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Morbiditet, telesni i rani psihomotorni razvoj prevremeno rođene dece začete vantelesnom oplodnjom / Morbidity, physical and early psychomotor development of prematurely born children conceived by assisted reproductive technologies

<p>Uvod: Infertilitet se defini&scaron;e kao bezuspe&scaron;na koncepcija nakon jedne godine seksualnih odnosa bez upotrebe kontracepcije u fertilnoj fazi menstrualnog ciklusa. Metode asistirane reprodukcije predstavljaju efektivan način lečenja infertiliteta. Ispitivanje i identifikacija kratkoročnih i dugoročnih efekata arteficijalnih reproduktivnih tehnologija je veoma izazovan zadatak. Prvenstveni razlog tome je velika heterogenost u načinu sakupljanja, obrade, klasifikacije i tumačenja, sada već, obilja informacija koje su prikupljene u različitim istraživanjima. Individualni pristup lečenju neplodnosti, brz napredak i stalne promene u metodologiji arteficijalnih reproduktivnih tehnologija, uz ranije navedene pote&scaron;koće u vezi sa prikupljanjem i analizom podataka, značajno otežavaju precizno sagledavanje svih mogućih rizika i posledica arteficijanog začeća. Uprkos brojnim istraživanjima, naučnim publikacijama i akumuliranim dokazima, ostale su mnoge dileme u vezi odgovora na pitanja - da li su arteficijalno začete trudnoće u većoj meri praćene rizicima za neadekvatan razvoj ploda, lo&scaron;ijim perinatalnim ishodom i kakve su dugoročne posledice po decu, kao i da li su ovi rizici podjednako zastupljeni u jednoplodnim i vi&scaron;eplodnim trudnoćama.<br />Cilj rada: Ciljevi rada su bili da se utvrdi struktura morbiditeta kod prevremeno rođene dece začete vantelesnom oplodnjom (iz jednoplodnih i vi&scaron;eplodnih trudnoća) u prve dve godine života, te da se identifikuju perinatalni faktori koji su povezani sa pojavom akutnih i hroničnih komplikacija i oboljenja kod prevremeno rođene dece začete vantelesnom oplodnjom. Takođe, cilj rada je bio da se utvrde karakteristike psihomotornog razvoja kod prevremeno rođene dece začete vantelesnom oplodnjom na kraju dvanestog, osamnaestog i dvadesetčetvrtog meseca života, kao i da se identifikuju specifični faktori rizika za nepovoljan telesni, neurolo&scaron;ki i psiholo&scaron;ki ishod lečenja kod prevremeno rođene dece začete vantelesnom oplodnjom.<br />Materijal i metode: U studiju su uključena prevremeno rođena deca koja su bila hospitalizovana u Službi za neonatologiju i intenzivnu i poluintenzivnu negu i terapiju, i koja su nakon toga, tokom prve dve godine života redovno praćena u neonatolo&scaron;koj ambulanti Instituta za zdravstvenu za&scaron;titu dece i omladine Vojvodine u Novom Sadu. Retrospektivnim delom studije su obuhvaćena deca koja su lečena u Službi i praćena u neonatolo&scaron;koj ambulanti, a koja su rođena počev od 01. 01. 2011. do 31.12.2012. godine i praćena do navr&scaron;ena puna 24 meseca života. Podaci o pacijentima koji su uključeni u retrospektivni deo istraživanja prikupljani su pregledom medicinske dokumentacije. U prospektivni deo studije su uključena deca koja su lečena u Službi i koja su praćena u neonatolo&scaron;koj ambulanti, a koja su rođena između 01.01. 2013.godine i 31.12.2014. godine i potom praćena do navr&scaron;enih 24 meseca života. Iz navedene kohorte, formirane se dve grupe: Ispitivana grupa (Grupa 1) je obuhavatila svu prevremeno rođenu decu začetu vantelesnom oplodnjom koja su bila hospitalizovana i praćena na Institutu u navedenom periodu. Kontrolna grupa (Grupa 2) obuhvatila je prevremeno rođenu decu začetu prirodnim putem. Deca iz kontrolne grupe izabrana su iz kohorte tako da njihov broj bude jednak broju dece iz ispitivane grupe. Ispitanici iz ove grupe su ujednačeni (&#39;&#39;mečovani&#39;&#39;) sa decom iz ispitivane grupe prema gestacijskoj starosti i datumu rođenja. Gestacijska starost ispitanika iz kontrolne grupe se ne razlikuje za vi&scaron;e od &plusmn; 4 dana u odnosu na decu iz ispitivane grupe. Datum rođenja ispitanika koji su uključeni u kontrolnu grupu se ne razlikuje za vi&scaron;e od &plusmn; 3 meseca u odnosu na decu iz ispitivane grupe.