ORIGINAL SCIENTIFIC PAPER |
https://doi.org/10.5005/jp-journals-10009-1917 |
Recent Advances in the Assessment of Fetal Behavior in Preeclamptic Patients
1Clinic of Gynecology and Obstetrics, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina; Department of Gynecology, School of Medicine, Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina
2Department of Obstetrics and Gynecology, Medical School University of Zagreb, Zagreb, Croatia
3,4Clinic of Gynecology and Obstetrics, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
Corresponding Author: Edin Medjedovic, Clinic of Gynecology and Obstetrics, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina; Department of Gynecology, School of Medicine, Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina, Phone: +387 33 250 250, e-mail: medjedovic.e@gmail.com
ABSTRACT
Preeclampsia has a significant effect on maternal and fetal health, and in the most severe cases may lead to significant early or late-onset intrauterine growth restriction (IUGR), which can be diagnosed by ultrasound. In moderately severe and mild preeclampsia, the consequences for the fetus may be less severe. The main effect of preeclampsia on the fetus is malnutrition as the result of hypoxia due to uteroplacental vascular insufficiency, which occurs in approximately 30% of fetuses from preeclamptic pregnancies. This leads to various perinatal and neonatal complications including IUGR, emergency cesarean section (CS), premature birth, low birth weight, low APGAR scores, and often a longer stay in the neonatal intensive care unit and more severe acute respiratory distress syndrome after birth. The question is whether these consequences can be detected, and are there any indicators of early fetal distress before the development of growth restriction? Therefore, the aim is to investigate if observation of fetal behavior using four-dimensional ultrasound (4D US) in pregnancies with preeclampsia can reveal signs which could be added to existing diagnostic criteria for preeclampsia. The four-dimensional US offers the possibility of simultaneous visualization of real-time movements of the head, body, and all four extremities in three dimensions. Using the 4D US for assessment of fetal behavior and postnatal neuropediatric knowledge, a group from Zagreb proposed a prenatal screening test for assessment of the motor activity of the fetus, known as the Kurjak Antenatal Neurodevelopmental Test (KANET). The aim of the paper is to show that KANET is one of the most relevant tools for the assessment of fetal behavior, particularly in patients who are affected by preeclampsia. Based on our investigation we showed that preeclampsia clearly affects fetal behavior. The KANET test has proven to be a safe tool in assessing fetal neurodevelopment, especially in those at risk affected by severe preeclampsia. Prenatal fetal assessment is of great help to neonatologists in preparing for adequate and timely resuscitation procedures at birth. Low KANET scores always prompted close and intensive follow-up in pregnancies with severe preeclampsia to avoid adverse outcomes in both pregnant women and fetuses.
How to cite this article: Medjedovic E, Kurjak A, Jonuzovic-Prosic S, et al. Recent Advances in the Assessment of Fetal Behavior in Preeclamptic Patients. Donald School J Ultrasound Obstet Gynecol 2022;16(1):11-18.
Source of support: Nil
Conflict of interest: None
Keywords: Fetal behavior, Four-dimensional ultrasound, Kurjak antenatal neurodevelopmental test, Preeclampsia
INTRODUCTION
Preeclampsia is defined as a systemic disease of hypertension (defined as systolic pressure ≥140 mm Hg or diastolic pressure ≥90 mm Hg) after the 20th gestational week, with at least one of the following symptoms: proteinuria, organ dysfunction (including kidney, liver, hematological, or neurological complications), and in some cases, the presence of fetal growth restriction. It is a cause of increased mortality and morbidity rates of the mother, fetus, and newborn due to impairment of the fetoplacental unit.1,2 Women who suffered from preeclampsia in a previous pregnancy are more frequently suffering from cerebrovascular diseases after birth.2
Preeclampsia occurs in about 0.5-15% of all pregnancies.3,4 It is estimated that the incidence of preeclampsia is 2-7% in developed western countries, whilst in developing countries, it is increasing and approaching 10% of all pregnancies.5 Primigravidas and younger women have a higher risk of preeclampsia, but it can occur in older women as well.3-5 Recent research has established that preeclampsia is more frequent in twin pregnancies conceived by in vitro fertilization procedures (IVF) in comparison with spontaneously conceived twin pregnancies.6 Pregnant women conceived by IVF procedure with twin pregnancies and preeclampsia have a higher risk of cesarean section (CS), preterm birth, and low birthweight.6 There is a higher incidence of