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Im Rahmen der Versorgungsforschung sollte die Ergebnisqualität der Betreuung schwangerer Typ-1- und Typ-2-Diabetikerinnen (PMDM) anhand des neonatalen Er-gebnisses und der Stoffwechselparameter geprüft und festgestellt werden, ob die Diag-nostik- und Therapieempfehlungen der Leitlinien realisiert wurden und welchen Einfluss die veränderten Betreuungsstrukturen im Gesundheitssystem nach 1990 darauf hatten. Dazu wurden die relevanten Daten zu Schwangerschaftsverlauf (einschließlich des ophthalmologischen Befundes) und Zustand der Neugeborenen (NG) von 104 Müt-tern erhoben und ausgewertet, die zu Beginn des strukturellen Wandels 1990-92 (n=56) und danach 2007-10 (n=48) im Zentrum betreut wurden. Der somatische Zustand der NG wurde nach der Gewichtsperzentile und der Perzentile des Gewichts-Längen-Index beurteilt. Die Einschätzung der Stoffwechselqualität erfolgte auf Basis der computerge-stützt (CAMIT) erfassten Blutglukosewerte des Selbstkontrollmonitoring und der HbA1c-Werte. Die Ergebnisse wurden an den Vorgaben der Leitlinien und der Hypertrophierate der Neugeborenen gemessen und untereinander verglichen. Die Stoffwechselparameter hypertropher (n=29) und eutropher (n=68) NG wurden verglichen und der Einfluss einer Mikroangiopathie bei Müttern mit (n= 20) und ohne (n= 56) Retinopathia diabetica untersucht. Bei zunehmend dezentralisierter Betreuung sank der Anteil im Zentrum entbundener Mütter von 88% auf 42% (2007-10) bei gleichzeitig signifikant späterem Betreuungsbe-ginn im Zentrum. Die signifikant älteren (30,8 vs. 25,9 Jahre) Mütter mit höherem Ge-wicht zu Schwangerschaftsbeginn (79,1 vs. 64,3kg) wurden von signifikant schwereren Kindern entbunden (MW 3642g vs. 3172g). Die Hypertrophierate >97.Perzentile des gestationsaltersbezogenen Geburtsgewichtes (29,2% vs. 12,3%) und >95.Perz. des Gewichts-Längen-Index (41,7% vs. 17,8%) stieg signifikant bei ebenfalls signifikant hö-heren HbA1c-Werten und Mittleren Blutglukosewerten im Schwangerschaftsverlauf in den Jahren 2007-10 im Vergleich zu 1990-92. Signifikante Unterschiede dieser Stoff-wechselparameter finden sich auch zwischen hypertrophen (n=29) und eutrophen NG (n=68) bei fehlenden signifikanten Unterschieden von Alter und Gewicht der Mütter. Mütter mit (n=20) und ohne (n=56) Retinopathie unterscheiden sich jedoch nur durch signifikant höhere HbA1c-Werte zu Schwangerschaftsbeginn. Bei 2007-10 signifikant weniger ophthalmologisch untersuchter Mütter. Die Strukturveränderungen wirkten sich auf die Arbeit des Zentrums aus. Der Anstieg der Hypertrophierate bei zunehmender Diskrepanz der Stoffwechselführung zwischen Leitlinienempfehlung und Praxis weist auf die notwendige Optimierung der interdisziplinären Zusammenarbeit in enger Kooperation zwischen Zentrum und nieder-gelassenen Diabetologen hin.