<br />U momentu uključivanja u studiju uzimani su sledeći anamezni podaci:<br />Podaci u vezi sa majkom, trudnoći i porođaju: starost majke u momentu koncepcije, broj prethodnih poku&scaron;aja asistirane koncepcije, stručna sprema, mesto stanovanja, hronične bolesti dijagnostikovane pre trudnoće, akutne i hronične bolesti dijagnostikovane tokom trudoće (hipertenzija, pre-eklampsija, eklampsija, o&scaron;tećenje jetre), prevremena ruptura plodovih ovojaka, primena lekova tokom trudnoće, jednoplodna ili vi&scaron;eplodna trudnoća. Podaci o poremećajima posteljice i ovojaka: ablacija, placenta previja, horioamnionitis. Podaci u vezi sa detetom: intrauterina infekcija, intrauterina restrikcija rasta, način porođaja, Apgar skor. Antropometrijski parametri (telesna masa, telesna dužina, obim glave) na rođenju i tokom perioda ambulantnog praćenja deteta. Dužina inicijalne hospitalizacije deteta. Dužina invazivne i/ili neinvazivne respiratorne potpore i oksigenoterapije. Dijagnoze na otpustu iz bolnice: prisustvo te&scaron;kih posledica prematuriteta, &scaron;to podrazumeva: intrakranijalnu hemoragiju 3. i 4. stepena (definisanu u međunarodnoj klasifikaciji bolesti &ndash; deseta revizija (MKB10) pod &scaron;ifrom P52.2), cističnu periventrikularnu leukomalaciju, retinopatiju prematuriteta, bronhopulmonalnu displaziju, nekrotizirajući enterokolitis, sepsu i/ili meningitis (mikrobiolo&scaron;ki ili klinički dijagnostikovanu). Prisustvo urođenih anomalija ili genetskih sindroma i bolesti (definisanih u MKB10 pod &scaron;iframa Q00 do Q99), kao i prisustvo urođenih bolesti metabolizma (definisanih u MKB10 pod &scaron;iframa E00 do E90).<br />U retrospektivnom delu studije, pregledani su specijalistički izve&scaron;taji iz neonatolo&scaron;ke ambulante pri posetama deteta u uzrastu deteta od 12, 18 i 24 meseca, i beleženi su sledeći podaci: sve prethodno postavljene dijagnoze koje su navedene na specijalističkim izve&scaron;tajima iz neonatolo&scaron;ke ambulante, antropometrijski prametri u momentu pregleda (telesna dužina, telesna masa i obim glave), neurolo&scaron;ki nalaz (tonus, trofika, kožni i tetivni refleksi, prisustvo lateralizacije u neurolo&scaron;kom nalazu), nalaz oftalmologa (uredan nalaz/patalo&scaron;ki nalaz), procena fine i grube motorike, govora, kognitivne funkcije i socijalnog kontakta i zbirna procena psihomotornog razvoja. U prospektivnom delu studije, pri kontrolnim pregledima u neonatolo&scaron;koj ambulanti, u uzrastu deteta od 12, 18 i 24 meseca, određivano je i beleženo sledeće: ranije postavljene dijagnoze koje su navedene u medicinskoj dokumentaciji, antropometrijski prametri u momentu pregleda (telesna dužina, telesna masa i obim glave), neurolo&scaron;ki nalaz (tonus, trofika, kožni i tetivni refleksi, prisustvo lateralizacije u neurolo&scaron;kom nalazu), nalaz oftalmologa (uredan nalaz/patalo&scaron;ki nalaz), procena fine i grube motorike, govora, kognitivne funkcije i socijalnog kontakta i zbirna procena psihomotornog razvoja.<br />Rezultati: Prosečna vednost TM ispitanika iz Grupe 1, u uzrastu od 12 meseci, bila je statistički značajno manja u odnosu na ispitanike iz Grupe 2 (Studentov t test). Prosečne vednosti TD ispitanika iz obe grupe, u uzrastu od 12 meseci, nisu se statistički značajno razlikovale (Studentov t test). Prosečne vednosti OGL ispitanika iz obe grupe, u uzrastu od 12 meseci, nisu se statistički značajno razlikovale (Studentov t test). Udeo ispitanika sa patolo&scaron;kim oftalmolo&scaron;kim nalazom nije se statistički značajno razlikovao između Grupe 1 i Grupe 2 (Fi&scaron;erov test tačne verovatnoće). Udeo ispitanika sa patolo&scaron;kim neurolo&scaron;kim nalazom nije se statistički značajno razlikovao između Grupe 1 i Grupe 2 (Hi kvadrat test). Prosečne vrednosti globalnog koeficijenta razvoja (RQ), kao i prosečne vrednosti skora za pojedine elemente za procenu razvoja (motorika, koordinacija, govor i dru&scaron;tvenost) po Brunet -L&eacute;zine skali, nisu se statistički značajno razlikovale između grupa (Studentov t test). U Grupi 1 bilo je 92 (59,740%) deteta čiji je nekorigovani RQ bio ispod 90, dok je u Grupi 2 bilo 61 (39,610%) dete čiji je nekorigovani RQ bio ispod 90. Ova razlika u broju dece sa RQ koji je ispod proseka