MD966Z - Method for predicting the risk of development of congenital pathology of the central nervous system in the fetus - Google Patents
Method for predicting the risk of development of congenital pathology of the central nervous system in the fetus Download PDFInfo
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Abstract
Description
Invenţia se referă la medicină, în special la neurologie şi pediatrie şi poate fi utilizată pentru pronosticarea riscului de dezvoltare a patologiei congenitale a sistemului nervos central la făt. The invention relates to medicine, in particular to neurology and pediatrics and can be used to predict the risk of developing congenital pathology of the central nervous system in the fetus.
Se cunoaşte metoda de pronostic al dereglării circulaţiei cerebrale la făt, care constă în aceea că la termenul de graviditate de 30...40 de săptămani se înregistrează densitatea optică a lichidului amniotic şi în cazul în care mărimea ei este mai mare de 0,04 un. optice se diagnostichează dereglarea circulaţiei cerebrale [1]. There is a known method for predicting cerebral circulation disorders in the fetus, which consists in recording the optical density of the amniotic fluid at 30...40 weeks of gestation, and if its size is greater than 0.04 optical units, cerebral circulation disorders are diagnosed [1].
Dezavantajul acestei metode este estimarea neveridică a dereglărilor posthipotoxice ale sistemului nervos central la făt, deoarece asupra stării lichidului amniotic influenţează diferiţi factori, atat de scurtă durată, cât şi de durată îndelungată. De aceea, să ne pronunţăm după densitatea lichidului amniotic despre starea sistemului nervos la făt este destul de greu. The disadvantage of this method is the unreliable estimation of posthypotoxic disorders of the central nervous system in the fetus, because the state of the amniotic fluid is influenced by various factors, both short-term and long-term. Therefore, it is quite difficult to make a decision about the state of the fetal nervous system based on the density of the amniotic fluid.
De asemenea, se cunoaşte metoda de diagnostic al dezvoltării sistemului nervos central la făt care constă în aceea că, începând cu a 20-a săptămână de graviditate, se efectuează electroencefalografia fătului, se analizează electroencefalograma şi în cazul în care se determină unde din banda delta de 0,5...3 oscilaţii/s şi unde din banda teta de 4...5 oscilaţii/s cu amplitudinea de 10...20 µW se pronostichează o dezvoltare normală a sistemului nervos central, dacă undele sunt polimorfe lente cu amplitudinea pană la 10 µW, se pronostichează riscul apariţiei encefalopatiei hipoxico-ischemice, dacă undele sunt de tipul suppression-burst se pronostichează riscul apariţiei unor malformaţii cerebrale, dacă se determină unde lente bilaterale din benzile delta-teta cu amplitudine mai mare de 40 µW, se pronostichează riscul apariţiei epilepsiei [2]. Also, there is a known method for diagnosing the development of the central nervous system in the fetus, which consists in the fact that, starting from the 20th week of pregnancy, the fetal electroencephalography is performed, the electroencephalogram is analyzed, and if waves from the delta band of 0.5...3 oscillations/s and waves from the theta band of 4...5 oscillations/s with an amplitude of 10...20 µW are determined, a normal development of the central nervous system is predicted, if the waves are slow polymorphic with an amplitude of up to 10 µW, the risk of hypoxic-ischemic encephalopathy is predicted, if the waves are of the suppression-burst type, the risk of cerebral malformations is predicted, if bilateral slow waves from the delta-theta bands with an amplitude greater than 40 µW are determined, the risk of epilepsy is predicted [2].
Dezavantajele metodei cunoscute sunt gradul complex de efectuare a ei, riscul comiterii unor erori pe parcursul măsurării mărimilor indicate mai sus. The disadvantages of the known method are the complex degree of its implementation, the risk of making errors during the measurement of the quantities indicated above.
Problema pe care o rezolvă invenţia este pronosticarea riscului de dezvoltare a patologiei congenitale a sistemului nervos central la făt la termene precoce ale sarcinii. The problem solved by the invention is predicting the risk of developing congenital pathology of the central nervous system in the fetus at early stages of pregnancy.