Pregnancies complicated with diabetes mellitus (DM) are associated with poor maternal and fetal outcomes, such as birth trauma, fetal overgrowth (macrosomia) and programming of the fetus to develop metabolic syndrome in adult life. Maternal hyperglycemia is thought to contribute to fetal macrosomia, however the role of the placenta in these pregnancies is incompletely understood, therefore we aimed to investigate the specific consequences of high glucose on placental metabolism. To achieve this aim an in vitro model of placental exposure to high glucose was developed. This model was used with the aim of analysing how high glucose alters the transcriptome and metabolome of these cells, using a systems biology approach to identify candidate functional pathways which may be altered in placenta as a result of hyperglycemia. These candidate functional pathways were validated in an ex vivo model of placenta exposed to high glucose and in placental tissue from pregnancies complicated by DM. A trophoblast cell line (BeWo) was cultured in low (5 mM) and high (12 mM or 25 mM) D-glucose conditions for 48 hours. Transcriptomic and metabolomic analysis of these cells was performed using microarrays, and gas- and liquid-chromatography-mass spectrometry, respectively. Transcript and metabolite changes were independently analysed and integrated, using network analysis. From the integrated analysis of the ‘omic datasets, β-fatty acid oxidation (β-FAO), purine metabolism, phosphatidylinositol/PI3K phosphate pathway and lipid metabolism, were identified as candidates for further study. Changes within the PI3K pathway and lipid metabolism/β-fatty acid oxidation were validated in an ex vivo placental explant model of high glucose and in placental tissue from women with DM, compared to uncomplicated pregnancies. mRNA, protein expression and protein activation of key molecules within the PI3K pathway were not significantly altered in placenta as a response of high glucose ex vivo or DM in vivo. The second candidate functional pathway, lipid metabolism, has previously been implicated in association with placental dysfunction in pregnancies complicated by DM. Placental fatty acid transporter and lipase protein expression, as well as, relative abundance of different fatty acids were unaltered in response to high glucose or DM. High glucose levels increased triglyceride levels within the placenta, indicating reduced rates of β-FAO. The effect of high glucose could be ameliorated using a PPARα agonist. This may provide a novel therapeutic intervention to prevent excess esterification of fatty acids to triglycerides in maternal diabetes, which may in turn influence fetal growth. This study illustrates how a systems biology approach can be used to identify novel candidate functional pathways that are altered within the trophoblast in response to high glucose. Thus, improving understanding of placental dysfunction in these pregnancies and providing novel candidate pathways for future study, which may represent potential therapeutic targets for intervention of fetal macrosomia in pregnancies complicated by DM.

Abstract The aim of this study was to evaluate the treatment, course and outcome of pregnancy in Finland using two cohorts of diabetic women. The clinical cohort consisted of data from all 210 women with Type 1 diabetes and their 296 pregnancies managed between 1986 and 1995 in the two northernmost provinces of Finland. The register-based study population included all 1442 mothers with a singleton birth who had insulin treatment during pregnancy in 1991-1995 according to the Medical Birth Register. Of these mothers, 954 (66%) had pre-existing diabetes. Insulin-treated diabetes complicated 4.5/1000 births in Finland in 1991-1995, the prevalence of Type 1 diabetes being 2.9/1000 in the whole country and 3.3/1000 in Northern Finland. In the 1990's the care of these women shifted from tertiary level only to include the secondary level hospitals as well, and was more often carried out on an out-patient basis. This care policy in association with the self-monitoring of blood glucose levels contributed to an obvious improvement in glycaemic control during pregnancy. Despite that, the high proportion (73%) of women entering pregnancy with unsatisfactory glycaemic control did not decrease during the study period. Retinopathy complicated 134 (45.3%) diabetic pregnancies, while clinical nephropathy was found in 23 (7.8%) cases. Although retinopathy was more often aggravated during the first pregnancy, the occurrence of retinopathy or its severe form was not increased at the beginning of consecutive pregnancies. Of the mothers, 50 (16.9%) had pre-eclampsia during pregnancy, and in 28% of these cases it was classified as superimposed. It was found more often among primiparous than multiparous (25.6% vs. 11.0%, respectively), and its occurrence rose with the severity of diabetes. In both cohorts, the rates of preterm deliveries, Caesarean sections and large for gestational age (LGA) infants were significantly (p < 0.001) higher in Type 1 diabetic pregnancies than in the background population. The rates of congenital anomalies (CA) were 540-629/10000 in two study populations, both being 2-3-fold as compared to the background population. Cardiac malformations were most common, with anomalies in the genitourinary tract and the musculoskeletal organs being next in frequency. Sixty-three percent of malformed infants were boys. Though pregnancy itself was not found to worsen the prognosis of diabetes, at least in the short term, pregnancy in diabetic women still remains a high risk state with an increased rate of prematurity, operative deliveries, CAs and peri- and neonatal mortality. In order to decrease the mortality rate in diabetic births, attention should be directed at both the prevention of CA and at identifying the foetuses at risk for intrauterine death. The postneonatal mortality rate is also high, reflecting a shift in the deaths from the early neonatal period to a later age. Therefore, a combined mortality, including induced abortions, stillborns and infant deaths, would give a more realistic idea of the outcomes in diabetic pregnancies.