za kalendarski uzrast je statistički značajna (Hi kvadrat test, p=0,0004). Relativni rizik za ispodprosečno postignuće na testu za procenu psihomotornog razvoja (RQ&lt;90), za decu iz Grupe 1 bio je vi&scaron;i, u odnosu na decu iz Grupe 2 (RR = 1,495; 95% CI 1,181 &ndash; 1,892). U Grupi 1, bilo je 87 (56,494%) dece koja su postigla ispodprosečne korigovane vrednosti skora na testu za procenu psihomotornog razvoja (korigovani RQ&lt;90). U Grupi 2 bilo je 69 (44,805%) dece koja su postigla ispodprosečne korigovane vrednosti skora na testu za procenu psihomotornog razvoja (korigovani RQ&lt;90). Ova razlika je statistički značajna (Hi kvadrat test, p =0,040). Relativni rizik za ispodprosečno postignuće na testu za procenu psihomotornog razvoja (korigovani RQ&lt;90), za decu iz Grupe 1 bio je vi&scaron;i, u odnosu na decu iz Grupe 2 (RR = 1,261; 95%CI 1,008 &ndash; 1,577). U kategoriji dece, koja su i pored korekcije u odnosu na GS imala ispodprosečno postignuće na testu za procenu psihomotornog razvoja, u Grupi 1 čak 81/87 (93,310%) dece je imalo vrednost korigovanog RQ &ge; 85, a u Grupi 2 ovu vrednost korigovanog RQ imalo je 60/69 (86,956%) dece.<br />Prosečne vednosti TM ispitanika iz obe grupe, u uzrastu od 18 meseci, nisu se statistički značajno razlikovale (Studentov t test). Prosečne vednosti TD ispitanika iz obe grupe, u uzrastu od 18 meseci, nisu se statistički načajno razlikovale (Studentov t test). Prosečne vednosti OGL ispitanika iz obe grupe, u uzrastu od 18 meseci, nisu se statistički značajno razlikovale (Studentov t test). Udeo ispitanika sa patolo&scaron;kim oftalmolo&scaron;kim nalazom nije se statistički značajno razlikovao između Grupe 1 i Grupe 2 (Hi kvadrat test). Udeo ispitanika sa patolo&scaron;kim neurolo&scaron;kim nalazom nije se statistički značajno razlikovao između Grupe 1 i Grupe 2 (Hi kvadrat test). Prosečne vrednosti RQ, kao i prosečne vrednosti skora za pojedine elemente za procenu razvoja (motorika, koordinacija, govor i dru&scaron;tvenost) po Brunet -L&eacute;zine skali su se statistički značajno razlikovale između grupa u uzrastu od 18 meseci (Studentov t test). U Grupi 1 bilo je 57 (37,013%) dece čiji je nekorigovani RQ bio ispod 90, dok je u Grupi 2 bilo 31 (20,130%) dete čiji je nekorigovani RQ bio ispod 90. Udeo dece sa RQ koji je ispod proseka za kalendarski uzrast je statistički značajno različit između grupa (Hi kvadrat test, p = 0,010). Relativni rizik za ispodprosečno postignuće na testu za procenu psihomotornog razvoja (nekorigovani RQ&lt;90), za decu iz Grupe 1 bio je vi&scaron;i, u odnosu na decu iz Grupe 2 (RR = 1,288; 95%CI 1,181 &ndash; 2,730). Statistički značajna razlika postojala je i kada je upoređen broj dece sa vrednostima korigovanog RQ ispod 90 u Grupi 1 i Grupi 2 (36 naspram 19 po redosledu navođenja; Hi kvardat test, p = 0,011). Relativni rizik za ispodprosečno postignuće na testu za procenu psihomotornog razvoja (korigovani RQ&lt;90), za decu iz Grupe 1 bio je vi&scaron;i, u odnosu na decu iz Grupe 2 (RR = 1,895; 95%CI 1,139 &ndash; 3,152).<br />Prosečne vednosti TM ispitanika iz obe grupe, u uzrastu od 24 meseca, nisu se statistički značajno razlikovale (Studentov t test). Prosečne vednosti TD ispitanika iz obe grupe, u uzrastu od 24 meseca, nisu se statistički značajno razlikovale (Studentov t test). Prosečne vednosti OGL ispitanika iz obe grupe, u uzrastu od 24 meseca, nisu se statistički značajno razlikovale (Studentov t test). Udeo ispitanika sa patolo&scaron;kim oftalmolo&scaron;kim nalazom nije se statistički značajno razlikovao između Grupe 1 i Grupe 2 (Hi kvadrat test). Udeo ispitanika sa patolo&scaron;kim neurolo&scaron;kim nalazom nije se statistički značajno razlikovao između Grupe 1 i Grupe 2 (Hi kvadrat test). Prosečne vrednosti RQ, kao i prosečne vrednosti skora za pojedine elemente za procenu razvoja (motorika, koordinacija, govor i dru&scaron;tvenost) po Brunet -L&eacute;zine skali, nisu se statistički značajno razlikovale između grupa, u uzrastu od 24 meseca (Studentov t test). U Grupi 1 bilo je 21 dete (13,636%) čiji je nekorigovani RQ bio ispod 90, dok je u Grupi 2 bilo 17 (11,049%) dece čiji je nekorigovani RQ bio ispod 90. Razlika u broju dece sa RQ koji je ispod proseka za kalendarski uzrast nije statistički značajna (Hi kvadrat test, p= 0,488). Statistički značajna razlika nije postojala ni kada je upoređen broj dece sa vrednostima korigovanog RQ ispod 90 u Grupi 1 i Grupi 2 (12 naspram 9 po redosledu navođenja; Hi kvardat test, p = 0,497).