Zika Virus Associated with Microcephaly Mlakar, Jernej; Korva, Misa; Tul, Nataša ...
The New England journal of medicine,
03/2016, Letnik:
374, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Zika virus is an emerging infectious disease that is spreading rapidly through the Americas. A major concern is the association with birth defects, especially microcephaly. This report shows evidence ...of Zika virus in the fetal brain.
ZIKV, an emerging mosquito-borne flavivirus, was initially isolated from a rhesus monkey in the Zika forest in Uganda in 1947.
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It is transmitted by various species of aedes mosquitoes. After the first human ZIKV infection, sporadic cases were reported in Southeast Asia and sub-Saharan Africa.
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ZIKV was responsible for the outbreak in Yap Island of Micronesia in 2007 and for major epidemics in French Polynesia, New Caledonia, the Cook Islands, and Easter Island in 2013 and 2014.
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In 2015, there was a dramatic increase in reports of ZIKV infection in the Americas. Brazil is the most affected country, with . . .
The aim of this work was to define a differential marker profile for pregnancy complications near delivery.
We enrolled pregnant women who were referred to the outpatient pregnancy clinic of the ...University Medical Center, Ljubljana, Slovenia, due to symptoms of pregnancy complications and women with a history of pregnancy complications attending the high-risk hospital clinic for close surveillance. They were evaluated for prior risk and were tested for biophysical and biochemical markers at the time of enrolment. Biochemical markers included the pro- and anti-angiogenic markers, along with additional previously reported markers of potential value, all tested by various formats of immuno-diagnostics. Biophysical markers included blood pressure, sonographic markers, and EndoPAT. Statistical differences were determined with Kruskal-Wallis and Mann-Whitney tests for continuous parameters, and Pearson χ2 for categorical values. p < 0.05 was considered significant.
The cohort included 125 pregnant patients, 31 developed preeclampsia (PE) alone (13 were <34 weeks' gestation), 16 had intrauterine growth restriction (IUGR) alone (12 were <34 weeks), 42 had both IUGR and PE (22 were <34 weeks), and 15 had an iatrogenic preterm delivery (PTD; 6 were <34 weeks). Twenty-one were unaffected and delivered a healthy baby at term. Mean arterial blood pressure and proteinuria were significantly higher in PE and PE+IUGR but not in pure IUGR or PTD. In PE, IUGR, and PE+IUGR, the levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were significantly higher, while placental growth factor (PlGF) was very low compared to unaffected controls and PTD. PE, IUGR, and PE+IUGR also had a high anti-angiogenic ratio (sFlt-1/PlGF) and a low proangiogenic ratio of PlGF/(sFlt-1+Eng). Levels of inhibin A were significantly higher in pure PE across subgroups but had many extreme values, which made it a poor differentiator. Higher uterine artery Doppler pulsatility indexes were detected in PE, IUGR, and PE+IUGR, with similar resistance indexes and peaks of systolic velocity. A significantly different marker level between PE and IUGR was found using arterial stiffness that was 10 times higher in PE; concurrently with an increase of the reactive hyperemia index, both were accompanied by a slight increase in placental protein 13. Higher tumor necrosis factor alpha (TNFα) differentially identified iatrogenic very early PTD (<34 weeks).
Arterial stiffness can serve as a major marker to differentiate PE (with/without IUGR) from pure IUGR near delivery. TNFα can differentiate iatrogenic early PTD from other complications of pregnancy and term IUGR.
Preeklampsija je pomemben vzrok maternalne in neonatalne umrljivosti in obolevnosti po vsem svetu. Opredeljena je kot pojav povečanega arterijskega tlaka po 20. tednu nosečnosti s pridruženo ...proteinurijo in/ali disfunkcijo materinih organov ali zastojem plodove rasti. Medtem ko je smrt mater zaradi preeklampsije v razvitih državah manj pogosta, pa je obolevnost velika in pomembno prispeva k pogostosti sprejemov na oddelke za intenzivno nego in terapijo. Preeklampsija je vzrok za približno 15–20 % vseh prezgodnjih porodov, kar povečuje neonatalno umrljivost in dolgoročno obolevnost novorojenčkov. Aspirin v majhnem odmerku ima preventivni učinek na pojav preeklampsije le v primeru, če se začne jemati pred 16. tednom nosečnosti. Da bi odkrili, pri katerih nosečnicah je tveganje za preeklampsijo povečano, potrebujemo učinkovito presejanje, ki bo organizacijsko, cenovno in po učinkovitosti najprimernejše za izvajanje na primarni ravni.