Im Rahmen der Versorgungsforschung sollte die Ergebnisqualität der Betreuung schwangerer Typ-1- und Typ-2-Diabetikerinnen (PMDM) anhand des neonatalen Er-gebnisses und der Stoffwechselparameter geprüft und festgestellt werden, ob die Diag-nostik- und Therapieempfehlungen der Leitlinien realisiert wurden und welchen Einfluss die veränderten Betreuungsstrukturen im Gesundheitssystem nach 1990 darauf hatten. Dazu wurden die relevanten Daten zu Schwangerschaftsverlauf (einschließlich des ophthalmologischen Befundes) und Zustand der Neugeborenen (NG) von 104 Müt-tern erhoben und ausgewertet, die zu Beginn des strukturellen Wandels 1990-92 (n=56) und danach 2007-10 (n=48) im Zentrum betreut wurden. Der somatische Zustand der NG wurde nach der Gewichtsperzentile und der Perzentile des Gewichts-Längen-Index beurteilt. Die Einschätzung der Stoffwechselqualität erfolgte auf Basis der computerge-stützt (CAMIT) erfassten Blutglukosewerte des Selbstkontrollmonitoring und der HbA1c-Werte. Die Ergebnisse wurden an den Vorgaben der Leitlinien und der Hypertrophierate der Neugeborenen gemessen und untereinander verglichen. Die Stoffwechselparameter hypertropher (n=29) und eutropher (n=68) NG wurden verglichen und der Einfluss einer Mikroangiopathie bei Müttern mit (n= 20) und ohne (n= 56) Retinopathia diabetica untersucht. Bei zunehmend dezentralisierter Betreuung sank der Anteil im Zentrum entbundener Mütter von 88% auf 42% (2007-10) bei gleichzeitig signifikant späterem Betreuungsbe-ginn im Zentrum. Die signifikant älteren (30,8 vs. 25,9 Jahre) Mütter mit höherem Ge-wicht zu Schwangerschaftsbeginn (79,1 vs. 64,3kg) wurden von signifikant schwereren Kindern entbunden (MW 3642g vs. 3172g). Die Hypertrophierate >97.Perzentile des gestationsaltersbezogenen Geburtsgewichtes (29,2% vs. 12,3%) und >95.Perz. des Gewichts-Längen-Index (41,7% vs. 17,8%) stieg signifikant bei ebenfalls signifikant hö-heren HbA1c-Werten und Mittleren Blutglukosewerten im Schwangerschaftsverlauf in den Jahren 2007-10 im Vergleich zu 1990-92. Signifikante Unterschiede dieser Stoff-wechselparameter finden sich auch zwischen hypertrophen (n=29) und eutrophen NG (n=68) bei fehlenden signifikanten Unterschieden von Alter und Gewicht der Mütter. Mütter mit (n=20) und ohne (n=56) Retinopathie unterscheiden sich jedoch nur durch signifikant höhere HbA1c-Werte zu Schwangerschaftsbeginn. Bei 2007-10 signifikant weniger ophthalmologisch untersuchter Mütter. Die Strukturveränderungen wirkten sich auf die Arbeit des Zentrums aus. Der Anstieg der Hypertrophierate bei zunehmender Diskrepanz der Stoffwechselführung zwischen Leitlinienempfehlung und Praxis weist auf die notwendige Optimierung der interdisziplinären Zusammenarbeit in enger Kooperation zwischen Zentrum und nieder-gelassenen Diabetologen hin.

Introduction: Diploma thesis deals with issues of gestational a pregestational diabetes and the influence od diabetic diet during pregnancy on eating habits. Goals: The theoretical part is focused on general summary of diabetes during pregnancy - its characteristic, epidemiology, risk factors, complications, treatment including glycemic self- monitoring, observation during and after the childbirth. The last part is focused on education, as the important part of the therapy. The emphasis is put on the practical part, which analyse eating habits including measures regime of women dealing with gestational a pregestational diabetes, before and after the pregnancy. Crucial task was the comparison of choice of the food, frequency of monitored food and the regularity of eating. Methods: Research took place through the anomyous questionnaires, obtained on Gynecological-obstetrical clinic of General hospital in Prague. Questionnaires were filled out by woman diagnosed gestational and pregestational diabetes type 1. The discovered data are given into graphs and charts and part of the thesis is dedicated to the analysis of the data. Outcome: According to researched data we can say, that the eating habits before the pregnancy are not sufficient in any of the groups. Due to pregnancy and resulting diatetic...