Dezvoltarea creierului la făt începe cu formarea şi închiderea tubului neural. Tubul neural se formează din placa neurală, care începe să se formeze la doar 16 zile după concepţie. Această placă se lungeşte şi începe să se plieze, formând un şanţ la 18 zile, care apoi începe să fuzioneze şi să se închidă într-un tub la 22 zile după concepţie. La a 27-a zi, tubul este închis în totalitate şi începe deja să se transforme în creier şi coloană vertebrală a embrionului. Creşterea cerebrală este legată pe de o parte de multiplicarea glială şi de debutul mielinizării, iar pe de altă parte de creşterea prelungirilor celulelor nervoase. Perturbarea etapelor de dezvoltare a creierului duce la patologii majore ale sistemului nervos al fătului. Acţiunea diferitor factori nocivi asupra fătului poate duce la reţinerea în dezvoltare a unor sectoare ale creierului. Patologia sistemului nervos la făt este diversă şi deseori depinde de acţiunea factorilor nocivi în anumite perioade de gestaţie. Acţiunea factorilor nocivi (patologiile lăuzei: anemia, hipertensiunea arterială, diabetul zaharat, toxemia gravidică, cardiopatiile decompensate pe parcursul sarcinii, epilepsia, vârsta înaintată, sarcini multiple etc.), poate provoca o suferinţă fătului, deseori manifestată prin hipoxie cronică cu afectarea creierului şi dezvoltarea unor anomalii ale creierului sau ale altor organe, fetopatii. Brain development in the fetus begins with the formation and closure of the neural tube. The neural tube is formed from the neural plate, which begins to form only 16 days after conception. This plate elongates and begins to fold, forming a groove at 18 days, which then begins to fuse and close into a tube at 22 days after conception. On the 27th day, the tube is completely closed and is already beginning to transform into the brain and spinal cord of the embryo. Brain growth is related, on the one hand, to glial multiplication and the onset of myelination, and on the other hand, to the growth of nerve cell extensions. Disruption of the stages of brain development leads to major pathologies of the fetal nervous system. The action of various harmful factors on the fetus can lead to the retention of some sectors of the brain in development. The pathology of the fetal nervous system is diverse and often depends on the action of harmful factors at certain periods of gestation. The action of harmful factors (pathologies of the fetus: anemia, hypertension, diabetes mellitus, pregnancy toxemia, decompensated heart disease during pregnancy, epilepsy, advanced age, multiple pregnancies, etc.) can cause suffering to the fetus, often manifested by chronic hypoxia with brain damage and the development of abnormalities of the brain or other organs, fetopathies.
Esenţa invenţiei constă în aceea că în ziua a 49…51 de sarcină în serul sangvin al gravidei se determină cantitatea de alfa-fetoproteină, fibronectină, proteină A plasmatică asociată sarcinii şi de progesteron seric, totodată în cazul când alfa-fetoproteina este mai mare de 124 µg/L, fibronectina mai mare de 400 mg/ml, proteina A plasmatică asociată sarcinii mai mică de 0,17 mU/ml şi progesteronul seric mai mare de 90 nmoli/L se pronostichează riscul de dezvoltare a patologiei congenitale a sistemului nervos central. The essence of the invention is that on day 49…51 of pregnancy, the amount of alpha-fetoprotein, fibronectin, plasma protein A associated with pregnancy and serum progesterone is determined in the blood serum of the pregnant woman, at the same time, in the case when alpha-fetoprotein is higher than 124 µg/L, fibronectin higher than 400 mg/ml, plasma protein A associated with pregnancy lower than 0.17 mU/ml and serum progesterone higher than 90 nmol/L, the risk of developing congenital pathology of the central nervous system is predicted.
Rezultatul invenţiei constă în aceea că la termene precoce se poate face cert pronosticarea riscului de dezvoltare a patologiei congenitale a sistemului nervos central la făt. The result of the invention is that at early stages it is possible to accurately predict the risk of developing congenital pathology of the central nervous system in the fetus.
Pentru determinarea cantităţii de fibronectină (FN) se utilizează metoda imunofermentativă utilizând testul Fibronectin ELISA Kit produs în Federaţia Rusă. To determine the amount of fibronectin (FN), the immunofermentative method is used using the Fibronectin ELISA Kit test produced in the Russian Federation.
Pentru determinarea cantităţii de alfa-fetoproteină (AFP) se utilizează metoda fazei dure a imunofermentării utilizând testul ELISA produs în Federaţia Rusă de întreprinderea “АЛКОРБИО”. To determine the amount of alpha-fetoprotein (AFP), the hard phase immunofermentation method is used using the ELISA test produced in the Russian Federation by the “ALKORBIO” enterprise.
