Severe Fetal Malformations Research Articles

Analysis of clinical characteristics of discordant structural malformations in one of monochorionic diamnionic twins

Objective: To analyze the clinical characteristics of structural malformations in one of monochorionic diamnionic twins (MCDA). Methods: The clinical data of 77 MCDA patients with structural malformations diagnosed by ultrasound were retrospectively reviewed from January 2012 to May 2017. The distribution of structural malformations, prenatal chromosomal karyotyping and pregnancy outcomes were analyzed. Results: (1)Among the 77 MCDA patients with structural malformations, the single malformation accounted for 79%(61/77), the multiple malformations accounted for 21%(16/77). And there were a total of 94 types of malformations, the top three malformations were neurological malformations (32%, 30/94), cardiovascular malformations (29%, 27/94) and twin reversed arterial perfusion sequence (TRAPS;10%,9/94).(2)Among the 77 patients with structural malformation, 64 cases (83%, 64/77) were examined for fetal chromosomes, of whom 14 cases (22%,14/64) were examined for fetal chromosomes of both twins, with 1 case (1/14) of discordant fetal chromosome. (3)Among the 77 patients, 4 cases (5%, 4/77) with severe fetal malformations terminated pregnancy. Totally 29 cases (38%,29/77) with severe malformations were treated with selective fetal reduction, among whom 7 cases (24%, 7/29) experienced unexplained fetal death within 24 hours after the operation; 2 cases (7%, 2/29) happened inevitable abortion, and 2 cases (7%, 2/29) underwent unexplained fetal death during the late pregnancy. Of the remaining 44 patients (57%,44/77) with expectant treatment, 13 cases (30%,13/44) occurred twin transfusion syndrome (Ⅱ-Ⅳ), and were treated with fetoscopic laser occlusion. Eight patients had 2 survival twins, 4 patients delivered 1 survival twin, and 1 patient had dead twins. Conclusions: The most common malformations in MCDA twins are the nervous malformations, cardiovascular malformations and TRAPS. The chromosome karyotype of MCDA twins with structural malformations are sometimes discordant, and separate samling of the twins is suggested for prenatal diagnosis. Selective fetal reduction could be given to severe structural malformation in MCDA patients safely and effectively. For non-severe structural malformation in MCDA patients with twin transfusion syndrome, fetoscopic laser occlusion is safe and effective.

Assessment of immune susceptibility to rubella among pregnant women in Hilla City

Background: Rubella (German measles) is a viral infection, which is contagious disease and self-limiting. Nonimmune adult women may be infected during pregnancy; the 1st-trimester rubella infection is very dangerous and may lead to miscarriage or severe fetal malformation (congenital rubella syndrome). That is why basic epidemiological data concerning rubella (immunity and seropositivity) is necessary for health planners and health-care providers in preventive medicine. Objective: The main objective of the study was to assess the immune susceptibility to rubella among pregnant women by checking serum immunoglobulin (Rubella IgG) using enzyme-linked immunosorbent assay (ELISA) test. Materials and Methods: The study protocol was approved by the Ethical Committee of Babylon University, College of Medicine. A cross-sectional study was to investigate the seroprevalence of rubella infection and associated possible risk factors among pregnant women. A total of 100 pregnant women in their first trimester of pregnancy were enrolled from four different primary health-care centers in Al-Hilla city. Filling a prepared structured questionnaire followed by ELISA test to detect IgG against rubella in the blood samples was collected. Results: A total of 100 pregnant women with a mean age of 24.78 ± 5.74 years who are in their first trimester of pregnancy, the study shows that 58 (58%) of the pregnant women have negative IgG against rubella (none immune), whereas the remaining 42 (42%) have positive IgG (either by previous infection with rubella or through vaccination). Living in rural area was highly significant among the seronegative pregnant women, 32 out of 58 seronegative women (55.2%), 41 (97%) of the seropositive group had regular vaccination program, whereas 36 (62%) of the seronegative group had irregular or unknown vaccination history, and 18 (31%) have no vaccination at all with a P < 0.001. The primary level of education was dominant among all the studied women with a P = 0.017. Conclusion: A high percentage of women of reproductive age group, mainly those living in the rural area are considered (at risk) population which necessitates an action by the health services provider.