<br />Logističkom regresionom analizom pokazano je da su ve&scaron;tačko začeće, vi&scaron;eplodnost trudnoće i IUGR nezavisni faktori rizika za manju TM u kalendarskom uzrastu od 12 meseci. Logističkom regresionom analizom dobijena je statistički značajna korelacija između vrednosti RQ u uzrastu od 18 meseci i sledećih nezavisnih varijabli: arteficijalno začeta trudnoća i vi&scaron;eplodna trudnoća. Isptanici iz Grupe 1 i Grupe 2 nisu se statistički značajno razlikovali ni po jednom od posmatranih pokazatelja telesnog i psihomotornog razvoja u uzrastu od 24 meseca.<br />Struktura morbiditeta kod dece, tokom dvogodi&scaron;njeg perioda praćenja, nije se značajno razlikovala između grupa. Jedina razlika između grupa, konstatovana je u uzrastu od 12 i 18 meseci, bila je u učestalosti akutnih respiratornih infekcija, čija je pojava, pak, bila direktno povezana sa vi&scaron;eplodnim trudnoćama, odnosno brojem siblinga u domaćinstvu.<br />Zaključak: Prosečna starost majki dece koja su začeta IVF-om je veća od prosečne starosti majki dece koja su spontano začeta. Struktura morbiditeta majki dece koja su začeta IVF-om i majki dece koja su začeta spontanom koncepcijom je ista, ali je stopa morbiditeta veća kod majki dece koja su začeta IVF-om. Vi&scaron;eplodne trudnoće su veoma zastupljene kod začeća IVF-om. Trudnoće začete IVF-om se dominantno i skoro ekskluzivno okončavaju carskim rezom. Prevremena ruptura ovojaka ploda je česta komplikacija trudnoća koje su začete IVF-om. Stopa morbiditeta prevremeno rođene dece začete vantelesnom oplodnjom nije veća u odnosu na prevremeno rođenu decu začetu prirodnim putem. U strukturi morbiditeta kod dece koja su začeta vantelesnom opodnjom, zastupljena su ista oboljenja i komplikacije kao kod prevremeno rođene dece začete prirodnim putem. Incidencija pojedinih oboljenja je ista, sa izuzetkom bronhopulmonalne displazije koja se javlja če&scaron;če kod dece začete vantelesnom oplodnjom i retinopatije prematuriteta koja se javlja če&scaron;če kod dece začete prirodnim putem. Porođajna telesna masa, intrauterina restrikcija rasta, starost majke, stručna sprema majke, prethodna hronična oboljenja majke, bolesti majke dijagnostikovane tokom trudnoće, jednoplodna i vi&scaron;eplodna trudnoća, način porođaja i PROM su potencijalni faktori rizika za lo&scaron;iji postnatalni ishod kod dece iz arteficijalno začetih trudnoća. U uzrastu od 12 meseci, prevremeno rođena deca začeta tehnikama in vitro fetrilizacije, sem po dostignutoj telesnoj masi, ne razlikuju se značajno po drugim telesnim karakteristikama, od prevremeno rođene dece koja su začeta prirodnim putem. Faktori rizika za manju telesnu masu kod prevremeno rođene dece, u uzrastu od 12 meseci su: arteficijalno začeće, vi&scaron;eplodne trudnoće i intrauterina restrikcija rasta. U uzrastu od 12 meseci, prevremeno rođena deca začeta in vitro fertilizacijom, imaju blago lo&scaron;ije (ali ne i značajno niže) postignuće na testovima za procenu psihomotornog razvoja, odnosno imaju vi&scaron;i rizik da postignu ispodprosečne vrednosti skora na testu za procenu psihomotornog razvoja. U uzrastu od 18 meseci, nema razlike u pokazateljima telesnog razvoja između prevremeno rođene dece koja su arteficijalno začeta i dece koja su rođena iz spontano začetih trudnoća. U uzrastu od 18 meseci, prevremeno rođena deca iz arteficijalno začetih trudnoća imaju niže postignuće na testovima za procenu psihomotornog razvoja u odnosu na prevremeno rođenu decu iz spontano začetih trudnoća. Faktori rizika koji su povezani sa lo&scaron;ijim postignućem na testu za procenu psihomotornog razvoja kod prevremeno rođene dece su arteficijalno začeće trudnoće i vi&scaron;eplodnost trudnoće. U uzrastu od 24 meseca nema razlike u telesnim parametrima između prevremeno rođene dece koja su arteficijalno začeta i prevremeno rođene dece koja su začeta prirodnim putem. U uzrastu od 24 meseca nema razlike u postignuću na testu za procenu psihomotornog razvoja kod prevremeno rođene dece su arteficijalno začeće trudnoće i vi&scaron;eplodnost trudnoće. U uzrastu od 24 meseca, prevremeno rođena deca, i iz arteficijalno, i iz spontano začetih trudnoća, na testu za procenu psihomotornog razvoja postižu rezultate koji su u skladu sa njihovim kalendarskim uzrastom.