Objectives—To conduct a secondary analysis of prediction accuracy of biophysical markers for suspected Preeclampsia (PE), Fetal Growth Restriction (FGR) and the two combined near delivery in a ...Slovenian cohort. Methods—This was a secondary analysis of a database of a total 125 Slovenian pregnant women attending a high-risk pregnancy clinic due to suspected PE (n = 31), FGR (n = 16) and PE + FGR (n = 42) from 28–39 weeks gestation and their corresponding term (n = 21) and preterm (PTD, n = 15) controls. Data for Mean Arterial blood Pressure (MAP) and Uterine artery pulsatility index (UtA PI) estimated by Doppler sonography were extracted from the database of patients who were tested at admission to the high-risk clinic with the suspected complications. The reactive hyperemia index (RHI), and the Augmentation Index (AIX%) were extracted from the patient database using measured values obtained with the assistance of the Endo PAT, a device set to measure the signal of the peripheral arterial tone (PAT) from the blood vessels endothelium. Linear regression coefficients, Box and Whisker plots, Area under the Curve (AUC) of receiver Operation Characteristic (ROC) curves, and multiple regression were used to assess the marker accuracy using detection rate (DR) and false-positive rate (FPR) and previously reported cut-offs for estimating the positive and negative predictive value (NPV and PPV). The SPSS non-parametric statistics (Kruskal Wallis and Mann–Whitney) and Spearman’s regression coefficient were used to assess marker accuracy; p < 0.05 was considered significant. Results—MAP values reached diagnostic accuracy (AUC = 1.00, DR = 100%) for early PE cases delivered < 34, whereas UtA Doppler PI values yielded such results for early FGR < 34 weeks and the two combined reached such accuracy for PE + FGR. To reach diagnostic accuracy for all cases of the complications, the Endo PAT markers with values for MAP and UtA Doppler PI were required for cases near delivery. Multiple regression analyses showed added value for advanced maternal age and gestational week in risk assessment for all cases of PE, FGR, and PE + FGR. Spearman’s regression coefficient yielded r > 0.6 for UtA Doppler PI over GA for PE and FGR, whereas for RHI over BMI, the regression coefficient was r > 0.5 (p < 0.001 for each). Very high correlations were also found between UtA Doppler PI and sFlt-1/PlGF or PlGF (r = −0.495, p < 0.001), especially in cases of FGR. Conclusion—The classical biophysical markers MAP and UtA Doppler PI provided diagnostic accuracy for PE and FGR < 34 wks gestation. A multiple biophysical marker analysis was required to reach diagnostic accuracy for all cases of these complications. The UtA Doppler PI and maternal serum sFlt-1/PlGF or PlGF were equally accurate for early cases to enable the choice of the markers for the clinical use according to the more accessible method.