Foetal Morbidity Depending on the Day and Time of Delivery.

Introduction It is known that perinatal mortality is increased with births at night and at the weekend. The aim of the study was to investigate whether there is also an association between the time of delivery (weekday, night, weekend) and perinatal morbidity. Material and Methods All births at Hannover Medical College between 2000 and 2014 were included in a retrospective data analysis. Multiple births, primary sections, severe foetal malformations and intrauterine deaths were not included. A 5-minute Apgar score ≤ 5 and cord arterial pH < 7.10 were defined as perinatal morbidity. Besides the time of delivery, different variables that are regarded as risk factors for increased perinatal morbidity were studied. Univariate logistical regression analysis was performed, followed by multivariate analysis. Results 18 394 deliveries were included in the study. Pathological prepartum Doppler, medical induction of labour and delivery at night and/or at the weekend significantly increased the probability of an Apgar score ≤ 5 after 5 minutes. The probability that a child will have cord arterial pH < 7.1 post partum is significantly increased with a BMI > 25 before pregnancy, primiparity, medical induction of labour, peripartum administration of oxytocic agents, when the delivery took place at night and weekend combined, but also when the delivery took place at night or at the weekend/on a public holiday. Multivariate regression analysis showed that a time of delivery at night and/or at the weekend or on a public holiday is not a prognostic factor for a 5-minute Apgar score ≤ 5 (p = 0.2377) but is a prognostic factor for cord arterial pH < 7.1 (p = 0.0252). Conclusion The time of delivery at night or at the weekend/on a public holiday increases the risk for cord arterial pH < 7.1 by ~ 30% compared with delivery on a weekday. However, the time of delivery at night or at the weekend/on a public holiday does not increase the risk for the baby of having a 5-minute Apgar score ≤ 5.

Prediction of Zika-confirmed cases in Brazil and Colombia using Google Trends.

Zika virus infection in humans has been linked to severe neurological sequels and foetal malformations. The rapidly evolving epidemics and serious complications made the frequent updates of Zika virus mandatory. Web search query has emerged as a low-cost real-time surveillance system to anticipate infectious diseases' outbreaks. Hence, we developed a prediction model that could predict Zika-confirmed cases based on Zika search volume in Google Trends. We extracted weekly confirmed Zika cases of two epidemic countries, Brazil and Colombia. We got the weekly Zika search volume in the two countries from Google Trends. We used standard time-series regression (TSR) to predict the weekly confirmed Zika cases based on the Zika search volume (Zika query). The basis TSR model - using 1-week lag of Zika query and using 1-week lag of Zika cases as a control for autocorrelation - was the best for predicting Zika cases in Brazil and Colombia because it balanced the performance of the model and the advance time in the prediction. Our results showed that we could use Google search queries to predict Zika cases 1 week earlier before the outbreak. These findings are important to help healthcare authorities evaluate the outbreak and take necessary precautions.

Pfeiffer syndrome type 2 – two cases from the Pleven Registry of Congenital Anomalies

Pfeiff er syndrome is a rare autosomal dominant congenital disorder with the main features of acrocephalic skull, midfacial hypoplasia,syndactyly of hands and feet, broad thumbs and big toes. Three clinical subtypes (with diff erent diagnostic and prognostic implications)have been identifi ed. We report on two cases of Pfeiff er syndrome type 2 (one of them diagnosed prenatally and theother detected in the newborn), identifi ed through screening for congenital defects as an activity of the Pleven Registry of CongenitalAnomalies (member of EUROCAT). Case 1 was a male foetus from terminated pregnancy following prenatal diagnosis. Foetal morphologyultrasound in the 28th week of gestation revealed craniosynostosis, cloverleaf skull, fl at face, exophthalmos, macroglossia,short ribs, deformed spine, and abnormally shortened limbs (micromelia). Clinical examination after birth confi rmed the diagnosisof Pfeiff er syndrome type 2. Case 2 was a boy (born at term, 40th week of gestation) diagnosed with Pfeiff er syndrome type 2 at birth.Multiple malformations were presented including cloverleaf skull, craniosynostosis of coronal suture, midfacial hypoplasia, depressednasal bridge, high palate, exophthalmos, down-slanted palpebral fi ssures, hypertelorism, low-set ears, short neck, broad andmedially deviated thumbs and hallux, clinodactyly V, skin syndactyly of II-III toe, short thorax with sternal depression, and anal atresia.The patient died from respiratory distress syndrome on the ninth day after birth. Severe malformations, high mortality andproblems in clinical management determine poor prognosis in most cases of Pfeiff er syndrome type 2. Early prenatal diagnosis inpregnancies with severe foetal malformations and poor prognosis gives parents more time and opportunities for reproductivechoices.