Pentru determinarea cantităţii de proteina A plasmatică asociată sarcinii (PAPP-A) se utilizează metoda semiluminiscentă a fazei dure de imunofermentare (Body R., Ferguson C. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464389/?tool=pmcentrez. Emerg Med J. 2006 November; 23(11): 875-877. PMCID: PMC2464389). To determine the amount of pregnancy-associated plasma protein A (PAPP-A), the semiluminescent hard phase immunofermentation method is used (Body R., Ferguson C. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464389/?tool=pmcentrez. Emerg Med J. 2006 November; 23(11): 875-877. PMCID: PMC2464389).
Progesteronul seric se determină prin metoda clasică radioimună utilizând testul Progesterone ELISA produs în Federaţia Rusă de întreprinderea “АЛКОРБИО”. Serum progesterone is determined by the classical radioimmunoassay method using the Progesterone ELISA test produced in the Russian Federation by the “ALKORBIO” enterprise.
Avantajele invenţiei revendicate constau în accea că în rezultatul utilizării a 4 markeri care se întâlnesc la gravide în termene precoce se poate face o pronosticare a evoluţiei sistemului nervos central deja la săptămâna a 7-a de gestaţie, care poate permite medicului şi gravidei de a decide o tactică mai eficientă de tratament, la fel dacă să luăm fiecare marker în parte ei nu sunt informativi şi specifici în ceea ce priveşte rezultatul obţinut, iar la determinarea lor în cumul, şi anume în săptămâna a 7-a ne permite cu certitudine să deteminăm evoluţia dezvoltării sistemului nervos central, pentru a decide conduita de mai departe. The advantages of the claimed invention consist in the fact that as a result of using 4 markers that are found in pregnant women in early terms, a prognosis of the evolution of the central nervous system can be made already at the 7th week of gestation, which can allow the doctor and the pregnant woman to decide on a more effective treatment tactic, as if we were to take each marker separately they are not informative and specific in terms of the result obtained, and when determining them in total, namely at the 7th week, it allows us to determine with certainty the evolution of the development of the central nervous system, in order to decide on further conduct.
Alfa-fetoproteina (AFP) este o componentă de bază a serului la fătul în formare. Această proteină produsă de corpul galben şi ficatul fătului este eliberată în lichidul amniotic împreună cu urina lui şi prin placentă trece în sângele mamei. Analiza sângelui prelevat din vena mamei la a 35 zi de graviditate deja indică cantitatea de alfa-fetoproteină produsă şi eliberată de făt. Cantitatea de AFP din sângele mamei se schimbă în cazul când această componentă este eliberată într-o cantitate mare. O cantitate ridicată de AFP în sângele matern care trece peste limitele valorilor normale poate indica un risc crescut pentru: Alpha-fetoprotein (AFP) is a major component of the serum of the developing fetus. This protein, produced by the corpus luteum and liver of the fetus, is released into the amniotic fluid along with its urine and passes through the placenta into the mother's blood. Analysis of blood taken from the mother's vein on the 35th day of pregnancy already indicates the amount of alpha-fetoprotein produced and released by the fetus. The amount of AFP in the mother's blood changes when this component is released in large quantities. A high amount of AFP in the mother's blood that exceeds the limits of normal values may indicate an increased risk for:
- defecte ale tubului neural (hernia encefalului sau a măduvei spinării), - neural tube defects (hernia of the brain or spinal cord),
- defecte ale peretelui abdominal posterior, - defects of the posterior abdominal wall,
- anomalii ale rinichilor, - kidney abnormalities,
- defecte ale duodenului. - duodenal defects.
Dar, atenţie, schimbarea nivelului de AFP nu indică neapărat o patologie a fătului. Există şi alte motive de schimbare a nivelului de AFP, de exemplu, sarcina gemelară (în timpul căreia această proteină este produsă de 2 sau mai mulţi feţi). La fel s-a observat schimbarea nivelului de AFP şi în alte situaţii: risc de avort spontan legat de insuficienţa feto-placentară când este dereglată circulaţia între placentă şi făt. În 30% din cazurile de defecte cromozomiale, când apar cromozomi în plus într-o pereche sau alta de cromozomi, fapt ce duce la formarea unor anomalii de dezvoltare (sindromul Down, Edward, Seresevschii-Terner), nivelul de AFP este mai mic decât valoarea medie. But, be careful, a change in AFP levels does not necessarily indicate a pathology of the fetus. There are other reasons for a change in AFP levels, for example, twin pregnancy (during which this protein is produced by 2 or more fetuses). A change in AFP levels has also been observed in other situations: risk of spontaneous abortion related to feto-placental insufficiency when the circulation between the placenta and the fetus is disrupted. In 30% of cases of chromosomal defects, when extra chromosomes appear in one or another pair of chromosomes, which leads to the formation of developmental anomalies (Down, Edward, Seresevschii-Terner syndrome), the AFP level is lower than the average value.