preeclampsia in the sisters of women who had preeclampsia in their first pregnancy, in comparison with the sisters of women who did not have preeclampsia, also in women with a rapidly growing mola hydatidosa, antiphospholipid syndrome and polyhydramnios and Black women.7,8 Complications of preeclampsia also contribute to mortality related to pregnancy of about one in 10, due to anesthesia, cardiomyopathy, placental abruption, and cerebrovascular insult.9-13 Besides the risk to the mother, preeclampsia also dramatically increases the risk for the fetus and newborn, including intrauterine growth restriction (IUGR), low gestational age, low birth weight, premature birth, oligohydramnios, placental abruption, a low APGAR score, admission to neonatal intensive care, stillbirth, and neonatal death.8,14
The etiology of preeclampsia is still a mystery. Preeclampsia, as is understood nowadays, is an inflammation that includes impairment of placentation and oxidative stress resulting in the development of clinical symptoms.15 Impaired placentation occurs due to unsuccessful transformation of uterine spiral arteries at about 12-16 weeks of pregnancy, resulting in placental ischemia, increased level of inflammatory factors, and oxidative stress.16 It is believed that hypertension in pregnancy, diabetes, and other inflammatory conditions, and multiple pregnancies, may result in an inflammatory response and oxidative stress providing to preeclampsia.17,18 Women with early-onset preeclampsia may present with abnormal morphology of the placenta depicted by ultrasound and impaired Doppler blood flow through the spiral and uterine arteries.19,20 Decreased placental perfusion may result in generalized endothelial activation with endothelial hypertrophy of glomerular capillary vessels.3 Endothelial activation followed by vasoconstriction in preeclampsia is caused by oxidative stress, impaired synthesis of nitric oxide, impaired renin-angiotensin-aldosterone mechanism, with the disturbed balance between prostacyclin and thromboxane A2, increased concentrations of endothelin 1, fibronectin growth factor, and thrombocytosis.15-17
Still, cause of preeclampsia is unknown, and the only effective therapy recognized so far is birth, with a recovery expected 6 weeks after delivery.1 However, premature birth in many cases is linked to considerable mortality and morbidity in the premature child.1 These children most often require extensive intensive care followed with many severe complications, with a possibility for development of life-long disability, which leads to major expenses in healthcare.2 Preeclampsia is a pathological condition that might be accompanied by encephalopathy in the neonate due to fetal vascular cerebral vasoconstriction, with all neurodevelopmental short- and long-term consequences.2 A primary goal of antenatal care is the early identification of women at risk for preeclampsia with close follow-up of the mother and the fetus to prevent development of long-term morbidity.
The aim of the paper is to show importance of assessment of KANET as the most relevant tool for the assessment of fetal behavior, particularly in preeclamptic pregnant women.
Fetal Behavior: Hints and Tips
It was Prechtl who introduced almost 40 years ago assessment of fetal behavior into research using 2D US noticing that there are so-called general movements (GMs) appearing from 7.5 GW till 60 postmenstrual weeks postnatally.21 Prechtl and his group showed that longitudinal follow-up of fetal behavior may be a better predictor of neurodevelopmental disability than clinical examination or even some neuroimaging methods.22 Original Prechtl’s classification of general movement impairment has been modified by Hadders Algra, and her modification is accepted in most of the countries, with Bosnia and Herzegovina among them.23 As pointed out before, endogenously generated spontaneous activity occurring without stimulation of the fetus can be observed by 2D US, and even better by 4D US from 7-8 weeks prenatally, with the longitudinal follow-up postnatally using video recordings of infants from birth till postmenstrual age (PMA) of 60 weeks24-26 (Fig. 1). This possibility to follow GMs longitudinally from prenatal to the postnatal period represents an important opportunity for the detection of high-risk fetuses and infants, who are at neurodevelopmental risk.26 GMs include movements of different parts of the body, with high variability, with the movement of upper and lower extremities, hand, head, and neck with very gradual onset and end.23-25 They appear and gradually fade, have different intensity, strength, and speed, so that they are sometimes harmonious and elegant, creating the impression of complexity and variability.23-25 GMs appearing from 28-36 or 38 weeks of the PMA are called premature, those appearing from 36-38 up to 46-52 weeks of PMA are writhing, while fidgety movements appear to 54-58 weeks of the PMA.23-25 A lack of variability and complexity of GMs is a sign of mild abnormality of GMs.23-25 Abnormal GMs are characterized by the absence of complexity and variability with their poor repertoire and appearance of cramped-synchronized or chaotic movements.23-25 The quality of each individual movement includes speed, amplitude, and strength, which are combined during the very complex perception of movements.23-26