Blurred Lines: Disentangling the Concept of Fetal Viability from Abortion Law.

Blurred Lines: Disentangling the Concept of Fetal Viability from Abortion Law.

Roles of venovenous anastomosis and umbilical cord insertion abnormalities in birthweight discordance in monochorionic-diamniotic twin pregnancies without twin-twin transfusion syndrome.

We evaluated risk factors for birthweight discordance in monochorionic diamniotic (MCDA) twin pregnancies without twin-twin transfusion syndrome (TTTS). We investigated all MCDA twin placentas injected with colored dye at our institution between 2007 and 2015. We excluded pairs of twins with TTTS, fetal demise, or severe fetal malformation. All pairs of twins were assigned to the discordant group (birthweight discordance ≥ 25%) or the concordant group (birthweight discordance < 25%). In each pair of twins, we described vascular anastomoses as either arterioarterial, venovenous (VV), or arterial-venous, and abnormal umbilical cord insertion as either marginal or velamentous. We also recorded placental sharing discordance. A total of 150 placentas were analyzed. The incidence of VV anastomosis in the discordant group (40%) was significantly higher than that in the concordant group (12%, P = 0.005). Unilateral abnormal umbilical cord insertion was significantly more common in the discordant group (85%) than in the concordant group (38%, P < 0.001). Placental sharing discordance was seen more frequently in the discordant group than in the concordant group. Multiple logistic analysis revealed that VV anastomosis (odds ratio: 4.7; 95% confidence interval: 1.2-18.6, P < 0.01) and unilateral abnormal umbilical cord insertion of the smaller twin (odds ratio: 5.7; 95% confidence interval: 1.4-22.9, P < 0.01) were independent risk factors for birthweight discordance. VV anastomoses and unilateral abnormal umbilical cord insertion of the smaller twin are independent risk factors for birthweight discordance in MCDA twin pregnancies without TTTS.

First Experience Using Brazilian Ingamed&amp;lt;sup&amp;gt;&amp;amp;reg&amp;lt;/sup&amp;gt; Cervical Pessary in Twin Pregnancy: A Case Series

Background: The rate of prematurity in twin pregnancies is higher than 50%. Due to its multifactorial nature, different strategies are necessary to reduce the incidence of premature birth or to increase the gestational age at birth of pregnancies at risk. In this context, cervical pessary may be indicated in twin pregnancies with short cervix. Methods: In this case series, we describe six twin pregnancies that were considered as high-risk for preterm labor due to short cervix (CL < 30 mm) at second trimester and multiple risk factors for prematurity. Several strategies were associated for the goal of delaying gestational age at birth. The main strategies were: removal of labor activities, treatment of infections, vaginal micronized progesterone 400 mg/day and vaginal pessary insertion (Ingamed&reg Brazil). Results: The gestational age of insertion of the pessary ranged from 16 to 24 weeks. The gestational age of birth ranged from 26 to 34 weeks. Three of the pregnancies were delivered due to spontaneous onset of labor, and three were delivered due to medical reasons. The mean length of pregnancy since pessary insertion to birth was 9 weeks (range 2 to 17 weeks). All infants without severe fetal malformation were discharged from the hospital without major sequelae. Conclusion: The use of cervical pessaries associated to micronized progesterone at a dose of 400 mg/day may be an option in the management of twins at risk for preterm birth. More controlled studies are needed to evaluate the simultaneous use of cervical pessary and progesterone on twin pregnancies.

