The aim of the study was to verify if quantification of placental specific C19MC microRNAs in plasma exosomes would be able to differentiate during the early stages of gestation between patients subsequently developing pregnancy-related complications and women with the normal course of gestation and if this differentiation would lead to the improvement of the diagnostical potential. The retrospective study on singleton Caucasian pregnancies was performed within 6/2011-2/2019. The case control study, nested in a cohort, involved women that later developed GH (n = 57), PE (n = 43), FGR (n = 63), and 102 controls. Maternal plasma exosome profiling was performed with the selection of C19MC microRNAs with diagnostical potential only (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) using real-time RT-PCR. The down-regulation of miR-517-5p, miR-520a-5p, and miR-525-5p was observed in patients with later occurrence of GH and PE. Maternal plasma exosomal profiling of selected C19MC microRNAs also revealed a novel down-regulated biomarker during the first trimester of gestation (miR-520a-5p) for women destinated to develop FGR. First trimester circulating plasma exosomes possess the identical C19MC microRNA expression profile as placental tissues derived from patients with GH, PE and FGR after labor. The predictive accuracy of first trimester C19MC microRNA screening (miR-517-5p, miR-520a-5p, and miR-525-5p) for the diagnosis of GH and PE was significantly higher in the case of expression profiling of maternal plasma exosomes compared to expression profiling of the whole maternal plasma samples.

• MeSH
• biologické markery MeSH
• cirkulující mikroRNA * MeSH
• exozómy * metabolismus   MeSH
• hypertenze indukovaná těhotenstvím krev   diagnóza   MeSH
• lidé MeSH
• preeklampsie krev   diagnóza   MeSH
• prognóza MeSH
• první trimestr těhotenství MeSH
• ROC křivka MeSH
• růstová retardace plodu krev   diagnóza   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND METHODS: Gene expression of 29 cardiovascular and cerebrovascular disease associated microRNAs was assessed in whole umbilical cord blood, compared between groups [47 gestational hypertension (GH), 56 preeclampsia (PE), 37 fetal growth restriction (FGR) and 44 normal pregnancies] and correlated with the severity of the disease with respect to clinical signs (mild PE vs. severe PE), delivery date (before and after 34weeks of gestation), and Doppler ultrasound parameters [pulsatility index (PI) in the umbilical artery, PI in the middle cerebral artery and the cerebroplacental ratio]. RESULTS: GH showed a down-regulation of miR-195-5p (p=0.025). The down-regulation of miR-26a-5p (p=0.031, p=0.05), miR-145-5p (p=0.042, p=0.015), and miR-574-3p (p=0.002, p=0.022) was observed in severe PE pregnancies requiring termination before 34weeks of gestation. Severe PE occurring regardless of the delivery date was associated with downregulation of miR-195-5p (p=0.01), miR-199a-5p (p=0.048), and miR-221-3p (p=0.028). On the other hand, mild PE showed upregulation of miR-92a-3p (p=0.044). The centralization of fetal circulation tended to higher levels of miR-1-3p (ρ=-0.302, p=0.045) and miR-133a-3p (ρ=-0.348, p=0.020) in PE pregnancies. FGR pregnancies with abnormal values of flow rate in the umbilical artery (miR-221-3p: ρ=-0.390, p=0.017) and the middle cerebral artery (miR-143-3p: ρ=0.350, p=0.036) demonstrated down-regulation of relevant microRNAs. CONCLUSION: Epigenetic changes induced by pregnancy-related complications in umbilical cord blood may appear as a result of dysfunctional placenta and impaired maternal cardiovascular function (hidden cardiovascular and cerebrovascular diseases) and may cause later onset of cardiovascular and cerebrovascular diseases in offspring.

