, Başkent University Faculty of Medicine, Başkent University, Ankara, Turkey

Corresponding Author: Sertaç Esin, Division of Perinatology, Department of Obstetrics and Gynecology, Başkent University Faculty of Medicine, Başkent University, Ankara, Turkey, Phone: +905323868537, e-mail: sertacesin@gmail.com

Received on: 16 January 2023; Accepted on: 07 February 2023; Published on: 14 April 2023

ABSTRACT

Aim & Background: Kurjak’s antenatal development test (KANET) have been developed and aimed to detect fetuses at high neurodevelopmental risk by four-dimensional (4D) ultrasound. Congenital anomalies are one of the most important causes of infant mortality, and CHD remain at the forefront. With abnormal development of the cardiac structures, decreased cerebral oxygen or substrate supply may place the developing fetus at risk for altered brain growth or brain injury.

Methods: In this study, we aimed to perform KANET test on fetuses with CHD in the antenatal period and Amiel-Tison (AT) test and General movements (GMs) in the postnatal period and compare antenatal and postnatal scores.

Results: We have completed 38 KANET, 28 AT and 26 GMs tests in our cohort. Of thirty-eight infants who had KANET, median score was 15 (4–16). One patient (3%) had abnormal, 6 patients (16%) had borderline and 31 patients (81%) had normal scores. Five patients (18%) had minor, 14 patients (50%) had borderline and 9 patients (32%) had normal AT scores. Ten patients (38%) had normal and 16 (62%) patients had PR GMs scores. Of thirty patients who had normal KANET test scores, 25 patients had AT and 8 (32%) had normal, 4 (16%) had minor and 13 (52%) had borderline scores and 23 patients had GMs and 9 (39%) had normal and 14 (61%) had PR scores. There was only one patient with an abnormal KANET test. This patient’s karyotype was turned out to be Trisomy 18. Antenatal KANET and postnatal AT and GMs test results were compared and there was no significant correlation between test results.

Conclusion: KANET has become a valuable functional test for identifying fetuses at high risk for various neurological impairments.

Clinical Significance: In our study, KANET test results were impressive and informative. Two trisomy 18 cases who died in the first day of life had lowest KANET test scores in our cohort. Thirty three percent of cases who had borderline scores at KANET resulted in postnatal exitus. Despite these results, most cases with moderate AT and PR GMs results had good outcomes according to follow up.

How to cite this article: Esin S, Balci NC, Ince DA, et al. Kurjak Antenatal Neurodevelopmental Test in Fetal Congenital Heart Defects: A Comparison of Antenatal and Postnatal Tests. Donald School J Ultrasound Obstet Gynecol 2023;17(1):91-96.

Source of support: Nil

Conflict of interest: Dr. Sertaç Esin is associated as the International Editorial Board Member of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of this Editorial Board Member and his research group.

Keywords: Amiel-tison neurological assessment at term, Congenital heart defects, Fetal neurologic development, General movements assessment, Kurjak antenatal neurodevelopmental test.

This paper was presented at the symposium Zagreb—New York ethical and perinatal dialogue (first International symposium when does human life begin? Ethics, law, and professionalism in reproductive medicine; and fetal neurology—from short to long-term follow-up—how to proceed? Multicenter results on the clinical use of Kurjak’s antenatal neurodevelopmental test), held on 8–9th October 2022 in Zagreb, Croatia.

INTRODUCTION

Life is a continuous process and events during the prenatal period may impair fetal brain and central nervous system (CNS) functions, leading to future adult diseases including but not limited to cerebral palsy, autism spectrum disorders, and developmental disability. Until recently, we lacked a prenatal test which has the ability to detect impaired fetal brain and CNS functions in utero. KANET have been developed and aimed to detect fetuses at high neurodevelopmental risk by the assessment of fetal GMs and other neurological signs like facial movements, skull sutures, and neurological thumb by using 4D ultrasound.1 The predictivity of the test has been well established and is recommended as a valuable diagnostic tool to be used in clinical practice.2,3