Fibronectina (FN) este o glicoproteină modulară tridimensională ubicuitară, cu legături carboxilice şi aminoacide şi se găseşte în ţesuturile de legătură, în matrix-ul extracelular şi în fluidele corpului (plasmă şi alte lichide). Pe cale empirică pe un lot statistic veridic de gravide s-a arătat corelaţia dintre conţinutul de FN şi dezvoltarea hipertensiunii arteriale induse de sarcină (H.I.S.). Fibronectin (FN) is a ubiquitous three-dimensional modular glycoprotein with carboxyl and amino acid linkages and is found in connective tissues, in the extracellular matrix and in body fluids (plasma and other liquids). Empirically, in a statistically valid group of pregnant women, the correlation between FN content and the development of pregnancy-induced hypertension (PIH) has been shown.
S-a arătat că ridicarea nivelului de fibronectină în serul sangvin mai sus de 5 ng/ml duce sigur la dezvoltarea hipertensiunii arteriale. O atare ridicare a nivelului de fibronectină se poate determina deja la termenele incipiente ale sarcinii, şi anume la 16…18 săptămâni (112…126 zile), şi pot fi luate măsuri de profilaxie, de exemplu administrarea zilnică, o dată pe zi, a 0,75 g de aspirină (MD 2352 2004.08.31). It has been shown that an increase in the level of fibronectin in the blood serum above 5 ng/ml certainly leads to the development of arterial hypertension. Such an increase in the level of fibronectin can be determined already at the early stages of pregnancy, namely at 16…18 weeks (112…126 days), and prophylactic measures can be taken, for example, daily administration, once a day, of 0.75 g of aspirin (MD 2352 2004.08.31).
Proteina A plasmatică asociată sarcinii (PAPP-A) este o metaloproteină care este utilizată în cadrul screeningului genetic prenatal şi în studiul aterosclerozei. Un nivel scăzut poate semnifica un risc de: retard de creştere intrauterină, prematuritate, preeclampsie, sindrom Down. De asemenea nivelul acestei proteine este crescut în sindroame coronariene acute. Nivelul seric al acestei proteine creşte odată cu vârsta gestaţională. Pregnancy-associated plasma protein A (PAPP-A) is a metalloprotein that is used in prenatal genetic screening and in the study of atherosclerosis. A low level may indicate a risk of: intrauterine growth retardation, prematurity, preeclampsia, Down syndrome. The level of this protein is also increased in acute coronary syndromes. The serum level of this protein increases with gestational age.
Metoda revendicată se efectuează în felul următor: în ziua a 49…51 de sarcină în serul sangvin al gravidei se determină cantitatea de alfa-fetoproteină, fibronectină, proteină A plasmatică asociată sarcinii şi de progesteron seric, totodată în cazul când alfa-fetoproteina este mai mare de 124 µg/L, fibronectina mai mare de 400 mg/ml, proteina A plasmatică asociată sarcinii mai mică de 0,17 mU/ml şi progesteronul seric mai mare de 90 nmoli/L se pronostichează riscul dezvoltării patologiei congenitale a sistemului nervos central. The claimed method is performed as follows: on day 49…51 of pregnancy, the amount of alpha-fetoprotein, fibronectin, plasma protein A associated with pregnancy and serum progesterone is determined in the pregnant woman's blood serum, while in the case when alpha-fetoprotein is greater than 124 µg/L, fibronectin greater than 400 mg/ml, plasma protein A associated with pregnancy less than 0.17 mU/ml and serum progesterone greater than 90 nmol/L, the risk of developing congenital pathology of the central nervous system is predicted.