</p> / <p>Introduction: Infertility is defined as an unsuccessful conception after one year of sexual intercourse without the use of contraception in the fertilizing phase of the menstrual cycle. Assisted reproduction methods represent an effective way of treating infertility. Examination and identification of short-term and long-term effects of artificial reproductive technologies is a very challenging task. The primary reason for this is the great heterogeneity in the way of collecting, processing, classifying and interpreting, now, the abundance of information that has been gathered in various studies. Individual approach to the treatment of infertility, rapid progress and constant changes in the methodology of the artificial reproductive technologies, in addition to the aforementioned difficulties associated with the collection and analysis of data, significantly hamper accurate assessment of all possible risks and consequences artificial conception. Despite numerous studies, scientific publications and the accumulated evidence, many doubts about the question whether artificially conceived pregnancies are accompanied by the higher risks or inadequate fetal development, poor perinatal and long-term outcomes still remained.<br />The Aim: The objectives of this work were to determine the structure of morbidity in prematurely born children conceived by artificial reproductive technologies (from single and multiple pregnancies) in the first two years of life, and to identify perinatal factors that are associated with the occurrence of acute and chronic complications and diseases in prematurely born children from this pregnancies. In addition, the aim of the study was to determine the characteristics of psychomotor development in prematurely born children conceived by artificial reproductive technologies at the end of the twelfth, eighteenth and twenty-fourth month of life, as well as to identify specific risk factors for the unfavorable physical, neurological and psychological outcome of those children.<br />Materials and Methods: The study included premature born newborns who were hospitalized in the Department for neonatology and intensive and semi-intensive care unit, and are thereafter, during the first two years of life. The retrospective part of the study included children who were hospitalized at the Institute, and who were born from January 1st 2011. to December 31st 2012. and were followed up to 2 years of life. Data on patients included in the retrospective part of the survey were collected through a review of medical records. The prospective part of the study included children who were treated and followed up at the Institute, and who were born between January 1st 2013 and December 31st 2014. and then followed up to 2 years of life. From this cohort two groups were formed: The tested group (Group 1) included all preterm infants who were conceived by ART. The control group (Group 2) included naturally conceived prematurely born children. The children in the control group were selected from the cohort so that their number was equal to the number of children in the study group. The gestational age of the examinees from the control group does not differ for more than &plusmn; 4 days from the children from the study group. The date of birth of subjects included in the control group does not differ for more than &plusmn; 3 months from the children in the study group.