Among the causes of infant mortality in developed countries, congenital anomalies account for the largest diagnostic category, with CHD leading the list of malformations. With improvements in cardiac surgical techniques and care medicine, infants at greatest risk for brain injury now are surviving, and a new profile of neurologic abnormalities has emerged, reflecting the effects of early hemodynamic disturbances believed to occur in utero. Normal fetal brain growth and development is a function of adequate oxygen and substrate delivery, and this depends on intact maternal, placental, and normal fetal brain circulation. Both maternal and placental circulations likely play an important role in the genesis of prenatal cerebrovascular injury and impaired fetal brain growth and development. With abnormal development of the cardiac structures, the pathways favoring the streaming of oxygen and substrate-rich blood to the brain may be disrupted and consequently, in the fetus with CHD, decreased cerebral oxygen or substrate supply may place the developing fetus at risk for altered brain growth or brain injury.

For high-risk infants, clinical assessment of the CNS and motor functions may be performed by Amiel-Tison and GM tests. Amiel-Tison neurological assessment is a simple and practical test that can be performed as part of the routine examination of the infant at term and enables us to identify a group of children with different degrees of neurological impairment right from the neonatal period, being of real use in both daily practice and research. It is valid for all full-term neonates or at 40 weeks corrected age and can be used up to the age of 6 years.4 GMs are complex movements involving the infant’s head, trunk, arms, and legs, and GMs are a reliable tool that provides information about the motor abilities of infants from the preterm period to the postnatal 5th month and shows neuromotor developmental deficiencies. Especially after the 1990s, research has increasingly emphasized the importance of GMs assessments in predicting motor dysfunction in infants.5

In this prospective study, we aimed to perform the KANET test on fetuses with CHD in the antenatal period and ATNAT and GMs in the postnatal period and compare antenatal and postnatal scores.

MATERIALS AND METHODS

Study Design and Participants

This was a prospective comparative study and had two steps due to three tests to be performed in the antenatal and postnatal periods. Pregnant patients followed in the perinatology department of the Baskent University, Department of Obstetrics and Gynecology, Ankara, Central Anatolia Region, Turkey, and diagnosed with fetal heart anomaly in the antenatal period represent the study population. A total 30 pregnant women and their infant infants diagnosed with CHD participated in the study between February 2019 and November 2020. Inclusion criteria were as follows—(1) pregnant patients between the ages of 18 and 45 at 28–38 weeks of gestation and their new born infants; (2) infants diagnosed with fetal heart anomaly [transposition of great arteries (TGA), tetralogy of Fallot (TOF), hypoplastic left heart syndrome (HLHS), hypoplastic right heart syndrome, aortic or pulmonary artery stenosis or atresia, aortic coarctation or interruption, ventricular septal defect (VSD), double outlet right ventricle (DORV), or any combination of above]. Exclusion criteria were multiple pregnancies; vaginal bleeding; preterm rupture of membranes; intrauterine growth restriction (IUGR); oligohydramnios; fetuses with other congenital anomalies; pregnancies complicated by gestational diabetes, hypertension, or other maternal medical diseases; acute use of maternal steroids for lung maturation; substance or tobacco use; and infants who were mechanically ventilated and intubated for >1 week after the birth. Written informed consent was obtained from all participants prior to participation in the study. All procedures were conducted in agreement with the World Medical Association Declaration of Helsinki principles. Lastly, all protocols were approved by the Ethics Committee of Baskent University (KA19/385).

Assessments

Patients were assessed in the antenatal and postnatal periods. Demographics, medical, and obstetrical history was recorded. Mode of delivery, neonatal demographics, and further pediatric history were also obtained.

Antenatal Period

KANET Test

The KANET test was performed by the senior maternal–fetal medicine specialist (Sertaç Esin) to the patients who met the inclusion criteria and gave consent to participate in the study once between 28 and 38 weeks of pregnancy. After the patient’s routine ultrasound examinations were performed with the GE E10 (GE Healthcare, Zipf, Austria–RAB4-8-D WideBandConvex Volume Probe) device; three-dimensional (3D), 4D ultrasound, and KANET tests were performed with the same device. The parameters to be looked at in the KANET test were scored appropriately and stored for comparison with the postpartum Amiel-Tison test score. Eight types of fetal movements were analyzed, studied, and recorded (isolated head anteflexion, cranial sutures, head circumference, isolated eye blinking, facial alteration or mouth opening, isolated leg movement, isolated hand movement or hand-to-face movements, finger movements, and gestalt perception of GM). The scoring system was as follows—0–5 was abnormal, 6–9 was borderline, and 10–16 was normal.6-8