Exemplul 1 Example 1
Gravida G., 36 ani, la a 2-a graviditate, anterior a suportat 2 avorturi. Gravida a fost examinată la IMSP Chişinău. În baza investigaţiilor s-a stabilit: sarcină 7 săptămâni. Examenele obstetrical (somatic şi local) şi ecosonografic au evidenţiat evoluţia sarcinii în parametri normali. S-a aplicat metoda revendicată de pronosticare a riscului de dezvoltare a patologiei congenitale a sistemului nervos central la făt, s-au stabilit următorii parametri în serul femeii gravide: alfa-fetoproteina (AFP) - 7 µg/L, fibronectina (FN) - 189 mg/ml, proteina A plasmatică asociată sarcinii (PAPP-A) - 1,56 mU/ml şi progesteronul seric - 75 nmoli/L, la gravidă s-a pronosticat o evoluţie favorabilă de dezvoltare a sistemului nervos la făt. Femeia a născut în termen fiziologic şi sistemul nervos central a fost apreciat ca dezvoltat la naştere, la 1 lună şi la 6 luni după naştere. Pregnant woman G., 36 years old, on her 2nd pregnancy, previously suffered 2 abortions. The pregnant woman was examined at the Chisinau IMSP. Based on the investigations, it was established: 7 weeks of pregnancy. Obstetrical examinations (somatic and local) and echosonographic examinations revealed the evolution of the pregnancy within normal parameters. The claimed method of predicting the risk of developing congenital pathology of the central nervous system in the fetus was applied, the following parameters were established in the pregnant woman's serum: alpha-fetoprotein (AFP) - 7 µg/L, fibronectin (FN) - 189 mg/ml, plasma protein A associated with pregnancy (PAPP-A) - 1.56 mU/ml and serum progesterone - 75 nmol/L, the pregnant woman was predicted to have a favorable evolution of the development of the nervous system in the fetus. The woman gave birth at term and the central nervous system was assessed as developed at birth, 1 month and 6 months after birth.
Exemplul 2 Example 2
Gravida G., 40 ani, la a 2-a sarcină, anterior a suportat 1 avort, a fost examinată la IMSP Chişinău. În baza investigaţiilor s-a stabilit: sarcină 7 săptămâni. Examenele obstetrical (somatic şi local) şi ecosonografic au evidenţiat evoluţia sarcinii în parametri normali. S-a aplicat metoda revendicată de pronosticare a riscului de dezvoltare a patologiei congenitale a sistemului nervos central la făt, s-au stabilit următorii parametri în serul femeii gravide: alfa-fetoproteina (AFP) mai mare de 138 µg/L, fibronectina (FN) mai mare de 424 mg/ml, proteina A plasmatică asociată sarcinii (PAPP-A) mai mică de 0,13 mU/ml şi progesteronul seric mai mare de 103 nmoli/L. S-a pronosticat o evoluţie nefavorabilă de dezvoltare a sistemului nervos central la făt. Femeia a născut în termen fiziologic. La copil s-au depistat semnele specifice patologiei „Spina Bifida”, adică un sac cu fluid vizibil pe spate. Sacul era acoperit de un strat subţire de piele de dimensiunile unui strugure. A fost stabilit diagnosticul de „Spina Bifida”, forma meningocel, care reprezintă un defect congenital şi implică dezvoltarea incompletă a tubului neural. Pregnant G., 40 years old, on her 2nd pregnancy, previously suffered 1 abortion, was examined at the Chisinau IMSP. Based on the investigations, it was established: 7 weeks of pregnancy. Obstetrical examinations (somatic and local) and echosonographic examinations revealed the evolution of the pregnancy within normal parameters. The claimed method of predicting the risk of developing congenital pathology of the central nervous system in the fetus was applied, the following parameters were established in the pregnant woman's serum: alpha-fetoprotein (AFP) higher than 138 µg/L, fibronectin (FN) higher than 424 mg/ml, plasma protein A associated with pregnancy (PAPP-A) lower than 0.13 mU/ml and serum progesterone higher than 103 nmol/L. An unfavorable evolution of the development of the central nervous system in the fetus was predicted. The woman gave birth at physiological term. The child was found to have signs of the pathology "Spina Bifida", i.e. a sac of fluid visible on the back. The sac was covered by a thin layer of skin the size of a grape. The diagnosis of "Spina Bifida", a form of meningocele, was established, which is a congenital defect and involves incomplete development of the neural tube.