<p>Uprkos op&scaron;te prihvaćenom stavu da u trudnoći lekove treba izbegavati, veliki broj trudnica tokom trudnoće uzima lekove sa manje ili vi&scaron;e opravdanja. Primena lekova u trudnoći zahteva dodatnu patnju, jer se mora voditi računa o zdravlju majke i zdravlju jo&scaron; nerođenog&nbsp; deteta. Većina lekova koji nalaze primenu u trudnoći, nisu ispitani u kontrolisanim studijama na trudnicama, već se njihov uticaj naljudski fetus, bazira na predpostavkama i kliničkim istraživanjima na životinjama. Odsustvo studija dovodi do toga da se trudnicama obično prepisuju lekovi u dozi za odrasle osobe, koje ne prate fiziolo&scaron;ke promene u trudnoći. Tokom trudnoće u telu trudnica dolazi do promena u funkciji organa i organskih sistema, a zbog nastalih promena menja se i sudbina leka u organizmu. Sistemske bolesti trudnice poput hipertenzije i dijabetesa dovode do hemodinamskih promena i utiču na nastanak patolo&scaron;kih promena posteljice, &scaron;to sve zajedno menja farmakokinetiku lekova i njihov transplacentrarni transport. Ukupno 75 trudnica je uključeno u studiju i podeljeno u tri grupe: zdrave trudnice-kontrolna grupa (n=31), trudnice sa hipertenzijom (n=30) i trudnice sa dijabetesom (n=14). Sve trudnice su u premedikaciji primile iste lekove koji su deo standardne kliničke&nbsp; procedure. Trudnice su primile jednu dozu diazepama intramuskularnom injekcijom (10mg/2ml), a intravenski su primile pojedinačne doze cefuroksima (1,5g), metoklopramida (10mg/2ml) i ranitidina (50mg/2ml). Od svakog para majka-dete ukupno je analizirano po 5 uzoraka. Uzorci krvi od majke uzimani su u tri vremenske tačke: nakon davanja leka, u momentu ekstrakcije deteta i nakon porođaja. Uzorci&nbsp; krvi&nbsp; deteta&nbsp; uzimani su&nbsp; nakon&nbsp; porođaja iz pupčane vene i arterije. Prikupljeni uzorci plazme analizirani su metodom tečne hromatografije visokih performansi (HPLC). Istraživanje je pokazalo da lekovi&nbsp; primenjeni u premedikaciji&nbsp; carskog reza prolaze transplacentarnu membranu i da se ni jedan&nbsp; od&nbsp; lekova&nbsp; primenjenih&nbsp; u studiji nije akumulirao u fetusu i nije imao neželjeno dejsvo na novorođenče. Cefuroksim, ranitidin i metoklopramid pokazali su nizak feto-maternalni transfer, dok je diazepam pokazao visok&nbsp; feto-maternalni transfer. Izmerene koncentracije cefuroksima u plazmi trudnica u momentu porođaja bile su &ge;8 &mu;g/ml, &scaron;to je koncentracija veća od MIC za većinu patogena odgovornih za nastavak infekcija u aku&scaron;erstvu. Koncentracije cefuroksima u fetalnoj plazmi bile su &ge;4&mu;g/ml &scaron;to je veće od&nbsp; MIC koncentracija za veliki broj patogena. Gestacijska starost trudnoće nije uticala na obim prolaska cefuroksima&nbsp; kroz placentu, koji je prolazi uglavnom pasivnom difuzijom. Farmakokinetski parametri cefuroksima razlikovali su se kod hipertenzivnih i dijabetičnih trudnica, u odnosu kontrolnu grupu, ali ove bolesti nisu imale značajan uticaj na smanjenje terapijske efikasnosti cefuroksima. Farmakokinetika cefuroksima kod hipertenzivnih&nbsp; trudnica&nbsp; ukazala je na bržu eliminaciju cefuroksima iz krvi majke i na veću distribuciju leka u okolna tkiva. U dijabetičnoj grupi trudnica i novorođenčadi koncentracije cefuroksima su bile vi&scaron;e u odnosu na druge ispitivane grupe, dok je feto-maternalni odnos bio niži, &scaron;to ukazuje na postojanje strukturalne i funkcionalne pomenu posteljice u dijabetesu. Hipertenzija i dijabetes trudnica nisu imali uticaj na prodor ranitidina kroz placentu. Hipertenzija i dijabetes trudnica nisu uticali na većinu farmakokinetskih parametara ranitidina, mada je zabeleženo smanjenje volumena distribucije u ovim grupama trudnica, &scaron;to bi moglo da ukazuje na njihovu hemodinamsku nestabilnost i povećanje slobodne frakcije ranitidina. Koncentracija metoklopramida bila veća u krvi majki u odnosu na krv fetusa. Transport metoklopramida iz fetusa ka majci bio je dominantniji, a naročito u hipertenzivnoj i dijabetičnoj grupi trudnica. Hipertenzija i dijabetes trudnica uticali su na zadržavanje metoklopramida u fetusu. Koncentracije dijazepama u majčinoj i fetalnoj krvi bile su vi&scaron;e u kontrolnoj i hipertenzivnoj grupi trudnica. Hipertenzija i dijabetes trudnica povećavaju&nbsp; transfer diazepama kroz placentu, povećanjem koncentracije slobodnih masnih kiselina, steroidnih hormona, smanjenjem vezivnog kapaciteta potencijalna opasnost od neželjenog dejstva diazepama i njegovih metabolita na fetus i novorođenče. Ova doktorska studija ukazuju na potrebu obimnijih farmakokinetskih istraživanja kako na zdravim tako i na bolesnim trudnicama, koja će dati zaključke utvrđene na dokazima i pomoći u individualnom terapijskom pristupu svakoj trudnici.