Postnatal Period

All patients were followed up and delivered at our hospital. After delivery, all neonates were transferred to the neonatal intensive care unit (NICU) in order to observe, and a physical examination was done by the neonatologist. When the infant was stable, echocardiography was performed by the pediatric cardiologist on every patient. Those who required a heart operation were operated by our Pediatric Cardiovascular Surgery Department and then were followed up in the NICU. After discharge, they were followed up by outpatient clinics. Those who were not followed up in our outpatient clinics were contacted by telephone, if possible.

ATNAT

After the birth, the infant was taken to the NICU in order to observe the infant and to carry out the diagnosis/treatment under optimal conditions. The Amiel-Tison test was performed by the neonatal physiotherapist when the infant was stable after a routine evaluation by the pediatric cardiologist. The scoring of the test was not numeric; it was due to emerging symptoms and findings. During the test, the infant’s cranial characteristics, alertness, behavior, spontaneous activity, active and passive tone in the infant’s trunk, wakefulness, primary reflexes, and extremity tone were evaluated. The test result was determined according to the severity of the evaluated neuromotor parameters. Evaluation parameters were scored as “0—typical result in the normal range, 1—moderately abnormal result, 2—severely abnormal result.” If the infants got 0 points from all parameters, the score of “CNS function is optimal” is given. If the infant got a score of 1–2 from some of the evaluation parameters, one of the results of “mild, moderate, or severe exposure in the CNS” is marked. In premature infants who had reached the corrected term age, the result of “CNS function is optimal” was marked if it scored 0 in all parameters, and one of the results of “mildly moderate or severely affected in the CNS” if it scored 1–2 from some of the evaluation parameters. During the evaluations, infants who were mechanically ventilated and intubated received the score of “severe exposure.” It is preferred for evaluation when the infant is awake and calm and not hungry.4,9,10

GM

General movements (GMs) are complex movements involving the infant’s head, trunk, arms, and legs. Prof Heinz Prechtl, interested in early neurodevelopment, stated that spontaneous motor movements are important in infants in the early period. Therefore, Hadders Algra and Prechtl found that the quality of infants’ spontaneous movements informs the state of the fetus or the infant’s nervous system. These movements are defined as the general of some serial movements of all parts of the body at various speeds and amplitudes.11,12 GMs, which are the first movements developed by the human fetus, appear before isolated extremity movements. From birth to term (40 weeks) there is a rich variety of movements, including pelvic tilt and trunk movements. This period is called “preterm GMs.” Starting from the term, powerful movements called “writhing” have been added to the variety of movements. This period is defined as “writhing GMs.” In the 8th week from the term (40 weeks) period to the postterm 8th week, the writhing feature of GMs disappears, and instead, the “fidgety GMs” period begins, which includes small and gentle movements called “fidgedty” movements throughout the whole body, including the head, trunk, and extremities. Evaluation of the movements in this period is between 6–8 and 15–20 postterm weeks.11,12 There are three types of abnormal motor patterns from preterm to the 9th postterm week and are classified as PR, cramp synchronized (CS), and chaotic. CS movements, in particular, are the cases in which the trunk and extremities move in a rigid and synchronized way, indicative of a neurological and developmental problem that may occur in the future.5,13 For our patients, evaluation was performed by the neonatal physiotherapist when the infants were in the supine position, without clothes that may prevent spontaneous movements, preferably with only diapers or short clothes, leaving the extremities exposed, and the bed adjusted to 30°. The time when the infant was fully awake and not hungry was preferred, and the infant should not have been manipulated, crying, or excited during the evaluation. Infants were recorded on camera for 15–20 minutes. Then, the quality of the movements were evaluated and scored by watching the camera recordings again. GMs were considered normal if the sequence, amplitude, speed, and intensity of the infant’s movements varied. Abnormal GMs were said to be present if one or more of these features were deficient.14-17

Statistical Analysis

The International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) statistical software version 20 for Mac (IBM SPSS Inc., Chicago, Illinois, United States of America) was used for statistical calculations. Comparisons between groups were performed by using the Pearson chi-square or the Fisher’s exact test, the student t-test, or the Mann–Whitney U test. Correlations were determined by using the Spearman’s rank correlation test. Statistical tests were considered significant at the 95% level.