• MeSH
• cerebrovaskulární poruchy krev   diagnostické zobrazování   epidemiologie   MeSH
• dospělí MeSH
• epigeneze genetická fyziologie   MeSH
• exprese genu MeSH
• fetální krev metabolismus   MeSH
• hypertenze indukovaná těhotenstvím krev   diagnostické zobrazování   epidemiologie   MeSH
• kardiovaskulární nemoci krev   diagnostické zobrazování   epidemiologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• mikro RNA krev   genetika   MeSH
• mladý dospělý MeSH
• preeklampsie krev   diagnostické zobrazování   epidemiologie   MeSH
• retrospektivní studie MeSH
• růstová retardace plodu krev   diagnostické zobrazování   epidemiologie   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy. METHODS: The expression of placental specific C19MC microRNAs (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) was determined in plasma samples from pregnancies that subsequently developed preeclampsia (n = 21), IUGR (n = 18), and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39). RESULTS: Circulating C19MC microRNAs were up-regulated (miR-517-5p, p = 0.005; miR-518b, p = 0.013; miR-520h, p = 0.021) or showed a trend toward up-regulation in patients destined to develop preeclampsia (miR-520a-5p, p = 0.067; miR-525-5p, p = 0.073). MiR-517-5p had the best predictive performance for preeclampsia with a sensitivity of 42.9%, a specificity of 86.2%, a PPV of 52.9% and a NPV of 80.6%. The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of preeclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%). CONCLUSIONS: Up-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of preeclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent preeclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• prediktivní hodnota testů MeSH
• preeklampsie krev   diagnóza   MeSH
• prenatální diagnóza metody   MeSH
• první trimestr těhotenství krev   MeSH
• růstová retardace plodu krev   diagnóza   MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 29 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in maternal whole peripheral blood, compared between groups (39 gestational hypertension, 68 preeclampsia, 33 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in patients affected by pregnancy-related complications have been carried out. RESULTS: The expression profile of microRNAs was different between pregnancy-related complications and controls. The down-regulation of miR-100-5p, miR-125b-5p and miR-199a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Moreover, IUGR pregnancies induced down-regulation of miR-17-5p, miR-146a-5p, miR-221-3p and miR-574-3p in maternal circulation. Irrespective of the severity of the disease, preeclampsia was associated with the dysregulation of miR-100-5p and miR-125b-5p and IUGR with dysregulation of miR-199a-5p. Preeclampsia requiring termination of gestation before 34 weeks was associated with down-regulation of miR-146a-5p, miR-199a-5p and miR-221-3p. Weak negative correlation between miR-146a-5p and miR-221-3p expression and the pulsatility index in the umbilical artery was found. Additional microRNAs (miR-103a-3p, miR-126-3p, miR-195-5p and miR-499a-5p) showed a trend to down-regulation in appropriate pregnancy-related complications. CONCLUSION: Epigenetic changes are induced by pregnancy-related complications in maternal whole peripheral blood.

• MeSH
• cerebrovaskulární poruchy krev   genetika   MeSH
• dospělí MeSH
• epigeneze genetická genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• hypertenze indukovaná těhotenstvím krev   genetika   MeSH
• kardiovaskulární nemoci krev   genetika   MeSH
• lidé MeSH
• mikro RNA krev   genetika   MeSH
• preeklampsie krev   genetika   MeSH
• růstová retardace plodu krev   genetika   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND & OBJECTIVES: Heat shock proteins (Hsp) are ubiquitously distributed phylogenetically conserved molecules that regulate cellular homeostasis and maintain the integrity and function of cellular proteins. Increased levels of Hsp in maternal circulation have been shown to be associated with increased risk of pregnancy related complications. The objective of this study was to explore extracellular Hsp mRNA levels in maternal circulation and quantified Hsp27, Hsp60, Hsp70, Hsp90 and Hsp70 binding protein 1 (HspBP1) mRNAs in maternal plasma samples using real-time reverse-transcriptase polymerase chain reaction. METHODS: Pregnancies with gestational hypertension (GH) (n = 33), pre-eclampsia (PE) with or without foetal growth restriction (FGR) (n = 78) and FGR (n = 25) were involved in the study. Hsp gene expression was analysed in relation to the severity of the disease with respect to the degree of clinical signs, requirements for the delivery and Doppler ultrasound parameters. RESULTS: Upregulation of Hsp70 was observed in patients with mild and severe PE (P = 0.004 and P = 0.005, respectively) and in pregnancies complicated with PE delivering before and after 34 wk of gestation regardless of the degree of clinical signs (P = 0.015 and P = 0.009, respectively). No difference in the expression of other Hsp genes among the studied groups was observed. No association between Hsp gene expression and Doppler ultrasonography parameters was found. INTERPRETATION & CONCLUSIONS: These data support that maternal circulation can reflect both maternal and foetal pathologic conditions. Hsp70 represents the sole plasmatic marker, and increased Hsp70 mRNA levels reflect maternal and placental stress response to pregnancy-related complications such as GH and PE, irrespective of the severity of the disease.