The mobility of the fetus is dependent on the development of neuronal synapses developing between the 6th and 7th GW in the spinal cord and innervated muscle fibers.27 The establishment of a connection between motoneurons results in neuron activity, and the appearance of spontaneous vermicular bursts of twitching movements, at 7th GW.28 These are slow movements of flexion and extension of the trunk, accompanied by passive movements of the arms and legs and reflexes appearing due to the first afferent-efferent neuronal pathways in the spinal cord.28 From the 8th GW on, complex, well-organized movements occur due to the supraspinal influence on fetal motoric activities, called GMs which include the head, trunk, and limbs.22 From the 10th GW, the frequency of fetal movements is increasing, while by the end of the 10-11th GW movements resembling breathing appear together with facial movements.29 From the 13th GW on, it is possible to recognize targeted movements of the arms and isolated movements of the fingers.30,31 In the second trimester of pregnancy, the amplitude, speed and complexity of fetal behavioral patterns are increasing. In the second half of pregnancy, fetal active and resting states alternate, and breathing movements and heart frequency are changing with the circadian rhythm due to the maturation of the hypothalamic suprachiasmatic nucleus.32 In the 28th GW the isolated eye blinking, which occurs for the first time at around 18 weeks, becomes one of the most frequent facial movements as the result of the maturation of the mesencephalon in the second trimester, together with grimacing, sucking and swallowing.33 In the third trimester, there is a reduction in facial movements and GMs and movements of the head and arms, but they become increasingly complex due to the maturation of medulla oblongata and the more stable intrinsic activity of the brain stem, which is involved with the control of the fetal spontaneous movements.34 The brain stem remains the main regulator of fetal behavioral patterns up until the end of the pregnancy.35 The functional connections between the periphery and the cortex appear from the 26th to the 28th GW, indicated by the evoked potentials that can be registered from the cortex.34 Between the 24th and 34th GW differentiation of the cortical areas begins, and after the 32nd GW the six layers of the neocortex are formed.36 In the 30th GW, EEG can record sleeping and waking patterns, which reflect the maturation of the brain stem.36
During intrauterine development, in general, each new form of motor activity is caused by the previous development of certain parts of the fetal central nervous system (CNS).29 Fetal movements are spontaneous as an expression of CNS development.29 Regulation of fetal sleep is a well-controlled and complex behavior, which reflects the primary activity of the brain at the end of pregnancy.37 Measuring normal phenomena and the development of fetal motor patterns and behavioral states can therefore be used for diagnostic purposes, that is, for assessing the integrity of the fetal CNS.38 This is vital for differentiating fetuses that are healthy from those that are in distress, whose condition is deteriorating or that have a chronic dysfunction. The end goal of studying fetal behavior is to detect the effects of certain antenatal disorders affecting brain development adversely and to characterize those effects.
Continuity of Prenatal and Postnatal Behavior
There are no movements in fetal life that are not present in the neonatal period.37-41 Therefore, prenatal-neonatal continuity exists even in subtle, fine movements, such as facial expressions37 (Fig. 2). Moreover, for the neurodevelopment of the fetus, being born does not mean that alertness and memory are not already developed before birth, and from that point of view moment of birth is not so essential. One study showed that in the 38th and at 41-42 weeks fetuses spend the same amount of time awake as a newborn born at 38 or 1 GW.42 This proves that wakefulness is not “induced” by birth, but the development of that state is a continuum for which birth is not an important phenomenon. There is some evidence that healthy fetuses who demonstrated synchronized state transitions (min) close to term achieved a higher level of self-control at the ages of 8 and 15 years, in comparison with fetuses who did not.43 That study suggests a connection between prenatal regulatory processes and self-regulation in childhood and adolescence43 (Fig. 3).