Metoda dată a fost evaluată pe un lot de 36 de gravide la a 7-a săptămână de graviditate cu vârsta cuprinsă între 35 şi 43 de ani. La 29 de gravide a fost pronosticată o evoluţie favorabilă, iar la 7 gravide o evoluţie nefavorabilă, dintre care la 6 s-a diagnosticat “Spina Bifida”, iar la una sindromul Edward. This method was evaluated on a group of 36 pregnant women at the 7th week of pregnancy, aged between 35 and 43. A favorable outcome was predicted for 29 pregnant women, and an unfavorable outcome for 7 pregnant women, of whom 6 were diagnosed with "Spina Bifida", and one with Edward's syndrome.
1. RU 2164082 C1 2001.03.20 1. RU 2164082 C1 2001.03.20
2. MD 3883 F1 2009.04.30 2. MD 3883 F1 2009.04.30
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD1170C2 (en) * | 1997-06-24 | 1999-08-31 | Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова | Method for treatment of the fetal intra-uterine infection |
| RU2164082C1 (en) * | 2000-03-07 | 2001-03-20 | Новокузнецкий государственный институт усовершенствования врачей | Method for diagnosing the central nervous system stage of a fetus |
| UA55920A (en) * | 2002-07-23 | 2003-04-15 | Харківська Медична Академія Післядипломної Освіти | Method for predicting neurologic after-effects in new-born children with heavy perinatal affection of the central nervous system (cns) |
| RU2231074C1 (en) * | 2003-02-11 | 2004-06-20 | Клюшник Татьяна Павловна | Method for detecting the character of pathophysiological lesions in psychomotor development in children of first year of life |
| RU2003103791A (en) * | 2003-02-11 | 2004-08-20 | Татьяна Павловна Клюшник | METHOD FOR DETERMINING THE CHARACTER OF PATHOPHYSIOLOGICAL DISORDERS OF PSYCHOMOTOR DEVELOPMENT OF CHILDREN OF THE FIRST YEAR OF LIFE |
| MD3341G2 (en) * | 2006-10-27 | 2008-01-31 | Светлана ХАДЖИУ | Method of treating the organic central nervous system lesions to infants |
| MD3425G2 (en) * | 2007-05-17 | 2008-06-30 | ИЛИЧУК Ион | Method of prophylaxis and treatment of nervous system pathologies to children |
| MD3883F1 (en) * | 2008-03-31 | 2009-04-30 | Svetlana Hadjiu | Method for predicting the evolution of development of the central nervous system of fetus |
| RU2475747C1 (en) * | 2011-12-15 | 2013-02-20 | Учреждение Российской академии медицинских наук Научный центр здоровья детей РАМН (НЦЗД РАМН) | Method of predicting psychomotor development of children with perinatal affection of central nervous system |
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Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD1170C2 (en) * | 1997-06-24 | 1999-08-31 | Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова | Method for treatment of the fetal intra-uterine infection |
| RU2164082C1 (en) * | 2000-03-07 | 2001-03-20 | Новокузнецкий государственный институт усовершенствования врачей | Method for diagnosing the central nervous system stage of a fetus |
| UA55920A (en) * | 2002-07-23 | 2003-04-15 | Харківська Медична Академія Післядипломної Освіти | Method for predicting neurologic after-effects in new-born children with heavy perinatal affection of the central nervous system (cns) |
| RU2231074C1 (en) * | 2003-02-11 | 2004-06-20 | Клюшник Татьяна Павловна | Method for detecting the character of pathophysiological lesions in psychomotor development in children of first year of life |
| RU2003103791A (en) * | 2003-02-11 | 2004-08-20 | Татьяна Павловна Клюшник | METHOD FOR DETERMINING THE CHARACTER OF PATHOPHYSIOLOGICAL DISORDERS OF PSYCHOMOTOR DEVELOPMENT OF CHILDREN OF THE FIRST YEAR OF LIFE |
| MD3341G2 (en) * | 2006-10-27 | 2008-01-31 | Светлана ХАДЖИУ | Method of treating the organic central nervous system lesions to infants |
| MD3425G2 (en) * | 2007-05-17 | 2008-06-30 | ИЛИЧУК Ион | Method of prophylaxis and treatment of nervous system pathologies to children |
| MD3883F1 (en) * | 2008-03-31 | 2009-04-30 | Svetlana Hadjiu | Method for predicting the evolution of development of the central nervous system of fetus |
| RU2475747C1 (en) * | 2011-12-15 | 2013-02-20 | Учреждение Российской академии медицинских наук Научный центр здоровья детей РАМН (НЦЗД РАМН) | Method of predicting psychomotor development of children with perinatal affection of central nervous system |
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