</p> / <p>In spite of&nbsp; the widespread opinion&nbsp; that&nbsp; drugs should be avoided in pregnancy, a great number of&nbsp; pregnant&nbsp; women&nbsp; take drugs with more or less justification.&nbsp; Administration of drugs in pregnancy requires additional attention because the health of&nbsp; both the mother and&nbsp; her unborn child must be protected. Majority of drugs administered in pregnancy have not been tested&nbsp; within the controlled studies performed on pregnant women, but&nbsp; their effect on the human foetus is based on assumptions and clinical trials performed on animals. This absence of studies results in the situation that pregnant&nbsp; women are usually prescribed drugs in a dose&nbsp; for adults, which does not take into account the physiological changes happening in pregnancy. During pregnancy, the pregnant woman&rsquo;s body undergoes changes in the<br />functions of organs and organ systems. These changes further affect the destiny of a&nbsp; drug in the organism. In pregnant women, systemic diseases such as hypertension&nbsp;&nbsp; and diabetes mellitus lead to hemodynamic changes and cause pathological&nbsp; changes in placenta, thus changing the pharmacokinetics of drugs and their transplacental transport. The study sample consisted of 75 pregnant women, who were divided into three groups as follows: the control group included healthy pregnant&nbsp; women (n=31), a group of pregnant women&nbsp; with&nbsp; hypertension (n=30) and&nbsp; a group of&nbsp; those&nbsp; with&nbsp; diabetes mellitus (n=14). All of them were administered the same drugs as a part of standard clinical procedure in premedication. The pregnant women received a single dose of diazepam by intramuscular injection (10mg/ml), and individual doses of cefuroxime (1.5mg), metoclopramide (10mg/2ml) and ranitidine (50mg/2ml). Five samples taken from each mother-infant pair were analyzed. Blood samples were taken from the mother three times: after drug administration, at the moment of extraction of baby and after delivery. Baby&rsquo;s blood samples were taken from the umbilical cord vein and artery after delivery. Plasma samples were analyzed by the method of high-performance liquid chromatography (HPLC). The research has shown that drugs administered in premedication of caesarean section went through the transplacental membrane and that none of the tested drugs accumulated in the foetus and had an adverse effect on the newborn. Cefuroxime, ranitidine and metoclopramide were shown to have a low transfer between the mother and her foetus, whereas diazepam showed a high foetal-maternal transfer. Cefuroxime concentrations measured in the pregnant woman&rsquo;s and foetal plasma at the moment of delivery were &ge;8&mu;g/ml and &ge;4&mu;g/ml, respectively, that&nbsp; being above the minimum inhibitory concentration (MIC) for most pathogens responsible for the development of infection in obstetrics. Gestational age had no effect on the range of cefuroxime flow through the placenta, which happens mostly by&nbsp; passive diffusion. Pharmacokinetic parameters of cefuroxime differed in the pregnant&nbsp; women having hypertension and diabetes mellitus from the controls; however, these diseases did not significantly reduce the therapeutic efficacy of cefuroxime. Pharmacokinetics of cefuroxime indicated faster elimination of&nbsp; cefuroxime into the maternal blood and greater distribution of the drug into the surrounding tissues in the hypertensive pregnant women. In the group consisting of pregnant women and newborns having diabetes, the cefuroxime concentrations were higher than in other groups, whereas foetal-maternal relation was lower, which suggests the presence of structural and functional change in the placenta in diabetes. Hypertension and diabetes mellitus had no affect either on the flow of ranitidine through the placenta in the pregnant women or on&nbsp; the&nbsp; majority of pharmacokinetic parameters of ranitidine, although a certain reduction in the volume&nbsp; of distribution was recorded in these groups of pregnant women, which could suggest their hemodynamic instability and increased free fractions of ranitidine. The concentration of metocloporamide was higher in the maternal blood than in the&nbsp; foetal blood, and&nbsp; the transport of metocloporamide from the foetus towards the mother was more dominant, particularly in&nbsp; the&nbsp; group