Fever in pregnancy and the risk of congenital malformations: a cohort study

BackgroundIn a variety of animal species, hyperthermia in pregnancy has been recognized as teratogenic. Hyperthermia interferes with protein synthesis via heat-shock proteins, which can entail membrane disruption, cell death, vascular disruption, and placental infarction. This can induce severe fetal malformations or death. Fever during pregnancy, especially during embryogenesis, has also been associated with congenital malformations in human offspring.The purpose of this large cohort study of clinically recognized pregnancies was to investigate whether fever during first trimester was associated with an increased risk of congenital malformations in the offspring.MethodsThe Danish National Birth Cohort is a population-based cohort of 100,418 pregnant women and their offspring recruited in 1996 to 2002. Information on fever during pregnancy was collected prospectively by means of two telephone interviews.The study population comprised the 77,344 pregnancies enrolled in the Danish National Birth Cohort where self-reported information on fever during first trimester of pregnancy was available. Pregnancy outcomes were identified through linkage with the National Patient Registry. Congenital malformations within the first three and a half years of life were categorized according to EUROCAT’s classification criteria. Logistic regression models were used to estimate the associations between fever in first trimester and overall congenital malformations and congenital malformations by subgroups.ResultsEight thousand three hundred twenty-one women reported fever during first trimester (10.8%) and 2876 infants were diagnosed with a congenital malformation (3.7%). Fever during first trimester did not affect the risk of overall fetal congenital malformation (OR 0.99, 95% CI 0.88–1.12). The subgroup analyses indicated slightly higher risk of congenital anomalies in the eye, ear, face and neck (OR 1.29, 95% CI 0.78–2.12) and in the genitals (OR 1.17, 95% CI 0.79–1.12), whereas lower risk of malformations in the nervous system (OR 0.47, 95% CI 0.21–1.08), the respiratory system (OR 0.56, 95% CI 0.23–1.29) and in the urinary subgroup (OR 0.58, 95% CI 0.35–0.99) was suggested, the latter constituting the only statistically significant finding.ConclusionsOverall, this study did not show any association between maternal fever in pregnancy and risk of congenital anomalies.

From women’s ‘irresponsibility’ to foetal ‘patienthood’: Obstetricians-gynaecologists’ perspectives on abortion and its stigmatisation in Italy and Cataluña

ABSTRACTThis article explores obstetricians-gynaecologists’ experiences and attitudes towards abortion, based on two mixed-methods studies respectively undertaken in Italy in 2011–2012, and in Spain (Cataluña) in 2013–2015. Short questionnaires and in-depth interviews were conducted with 54 obstetricians-gynaecologists at 4 hospitals providing abortion care in Rome and Milan, and with 23 obstetricians-gynaecologists at 2 hospitals and one clinic providing abortion care in Barcelona. A medical/moral classification of abortions, from those considered ‘more acceptable’, both medically and morally – for severe foetal malformations – to the ‘least acceptable’ ones – repeated ‘voluntary abortions’, emerged in the discourse of most obstetricians-gynaecologists working in public hospitals, regardless of their religiosity. I argue that this is the result of the increasing medicalisation of contraception as well as of reproduction, which has reinforced the stigmatisation of ‘voluntary abortion’ (in case of unintended pregnancy) in a context of declining fertility rates. This contributes to explain why obstetricians-gynaecologists working in Catalan hospitals, which provide terminations only for medical reasons, unlike Italian hospitals, do not experience abortion stigma and do not object to abortion care as much as their Italian colleagues do.

Linear association between maternal age and spontaneous breech presentation in singleton pregnancies after 32 weeks gestation

Purpose: To investigate the association between maternal age and spontaneous breech presentation.Material and methods: Fifteen-year observational study over (2001–2015). All consecutive singleton births delivered at the Centre Hospitalier Universitaire Sud Reunion’s maternity. The only single exclusion criterion was uterine malformations (N = 123) women.Results: Of the 60,963 singleton births, there was a linear association (χ2 for linear trend, p< 0.0001) between maternal age and spontaneous breech presentation. Overall rate of breech presentation was 2.7% in deliveries over 32 weeks gestation, while it was 1.9% in women aged 15 to 19 years and 4.0% in women aged 45+, with a linear progression for each 5-year age category. This linearity remained significant controlling for early prematurity (<33 weeks) and severe fetal malformations (χ2 for linear trend = 64, p < 0.0001). Controlling in a multiple logistic regression model for other major risk factors gestational age, female sex, primiparity, maternal age remained significantly an independent risk factor, p < 0.0001.Conclusion: Maternal age (x) is an independent factor for breech presentation in singleton pregnancies after 32 weeks gestation with a linear association that may be approximated at y = 0.1x. (y: incidence, percent).

