Zika Virus Associated with Microcephaly Mlakar, Jernej; Korva, Misa; Tul, Nataša ...
New England journal of medicine/The New England journal of medicine,
2016-Mar-10, Letnik:
374, Številka:
10
Journal Article
Recenzirano
Odprti dostop
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased ...incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.
Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains ...poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice.
We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors.
Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6-6.0 and 2.8-5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25-50% and 11-16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted.
We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions.
Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show ...poor specificity and selectivity for diagnosing maternal malignancies.
This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers.
Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%.
The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies-positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.
To evaluate the impact of prenatal screening and genetic testing for trisomy 21 (T21) on the prevalence of T21 in Slovenia.
Data about all prenatally and postnatally confirmed cases of T21 in ...Slovenia between 1981 and 2012 were collected retrospectively from all genetic laboratories in Slovenia. The expected number of babies with T21 according to maternal age was calculated.
The primary outcomes measures were number of fetuses and newborn infants with T21 diagnosed prenatally and postnatally and the impact of advances in screening and genetic diagnostics on the prevalence of newborns with T21 in Slovenia.
Despite a significantly increased mean maternal age from 25.4 years in year 1981 to 30.3 years in year 2012 the prevalence of newborn infants with T21 was 0.51 per 1000 births compared to 0.55 per 1000 births, respectively. The prevalence of prenatally diagnosed cases increased from 0.03 per 1000 births to 2.06 per 1000. The detection rate of T21 in year 2012 was 78,9%. The total number of prenatal invasive procedures (chorionic villous sampling and amniocenteses) carried out during that period was rising until 2002, since when it is stable at around 7%.
The advancement and implementation of screening tests and prenatal diagnostic procedures in Slovenia caused an important improvement in the efficiency of the prenatal detection of T21.
Macrosomia in singleton pregnancies and associated risks have been well characterized. Less is known about the outcomes of macrosomic newborns in twin pregnancy.Objective of this study was to compare ...maternal characteristics and perinatal outcomes of "growth promoted twins" (twin pairs with a total twin birth weight above 90th percentile) to "normally grown twins" (twin pairs with a total twin birth weight between 50th and 90th percentile).
We evaluated data (maternal characteristics and perinatal outcomes) of dichorionic–diamniotic twins born at 34 weeks of gestational age or later over a sixteen-year period (2002–2018) in two birth weight groups. We excluded twin pairs born before 34th week of gestation and discordant twin pairs. We used data from the Slovenian National Perinatal Information System.To define the percentiles, twin-specific growth curves have been used.
Our study population consisted of 390 twin pregnancies with a twin total birth weight over 90th percentile and 1618 pregnancies with a total twin birth weight between 50th and 90th percentile for gestational age. Women in "growth promoted" twin group were significantly taller, heavier and more often multiparous. There was a higher incidence of gestational diabetes (10.8% vs 7.3%, OR 1.53 95% CI 1.06 – 2.22), a lower rate of caesarean births (48.2% vs 53.9%, OR 0.80 CI 0.64 – 0.99) and lower rate of assisted reproduction (21.0% vs 27.1%, OR 0.71 CI 0.55 – 0.93) in women in "growth promoted" twin group. There were no statistically significant differences in neonatal outcomes in both groups.
In contrast to macrosomia in singletons, macrosomia in twins does not appear to increase the risk for adverse perinatal outcomes.
-The 2015 outbreak of Zika virus in Brazil resulted in a 20-times increased prevalence of congenital microcephaly in stillborns and neonates and was instrumental in raising the suspicion of a causal ...association between Zika virus and microcephaly.
-To provide a comprehensive description of the neuropathologic features of congenital Zika virus infection.
-Autopsy evaluation of the brain from a fetus of 32 weeks and 6 days of gestation, with a prenatal diagnosis of microcephaly associated with polymerase chain reaction-confirmed, fetal, Zika virus infection.
-Multiple severe pathology findings were present. These included lissencephaly, except for the occipital lobes, where some pachygyria was observed. Also present was reduction and thinning of white matter, ventriculomegaly of the lateral ventricles, and coalescent calcifications in the cortical-subcortical white matter border associated with glioneuronal outbursting into the subarachnoid space above and heterotopias below. There were small, scattered calcifications in the basal ganglia, with fewer in the white matter and germinal matrix, and none in the cerebellum and brainstem. The cerebellum and pontine base were atrophic because of Wallerian degeneration or maldevelopment of descending tracts and pontocerebellar connections.
