Is Four-Dimensional (4D) Ultrasound Entering a New Field of Fetal Psychiatry?

The aim of is to explore whether by observing the fetus by 4D US it is possible to enter fetal behavior, emotions, mental status, consciousness, awareness and other states connected with fetal mind and ability of self-regulation. It is well known that fetal motoric activity is enabling the development of central and peripheral nervous system and the muscles. It is 4D US which enabled to investigate fetal movement patterns from the first trimester of pregnancy throughout the whole pregnancy. Based on the evaluation of fetal spontaneous motor activity by 4D US, a prenatal neurologic scoring test named Kurjak Antenatal Neurodevelopmental Test (KANET) was created. This test has been used to assess almost 2000 fetuses and our results have indicated that KANET has an ability to recognize normal, borderline, and abnormal behavior in fetuses from normal and abnormal pregnancies. The fetus is able to process tactile, vestibular, taste, olfactory, auditory and visual sensations. The fetus responds to painful stimuli with a wide spectrum of reactions. Important external signs of emotion are facial expressions. The existence of a wide range of facial expressions, including grimacing, smiling, crying, similar to emotional expressions in adults, has been revealed by 4D sonography in the 2nd and 3rd trimesters of pregnancy. It is questionable if mental, emotional and behavioral conditions of the fetus were covered in this paper and whether we are able to perceive the fetus as the patient who may develop communication or some other psychiatric disorders which we will be hopefully able to recognize prenatally. Although it seems as the speculation from the point of view of our recent diagnostic possibilities, it is apparent that the day when this will be a reality is rapidly approaching.

Assessment of motoric and hemodynamic parameters in growth restricted fetuses - case study.

OBJECTIVE: In order to more accurately assess fetal neurological status in five fetuses with severe intrauterine growth restriction (IUGR), combined assessment of their hemodynamics and motor activity was undertaken in this study. METHOD: Hemodynamic changes in the placental and fetal cerebral vessels were evaluated using the umbilical artery resistance index (URI), and the middle cerebral artery resistance index (CRI). The blood flow redistribution towards the fetal brain in response to fetal hypoxia was detected by the C/U (cerebro - umbilical) ratio, expressed as CRI/URI. Motoric parameters were assessed by new antenatal neurologic scoring test named Kurjak Antenatal Neurodevelopmental Test (KANET), based on evaluation of spontaneous motor activity using four-dimensional (4D) ultrasound. RESULTS: KANET has potential in recognizing pathologic and borderline behavior in IUGR fetuses with or without blood flow redistribution towards the fetal brain. Very low values of C/U ratio and abnormal KANET score have indicated adverse pregnancy outcome. CONCLUSION: In some pregnancies complicated with IUGR, estimation of the risk of hypoxia versus prematurity can be extremely puzzling. Combined assessment of hemodynamic and motoric parameters in IUGR fetuses could allow construction of an algorithm, which would be helpful in the decision making process of pregnancy termination.

Fetal neurophysiology according to gestational age.

More than 99% of the human neocortex is fashioned during intrauterine life, resulting in the fascinating diversity of fetal functions and activities. The objective of this review is to present the most significant neurodevelopmental events, as well as new findings about prenatal motor and sensory development.

Neurobehavioral continuity from fetus to neonate.

Neurobehavior represents development of the central nervous system (CNS). Fetuses and newborns exhibit a large number of endogenously generated motor patterns, among which general movements are often investigated pre- and post-natally. Spontaneous activity is probably a more sensitive indicator of brain dysfunction than reactivity to sensory stimuli while testing reflexes. Nutritional stress at critical times during fetal development can have persistent and potentially irreversible effects particularly on brain growth and function. Unfavorable intrauterine environment can affect adversely brain growth. All endogenously generated movement patterns from un-stimulated CNS might be observed as early as from the seven to eight weeks' gestation, with a rich repertoire of movements within the next two or three weeks, continuing for five to six months postnatally. It is still uncertain whether a new scoring system for prenatal neurological assessment will be adequate for the distinction between normal and abnormal fetuses in low-risk pregnancies. The continuity of behavioral patterns from prenatal to postnatal life might answer these intriguing questions.

Nitric oxide synthesis in placenta is increased in intrauterine growth restriction and fetal hypoxia.