RESULTS

After Institutional Ethics Committee approval, we started to recruit patients in February 2019. Until March 2020, we performed 25 KANET and postnatal tests, but then due to coronavirus disease 2019 restrictions all over the country, less than the normal patient has admitted to our hospital due to fetal heart abnormalities. As of September 2022, we have completed 38 KANET (one patient was lost to follow-up).

Our study population consisted of 38 patients with fetal heart disease. Type of fetal heart disease and frequencies were TOF (n:8, 21%), VSD (n:15, 39.4%), aortic coarctation (n:7, 18.4%), TGA (n:7, 18.4%), DORV (n:6, 15.8%), and Ebstein anomaly (n:1, 2.6%). The majority of fetuses had more than one abnormality (n:26, 68.4%).

Of 38 infants who had KANET, one was lost to follow-up and 11 infants had critical condition after birth, needed resuscitation/intubation or underwent an emergency operation, and a postnatal test was not performed for them.

The median age of the patients was 31 weeks. Median gestational week at the time of KANET and delivery were 32 and 38 weeks, respectively.

Of 38 infants who had KANET, the median score was 15 (4–16). One patient (3%) had abnormal, six patients (16%) had borderline, and 31 patients (81%) had normal scores.

Amiel-Tison neurological assessment was performed on 28 patients. The median score was 7 (2–25). Five patients (18%) had minor, 14 patients (50%) had borderline, and nine patients (32%) had normal scores.

General movements (GMs) were performed in 26 patients. Two infants who had Amiel-Tison neurological assessment did not have GMs because the infant did not spontaneously move. The median score was 34 (13–42) in GMs. A total of 10 patients (38%) had normal, and 16 (62%) patients had PR scores.

Of 30 patients who had normal KANET test scores, 25 patients had ATNAT [eight (32%) had normal, four (16%) had minor, and 13 (52%) had borderline scores] and 23 patients had GMs test [nine (39%) had normal and 14 (61%) had PR scores] (Fig. 1). In the postnatal period, of 30 patients who had normal KANET test scores, 11 (37%) infants were operated and were in good condition, nine (30%) infants were not operated and were in good condition, three (10%) infants were operated but had mild growth retardation, three (10%) were operated but died in the postoperative period, and four (13%) could not be reached.

Fig. 1: Comparison of normal KANET scores with ATNAT and GMs scores

Of six patients who had normal KANET test scores, four patients had ATNAT [one (25%) had normal, one (16%) had minor, and two (50%) had borderline scores] and four patients had GMs [two (50%) had normal and two (50%) had PR scores]. There was only one patient with an abnormal KANET test. This patient’s karyotype turned out to be trisomy 18 at the postnatal period and died on postpartum day 1 without a postnatal test. In the postnatal period, of six patients who had borderline KANET test scores, three (50%) infants were operated and were in good condition, one (15%) infant was operated on and discharged could not be reached, one (15%) infant was operated but died in the postoperative period, and one (15%) died in the postoperative period before operation due to trisomy 18 and Ebstein’s anomaly.

We compared antenatal and postnatal test scores; KANET and ATNAT results were compared in 28 patients and there was no significant correlation between them (p:0.31). KANET and GMs results were compared in 26 patients as well, and there was again no significant correlation between test results (p:0.42).

DISCUSSION

For a long time, determining the behavior patterns of the baby in the mother’s womb, interpreting it, and detecting abnormalities have attracted the attention of not only obstetricians but also other disciplines of medicine. This follow-up, which started with the monitoring of the baby’s movements by the mother and the physician, has advanced to the direct observation stage with the discovery of the ultrasound. With the introduction of 3D and 4D ultrasound, it has become possible to evaluate fetal behaviors more realistically and holistically. With 3D and 4D ultrasound, the fetal body, arms, legs, hands, feet, and fingers can be monitored in real time, and all facial expressions can be evaluated.18-20 Different fetal behavioral characteristics have been determined for different weeks of gestation and it has been shown that these characteristics reflect different stages of fetal brain development.21,22 Neonatologists use tests, such as Amiel-Tison or Dubowitz, during the first few days after birth to perform a neurological examination of the baby. Kurjak et al. created the KANET so that this test can be done for the fetus with the help of ultrasound in the mother’s womb. The purpose of this test is to evaluate the neurodevelopmental characteristics of the fetus holistically and systemically, just as in the postnatal period. The KANET has been applied in many low and high-risk pregnant groups, and it has been suggested that abnormal scores reflect abnormal neurodevelopmental status.3