Schmallenberg Virus: A Novel Virus of Veterinary Importance.

In late 2011, unspecific clinical symptoms such as fever, diarrhea, and decreased milk production were observed in dairy cattle in the Dutch/German border region. After exclusion of classical endemic and emerging viruses by targeted diagnostic systems, blood samples from acutely diseased cows were subjected to metagenomics analysis. An insect-transmitted orthobunyavirus of the Simbu serogroup was identified as the causative agent and named Schmallenberg virus (SBV). It was one of the first detections of the introduction of a novel virus of veterinary importance to Europe using the new technology of next-generation sequencing. The virus was subsequently isolated from identical samples as used for metagenomics analysis in insect and mammalian cell lines and disease symptoms were reproduced in calves experimentally infected with both, this culture-grown virus and blood samples of diseased cattle. Since its emergence, SBV spread very rapidly throughout the European ruminant population causing mild unspecific disease in adult animals, but also premature birth or stillbirth and severe fetal malformation when naive dams were infected during a critical phase of gestation. In the following years, SBV recirculated regularly to a larger extend; in the 2014 and 2016 vector seasons the virus was again repeatedly detected in the blood of adult ruminants, and in the following winter and spring months, a number of malformed calves and lambs was born. The genome of viruses present in viremic adult animals showed a very high sequence stability; in sequences generated between 2012 and 2016, only a few amino acid substitutions in comparison to the initial SBV isolate could be detected. In contrast, a high sequence variability was identified in the aminoterminal part of the glycoprotein Gc-encoding region of viruses present in the brain of malformed newborns. This mutation hotspot is independent of the region or host species from which the samples originated and is potentially involved in immune evasion mechanisms.

Tomografía computarizada fetal de baja dosis para diagnosticar displasias óseas

We present a case of cleidocranial dysplasia diagnosed by low-dose fetal computed tomography (CT) in the 25th week of gestation. Severe bone dysplasia was suspected because of the fetus’ low percentile in long bones length and the appearance of craniosynostosis on sonography. CT found no abnormalities incompatible with life. The effective dose was 5 mSv, within the recommended range for this type of examination. Low-dose fetal CT is a new technique that makes precision study of the bony structures possible from the second trimester of pregnancy. In Spain, abortion is legal even after the 22nd week of gestation in cases of severe fetal malformations. Therefore, in cases in which severe bone dysplasia is suspected, radiologists must know the strategies for reducing the dose of radiation while maintaining sufficient diagnostic quality, and they must also know which bony structures to evaluate.

Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus

ABSTRACTZika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC50], <1:100 serum dilution; 18%) or moderate to high (EC50, >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV.

Update on the birth weight standard and its diagnostic value in small for gestational age (SGA) infants in China

Objectives: To identify the difference between the current newborn birth weight standard and the previous standard in China, and to evaluate the diagnostic value of newborn birth weight in small for gestational age (SGA) infants.Methods: A retrospective analysis was conducted of 112 441 delivery cases in 2011, from 39 hospitals at different levels in 14 provinces and autonomous regions. Cases with incomplete data, gestational age <24 weeks, or severe fetal malformations or fetal death were excluded. Data were recorded and entered on hard paper copies and into an online database. SPSS 18.0 and SAS 9.2 statistical software were used for data analysis.Results: This study included 109 004 valid cases with an average birth weight of 3226.02 ± 525.82 g. Birth weight changed significantly from 1988 for all gestational ages. In preterm infants with gestational age <37 weeks, birth weight for each gestational week was lower than that in the birth weight standard from 15 cities in China in 1988 (p < 0.001). Full-term infants with gestational ages from 37 to 41+6 weeks showed significantly higher average birth weights compared with the previous birth weight standards (p < 0.001). The birth weight standard in this study exhibited better correlations than did the previous standard with regard to the diagnoses of adverse pregnancy outcomes, including SGA infants, stillbirth, neonatal asphyxia, neonatal death and neonatal complications; with RR values of 18.843 (9.656–36.774; 95% CI), 33.125 (14.576–75.275), 24.254 (10.630–56.256) and 2.492 (0.328–18.909), respectively.Conclusions: The current birth weight standard used in Chinese medical institutions was enacted in 1988. This is not suitable for today’s socioeconomic and clinical requirements, and needs to be updated. Diagnosis of preterm infants with SGA based upon the updated demographic birth weight standard manifested higher accuracy and avoided unnecessary medical interventions. However, the updated demographic birth weight standards were no better diagnostically than the previous standard for full-term infants. Customized birth weight standards from larger sample sizes and multi-center studies will be necessary to determine the appropriate birth weight standards in developing countries.