• MeSH
• dospělí MeSH
• hypertenze indukovaná těhotenstvím krev   patologie   MeSH
• komplikace těhotenství krev   patologie   MeSH
• krevní tlak MeSH
• lidé MeSH
• messenger RNA biosyntéza   krev   MeSH
• placenta patologie   MeSH
• preeklampsie krev   patologie   MeSH
• proteiny tepelného šoku HSP70 biosyntéza   krev   MeSH
• růstová retardace plodu krev   patologie   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Intrauterinnní růstová restrikce (IUGR – intrauterine growth restriction) se řadí mezi relativně časté klinické a patofyziologické nálezy. Vzhledem k rozvoji fetoplacentárního řečiště a odlišné reakci plodu na tyto změny v průběhu gravidity existují odlišné diagnostické nálezy při stejné etiologii postižení vaskulárního řečiště placenty. Z klinického hlediska proto rozlišujeme časnou a pozdní formu IUGR. Časnou formu IUGR charakterizují relativně dobré diagnostické možnosti, porody ale zpravidla probíhají v nízkých gestačních týdnech, a jsou proto zatíženy vysokou perinatální morbiditou a mortalitou. Opačná situace je u pozdních forem IUGR, kde prematurita není zásadním problémem, ale kvůli změnám fetoplacentární hemodynamiky jsou diagnostické možnosti značně omezené.

Intrauterine growth restriction (IUGR) is relatively frequent clinical and pathophysiological finding. Due to the development of the foetoplacental unit and the different responses of the foetus to these changes during the pregnancy there are different diagnostic findings in presence of the similar affection of the vascular bed of the placenta. From a clinical point of view, therefore, there are early and late forms of IUGR. An early form of IUGR is characterized by relatively good diagnostic options, but the births usually occur in early gestational ages and are affected by high perinatal mortality and morbidity rates. There is opposite situation is in the late form of IUGR. The prematurity is not the crucial problem, but due to haemodynamic foetoplacental changes the diagnostic options are severely limited.

• MeSH
• arteria subclavia MeSH
• ductus arteriosus MeSH
• hypoxie MeSH
• komplikace těhotenství MeSH
• lidé MeSH
• plod MeSH
• pulzatilní průtok MeSH
• růstová retardace plodu * diagnóza   krev   patofyziologie   MeSH
• těhotenství MeSH
• ultrasonografie dopplerovská MeSH
• ultrasonografie prenatální MeSH
• venae umbilicales MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

OBJECTIVES: The aim of the study was to analyze polymorphisms of receptor for advanced glycation end products (RAGE) gene, and glyoxalase I gene and soluble RAGE, sRAGE, in physiological and pathological pregnancy. DESIGN AND METHODS: Polymorphisms of RAGE gene (-429 T/C, -374 T/A, 557 G/A, 2184 A/G) and glyoxalase I gene (A419C) and sRAGE serum levels were determined in 284 women with pathological and physiological pregnancy. RESULTS: No differences in distribution of genotype and allelic frequencies of studied polymorphisms were found. GA genotype of RAGE 557 G/A polymorphism (known as Gly82Ser) is associated with lower sRAGE serum levels in healthy pregnant women compared to GG genotype (483 ± 104 vs. 692 ± 262 pg/mL, p=0.008). sRAGE correlates negatively with ALT in patients with pregnancy intrahepatic cholestasis (r=-0.536, p=0.05). CONCLUSIONS: We did not show any association of RAGE and glyoxalase I gene polymorphisms with pathological pregnancy, however further studies are needed to confirm the results.