The Effect of Preeclampsia on Fetal Behavior
The main effect of preeclampsia on the fetus is malnutrition as the result of hypoxia due to uteroplacental vascular insufficiency, which occurs in approximately 30% of fetuses from pregnancies complicated with preeclampsia.44 This leads to various perinatal and neonatal complications including IUGR, emergency CS, premature birth, low birth weight, low APGAR scores, and often a longer stay in the neonatal intensive care unit and more severe acute respiratory distress syndrome after birth.44 In some cases, the damage to the fetus is so severe that it may result in intrauterine or postnatal death.44 There is evidence of suboptimal postnatal neurocognitive development of IUGR infants.44,45 Recent research has shown that preeclampsia is related to an increased risk of poor early linguistic development, low neuro-cognitive function, and attention deficit hyperactivity disorder.44,45 Also, there is increasing evidence showing that hypertensive disorders caused by pregnancy, especially preeclampsia, can have potentially long-term consequences on the neuro-behavioral development of offspring, through changes to the epigenome.44 The quality of movement patterns is altered in fetuses suffering from IUGR.39,40 Their movements become slower and more monotonous, resembling cramps, and their variability in strength and amplitude is reduced39,40 (Fig. 4). These changes may indicate the existence of brain lesions in growth-restricted fetuses, and potentially fetal hypoxia.38,41
Severe preeclampsia significantly affects maternal and fetal health and may lead to severe early or late IUGR, which can be diagnosed by ultrasound.46,47 In moderately severe and mild preeclampsia, fetus may be less severely affected. The question is whether these consequences can be detected, and are there indicators of early fetal distress before the development of growth restriction? The diagnostic criteria invented, presented, and used so far do not include the fetus in any way.48,49 Therefore, the aim is to investigate if observation of fetal behavior using 4D US in preeclamptic pregnancies can be used to be added to existing diagnostic criteria for preeclampsia.
From the data presented up to now concerning preeclampsia, obviously, it affects adversely both the mother and the fetus and neonates after birth. It is needed to monitor the fetuses from high-risk pregnancies assessing their biophysical profile by two-dimensional ultrasound (2D US) and fetal behavior using 4D US. In cases of preeclampsia fetal behavior may be affected for at least two reasons: firstly, as a result of the circulatory adaptation of the fetus to preeclampsia with redistribution of the blood flow, and secondly as a result of brain damage which may occur due to fetoplacental blood flow impairment.48,49 In the case of preeclampsia, many fetuses experience IUGR with reduced fetal movements which can be reported by pregnant women affected by manifest preeclampsia.3
The Kurjak Antenatal Neurodevelopmental Test (KANET)
As has already been emphasized, with the introduction of 2D US, it is possible to follow normal fetal behavior during gestation. Since normal behavior and its development during pregnancy have been described, it is possible to recognize abnormal behavior or specific changes in fetal behavior. Many studies using conventional 2D US have shown that a normally developing fetus and fetus at risk exhibit different behavioral patterns.50,51 This led to the conclusion that fetal behavioral patterns directly reflect the processes of development and maturation of the CNS. It also led to the conclusion that assessment of fetal neurobehavior can make it possible to differentiate between normal and abnormal brain development, and also the early diagnosis of various structural and functional abnormalities of the brain.52 Four-dimensional (4D) ultrasound offers the possibility of simultaneous visualization of movements of the head, body and all four extremities in three dimensions and in real-time. Using 4D US in obstetrics makes it possible to monitor the quality (complexity and variability) and quantity of fetal movements.