<br />At the moment of inclusion in the study, the following individual data were taken:<br />Maternal data, pregnancy and childbirth: the age of the mother at the moment of conception, the number of previous attempts at assisted conception, professional care, place of residence, chronic diseases diagnosed before pregnancy, acute and chronic diseases diagnosed during pregnancy (hypertension, pre-eclampsia, eclampsia, liver damage), premature rupture of the fetuses, the use of medication during pregnancy, single or multiple pregnancy. Data on placental disorders and abnormalities: ablation, placenta overdose, horioamnionitis. Child-related data: intrauterine infection, intrauterine growth restriction, delivery method, Apgar score. Anthropometric parameters (body weight, body length, head circumference) at birth and during the period of outpatient monitoring of the child. Length of initial hospitalization of the child. Length of invasive and / or non-invasive respiratory support and oxygen therapy. Diagnosis on discharge from the hospital: the presence of severe consequences of prematurity, which implies intracranial hemorrhage of 3rd and 4th degree (defined in International Classification of Disease - Tenth Revision (MKB10) under code P52.2), cystic periventricular leukomalacia, retinopathy of prematurity, bronchopulmonary dysplasia , necrotizing enterocolitis, sepsis and / or meningitis (microbiologically or clinically diagnosed). Presence of congenital anomalies or genetic syndromes and diseases (defined in MKB10 under codes Q00 to Q99), as well as the presence of congenital metabolic diseases (defined in MKB10 under codes E00 to E90).<br />In the retrospective part of the study, specialist reports from a neonatological clinic were examined for child visits at the age of 12, 18 and 24 months, and the following data were ecorded: all pre-diagnosis reported on specialist reports from a neonatological clinic, anthropometric arms at the moment examination (body length, body weight and head circumference), neurological findings (tone, trophic, skin and tendon reflexes, presence of lateralization in neurological findings), ophthalmologist findings (neat / patial findings), assessment of fine and coarse motoring, speech, cognitive functions and social contact and a collective assessment of psychomotor development. In the prospective part of the study, during control examinations in a neonatological clinic, at the age of 12, 18 and 24 months, the following were determined and recorded: previously set out in the current medical documentation, anthropometric parameters at the moment of examination (body length, body weight and the volume of the head), neurological findings (tone, trophic, skin and tendon reflexes, presence of lateralization in neurological findings), ophthalmologist findings, assessment of fine and grose motor functions, speech, cognitive functions, social contact and psychomotor development.<br />Results: The average BW of subjects in Group 1 at the age of 12 months, was statistically significantly lower in relation to respondents from Group 2 (Student&#39;s T test). The average length of subjects from both groups at the age of 12 months did not statistically differ (Student&#39;s T test). The average head circumference between children from both groups, at the age of 12 months, did not statistically differ (Student&#39;s T test). The proportion of subjects with pathological ophthalmological findings did not statistically significantly differ between Group 1 and Group 2 (Fischer&#39;s exact probability test). The proportion of subjects with pathological neurological findings did not statistically significantly differ between Group 1 and Group 2 (Hi square test). The average values of the global development coefficient (RQ), as well as the average score values for individual elements of development evaluation test - Brunet-L&eacute;zine scale (motor function, coordination, speech and sociability) did not differ significantly between groups (Student t test). In Group 1 there were 92 (59.740%) of children whose uncorrected RQ was under 90, while in Group 2 there were 61 (39.610%) children whose uncorrected RQ was below 90. This difference in the number of children with RQ below the average for calendar age is statistically significant (Hi square test, p = 0.0004). The relative risk of under-achievement in the psychomotor evaluation test (RQ &lt;90) for children from Group 1 was higher than in children from Group 2 (RR = 1.495; 95% CI 1.181 - 1.922). In Group 1, there were 87 (56.494%) children who achieved sub-optimal corrected score values for the assessment of psychomotor development (corrected RQ &lt;90). In Group 2, there were 69 (44.805%) children who achieved sub-optimal corrected score values for the assessment of psychomotor development (corrected RQ &lt;90). This difference is statistically significant (Hi square test, p = 0.040). The relative risk for the suboptimal achievement in the psychomotor evaluation test (corrected RQ &lt;90) for children from Group 1 was higher than in Group 2 (RR = 1.261; 95% CI 1.008 - 1.577). In Group 1, as many as 81/87 (93.310%) of children had a corrected RQ value of &ge; 85, while in Group 2 this value of the corrected RQ there were 60/69 (86.956%) children.<br />At the age of 18 months, the average BW of subjects from both groups did not differ significantly (Student&#39;s T test). The average length of subjects from both groups, at the age of 18 months, did not statistically differ (Student&#39;s T test). The average head circumference of children from both groups, at the age of 18 months, did not statistically differ (Student&#39;s T test). The proportion of subjects with pathological ophthalmological findings did not statistically significantly differ between Group 1 and Group 2 (Hi square test). The proportion of subjects with pathological neurological findings did not statistically differ between Group 1 and Group 2 (Hi square test). The average RQ values, as well as the average scores for individual elements of psychomotor development (motor function, coordination, speech and sociability) according to the Brunet-L&eacute;zine scale, have been statistically significantly different between groups, at the age of 18 months (Student&#39;s T test). In Group 1 there were 57 (37.013%) children whose uncorrected RQ was below 90, while in Group 2 there were 31 (20,130%) children whose uncorrected RQ was below 90. The share of children with RQ below the average value for the calendar age is statistically significantly different between groups (Hi square test, p = 0.010). The relative risk for the suboptimal achievement in the Psychomotor Development Assessment (uncorrected RQ &lt;90) for Group 1 children was higher than in Group 2 (RR = 1.288; 95% CI 1.181 - 2.730). A statistically significant difference between Group 1 and Group 2 existed when the number of children with corrected RQ below 90 was compared (36 naspram 19 respectively, Hi quadrate test, p = 0.011). The relative risk for the suboptimal achievement on the Psychomotor Evaluation Test (corrected RQ &lt;90) for the children from Group 1 was higher when compared to children in Group 2 (RR = 1.895; 95% CI 1.139 &ndash; 3.152).<br />At the age of 24 months the average BW, body length and head circumference of subjects in both groups were not significantly different (Student&#39;s T test). The proportion of subjects with pathological ophthalmological findings did not statistically significantly differ between Group 1 and Group 2 (Hi square test). The proportion of subjects with pathological neurological findings did not statistically significantly differ between Group 1 and Group 2 (Hi square test). The average RQ values, as well as the average score values for individual elements for development evaluation (motor function, coordination, speech and sociability) according Brunet-L&eacute;zine scale, did not significantly differ between groups at the age of 24 months (Student&#39;s T test). In Group 1, there were 21 children (13.636%) whose uncorrected RQ was under 90, while in Group 2 there were 17 (11.049%) of children whose uncorrected RQ was below 90. The difference in the number of children with RQ below the average for the calendar age was not statistically significant (Hi square test, p = 0.488). A statistically significant difference did not exist even when the number of children with values of the corrected RQ below 90 in Group 1 and Group 2 (12 naspram 9 respectively, Hi quadrate test, p = 0.497) was compared.