-Our findings are in agreement with neuroimaging of Zika virus-associated fetal and infant micrencephalic brains and, to some extent, with neuroimaging of other intrauterine infections causing microcephaly.
Introduction: To estimate the procedure-related risks of pregnancy loss following chorionic villus sampling (CVS) and amniocentesis (AC) compared to pregnancies without procedure.
This cohort study ...enrolled all women who underwent CVS or AC at the Department of Perinatology, University Medical Centre, Ljubljana, Slovenia (from January 2013 to June 2015). For each group we obtained a maternal age and gestational age (11-14 weeks for CVS and >15 weeks for AC) for a matched control group without invasive procedures from the national database. The data was obtained from hospital records and telephone surveys concerning pregnancy outcomes. Pregnancy loss rates in intervention vs. control groups were compared by generating relative risk (RR) with a 95% confidence interval.
During the study period, 828 women underwent CVS and 2,164 women underwent AC. Complete outcome data was available in 2,798 cases (93.5%, 770 CVS, 2,028 AC). Pregnancy loss occurred in 8/770 (1.04%, 95% CI 0.4-2.0%) after CVS vs. 15/1130 (1.33%, 95% CI 0.8-2.2%) in matched control (RR 0.8, 95% CI 0.33-1.8, p=0.6). It occurred in 16/2028 (0.79%, 95% CI 0.5-1.3%) after AC vs. 14/395 (3.29%, 95% CI 2.1-5.8%) in matched control (RR 0.2, 95% CI 0.11-0.45, p<0.0001).
The pregnancy loss rates after CVS and AC were comparable to losses in pregnancies without these procedures. With the increasing use of non-invasive prenatal testing, information that the invasive procedures are safe when indicated is essential.
Background
The implementation of molecular karyotyping has resulted in an improved diagnostic yield in the genetic diagnostics of congenital anomalies, detected prenatally or after the termination of ...pregnancy. However, the systematic epidemiologic ascertainment of copy number variations in the etiology of congenital anomalies has not yet been sufficiently explored.
Methods
Consecutive fetuses, altogether 204, with major single or multiple congenital anomalies were ascertained by using the SLOCAT registry for the period from 2011 to 2015. After excluding aneuploidies by using conventional karyotyping or Quantitative Fluorescence‐Polymerase Chain Reaction, array comparative genomic hybridization was performed for the detection of copy number variations.
Results
We identified pathogenic or likely pathogenic copy number variations in 14 fetuses (6.8%); 2.9% in fetuses with isolated, and 3.9% in fetuses with multiple congenital anomalies. Additionally, aneuploidies and major structural chromosomal abnormalities were detected in 40.2%.
Conclusion
Our systematic approach of ascertaining congenital anomalies resulted in explaining the etiology of congenital anomalies in 47% of fetuses after the termination of pregnancy. By using array comparative genomic hybridization, we found that copy number variations represent an important part in the etiology of multiple, as well as isolated congenital anomalies, which indicates the importance of analyzing copy number variations in the diagnostic approach of fetuses with congenital anomalies after the termination of pregnancy.
In our study, which was ascertained on a cohort population of consecutive fetuses with unselected isolated and multiple CAs after the termination of pregnancy, the frequency of CNVs was 6.8%, which implicates an important role of aCGH in the genetic diagnostics of fetuses with CAs after the termination of pregnancy.
Objective: To evaluate changes in vascular function and serum biomarkers in women with and without preeclampsia (PE) to create a model for the easier and more precise diagnosis of PE in the future. ...Methods: Endothelial function and arterial stiffness were evaluated using peripheral arterial tonometry and concentrations of placental growth factor (PlGF), soluble fms like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were determined by immunoassay. Results: Arterial stiffness deteriorates and endothelial function is better in women with PE compared with a healthy pregnancy. Women who developed PE had a decreased PlGF and PlGF/(sFlt-1+ sEng) ratio and an increased sEng, and sFlt-1/PlGF ratio. Conclusion: Peripheral arterial analysis did provide additional information beyond serum biomarkers in the diagnosis of PE.
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