Zika Virus Disease.

The history of Zika virus disease serves as a paradigm of a typical emerging viral infection. Zika virus disease, a mosquito-borne flavivirus, was first isolated in 1947 in the Zika forest of Uganda. The same virus was also isolated from jungle-dwelling mosquitoes (Aedes [Stegomyia] africanus). In many areas of Africa and South Asia human infections with Zika virus were detected by both serology and virus isolation. About 80% of infections are asymptomatic, and in 20% a mostly mild disease with fever, rash, arthralgia, and conjunctivitis may occur. Fetal infections with malformations were not recorded in Africa or Asia. Zika virus was imported to northern Brazil possibly during the world soccer championship that was hosted by Brazil in June through July 2014. A cluster of severe fetal malformations with microcephaly and ocular defects was noted in 2015 in the northeast of Brazil, and intrauterine infections with Zika virus were confirmed. The dramatic change in Zika virus pathogenicity upon its introduction to Brazil has remained an enigma.

Rare detection of cytomegalovirus in severe fetal malformations in China

BackgroundCytomegalovirus (CMV) is a significant cause of fetal abnormalities in developed world. Whether this could be applied in developing world remains unknown. ObjectivesTo investigate CMV infection in severe fetal malformations in China. Study designDuring 2007–2014, 436 fetuses (237 males) with severe malformations and terminated pregnancy at median gestational age of 26+1 weeks were enrolled. CMV DNA was detected in fetal kidneys and other tissues by real-time PCR, and CMV IgG and IgM were measured by ELISA. ResultsCMV DNA was positive in kidneys and other tissues of seven (1.60%) fetuses. Hematoxylin-eosin staining showed intranuclear and intracytoplasmic inclusion bodies in kidneys of three fetuses, which was also positive for CMV antigens in immunohistochemistry. CMV DNA was found in 5 (6.1%) of 82 fetuses with central nervous system anomalies, 1 (11.1%) of 9 fetuses with abdominal anomalies, 1 (0.59%) of 168 fetuses with multiple congenital malformations, and none of fetuses with other anomalies (177). Of 293 pregnant women with plasma available, 279 (95.2%) were CMV IgG positive only and 6 (2.1%) were CMV IgG and IgM positive. Of 5 mothers with infected fetuses 1 (20%) was CMV IgG and IgM positive, while 5 (1.7%) of 288 mothers with uninfected fetuses were positive respectively (P=0.099). ConclusionsCongenital CMV infection in fetuses with severe congenital malformations is rare, indicating no close association between CMV infection and severe fetal malformations in China. Maternal screening for CMV may have minimal value in identifying fetal malformations in developing world.

Future healthcare professionals' knowledge about the Argentinean abortion law.

ObjectivesWe assessed healthcare students’ knowledge and opinions on Argentinian abortion law and identified differences between first- and final-year healthcare students.MethodsIn this cross-sectional study, self-administered anonymous questionnaires were administered to 760 first- and 695 final-year students from different fields of study (medicine, midwifery, nursing, radiology, nutrition, speech therapy, and physiotherapy) of the School of Medicine at the University of Buenos Aires, in 2011-2013.ResultsCompared to first-year students, a higher percentage of final-year students knew that abortion is legally restricted in Argentina (p < 0.001). A significantly higher percentage of final-year students could correctly identify the circumstances in which abortion is legal: woman´s life risk (87.4% last vs. 79.1% first year), rape of a woman with developmental disability (66.2% first vs. 85.4% last-year; p < 0.001). More final-year students chose severe foetal malformations (37.3% first year vs. 57.3% final year) despite its being illegal.ConclusionsAlthough most final-year students knew that abortion is legally restricted in Argentina, misconceptions regarding circumstances of legal abortion were observed; this may be due to the fact that abortion is inadequately covered in the medical curricula. Medical schools should ensure that sexual and reproductive health topics are an integral part of their curricula. Healthcare providers who are aware of the legality of abortion are more likely to provide the public with sound information and ensure abortions are appropriately performed.