Objective—the objective of this study was to assess the accuracy of placental growth factor (PlGF), soluble Fms-like Tyrosine Kinase 1 (sFlt-1), and endoglin (sEng) in the diagnosis of suspected ...preeclampsia (PE) with and without fetal growth restriction (FGR) near delivery. Methods—this is a secondary analysis of a dataset of 125 pregnant women presenting at the high risk pregnancy clinic with suspected PE, FGR or PE + FGR in the University Medical Center of Slovenia. The dataset included 31 PE cases, 16 FGR cases, 42 PE + FGR cases, 15 cases who developed with unrelated complications before 37 weeks (wks) (PTD), and 21 unaffected controls who delivered a healthy baby at term. We also analyzed a sub-group of women who delivered early (<34 wks) including 10 PE, 12 FGR, 28 PE + FGR, and six PTD. Clinical management adhered to hospital guidelines. Marker levels were extracted from the dataset and were used to develop Receiver Operating Characteristic (ROC) curves and to calculate the area under the curve (AUC), the detection rates (DRs), and the false positive rates (FPRs). Previously published marker cutoffs for yes/no admission to hospital wards were extracted from the literature. Negative and positive predictive values (NPVs and PPVs) were evaluated for their value in determining whether hospital admission was required. Non-parametric tests were applied for statistical analysis; p < 0.05 was considered significant. Results—near delivery, all the pro-and anti-angiogenic markers provided diagnostic (ROC = 1.00) accuracy for the early (<34 wks) group of FGR. Diagnostic or near diagnostic (ROC = 0.95) accuracy was achieved by all marker for early PE + FGR but lower accuracy was achieved for early PE. For all cases, all markers, especially PlGF reached diagnostic or near diagnostic accuracy for FGR and PE + FGR. At this accuracy level, they can contribute to the clinical management of FGR, and PE + FGR. All the markers were less accurate for all PE cases. The use of published cutoffs was adequate for clinical management of FGR, whether early or for all cases, using an NPV > 90%. For PE + FGR, the PPV value approached 100%, especially for early cases, and can thus be implemented in clinical management. Neither NPV nor PPV were high enough for managing all cases of PE. There was no added value in measuring the PlGF/(sFlt-1 + sEng) ratio. Conclusion—This is the first study on a Slovenian population. It shows that near-delivery angiogenic biomarkers tests may be useful for confirming the diseases in cases where there is a diagnostic doubt. However, the clinical use of the biomarkers needs to be weighed against resources available and degree of certainty of the diagnosis made with and without them for managing suspected FGR and PE + FGR requiring delivery <34 wks, where they are very accurate, and furthermore in the management of all cases of FGR and FGR+PE. The markers were less accurate for the clinical diagnosis of PE.
Objective: We previously provided evidence to confirm that maternal serum levels of soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio are useful tools to ...direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this secondary analysis, we further examine the potential additive value of maternal serum Inhibin-A, which is a hormone marker of the transforming growth factor family, to the accuracy provided by maternal serum PlGF and sFlt-1. Methods: We conducted a secondary analysis where we extracted the data of a cohort of 125 pregnant women enrolled near delivery at the clinics of the University Medical Center of Ljubljana, Slovenia. The dataset included 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 10 of PE, 12 of FGR, 28 of PE+FGR, and 6 of PTD. In addition to the recorded demographic characteristics and medical history and the maternal serum levels of PlGF and sFlt-1/PlGF ratio, which were previously published, we evaluated the added value of maternal serum Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations were estimated from areas under the curve (AUC) of receiver operating characteristics (ROC) curves, Box and Whisker plots, and by multiple regression. We estimated accuracy by the continuous marker model and a cutoff model. Results: In this study, we combined Inhibin-A with PlGF or with the sFlt-1/PlGF ratio and showed a 10–20% increase in AUCs and 15–45% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR and FGR in all cases but not for FGR in early cases delivered < 34 weeks. The use of a cutoff model was adequate, although a bit higher accuracy was obtained from the continuous model. The highest correlation was found for PlGF with all three complications. Conclusion: In this secondary analysis, we have found that maternal serum Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by maternal serum angiogenic markers alone, bringing the results to a diagnostic level; thus, it could be considered for directing clinical management. Inhibin-A had smaller or no added value for the accuracy of predicting FGR alone, mainly of early cases delivered <34 weeks.
Objective
To examine if a “dose–response” relation exists between different classes of pre-gravid obesity and selected perinatal outcomes.
Methods
We evaluated 16,566 obese mothers, including 12,064 ...(72.8%), 3410 (20.6%), and 1092 (6.6%) with obesity class I, II, and III, respectively. We compared maternal age, primiparity, gestational age at birth, birth weight, GDM, hypertensive disorders, and the incidence of cesarean sections.
Results
There was a significantly increased incidence (from class I to class III) for GDM (8.5–14.4%), chronic hypertension (2.8–9.0%), gestational hypertension (6.7–14.2%), and for preeclampsia (5.3–9.3%). No such relationship existed for birth weight and gestational duration.
Conclusion
Classes of obesity during pregnancy exhibit a “dose–response” relationship with maternal morbidity, but no such relationship was found with pregnancy duration and birth weight.