of&nbsp; hypertensive and diabetic&nbsp;&nbsp;&nbsp; pregnant women. Metoclopramide tended to retain in the foetuses of mothers having&nbsp; hypertension and diabetes. The concentrations of diazepam in maternal and foetal blood were higher in the controls&nbsp; and hypertensive&nbsp; pregnant&nbsp; women. Hypertension and diabetes in pregnant&nbsp; women increase the transfer of diazepam through the placenta by increasing the concentration of free fatty acids and steroid hormones and by reducing the binding capacity of carrier proteins and the concentration of plasma&nbsp;&nbsp; proteins, thus increasing the potential danger of adverse effects of diazepam and its metabolites on the foetus and the newborn. This doctoral study suggests the necessity for more extensive pharmacokinetic research including both healthy and affected pregnant women that would lead to conclusions based on evidence and help to develop individual therapeutic approach to each pregnant woman.</p>

<p>Uvod: Vi&scaron;eplodne trudnoće se javljaju u 1,5% svih trudnoća nakon spontane koncepcije, dok nakon postupaka vantelesne oplodnje ovaj postotak u Evropi iznosi preko 20% uz velike varijacije među zemljama. U na&scaron;oj sredini, stopa vi&scaron;eplodnih trudnoća nakon postupaka vantelesne oplodnje iznosi daleko iznad 30%. Pojava hipertenzivnog sindroma u trudnoći, gestacijskog dijabetesa, operativnog zavr&scaron;avanja trudnoće, prevremenog porođaja, male porođajne telesne mase, neurolo&scaron;kih sekvela kod rođene dece i gotovo svih drugih komplikacija po majku i plod, kao i celokupno opterećenje zdravstvenog sistema vi&scaron;estruko su veći kod vi&scaron;eplodnih u odnosu na jednoplodne trudnoće i udeo navednih komplikacija raste sa brojem plodova. Sa druge strane deca iz postupaka vantelesne oplodnje čine i do 4,5% sve živorođene dece u pojedinim zemljama, &scaron;to uz činjenicu da infertilitet pogađa 16-18% parova u na&scaron;oj sredini daje ovoj pojavi posebnu dimenziju i činije i dru&scaron;tvenim problemom. Perinatalni ishodi trudnoća iz postupaka vantelesne oplodnje su u velikoj meri kompromitovani visokom stopom multiplih trudnoća, koje se danas smatraju komplikacijom, a ne uspehom postupaka vantelesne oplodnje. Jednoplodne trudnoće iz postupaka vantelesne oplodnje u većim studijama pokazuju diskretno slabije perinatalne ishode u odnosu na one spontano začete, dok kod vi&scaron;eplodnih trudnoća ova korelacija nije jasno izražena i dokumentovana, uz prisutnu dilemu da li je vi&scaron;eplodnost sama po sebi ili način koncepcije glavni problem u zapaženoj pojavi. Cilj rada: Uporediti perinatalne ishode vi&scaron;eplodnih trudnoća nastalih postupcima vantelesne oplodnje i spontano začetih kao i perinatalne ishode jednoplodnih i vi&scaron;eplodnih trudnoća iz postupaka vantelesne oplodnje. Pored navdenog cilj rada je i ukazati sveobuhvatnost navedenog problema i na moguća re&scaron;enja za smanjenje njihove učestalosti. Materijal i metode: Kombinacijom retrospektivne opservacione studije i prospektivne longitudinalne kohortne studije u periodu analizom perinatalnih ishoda pacijentkinja porođenih na Klinici za ginekologiju i aku&scaron;erstvo Kliničkog centra Vojvodine u periodu od od 01.01.2008. do 31.12.2010. godine, studija je analizirala i poredila perinatalne ishode kod 174 spontano začete vi&scaron;eplodne trudnoće, 163 vi&scaron;eplodne trudnoće nastale postupkom vantelesne oplodnje, kao i 155 jednoplodnih trudnoća začete postupkom vantelesne oplodnje. Analizirani parametric bili su telesna masa novorođenčeta, dostignuta gestacijska starost, vrednosti Apgar skora, učestalost hipertenzivnog sindroma kod majke i brojni drugi parametri perinatalnog ishoda. Uzeti od strane obučenih kliničara i uno&scaron;eni u posebno dizajniranu bazu podataka, rezultati su statistički analizirani u program JMP ver 9.0 (SAS publisher) uz kori&scaron;ćenje ANOVA analize za testiranje statističke značajnosti između srednjih vrednosti kontinuiranih varijabli, dok je statistička značajnost razlike učestalosti kategorijskih varijabli je određivana Pearsonovim &chi;2 testom. Rezultati: Jednoplodne ART trudnoće uz prosečnu starost od 33,5 godine, prosečnu gestacijsku starost na porođaju od 38,26 gn, udeo prevremenih porođaja od 12,9%, prosečnu telesnu masu od 3258 g, AS u prvom minutu od 8,35 i u petom minutu od 9,2, stopu carskog reza od 65,81%, udeo GDM-a od 7,1%, anemije od 41,94% i preeklampsije od 4,52%, ima sve relevantne parametre perinatalnog ishoda statistički značajno (p&lt;0.0001) superiornije od kako ART tako i non ART blizanačkih trudnoća. ART