• MeSH
• alanintransaminasa krev   MeSH
• antigeny nádorové krev   genetika   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetické asociační studie MeSH
• intrahepatální cholestáza krev   genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• komplikace těhotenství krev   genetika   MeSH
• laktoylglutathionlyasa genetika   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy krev   genetika   MeSH
• předčasná porodní činnost krev   genetika   MeSH
• preeklampsie krev   genetika   MeSH
• růstová retardace plodu krev   genetika   MeSH
• sekvenční analýza DNA MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Mitochondrial disorders (MD) may manifest in neonates, but early diagnosis is difficult. In this study, clinical and laboratory data were analyzed in 129 patients with neonatal onset of MD to identify any association between specific mitochondrial diseases and their symptoms with the aim of optimizing diagnosis. MATERIALS AND METHODS: Retrospective clinical and laboratory data were evaluated in 461 patients (331 families) with confirmed MD. RESULTS: The neonatal onset of MD was reported in 28% of the patients. Prematurity, intrauterine growth retardation and hypotonia necessitating ventilatory support were present in one-third, cardiomyopathy in 40%, neonatal seizures in 16%, Leigh syndrome in 15%, and elevated lactate level in 87%. Hyperammonemia was observed in 22 out of 52 neonates. Complex I deficiency was identified in 15, complex III in one, complex IV in 23, complex V in 31, combined deficiency of several complexes in 53, and PDH complex deficiency was identified in six patients. Molecular diagnosis was confirmed in 49 cases, including a newborn with a 9134A>G mutation in the MTATP6 gene, which has not been described previously. CONCLUSION: The most significant finding is the high incidence of neonatal cardiomyopathy and hyperammonemia. Based on our experience, we propose a diagnostic flowchart applicable to critically ill neonates suspicious for MD. This tool will allow for the use of direct molecular genetic analyses without the need for muscle biopsies in neonates with Alpers, Barth, MILS and Pearson syndromes, SCO1, SCO2, TMEM70, ATP5E, SUCLG1 gene mutations and PDH complex deficiency.

• MeSH
• hyperamonemie diagnóza   genetika   MeSH
• kardiomyopatie diagnóza   genetika   MeSH
• Leighova nemoc krev   diagnóza   genetika   MeSH
• lidé MeSH
• mitochondriální nemoci krev   diagnóza   genetika   MeSH
• mutace MeSH
• novorozenec nedonošený MeSH
• novorozenec MeSH
• retrospektivní studie MeSH
• růstová retardace plodu krev   diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• preeclampsie, uteroplacentární insuficience,
• MeSH
• biologické markery krev   analýza   krev   MeSH
• hormon uvolňující kortikotropin diagnostické užití   MeSH
• komplikace těhotenství krev   diagnóza   krev   MeSH
• lidé MeSH
• placentární insuficience diagnóza   krev   MeSH
• preeklampsie diagnóza   krev   MeSH
• růstová retardace plodu diagnóza   krev   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