In order to study the possible role of nitric oxide (NO) in the human placenta, we measured the concentration of its stable metabolite nitrite (NO2-) in the placentas of women with normal pregnancies and those from pregnancies complicated by intrauterine growth restriction (IUGR) with or without fetal hypoxia. We have measured nitrites by the Griess reaction in 15 placentas from IUGR pregnancies and 12 controls. Cerebroumbilical ratio (C:U) was recorded by color Doppler ultrasound and values below 1 were considered to be a predictor for fetal hypoxia. NO2- levels measured in pathological placentas were increased for at least 93% as compared to control. Subjects from pregnancies complicated by IUGR and fetal hypoxia had increased NO2- as compared to the placentas from pregnancies with IUGR and normal fetal oxygenation. NO production in placenta is increased in pregnancies with IUGR. This effect is more pronounced in those with compromised fetal oxygenation.

New scoring system for fetal neurobehavior assessed by three- and four-dimensional sonography.

AIM: To produce a new scoring system for fetal neurobehavior based on prenatal assessment by 3D/4D sonography. We identified severely brain damaged infants and those with optimal neurological findings and compared fetal with neonatal findings. RESULTS: The new scoring system was retrospectively applied in a group of 100 low-risk pregnancies. After delivery, postnatal neurological assessment was performed, and all neonates assessed as normal reached a score between 14 and 20, which we assumed to be a score of optimal neurological development. Subsequently, the same scoring system was applied in the group of 120 high-risk pregnancies in which, based on postnatal neurological findings, three subgroups of newborns were found: normal, mildly or moderately abnormal, and abnormal. Normal neonates had a prenatal score between 14 and 20, mildly or moderately abnormal neonates had a prenatal score of 5-13, whereas those infants who were assigned as neurologically abnormal had a prenatal score from 0-5. CONCLUSION: A new scoring system for the assessment of neurological status for antenatal application is proposed, similar to the neonatal optimality test of Amiel-Tison. This preliminary work may help in detecting fetal brain and neurodevelopmental alterations due to in utero brain impairment.

Three- and four-dimensional ultrasonography for the structural and functional evaluation of the fetal face.

Ultrasonographic examination of the fetal face can provide information that may lead to the diagnosis of anomalies in other organs or systems. Thus, the fetal face represents a "diagnostic window" for fetal diseases and syndromes. Three-dimensional ultrasonography (3DUS) improves the evaluation of anatomic fetal facial anomalies over what is possible by 2-dimensional ultrasonography (2DUS). Four-dimensional ultrasonography (4DUS), by adding the temporal component to the examination, allows visualization of facial expressions that might be useful in the study of fetal behavior and maternal-fetal bonding. In this article, we evaluate the potential of 3D/4DUS for the study of structural and functional development of the fetal face.

Fetal cerebrovascular response to chronic hypoxia--implications for the prevention of brain damage.

Fetal hypoxia is one of the leading causes of perinatal morbidity and mortality. One of the most severe sequels of fetal hypoxic insult is the development of perinatal brain lesions resulting in a spectrum of neurological disabilities, from minor cerebral disorders to cerebral palsy. One of the most important fetal adaptive responses to hypoxia is redistribution of blood flow towards the fetal brain, known as the 'brain sparing effect'. The fetal blood flow redistribution in favor of the fetal brain can be detected and quantified by the Doppler cerebral/umbilical ratio (C/U ratio = cerebral resistance index (CRI)/umbilical resistance index (URI)). Our studies on animal models and human fetuses have demonstrated clearly that this phenomenon cannot prevent the development of perinatal brain lesions in the case of severe or prolonged hypoxia. Fetal deterioration in chronic and severe hypoxia is characterized by the disappearance of the physiological cerebral vascular variability (vasoconstriction and vasodilatation), followed by an increase in cerebral vascular resistance. However, our latest study on growth-restricted and hypoxic human fetuses has shown that perinatal brain lesions can develop even before the loss of cerebrovascular variability. The fetal exposure to hypoxia can be quantified by using a new vascular score, the hypoxia index. This parameter, which takes into account the degree as well as duration of fetal hypoxia, can be calculated by summing the daily % C/U ratio reduction from the cut-off value 1 over the period of observation. According to our results, the use of this parameter, which calculates the cumulative, relative oxygen deficit, could allow for the first time the sensitive and reliable prediction and even prevention of adverse neurological outcome in pregnancies complicated by fetal hypoxia.