blizanačke trudnoće pokazale su prosečnu starost majke od 32,9 godina, prosečnu gestacijsku starost na porođaju od 35,6 gn, udeo prevremenih porođaja od 58,27%, prosečnu telesnu masu od 2374 g, AS u prvom minutu od 7,45 i u petom minutu od 8,65, stopu carskog reza od 83,7%, udeo GDM-a od 15,11%, anemije od 78,42% i preeklampsije od 12,23%, dok su non ART blizanačke trudnoće pokazale prosečnu starost majke od 28,8 godina, prosečnu gestacijsku starost na porođaju od 36,08 gn, udeo prevremenih porođaja od 49,71%, prosečnu telesnu masu od 2433 g, AS u prvom minutu od 7,75 i u petom minutu od 8,75, stopu carskog reza od 58,33%, udeo GDM-a od 7,02%, anemije od 67,84% i preeklampsije od 11,11%. Pored godina majke i udela carskog reza koji su bili vi&scaron;i u ART blizanačkim trudnoćama (&lt;0.0001), kao i blago veće pojavi poremećaja količine plodove vode (p=0,033), gotovo svi ostali pokazatelji toka i ishoda trudnoće bili su komparabilni u navedenim grupama. Diskusija i zaključak: Studija je pokazala da su tok i ishod vi&scaron;eplodnih trudnoća nastalih spontano i postupcima vantelesne oplodnje ekvivalentni u gotovo svim pokazateljima uz sličnu prosečnu telesnu masu i gestacijsku starost novorođenčadi, kao i da su svi navedeni parametri ovih vi&scaron;eplodnih trudnoća bez obzira na način koncepcije upadljivo i podjednako lo&scaron;iji u poređenju sa jednoplodnim trudnoćama iz postupka vantelesne oplodnje. Izuzimajući vi&scaron;eplodnost kao factor rizika deca iz postupaka vantelesne oplodnje su generalno zdrava. Sama vi&scaron;eplodnost, a ne način koncepcije predstavljaju problem, koje se sa pravom smatra najvećom komplikacijom vantelesne oplodnje. Dodatna analiza iskustava drugih zdravstvenih sistema ukazuje da jedino &scaron;iroka i sveobuhvatna implementacija strategije vraćanja samo jednog embriona (Single embryo transfer &ndash; SET) može da dovede do smanjivanje stope multiplih trudnoća nakon postupaka vantelesne oplodnje, i sledstvenih komplikacija, a bez ugrožavanja samog uspeha vantelesne oplodnje. Iskustva drugih zdravstvenih sistema ukazuju da je uspe&scaron;na implementacija SET-a jedino moguća uz angažovanje celog dru&scaron;tva, zajedno sa brojnim legislativnim merama iz domena nadzora, kontrole i finansiranja postupaka vantelesne oplodnje. Obim i način finansiranja postupaka vantelesne oplodnje od strane države (uz vi&scaron;e besplatnih poku&scaron;aja za infertilne parove) uz obaveznu upotrebu SET-a, i sistema krioprezervacije na osnovu primera iz prakse predstavlja ključ u borbi za smanjenje problema vi&scaron;eplodnih trudnoća nakon postupaka vantelesne oplodnje.</p> / <p>Introduction: Multiple pregnancies occur in 1.5% of all pregnancies after spontaneous conception and in more than 20 % of all pregnancies concieved after assisted reproductive technologies in Europe, with large variations between countries. In our setting, the rate of multiple pregnancies after the ART is well above 30%. The occurrence of hypertensive syndrome in pregnancy, gestational diabetes, operative delivery, premature birth, low birth weight, neurological and developmental impairment in children, and almost all the other complications for the mother and fetus, as well as the entire burden of the health system are several times higher in multiple pregnancies compared with singleton pregnancies. Incidence of&nbsp; forementioned complications rises with number of fetuses. On the other hand, children from in vitro fertilization procedures make up 4.5% of all live births in some countries, which together with the fact that infertility affects aproximately 16-18% of couples in our country gives an extra dimension to this phenomenon and makes it not just medical but wider social problem. Perinatal outcomes of pregnancies after assisted reproductive technologies (ART) are greatly compromised by the high rate of multiple pregnancies, which are now considered to be a complication rather than success of ART procedures. ART Singleton pregnancies have, in larger studies, show discretely lower perinatal outcomes compared with those conceived spontaneously, while for the multiple pregnancies, this correlation is not clearly expressed and documented. There remains dilemma whether multiplicity itself or the way of conception (ART vs. non ART) constitutes a major problem in the observed differences regarding perinatal outcome of ART pregnancies. Objective: To compare the perinatal outcomes of multiple pregnancies conceived by In vitro fertilization (IVF) and spontaneously and perinatal outcomes of IVF conceived singleton and multiple