Four-dimensional US has been used for the assessment of fetal behavior including some postnatal neurological signs in fetuses which have been introduced by postnatal Amiel Tison’s Neurological Assessment at Term (ATNAT). A group from Zagreb proposed prenatal screening test for assessment of the motor activity of the fetus, known as the Kurjak Antenatal Neurodevelopmental Test (KANET).50-54 As has been pointed out, in contrast to other authors who only observed spontaneous movements using 2D US, this test, in addition to spontaneous movements some elements from postnatal neurological assessment of newborns, known as ATNAT are used in fetuses.50-54 Clinical testing showed that the quantity of GMs is a poor indicator of fetal well-being due to the large intra-individual and inter-individual variability, and the major overlap between normal and abnormal findings.51,54 In contrast, it was shown that changes to elegance and fluency, as well as fluctuations in intensity and speed of movements (quality), are prominent in sick premature infants.51,54 In terms of gestalt (overall and inclusive) perception, GMs are assessed as abnormal if they are monotonous, repetitive, less complex or if they are cramped synchronized.51,54 Facial movements are also included in the KANET scoring because they reflect brain development. Finally, KANET assessment includes isolated head anteflexion, cranial sutures and head circumference (from the ATNAT), isolated eye blinking, facial grimacing, mouth opening, isolated hand and foot movements, hand-to-face movements, finger and thumb movements, and gestalt perception of GMs.50-54 Standardization of the KANET test was proposed in Osaka, Japan, during a meeting of the International Academy of Perinatal Medicine in October 2010 (ref). After that, eight of the 10 parameters are used, because facial and mouth movements were combined into a single category, and also isolated hand movements and movement of the hand to the mouth are considered as a joint category.50-54
The best time for performing KANET is between 28 and 38 GW.50-54 The test should also be performed by a certified and trained ultrasound examiner, for 15-20 minutes while the baby is awake. If the baby is not awake, the test should be repeated after 30 minutes or the next day.50-54 Each parameter in the test is given from 0-2 points. Abnormal or borderline results require repeated KANET assessment every 2 weeks until the birth. After many multicenter studies, KANET became a respected method used in perinatology to analyze the neuromotor status of the fetus.50 Until recently, it was mistakenly thought that most neuromotor disorders detected postnatally were related to specific intrapartal events. Most of risk factors causing neurological damage begin in pregnancy which can be proved by KANET, enabling early antenatal detection of fetuses at neurological risk.52
DISCUSSION
Hypertensive disorders in pregnancy are responsible for more than 60,000 maternal fatalities around the world each year, and cause complications in up to 12% of all pregnancies.2,5,7,17 Pregnancies complicated by preeclampsia show higher maternal and perinatal morbidity and mortality.2,5,7,17 Early detection using general or specialized screening tests can reduce health related consequences, especially in infants.2
Early diagnosis of preeclampsia remains one of the main aims of antenatal care.55-57 An important issue is an improvement of prediction models for preeclampsia to identify high-risk pregnant women and appropriate follow-up of the fetus who can be severely affected.55 Many studies that have analyzed the effect of preeclampsia on the overall status of fetuses imply that they are at high risk due to hypoxia caused by preeclampsia. In a large percentage of cases, the fetoplacental hemodynamics in preeclampsia shows adjustment at the beginning, but as the pathological process progresses and the clinical picture of preeclampsia develops, signs of decompensation may be detected.55 During the compensation phase, which is defined as the “brain sparing effect,” there is a substantial reduction of fetal movements.55 Fetal blood flow is centralized enabling blood supply to the brain and heart as the priority for survival. This stage is time limited, depending on the severity of the pathological process, and in most cases, it moves on to a state of increased hypoxia.56 It is thought that developed hypoxia leads to encephalopathy, which is the main cause of neuromotor deterioration in neonates who were exposed to preeclampsia in utero.56 Preeclampsia and assessment of fetal behavior are important part of fetal evaluation because many neonates with obvious neuromotor defects developing postnatally should be detected prenatally.55,56
The basic laboratory diagnostics, with a clinical and gynecological examination, together with anamnestic data can be of great importance to assess the risk, but also to classify the patients in relation to the risk of preeclampsia.58-65
As mentioned before, fetoplacental insufficiency is one of the characteristics of preeclampsia.17 In the study published by Medjedovic and Kurjak, the effect of impaired uterine artery flow on fetal behavior was investigated.66 Eighty pregnant women in the second trimester of pregnancy were included for Uterine Artery Doppler (UAD) assessment and then divided into two groups: a control group of 40 patients with normal UAD and an investigated group of 40 patient with abnormal UAD. All patients underwent a KANET test and were followed up to the end of their pregnancy. The results of this study showed a statistically significant difference in the average score of KANET tests between the two groups. All patients with KANET scores from 0-5 developed preeclampsia which clearly indicates that KANET is also associated with the occurrence of preeclampsia, especially with extreme scores. This study is the first comprehensive research that has found a correlation between abnormal flow in uterine arteries and KANET scores and can encourage new more extended prospective investigation.