<br />Logistic regression analysis has shown that artificial conception, multiple pregnancy and IUGR are independent risk factors for lesser BW in a calendar age of 12 months. By logistic regression analysis, a statistically significant correlation between RQ values at 18 months of age and the following independent variables was obtained: artificially started pregnancy and multiple pregnancy. Group 1 and Group 2 patients did not significantly differ by any of the indicators of physical and psychomotor development at the age of 24 months.<br />The structure of morbidity in children, during the two-year follow-up period, did not differ significantly between groups. The only difference between the groups was found in the rates of acute respiratory infections at the age of 12 and 18 months (rate of infections was higher in Group 1), whose occurrence, however, was directly related to multiple pregnancies, or the number of sibling in the household.<br />Conclusion: The average age of mothers of children conceived by the IVF is higher than the average age of mothers of children who were conceived spontaneously. The structure of the morbidity of mothers of children who were artificially conceived and mothers of children born after spontaneous conception is the same, but the morbidity rate is higher in the mothers of children who were conceived by IVF. Pregnancies concieved by IVF almost exclusively ended by cesarean section. Premature rupture of the membranes is a common complication of IVF pregnancies. The rate of morbidity of prematurely born children conceived by ART is not higher than that of prematurely born children conceived naturally. The structure of morbidity in children from ART pregnancies was the same as in naturally conceived prematurely born children. The incidence of specific illnesses is the same, with the exception of bronchopulmonary dysplasia that occurs more frequently in children born from ART pregnancies, and retinopathy of prematurity that occurs more frequently in spontaneously conceived children. Maternal birth weight, intrauterine growth restriction, mother&#39;s age, maternal care, previous mother&#39;s chronic illness, mother&#39;s disease diagnosed during pregnancy, single and multiple pregnancies and PROM are potential risk factors for worse postnatal outcome in children from artificially initiated pregnancies. Risk factors for lower body weight in premature babies, at the age of 12 months, are: artificial conception, multiple pregnancy and intrauterine growth restriction. At the age of 12 months, prematurely born children from IVF pregnancies, have slightly worse (but not significantly lower) psychomotor achievements. At the age of 18 months, there is no difference in the indicators of physical development between prematurely born children who are artificially conceived and children born from spontaneous pregnancies. At the age of 18 months, prematurely born children from ART pregnancies have lower achievement on tests for assessing psychomotor development compared to prematurely born children from spontaneously initiated pregnancies. Risk factors associated with a poor performance on the psychomotor development assessment tests, in preterm infants, are an artificial conception of pregnancy and a multi fertile pregnancy. At the age of 24 months, there is no difference in the physical parameters between prematurely born children from ART and naturally conceived pregnancies. At the age of 24 months, there is no difference in the achievement on the test for the assessment of psychomotor development between children from ART and spontaneous pregnancies. At the age of 24 months, on the psychomotor development assessment, prematurely born children achieve the results consistent with their calendar age.</p>

Identiferoai:union.ndltd.org:uns.ac.rs/oai:CRISUNS:(BISIS)106200
Date01 March 2018
CreatorsPavlović Vesna
ContributorsKonstantinidis Georgios, Ristivojević Anđelka, Velisavljev-Filipović Gordana, Stojadinović Aleksandra, Bjelica Artur, Radunović Nebojša
PublisherUniverzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, University of Novi Sad, Faculty of Medicine at Novi Sad
Source SetsUniversity of Novi Sad
LanguageSerbian
Detected LanguageUnknown
TypePhD thesis

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