pregnancies. Additional aim of this thesis is to point out the complexity of this problem and offer possible solutions. Materials and Methods: Design of a study was a combination of retrospective and prospective observational longitudinal cohort study. Analysis included pregnancies which had delivery at the Department of Gynecology and Obstetrics, Clinical Center of Vojvodina in the period from 1.01.2008. to 31.12.2010. The study analyzed and compared the perinatal outcomes in 174 spontaneous conceived multiple pregnancies, 163 multiple pregnancies resulting from IVF procedures, and 155 singleton pregnancies conceived by IVF procedure. Analyzed parameters were newborns birth weight, gestational age at delivery, the value of the Apgar score, occurrence of hypertensive syndrome in pregnancy, gestational diabetes, as well as numerous parameters of perinatal outcome. Taken by trained clinicians and were entered into a specially designed database, the results were statistically analyzed in JMP ver 9.0 software (SAS publisher) using ANOVA analysis to test the statistical significance between the mean values of continuous variables, while the statistical significance of the difference in frequency of categorical variables was assessed by Pearsons &chi;2 test. Results: ART singleton pregnancies had an average mothers age of 33.5 years, the average gestational age at birth of 38.26 gestational weeks (gw), preterm delivery rate of 12.9%, average birth weight 3258 g, Apgar score (AS) in the first minute 8.35, and in the fifth minute 9.2, cesarean section rate 65.81%, Gestational diabetes (GDM) in 7.1% pregnancies, anemia occurred in 41.94% of pregnancies, while preeclampsia was observed in 4.52% of all pregnancies. All relevant parameters of perinatal outcome were significantly (p&lt;0.0001) superior to both ART and non-ART twin pregnancies. ART twin pregnancy showed the average mothers age of 32.9 years, the average gestational age at birth of 35.6 gw, the preterm delivery rate 58.27%, the average body weight newborns 2374 g, AS in the first minute of 7.45, and in the fifth minute of 8.65, the cesarean section rate of 83.7%, GDM in 15.11% of all pregnancies, anemia occurred in 78.42% and preeclampsia in 12.23% of pregnancies, while the non-ART twin pregnancy showed an average mothers age of 28.8 years, the average gestational age at birth of 36.08 gw, the preterm delivery rate of 49.71%, the average body weight of 2433 g, AS in the first minute of 7.75 in the fifth minute 8.75, the caesarian section rate of 58.33%, GDM-a occurred in 7.02%, anemia in 67.84% and preeclampsia in 11.11% of pregnancies. Except for maternal age and the caesarean section rate, which were significantly higher in ART twin pregnancies (p&lt;0.0001), as well as small increase in proportion of amniotic fluid volume disorders (p = 0.033), almost all other parameters of perinatal outcome of were comparable in these groups. Discussion and Conclusion: The study showed that the course and outcome of multiple pregnancies conceived spontaneous and after IVF procedures are equivalent in almost all parameters with similar average body weight and gestational age at birth, and that all these parameters of multiple pregnancies regardless of the conception mode are equally worse compared with singleton pregnancies from IVF procedures. With the exception of multiplicity as a risk factor children from in vitro fertilization procedures are generally healthy. Multiplicity itself and not the mode of conception presented a problem, which is rightly considered the major complication of IVF today. Additional analysis of the experiences of other health system indicates that only a broad and comprehensive implementation of strategy to return only one embryo (SET&ndash;single embryo transfer) can lead to a reduction of the rate of multiple pregnancies after IVF procedures, and the accompanying complications, without compromising IVF success. The experience of other health systems indicate that a successful implementation of SET is only possible with the involvement of the whole society, along with a number of legislative measures in the field of monitoring, control and reimbursement of assisted reproduction procedures. The scope and funding of an IVF procedures (with more free attempts for infertile couples, reimbursed by public health) with mandatory use of SET, and good cryopreservation programs are, based on examples in other countries who had successfully dealt with his problem, is the key in reducing the problem of multiple pregnancies after IVF procedures.</p>