Slabokrvnost je najbolj pogost simptom v nosečnosti. Zaradi razvoja zarodka in hitre rasti ploda se močno povečajo potrebe organizma po železu in vitaminih. Zato je slabokrvnost zaradi pomanjkanja ...železa daleč najbolj razširjena oblika slabokrvnosti v nosečnosti. Anemija v nosečnosti je opredeljena z ravnijo hemoglobina (Hb), ki je manjša od 110 g/L. V normalni nosečnosti se sestava krvi pomembno spremeni. Povečanje celokupnega volumna krvi in hemostatske spremembe so fiziološke spremembe, ki omogočajo, da porodnica brez posledic prenese normalno izgubo krvi med porodom. Plazemski volumen se v nosečnosti poveča za 50 %, masa eritrocitov pa za 18 – 25 %, odvisno od razpoložljivega železa. Te spremembe povzročijo razredčitev koncentracije hemoglobna, kar poznamo kot fiziološko slabokrvnost v nosečnosti. Fiziološka slabokrvnost doseže vrh v 32. tednu nosečnosti. Zaradi fizioloških sprememb odkrijemo s presejalnimi testi v nosečnosti mnogo slabokrvnosti, ki bi sicer ostale neodkrite. Povečane ali spremenjene prehranske in presnovne zahteve v nosečnosti povzročijo, da je slabokrvnost zaradi pomanjkanja železa (sideropenična anemija) bolj pogosta. Prva nepravilnost v biokemičnih izvidih, ki kaže na pomanjkanje železa v nosečnosti, je zmanjšana koncentracija feritina (na pomanjkanje železa lahko sklepamo že, ko je vrednost feritina manjša od 20–30 g/L). Feritin je stabilen in zadovoljivo zrcali zaloge železa, za razliko od vrednosti serumskega železa. Zato učinkovito dodajanje železovih pripravkov in s tem preprečevanje sideropeničnih anemij lahko pričnemo že zelo zgodaj. Tako na zelo enostaven način učinkovito preprečimo nastanek zapletov v nosečnosti, ob porodu in v poporodnem obdobju. Slabokrvnost v nosečnosti je povezana s višjo pogostnostjo za prezgodnji porod, nizko porodno težo, z nujnostjo uporabe transfuzije ob in po porodu ter s poporodno depresijo.
Izhodišča: Pri ženskah se pogosto pojavijo spremenjen izcedek iz nožnice in drugi simptomi v nožnici, ki so posledica motenj v nožnični mikrobioti (disbioze), vaginitisa ali spolno prenosljivih ...okužb. Želeli smo ugotoviti pogostnost vzrokov za te težave. Preverili smo tudi ujemanje klinične diagnoze z rezultati laboratorijskih preiskav. Metode: Izvedli smo raziskavo primerov s kontrolno skupino. V skupino bolnic smo vključili ženske, ki so obiskale izbrano ginekologinjo na primarni ravni zdravstva zaradi težav v predelu spolovila, in ustrezno kontrolno skupino preiskovank. Opravili smo klinični pregled in mikrobiološke preiskave za bakterijsko vaginozo (BV), aerobni vaginitis (AV), kandidni vulvovaginitis (CV) in spolno prenosljive okužbe (SPO). Rezultati: V študiji je sodelovalo 74 bolnic in 64 preiskovank kontrolne skupine. Najpogostejši simptomi bolnic so bili nenormalen izcedek, srbenje, neprijeten vonj in pekoč občutek. Najpogostejši vzrok je bil CV (39,2 %), sledila je BV (31,1 %). Petina bolnic je imela eno SPO. AV je bil redek. Pri približno 17 % bolnic smo odkrili več sočasnih vzrokov vaginalnih težav (kombinacije BV, CV ali SPO). Klinična diagnoza in laboratorijski izvid sta se ujemala pri 26 % bolnic. Zaključek: Rezultati izpostavljajo pomen celovitega (t.i. sindromskega tipa) laboratorijskega diagnosticiranja pri ženskah z ginekološkimi težavami. Ozko usmerjena laboratorijska diagnostika ne daje koristnih rezultatov zaradi pogostih kombinacij BV, AV, CV in SPO, poleg tega pa so klinični znaki pri različnih vzrokih vaginalnih težav podobni. To otežuje izbiro ustreznega zdravljenja ter vodi do ponovitev bolezni. Glede na rezultate bi bilo potrebno uporabiti več modernejših laboratorijskih preiskav.
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