Rubella virus: first calcium-requiring viral fusion protein.

Rubella virus (RuV) infection of pregnant women can cause fetal death, miscarriage, or severe fetal malformations, and remains a significant health problem in much of the underdeveloped world. RuV is a small enveloped RNA virus that infects target cells by receptor-mediated endocytosis and low pH-dependent membrane fusion. The structure of the RuV E1 fusion protein was recently solved in its postfusion conformation. RuV E1 is a member of the class II fusion proteins and is structurally related to the alphavirus and flavivirus fusion proteins. Unlike the other known class II fusion proteins, however, RuV E1 contains two fusion loops, with a metal ion complexed between them by the polar residues N88 and D136. Here we demonstrated that RuV infection specifically requires Ca2+ during virus entry. Other tested cations did not substitute. Ca2+ was not required for virus binding to cell surface receptors, endocytic uptake, or formation of the low pH-dependent E1 homotrimer. However, Ca2+ was required for low pH-triggered E1 liposome insertion, virus fusion and infection. Alanine substitution of N88 or D136 was lethal. While the mutant viruses were efficiently assembled and endocytosed by host cells, E1-membrane insertion and fusion were specifically blocked. Together our data indicate that RuV E1 is the first example of a Ca2+-dependent viral fusion protein and has a unique membrane interaction mechanism.

Deletion mutants of Schmallenberg virus are avirulent and protect from virus challenge.

Since its emergence, Schmallenberg virus (SBV), a novel insect-transmitted orthobunyavirus which predominantly infects ruminants, has caused a large epidemic in European livestock. Newly developed inactivated vaccines are available, but highly efficacious and safe live vaccines are still not available. Here, the properties of novel recombinant SBV mutants lacking the nonstructural protein NSs (rSBVΔNSs) or NSm (rSBVΔNSm) or both of these proteins (rSBVΔNSs/ΔNSm) were tested in vitro and in vivo in type I interferon receptor knockout mice (IFNAR(-/-)) and in a vaccination/challenge trial in cattle. As for other bunyaviruses, both nonstructural proteins of SBV are not essential for viral growth in vitro. In interferon-defective BHK-21 cells, rSBVΔNSs and rSBVΔNSm replicated to levels comparable to that of the parental rSBV; the double mutant virus, however, showed a mild growth defect, resulting in lower final virus titers. Additionally, both mutants with an NSs deletion induced high levels of interferon and showed a marked growth defect in interferon-competent sheep SFT-R cells. Nevertheless, in IFNAR(-/-) mice, all mutants were virulent, with the highest mortality rate for rSBVΔNSs and a reduced virulence for the NSm-deleted virus. In cattle, SBV lacking NSm caused viremia and seroconversion comparable to those caused by the wild-type virus, while the NSs and the combined NSs/NSm deletion mutant induced no detectable virus replication or clinical disease after immunization. Furthermore, three out of four cattle immunized once with the NSs deletion mutant and all animals vaccinated with the virus lacking both nonstructural proteins were fully protected against a challenge infection. Therefore, the double deletion mutant will provide the basis for further developments of safe and efficacious modified live SBV vaccines which could be also a model for other viruses of the Simbu serogroup and related orthobunyaviruses. SBV induces only mild clinical signs in adult ruminants but causes severe fetal malformation and, thereby, can have an important impact on animal welfare and production. As SBV is an insect-transmitted pathogen, vaccination will be one of the most important aspects of disease control. Here, mutant viruses lacking one or two proteins that essentially contribute to viral pathogenicity were tested as modified live vaccines in cattle. It could be demonstrated that a novel recombinant double deletion mutant is a safe and efficacious vaccine candidate. This is the first description of a putative modified live vaccine for the complete genus Orthobunyavirus, and in addition, such a vaccine type has never been tested in cattle for any virus of the entire family Bunyaviridae. Therefore, the described vaccine also represents the first model for a broad range of related viruses and is of high importance to the field.