Honemayer et al. suggested, after research involving 56 fetuses, that KANET might be associated with fetal neurodevelopmental disorders.54 Luetic and Neto noticed that KANET is associated with impaired neurological development, and showed that assessment using 4D US must be established as an important tool in everyday clinical practice with high-risk pregnancies.67,68
Vladareanu et al. indicated that lower KANET scores are associated with high-risk pregnancies.69 Kurjak et al., after research on 869 pregnant women, stressed the importance of early detection of neurological disorders, and showed that KANET can be used for that purpose.70
Athanasiadis et al. showed the same on their sample of 152 high- and low-risk singleton pregnancies.71 Hanaoka et al. showed that ethnicity has nothing to do with the KANET score, and that KANET can be a universal scoring system for detecting neurodevelopmental disorders regardless of ethnicity.72
In their work in the population of 152 women, Athanasiadis et al. monitored 78 of them at low- and 74 at high-risk.71 There was a statistically significant difference in the mean KANET scores between the low-risk (14.49 ± 2.99) and the high-risk pregnancies (12.60 ± 2.88). In the subgroup of pregnancies complicated by IUGR, with an average score of 11.75 ± 3.5, of 12 fetuses, three (25%) had normal KANET scores, eight (66.7%) borderline, and one (8.3%) abnormal score (birth at 36 weeks, discharged without complications). The specific parameters which were significantly different from those in the control group were cranial sutures, finger movements, isolated eye blinking and gestalt perception. In the subgroup with hypertension, with an average KANET score of 11.76 ± 3.42, of 38 fetuses, 14 (36.8%) had a normal, and 24 (63.2%) borderline score. There was a statistically significant reduction in isolated head movements, cranial sutures, finger movements and gestalt perception. Moreover, there were seven unfavorable fetal and neonatal outcomes (three intrauterine deaths, two neonatal deaths within 24 hours after birth, and two infant deaths due to neonatal infection).
Okoye et al.73 included 200 newborns in their study, 100 whose mothers had preeclampsia and hypertensive disorders in pregnancy, and 100 whose mothers had normal blood pressure and uneventful pregnancy course. In their results, they stated that the APGAR scores were significantly lower in the group of newborns of preeclamptic mothers. These results are comparable with the results of the Medjedovic and Kurjak study66 which showed a connection between low APGAR and lower KANET scores. The Medjedovic and Kurjak study also showed a statistically significant correlation between body weight, 1 and 5 minutes APGAR scores, and the gestational week at birth. Therefore, we can expect that when a lower KANET score is found, immediately after birth the newborn might require resuscitation and close follow-up. Low birth weight was linked to fetuses with IUGR as well as fetuses who were born prematurely due to medical indications for delivery due to fetal condition.66
Talic et al. monitored 47 pregnancies complicated by IUGR.52 Their results showed 34 (72.3%) normal, 11 (23.4%) borderline, and two (4.3%) abnormal scores. A statistically significant difference was found in IUGR fetuses showing impairment of RI of the middle cerebral artery in comparison to IUGR with normal RI. All fetuses with normal KANET scores also had a normal RI, as well as two fetuses with borderline scores. The other nine fetuses with borderline scores and two with abnormal scores had a low RI. In 145 pregnancies complicated by hypertension, 129 fetuses (88.9%) had normal, 12 (8.3%) borderline, and four (2.8%) abnormal KANET scores. There was a statistically significant difference in KANET scores depending on the blood pressure (BP): normal KANET score was found in 95.3 % of fetuses, 3.8 % had borderline and 0.9 % had abnormal KANET scores if maternal BP was below 160/100 mm Hg. If maternal BP was above 160/100 mm Hg than 71 % of fetuses had normal KANET score, 21% had borderline, and 8% abnormal KANET score.
CONCLUSION
We can conclude that preeclampsia clearly affects fetal behavior. The KANET test has proven to be a safe tool in assessing the neurodevelopmental condition of fetuses exposed to preeclampsia which might be of great help to neonatologists in preparing for adequate and timely resuscitation procedures at birth. Lower KANET scores clearly directed the need to intensify supervision in such pregnancies and to avoid adverse outcomes in both pregnant women and fetuses.
ORCID
Edin Medjedovic https://orcid.org/0000-0003-2357-9580
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