Congenital anomalies are one of the most important causes of infant mortality, and CHD remains at the forefront.23,24 Due to the advancement of cardiac surgical techniques and the improvement of intensive care conditions, more infants with cardiac anomalies can survive. When the neurological development of these babies was evaluated, it was revealed that hemodynamic differences affect brain development while they were still in the mother’s womb. Adequate oxygen and nutrients are required for normal brain development, and maternal and placental circulation and fetal circulation must be normal in order for these to reach the fetal brain optimally. In order for fetal circulation to be adequate, fetal heart and myocardial functions must be good. It is known that complex heart diseases cause IUGR and smaller than normal head circumference. Especially in infants with TGA and HLHS, the baby’s head is measured smaller when compared to birth weight.25,26 The effects of heart diseases on brain development can also be demonstrated by Doppler measurements, which is a method of examining vascular blood flow. For example, the cerebral pulsatility index decreases in HLHS and TGA.27,28 It can be thought that fetal neurological development may also be affected by these diseases that cause changes in fetal brain development because fetal specific movements reflect neurological development, and the fetal face as a mirror of the brain, may indicate structural or functional changes that may occur in the brain.

When we compare antenatal KANET test scores with postnatal ATNAT and GMs, we found no correlation. Although the number of patients is limited and the groups are rather heterogenous due to various heart abnormalities and postnatal conditions, most of the patients who had good KANET scores had normal outcomes albeit worse postnatal test scores. Discordant test results between antenatal and postnatal test scores is important and may have different causes. We think one of the most important factors was the study population characteristics, which is fetal heart disease. All infants had to be transferred to NICU, and some had a critical condition which required comprehensive assessment and treatment, complicating postnatal evaluation. After stabilization of the infant, the postnatal 1st day was chosen for postnatal assessment tests in order to better evaluate the infant before invasive procedures or deterioration of their status due to inherent disease. However, on the 1st day, the heart disease itself and treatments caused feeding problems and hypotonia/movement limitation, which hampered postnatal evaluation.

The predictive value of neurologic assessment in the neonatal period decreases due to the nonspecificity and variability of neurological findings.4 Therefore, long-term neurological follow-up of infants is important. The presence of definitely abnormal GM at the fidgety age (at 3–5 months) increases the risk of neurologic deficit.12 Therefore, further evaluation of those infants in the later stages of life with the same tests would result in more robust information about their neurological development. In the future study, we planned to carry out the long-term neurological follow-up of the infants and analyze the correlation with the KANET test.

Dubowitz neurological assessment scale is another neurological evaluation method for newborn infants. It is a valid and reliable instrument and has 34 items for neurological examination. The test examines tone, tone pattern, reflexes, movement, abnormal findings, orientation, and behavior. It provides ease of application in the NICU.29,30 The reflex, visual, and hearing evaluation may be better with this test when compared with other tests; therefore, it can be compared in a future study in order to better assess the newborn infant on the 1st day of life.

In our study, the KANET test results were impressive and informative. Two trisomy 18 cases who died on the 1st day of life had the lowest KANET test scores in our cohort (one had 5 and the other had 9 points at KANET). Nearly 33% of cases who had borderline scores at KANET resulted in postnatal exitus. Despite these results, most cases with moderate Amiel-Tison and PR GMs results had good outcomes according to follow-up.

CONCLUSION

Kurjak antenatal neurodevelopmental test (KANET) has become a valuable functional test for identifying fetuses at high-risk for various neurological impairments caused by a variety of reasons and assessing the fetal neurological status in utero. Our preliminary findings support using the KANET test for identifying fetuses at risk for abnormal postnatal results. Further and long-term assessment of our results will provide more comprehensive information about the use of this promising test.

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