Normal standards for fetal neurobehavioral developments--longitudinal quantification by four-dimensional sonography.

AIM: To construct normal standards for fetal neurobehavioral development using longitudinal observations through all trimesters by four-dimensional sonography. SUBJECT AND METHODS: A group of 100 healthy normal singleton pregnancies were recruited for longitudinal 4D US examinations to evaluate fetal neurodevelopmental parameters between 7 to 40 weeks' gestation. Variables of maternal and fetal characteristics including gestational age, eight fetal movements patterns in the first trimester and 14 parameters of fetal movement and fetal facial expression patterns recorded thereafter for the construction of fetal neurological charts. RESULTS: Measurement of 7 parameters in the first trimester and 11 parameters in the second and third trimesters correlated with gestational age (P<0.05). Those parameters have been followed longitudinally through all trimesters and showed increasing frequency of fetal movements during the first trimester. A tendency towards decreased frequency of facial expressions and movement patterns with increasing gestational age from second to third trimesters has been noticed. CONCLUSION: With 4D sonography, it is possible to quantitatively assess normal neurobehavioral development. There is urgent need for further multicentric studies until a sufficient degree of normative data is available and the predictive validity of the specific relationship between fetal neurobehavior and child developmental outcome is better established.

New data about embryonic and fetal neurodevelopment and behavior obtained by 3D and 4D sonography.

The development of the human central nervous system (CNS) begins in the early embryonic period and proceeds through a sequence of very complicated processes long after delivery. Although the neurodevelopmental processes are genetically determined, their complexity and intensity implicates the vulnerability of the CNS to number of environmental factors. There is substantial evidence to show that many neurological problems, from minor cerebral dysfunction to the cerebral palsy, originate form the prenatal, rather than perinatal or postnatal periods of life. A variety of neurological and neuropsychiatric diseases is nowadays considered to originate, at least partly, from the prenatal incidents. In most of these conditions, there is no reliable parameter for detection or prediction of cerebral lesions and there is an urgent need to develop strategies that would enable the early detection of cerebral lesions or indications that such lesions might occur. The new, advanced, imaging techniques such as 3-dimensional and 4-dimensional sonography, opened a new perspective for the investigation of structural and functional development of fetal CNS. The application of these techniques might improve our understanding of the prenatal neurodevelopmental events and possibly facilitate the development of diagnostic strategies for early detection or prevention of brain dysfunctions and damage.

Structural and functional early human development assessed by three-dimensional and four-dimensional sonography.

OBJECTIVE: To summarize the role of three-dimensional and four-dimensional ultrasound in the assessment of early human development. DESIGN: Review of literature. SETTING: Ultrasound research center and obstetrics and gynecology department in a tertiary care facility. RESULT(S): The introduction of high-frequency transvaginal tranducers has resulted in remarkable progress in ultrasonographic visualization of early embryos and fetuses and the development of sonoembryology. Furthermore, recent introduction of three-dimensional and four-dimensional ultrasounds combined with the transvaginal approach has produced more objective and accurate information on embryonal and early fetal development. For the first time parallel analyses of structural and functional parameters in the first 12 weeks of gestation become possible. CONCLUSION(S): The anatomy and physiology of placental and embryonic development is a field where medicine exerts its greatest impact on early pregnancy at present time, and it opens fascinating aspects of embryonic differentiation. Clinical assessment of those stages of growth rely heavily on three-dimensional and four-dimensional sonography, one of the most promising forms of noninvasive diagnostics today and embryological phenomenon, once matters for textbooks are now routinely recorded with outstanding clarity.

The assessment of fetal behavior in early pregnancy: comparison between 2D and 4D sonographic scanning.

AIM: To determine the accuracy of 4D sonography in the assessment of embryonic and early fetal motor activity in the first trimester of normal pregnancy, in comparison to the 2D sonography. METHODS: Fifty pregnant women between 6-14 weeks of gestation with singleton pregnancy were assigned for the investigation. Two dimensional and four dimensional recordings were displayed on the screen and recorded on the videotape during the 15 minutes observation period. RESULTS: General body, head and limb movements recorded by 2D sonography were notable by 4D technique in the same gestational age. These movements were presented collectively with maximum, minimum, and median frequencies during 15 minutes observation period. Spearman rank order correlation reached statistical significance (P<0.05) between the frequencies of all observed movement patterns assessed by two different techniques. Several movement patterns, such as sideway bending, hiccup, breathing movements, mouth opening and facial movements could be observed only by 2D sonographic technique in this period of gestation. CONCLUSION: Presently, both 2D and 4D methods are required for the assessment of early fetal motor development and motor behavior. It is reasonable to expect that such technological improvement may provide some new information about the intrauterine motor activity and facilitate the prenatal detection of some neurological disorders.

[Nitric oxide--an important signalling molecule in normal and pathological pregnancy]. / Dusikov oksid--vazna signalna molekula u normalnoj i patoloskoj trudnoci.

The numerous studies on the multifunctional nature of the nitric oxide (NO) have suggested the wide variety of functions mediated by this molecule in vital processes in cardiovascular, nervous, gastrointestinal, urogenital system and during immunological reactions. In this review we present the results of experiments carried out on animal models, as well as the results of clinical studies considering the role of NO and its metabolites during pregnancy and delivery. During pregnancy NO is one of the most important relaxing factors of myometrium, and also no less important in the control of blood flow in uterus and placenta. Changes in NO production at the end of pregnancy could be important for the beginning of delivery and cervical maturation. Also it seems, and our preliminary results as well as results of other investigators suggest, that higher levels of NO are produced during some pathological conditions in pregnant women, e.g. IUGR, preeclampsia, preterm delivery. The implications of NO donors or inhibitors of NO synthesis used in therapy of previously mentioned conditions will be also discussed.

Behavioral pattern continuity from prenatal to postnatal life--a study by four-dimensional (4D) ultrasonography.

AIM: To investigate whether the same behavioral patterns were present pre- and postnatally, and whether there were any differences in the frequency of movements observed in fetal and in early neonatal life. SUBJECTS AND METHODS: Ten out of 37 pregnant women in the third trimester of pregnancy (median gestational age 34 weeks, range 33 to 35 weeks) in the two-month period (from November 1st to December 31st, 2003) were enrolled in the investigation. Ten term, appropriate for gestational age newborns (seven born vaginally, three by elective SC, six girls, six first-born) and were enrolled in the study. All 4D examinations were performed on Voluson 730 (Kretztechnik, Zipt, Austria) and Acuvix (Medison, Korea) with transabdominal 5 MHz transducer. After standard assessment in 2D B-mode ultrasound, a 4D mode was switched on and live 3D image was reconstructed by selecting the ideal representative 2D image placed in the region of interest (ROI). The recordings of neonatal behavior were made on the Sony P-612 OHMPL videotape by video camera (Sony Camcoder CC DTRV 318 Hv8) and reviewed on the videocassette recorder (Sony VHS SLV-N 900). The median of newborns' age at the moment of recording was 49 hours (range 4 to 112). During the examination, newborns were lying in the bed, separated from other infants in the nursery, dressed, and lying on their backs in a supine position with unrestrained hands. The temperature in the room was 22 to 24 degrees C. The video recording was performed mainly while the children were actively awake or during alert inactivity. RESULTS: There were no movements observed in fetal life that were not present in neonatal life, while the Moro reflex was present only in neonates. The most frequent fetal and neonatal movements were scowling, eye and mouth opening, and hand to face, hand to eye and hand to head movements. Isolated blinking, mouth to eyelid movement, yawning, tongue expulsion and scowling were more frequent in neonates than in fetuses, although the difference was not statistically significant. Hand to mouth movements were more frequent in neonatal than in fetal life while all other hand movements were less frequent in neonates than in fetuses, although the differences did not reach statistical significance. Spearman rank order correlation reached statistical significance in smiling (R=0.71; t=2.91; P=0.02) and in hand to ear movement (R = 0.80; t= 3.86; P = 0.005), and was almost statistically significant in isolated eye blinking (R=0.61; t=2.17; P =0.06), while the correlations between the rest of the movements were not statistically significant. CONCLUSIONS: 4D ultrasonography is a powerful tool in the assessment of fetal behavior, and our study showed that there is a continuity from fetal to neonatal behavior, especially in terms of isolated eye blinking movements, mouth and eyelid opening, yawning, tongue expulsion, smiling, scowling and hand movements directed to other parts of the face.