Cieľ: Cieľom tejto práce bolo zistiť na populácii gravidných žien mesta Košice možnosť predikcie intrauterinnej rastovej retardácie pomocou markerov integrovaného testu. Typ štúdie: Retrospektívna longitudinálna multicentrická štúdia. Názov a sídlo pracoviska: II. gynekologicko-pôrodnícka klinika LF UPJŠ a FN L. Pasteura, Košice, Slovenská republika. Materiál a metodika: Vyšetrovaný súbor tvorilo 578 tehotných pacientok II. gynekologicko-pôrodníckej kliniky od 01. 11. 2001 do 31. 01. 2005 za účelom vyšetrenia v integrovanom teste ( CRL, vyšetrenie koncentrácie PAPP- A, NT, vyšetrenie koncentrácie AFP, uE3, hCG). Údaje o pôrodnej hmotnosti plodov, ich pohlaví, o gestačnom týždni v čase pôrodu, výskyte preeklampsie a iných komplikáciách tehotnosti boli zistené u 578 pacientok retrospektívne. Vytvorili sme dve cieľové premenné: 1. intrauterinná rastová retardácia pod 5. percentilom hmotnosti plodov – IUGR 5 a intrauterinná rastová retardácia plodu pod 10. percentilom – IUGR 10. S cieľom využiť súhrnú informáciu, ktorú markery majú, bola využitá metóda logistickej regresie, ktorou boli identifikované štatisticky významné prediktory jednotlivých binárnych cieľových premenných (IUGR 5 a IUGR 10). Najprv bola zostrojená rovnica, ktorá využíva všetky dostupné prediktory. Štatisticky nevýznamné prediktory boli postupne vylučované z modelu (Stepwise regression) až zostal finálny model, pre ktorý bola zostrojená ROC krivka a určená senzitivita, špecificita, pozitívna a negatívna prediktívna hodnota pre nami určenú 5% FP. Výsledky: Finálny model IUGR 5, ktorý obsahuje len štatisticky významné markery integrovaného testu dosiahol pri 5% falošnej pozitivite a 95% špecificite 34,8% senzitivitu, 24,1% pozitívnu a 97,0% negatívnu prediktívnu hodnotu v rámci predikcie pôrodnej hmotnosti plodu pod 5. percentilom vzhľadom ku gestačnému veku a pohlaviu plodu. Finálny model IUGR 10, ktorý obsahuje len štatisticky významné markery integrovaného testu dosiahol pri 5% falošnej pozitivite a 95% špecificite 36,4% senzitivitu, 32,1% pozitívnu a 95,8% negatívnu prediktívnu hodnotu v rámci predikcie pôrodnej hmotnosti plodu pod 10. percentilom vzhľadom ku gestačnému veku a pohlaviu plodu. Záver: Z našich výsledkov, ako aj z výsledkov iných štúdií však vyplýva, že aj napriek veľkému množstvu biochemických markerov a rôznym možnostiam ich kombinácie s ultrazvukovými markermi sa doteraz nepodarilo nájsť takú kombináciu, ktorá by spĺňala nasledujúce podmienky: 1. vysoká senzitivita a špecificita pri nízkej falošnej pozitivite a vysokej pozitívnej a negatívnej prediktívnej hodnote, 2. využitie ako skríningovej metódy v rámci predikcie intrauterinnej rastovej retradácie a preklampsie v neselektovanej populácii gravidných žien.

Objective: Author's objective was to ascertain the option for prediction of intrauterine growth retardation using the integrated test markers on the population of pregnant women in Košice city. Design: Retrospective, longitudinal, multicenter study. Setting: 2nd Department of Obstetrics and Gynecology University of P. J. Šafárik, Košice, Slovak Republic. Methods: The study group comprised 578 pregnant patients of 2nd Department of Obstetrics and Gynecology, in the period from 01. 11. 2001 until 31. 01. 2005 for integrated test consisting of (examination of the gestation age using CRL, concentration of PAPP-A, NT, AFP, uE3, hCG). Information on birth weight, gender, gestation age at the time of delivery, occurrence of preeclampsia and other pregnancy complications were found in 578 patients retrospectivelly. We have designed two outcome criteria: 1. intrauterine growth retardation <5th fetal weight percentile – IUGR 5 – and intrauterine growth retardation <10th percentile – IUGR 10. In order to make use of the summary information provided by the markers, we have used the method of logistic regression to identify statistically significant predictors of individual binary outcomes (IUGR 5 and IUGR 10). First we developed an equation based on all available predictors. Statistically insignificant predictors were indikátogradually eliminated from the model (Stepwise regression) until the final model remained, for which a ROC curve was developed and values of sensitivity, specificity, positive and negative predictive values at 5% FP (false positivity) were calculated. Results: The final model of IUGR 5, containing only statistically significant markers of integrated test achieved – at 5% FP level and 95% specificity level – a 34.8% sensitivity, 24.1% positive and 97.0% negative predictive value - in prediction of birth weight under 5th percentile with respect to gestation age and gender. The final model of IUGR 10, containing only statistically significant markers achieved – at 5% FP level and 95% specificity level – a 36.4% sensitivity, 32.1% positive and 95.8% negative predictive value - in prediction of birth weight under 10th percentile with respect to gestation age and gender. Conclusion: Our results, as well as the results of other studies, lead to the conclusion, that in spite of the multitude of biochemical markers and various options for their combination with ultrasound markers, so far it has been impossible to find a combination which would meet the following criteria: 1. high sensitivity and specificity at low false positive values and high positive and negative predictive value, 2. application as a screening method for prediction of intrauterine growth retardation and preeclampsia in unselected population of pregnant women.

• MeSH
• biologické markery analýza   krev   MeSH
• lidé MeSH
• plošný screening metody   využití   MeSH
• retrospektivní studie MeSH
• růstová retardace plodu diagnóza   krev   MeSH
• senzitivita a specificita MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH