Epidemic of parvovirus B19 and disease severity in pregnant people, Denmark, January to March 2024.

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.

SARS-CoV-2 placentitis and severe pregnancy outcome after maternal infection: A Danish case series.

INTRODUCTION: SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood. MATERIAL AND METHODS: To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress. RESULTS: The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain. CONCLUSION: We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn.

SARS-CoV-2 infection in early first-trimester miscarriages: a prospective observational study.

RESEARCH QUESTION: Is there an association between SARS-CoV-2 infection and first-trimester miscarriage? DESIGN: This multicentre prospective study included a cohort of women with first-trimester miscarriages registered consecutively by seven Spanish hospitals where universal PCR screening for SARS-CoV-2 infection was implemented with both miscarriages and deliveries. The incidence of SARS-CoV-2 infection among women with first-trimester miscarriages was compared with the rate registered in women on admission to the delivery ward within the same time frame using a mixed-effects Poisson regression analysis, considering 'hospital' as random effect. The characteristics of SARS-CoV-2 positive and negative patients who miscarried were compared through two-sided univariable analyses. RESULTS: A total of 301 miscarriages were registered, 11 (3.7%) to SARS-CoV-2 infected and 290 to non-infected women. In the same time frame as the miscarriages, 1936 deliveries were registered, 44 [2.3%] of them were SARS-CoV-2 infected. No differences in terms of SARS-CoV-2 infection incidence were observed between infected miscarriages and infected deliveries (P = 0.233). Regarding the differences observed between miscarriages in SARS-CoV-2 positive and negative women, more inevitable miscarriages occurred in the group of infected women (36.4% versus 16.5% in non-infected women; P = 0.004), and there was greater surgical management of miscarriages (27.3% versus 8.2% in non-infected women; P = 0.036), probably in line with the greater number of inevitable miscarriages observed in this group. CONCLUSIONS: No association between SARS-CoV-2 infection and risk of first-trimester miscarriage was observed; however, the type of miscarriage seems to differ between SARS-CoV-2 positive and negative women, with inevitable miscarriage being more frequent among infected women.

Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast.

BACKGROUND: SARS-CoV-2 infection in term placenta is rare. However, growing evidence suggests that susceptibility of the human placenta to infection may vary by gestational age and pathogen. For several viral infections, susceptibility appears to be greatest during early gestation. Peri-implantation placental infections that result in pre-clinical pregnancy loss would typically go undetected. Little is known about the effects of SARS-CoV-2 on the peri-implantation human placenta since this time in pregnancy can only be modeled in vitro. METHODS: We used a human embryonic stem cell (hESC)-derived model of peri-implantation placental development to assess patterns of ACE2 and TMPRSS2 transcription and protein expression in primitive trophoblast. We then infected the same trophoblast cell model with a clinical isolate of SARS-CoV-2 and documented infection dynamics. RESULTS: ACE2 and TMPRSS2 were transcribed and translated in hESC-derived trophoblast, with preferential expression in syncytialized cells. These same cells supported replicative and persistent infection by SARS-CoV-2, while non-syncytialized trophoblast cells in the same cultures did not. CONCLUSIONS: Co-expression of ACE2 and TMPRSS2 in hESC-derived trophoblast and the robust and replicative infection limited to syncytiotrophoblast equivalents support the hypothesis that increased viral susceptibility may be a defining characteristic of primitive trophoblast.

Fetal and placental infection with SARS-CoV-2 in early pregnancy.

To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second- and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence, and electron microscopy methods. SARS-CoV-2 nucleocapsid protein, viral RNA, and particles consistent with coronavirus were found in the placenta and fetal tissues, accompanied by RNA replication revealed by double-stranded RNA (dsRNA) positive immunostain. Prominent damage of the placenta and fetal organs were associated with a hyperinflammatory process identified by histological examination and immunohistochemistry. The findings provided in this study document that congenital SARS-CoV-2 infection is possible during the first trimester of pregnancy and that fetal organs, such as lung and kidney, are targets for coronavirus. The infection and multi-organic fetal inflammation produced by SARS-CoV-2 during early pregnancy should alert clinicians in the assessment and management of pregnant women for possible fetal consequences and adverse perinatal outcomes.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Systematic review: fetal death reporting and risk in Zika-affected pregnancies.

OBJECTIVES: Zika virus is linked to several adverse pregnancy outcomes. We assessed whether Zika infection during pregnancy is associated with increased risk of foetal death (miscarriage, stillbirth, abortion) and whether there is incomplete reporting of such deaths. METHODS: We searched PubMed, Embase, CINAHL, Web of Science and LILACS for studies reporting Zika-affected completed pregnancies (ending in foetal death or live birth), excluding studies whose aim required live birth. Studies 'allowed' foetal death if their populations were defined to encompass both live births and foetal deaths, regardless of whether deaths were actually found. Two authors independently extracted data and assessed study quality. Foetal death absolute and relative risks in Zika-affected vs. unaffected pregnancies were calculated. RESULTS: We found 108 reports including 24 699 completed, Zika-affected pregnancies. The median absolute risk in 37 studies of completed, Zika-affected pregnancies was 6.3% (IQR 3.2%, 10.6%) for foetal death and 5.9% (IQR 0%, 29.1%) for non-fatal adverse outcomes (e.g. microcephaly). More studies allowed non-fatal adverse outcomes (95%) than foetal death (58%). Of studies which allowed them, 94% found at least one foetal death. In 37% of reports, it was unknown whether foetal deaths were allowed. Only one study had sufficient data to estimate a foetal death relative risk (11.05, 95% CI 3.43, 35.55). CONCLUSIONS: Evidence was insufficient to determine whether foetal death risk is higher in Zika-affected pregnancies, but suggests quality of foetal death reporting should be improved, including stating whether foetal deaths were found, how many, and at what gestational ages, or justifying their exclusion.

OBJECTIFS: Le virus Zika est lié à plusieurs issues défavorables de la grossesse. Nous avons évalué si l'infection à Zika pendant la grossesse était associée à un risque accru de mort fœtale (fausse couche, mortinaissance, avortement) et s'il y avait une déclaration incomplète de ces décès. MÉTHODES: Nous avons recherché dans PubMed, EMBASE, Cinahl, Web of Science et LILACS des études rapportant des grossesses terminées touchées par le virus Zika (se terminant par une mort fœtale ou une naissance vivante), à l'exclusion des études dont l'objectif nécessitait une naissance vivante. Les études «autorisaient¼ la mort fœtale si leur population était définie comme englobant à la fois les naissances vivantes et les décès fœtaux, indépendamment du fait que des décès aient été effectivement constatés. Deux auteurs ont indépendamment extrait les données et évalué la qualité des études. Les risques absolus et relatifs de mortalité fœtale dans les grossesses affectées par Zika par rapport aux grossesses non affectées ont été calculés. RÉSULTATS: Nous avons trouvé 108 reports dont 24.699 grossesses terminées et affectées par le virus Zika. Le risque médian absolu dans 37 études portant sur des grossesses terminées affectées par Zika était de 6,3% (IQR 3,2%, 10,6%) pour la mort fœtale et de 5,9% (IQR 0%, 29,1%) pour les issues indésirables non mortelles (par exemple microcéphalie). Plus d'études ont «autorisé¼ des résultats indésirables non mortels (95%) que la mort fœtale (58%). Parmi les études qui les ont «autorisé¼, 94% ont trouvé au moins un décès fœtal. Dans 37% des rapports, il n'est pas indiqué si la mort fœtale avait été «autorisée¼. Une seule étude contenait des données suffisantes pour estimer un risque relatif de mort fœtale (11,05 ; IC95%: 3,43, 35,55). CONCLUSIONS: Les données étaient insuffisantes pour déterminer si le risque de mort fœtale est plus élevé dans les grossesses touchées par le virus Zika, mais suggèrent que la qualité des reports sur les décès fœtaux devrait être améliorée, notamment en indiquant si des décès fœtaux ont été constatés, combien et à quel âge gestationnel, ou justifiant leur exclusion.

Evidence for HPV DNA in the placenta of women who resorted to elective abortion.

BACKGROUND: It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. METHODS: We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA. RESULTS: HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90. CONCLUSION: The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy.

COVID-19 pandemic effect on early pregnancy: are miscarriage rates altered, in asymptomatic women?

PURPOSE: To evaluate the effect of the COVID-19 pandemic state on early, first-trimester pregnancies. METHODS: A retrospective cohort study conducted at a university-affiliated fertility center in Montreal, Quebec, since the COVID-19 shut down, March 13 until May 6, 2020. Included: all women who came for a first-trimester viability scan during the study period (Study group) and between March 1, 2019 and May 17, 2019, approximately one year prior (Control). The study population denied symptoms of COVID-19. We reviewed all first trimester scans. Early first-trimester pregnancy outcomes (Viable pregnancy, arrested pregnancy including biochemical pregnancy loss and miscarriage, and ectopic pregnancy) were measured as total number and percentage. A multivariate analysis was performed to control for other potentially significant variables, as was a power analysis supporting sample size. RESULTS: 113 women came for a first-trimester viability scan in the study period, and 172 in the control period (5-11 weeks gestational age), mean maternal age 36.5 ± 4.5 and 37.2 ± 5.4 years (p = 0.28). Viable clinical pregnancy rate was not different between the two groups (76.1 vs. 80.2% in the pandemic and pre-pandemic groups p = 0.41). No significant difference was seen in the total number of arrested pregnancies (defined as the sum of biochemical, 1st trimester miscarriages, and blighted ova) (22.1 vs. 16.9% p = 0.32), or in each type of miscarriage. CONCLUSION: The COVID-19 pandemic environment does not seem to affect early first-trimester miscarriage rates in asymptomatic patients.

Droplet-digital PCR assay to detect Merkel cell polyomavirus sequences in chorionic villi from spontaneous abortion affected females.

Droplet-digital polymerase chain reaction (ddPCR) technique was set up to detect/quantify Merkel cell polyomavirus (MCPyV) DNA in clinical specimens, including chorionic villi and peripheral blood mononuclear cells (PBMCs) from spontaneous abortion (SA)-affected females. This ddPCR assay showed high accuracy, sensitivity, and specificity in detecting MCPyV DNA cloned in a recombinant plasmid vector, the control. ddPCR was extended to MCPyV DNA to investigate/quantify its sequences in clinical samples. Overall, 400 samples were analyzed, that is, 100 chorionic villi and 100 PBMCs, from SA females (n = 100), the cases, and 100 chorionic villi and 100 PBMCs from females who underwent voluntary pregnancy interruption (VI, n = 100), the control. MCPyV DNA was detected in 4/100 (4%) and 5/100 (5%) of SA and VI chorionic villi, respectively. The mean viral DNA load was 1.99 ( ± 0.94 standard mean deviation [SD]) copy/104 cells in SA and 3.02 ( ± 1.86 [SD]) copy/104 cells in VI. In PBMCs, MCPyV DNA was revealed in 9/100 (9%) and 14/100 (14%) of SA and VI, with a mean of 2.09 ( ± 1.17 [SD]) copy/104 cells and 4.09 ( ± 4.26 [SD]) copy/104 cells in SA and VI, respectively. MCPyV gene expression analysis by quantitative PCR for the large T antigen (LT) and viral capsid protein 1 (VP1) showed their mRNAs in 2/4 (50%) SA- and 2/5 (40%) VI-MCPyV-positive samples. MCPyV DNA was detected/quantified using the ddPCR technique, in chorionic villi and PBMCs from SA and VI. In our experimental conditions, ddPCR provided a powerful tool to detect/quantify MCPyV DNA sequences in clinical samples.

Coronavirus disease 2019 in pregnant women: a report based on 116 cases.

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.

Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review.

OBJECTIVE: To evaluate the effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome by performing a systematic review of available published literature on pregnancies affected by COVID-19. METHODS: We performed a systematic review to evaluate the effect of COVID-19 on pregnancy, perinatal and neonatal outcome. We conducted a comprehensive literature search using PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure Database and Wan Fang Data up to and including 20 April 2020 (studies were identified through PubMed alert after that date). For the search strategy, combinations of the following keywords and medical subject heading (MeSH) terms were used: 'SARS-CoV-2', 'COVID-19', 'coronavirus disease 2019', 'pregnancy', 'gestation', 'maternal', 'mother', 'vertical transmission', 'maternal-fetal transmission', 'intrauterine transmission', 'neonate', 'infant' and 'delivery'. Eligibility criteria included laboratory-confirmed and/or clinically diagnosed COVID-19, patient being pregnant on admission and availability of clinical characteristics, including at least one maternal, perinatal or neonatal outcome. Exclusion criteria were non-peer-reviewed or unpublished reports, unspecified date and location of the study, suspicion of duplicate reporting and unreported maternal or perinatal outcomes. No language restrictions were applied. RESULTS: We identified a high number of relevant case reports and case series, but only 24 studies, including a total of 324 pregnant women with COVID-19, met the eligibility criteria and were included in the systematic review. These comprised nine case series (eight consecutive) and 15 case reports. A total of 20 pregnant patients with laboratory-confirmed COVID-19 were included in the case reports. In the combined data from the eight consecutive case series, including 211 (71.5%) cases of laboratory-confirmed and 84 (28.5%) of clinically diagnosed COVID-19, the maternal age ranged from 20 to 44 years and the gestational age on admission ranged from 5 to 41 weeks. The most common symptoms at presentation were fever, cough, dyspnea/shortness of breath, fatigue and myalgia. The rate of severe pneumonia reported amongst the case series ranged from 0% to 14%, with the majority of the cases requiring admission to the intensive care unit. Almost all cases from the case series had positive computed tomography chest findings. All six and 22 cases that had nucleic-acid testing in vaginal mucus and breast milk samples, respectively, were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Only four cases of spontaneous miscarriage or termination were reported. In the consecutive case series, 219/295 women had delivered at the time of reporting and 78% of them had Cesarean section. The gestational age at delivery ranged from 28 to 41 weeks. Apgar scores at both 1 and 5 min ranged from 7 to 10. Only eight neonates had birth weight < 2500 g and nearly one-third of neonates were transferred to the neonatal intensive care unit. There was one case of neonatal asphyxia and death. In 155 neonates that had nucleic-acid testing in throat swab, all, except three cases, were negative for SARS-CoV-2. There were no cases of maternal death in the eight consecutive case series. Seven maternal deaths, four intrauterine fetal deaths (one with twin pregnancy) and two neonatal deaths (twin pregnancy) were reported in a non-consecutive case series of nine cases with severe COVID-19. In the case reports, two maternal deaths, one neonatal death and two cases of neonatal SARS-CoV-2 infection were reported. CONCLUSIONS: Despite the increasing number of published studies on COVID-19 in pregnancy, there are insufficient good-quality data to draw unbiased conclusions with regard to the severity of the disease or specific complications of COVID-19 in pregnant women, as well as vertical transmission, perinatal and neonatal complications. In order to answer specific questions in relation to the impact of COVID-19 on pregnant women and their fetuses, through meaningful good-quality research, we urge researchers and investigators to present complete outcome data and reference previously published cases in their publications, and to record such reporting when the data of a case are entered into one or several registries. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Efecto de la enfermedad coronavirus 2019 (COVID-19) en el resultado materno, perinatal y neonatal: revisión sistemática OBJETIVO: Evaluar el efecto de la enfermedad coronavirus 2019 (COVID-19) en el resultado materno, perinatal y neonatal por medio de una revisión sistemática de la literatura publicada disponible sobre los embarazos afectados por COVID-19. MÉTODOS: Se realizó una revisión sistemática para evaluar el efecto de COVID-19 en el resultado del embarazo, perinatal y neonatal. Se realizó una búsqueda exhaustiva de literatura utilizando PubMed, EMBASE, la Biblioteca Cochrane, la Base de Datos de la Infraestructura Nacional de Conocimiento de China y Wan Fang Data hasta el 20 de abril de 2020 inclusive (los estudios se identificaron mediante el sistema de alertas de PubMed después de esa fecha). Para la estrategia de búsqueda, se utilizaron combinaciones de las siguientes palabras clave y términos (en inglés) de Medical Subject Headings (MeSH): 'SARS-CoV-2', 'COVID-19', 'enfermedad coronavirus 2019', 'embarazo', 'gestación', 'materno', 'madre', 'transmisión vertical', 'transmisión materno-fetal', 'transmisión intrauterina', 'neonato', 'bebé' y 'parto'. Los criterios de elegibilidad fueron COVID-19 confirmado por laboratorio y/o diagnosticado clínicamente, el hecho de que la paciente estuviera embarazada en el momento del ingreso y la disponibilidad de características clínicas, con al menos un resultado materno, perinatal o neonatal. Los criterios de exclusión fueron los informes no revisados por pares o no publicados, la fecha y el lugar del estudio sin especificar, la sospecha de informes duplicados y los resultados maternos o perinatales no reportados. No se aplicaron restricciones de idioma. RESULTADOS: Se identificó un elevado número de informes de casos y series de casos pertinentes, pero sólo 24 estudios, que incluían un total de 324 mujeres embarazadas con COVID-19, cumplieron los criterios de elegibilidad y se incluyeron en la revisión sistemática. Estos comprendían nueve series de casos (ocho consecutivas) y 15 informes de casos. Los informes de casos se referían a un total de 20 pacientes embarazadas con COVID-19 confirmado por un laboratorio. En los datos combinados de las ocho series de casos consecutivas, que incluían 211 (71,5%) casos de COVID-19 confirmados por laboratorio y 84 (28,5%) casos diagnosticados clínicamente, la edad materna varió entre 20 y 44 años y la edad gestacional en el momento del ingreso fue entre 5 y 41 semanas. Los síntomas más comunes del cuadro clínico inicial fueron fiebre, tos, disnea/dificultad para respirar, fatiga y mialgia. La tasa de neumonía grave reportada en las series de casos varió entre el 0% y el 14%, y la mayoría de los casos requirieron el ingreso en la unidad de cuidados intensivos. Casi todos los casos de la serie de casos tuvieron resultados positivos en la tomografía axial computerizada. Los 6 y 22 casos en que se realizaron pruebas de ácido nucleico en muestras de mucosidad vaginal y leche materna, respectivamente, dieron negativo para el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2). Sólo se notificaron cuatro casos de aborto o interrupción del embarazo. En la serie de casos consecutivos, 219 de 295 mujeres habían dado a luz en el momento de la presentación del informe y el 78% de ellas lo hicieron mediante cesárea. La edad gestacional en el momento del parto varió entre 28 y 41 semanas. Las puntuaciones de Apgar a 1 minuto y a 5 minutos variaron entre 7 y 10. Sólo ocho recién nacidos pesaron al nacer <2500 g y casi un tercio de los recién nacidos fueron transferidos a la unidad de cuidados intensivos para recién nacidos. Hubo un caso de asfixia y muerte neonatal. Excepto tres casos, el resto de los 155 neonatos a los que se les hicieron pruebas de ácido nucleico en un frotis faríngeo, dieron negativo para el SARS-CoV-2. No hubo casos de muerte materna en las ocho series consecutivas de casos. Se reportaron siete muertes maternas, cuatro muertes fetales intrauterinas (una con embarazo de gemelos) y dos muertes de recién nacidos (embarazo de gemelos) en una serie no consecutiva de nueve casos con COVID-19 grave. En los informes de casos se comunicaron dos muertes maternas, una muerte de recién nacido y dos casos de infección de recién nacidos por SARS-CoV-2. CONCLUSIONES: A pesar del creciente número de estudios publicados sobre COVID-19 en embarazos, no hay suficientes datos de buena calidad para sacar conclusiones no sesgadas con respecto a la gravedad de la enfermedad o a las complicaciones específicas de COVID-19 en las mujeres embarazadas, así como a la transmisión vertical y a las complicaciones perinatales y neonatales. A fin de responder a preguntas específicas en relación con los efectos de COVID-19 en mujeres embarazadas y sus fetos, mediante una investigación significativa de buena calidad, se insta a los investigadores y a los encargados de investigaciones a que presenten en sus publicaciones datos completos sobre los resultados y casos de referencia publicados anteriormente, y a que registren esos informes cuando los datos de un caso se introduzcan en uno o varios registros. © 2020 Los autores. Ultrasonido en Obstetricia y Ginecología publicado por John Wiley & Sons Ltd. en nombre de la Sociedad Internacional de Ultrasonido en Obstetricia y Ginecología.

Footprints of BK and JC polyomaviruses in specimens from females affected by spontaneous abortion.

STUDY QUESTION: Are JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) infections associated with spontaneous abortion (SA)? SUMMARY ANSWER: There is no association of JCPyV or BKPyV with SA. WHAT IS KNOWN ALREADY: A large number of risk factors have been associated with SA. The role of polyomaviruses, including JCPyV and BKPyV, in SA remains to be clarified. STUDY DESIGN, SIZE, DURATION: This is a case-control study including women affected by spontaneous abortion (SA, n = 100, the cases) and women who underwent voluntary interruption of pregnancy (VI, n = 100, the controls). PARTICIPANTS/MATERIALS, SETTING, METHODS: Viral DNAs were investigated by qualitative PCR and quantitative droplet-digital PCR (ddPCR) in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from SA (n = 100) and VI (n = 100). Indirect ELISAs with mimotopes/synthetic peptides corresponding to JCPyV and BKPyV viral capsid protein 1 epitopes were then employed to investigate specific IgG antibodies against JCPyV and BKPyV in human sera from SA (n = 80) and VI (n = 80) cohorts. MAIN RESULTS AND THE ROLE OF CHANCE: JCPyV DNA was detected in 51% and 61% of SA and VI samples, respectively, with a mean viral DNA load of 7.92 copy/104 cells in SA and 5.91 copy/104 cells in VI (P > 0.05); BKPyV DNA was detected in 11% and 12% of SA and VI specimens, respectively, with a mean viral DNA load of 2.7 copy/104 cells in SA and 3.08 copy/104 cells in VI (P > 0.05). JCPyV was more prevalent than BKPyV in both SA and VI specimens (P < 0.0001). In PBMCs from the SA and VI cohorts, JCPyV DNA was detected with a prevalence of 8% and 12%, respectively, with a mean viral DNA load of 2.29 copy/104 cells in SA and 1.88 copy/104 cells in VI (P > 0.05). The overall prevalence of serum IgG antibodies against JCPyV detected by indirect ELISAs was 52.5% and 48.7% in SA and VI groups, respectively, whereas BKPyV-positive sera were found in 80% SA and 78.7% VI samples. LIMITATIONS, REASONS FOR CAUTION: This study did not investigate the presence of viral mRNA and/or proteins, which are indicative of an active viral infection, and these might be taken into consideration in future studies. WIDER IMPLICATIONS OF THE FINDINGS: JCPyV and BKPyV DNA sequences were detected and quantitatively analyzed for the first time by PCR/ddPCR in chorionic villi tissues and PBMCs from SA and VI specimens. Moreover specific immunological approaches detected serum IgG against JCPyV/BKPyV. Statistical analyses, however, do not indicate an association between these polyomaviruses and SA. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University of Ferrara, FAR research grants and the University Hospital of Ferrara/University of Ferrara joint grant. No potential conflicts of interest were disclosed.

Dengue infection during pregnancy in Burkina Faso: a cross-sectional study.

BACKGROUND: Dengue fever is prevalent in the world; in recent years, several outbreaks occurred in West Africa. It affects pregnant women. We aimed to assess the consequences of dengue fever on pregnant women and their fetuses during dengue epidemic in Burkina Faso. METHODS: We conducted a cross-sectional study from November 1, 2015 to January 31, 2017 in 15 public and private health facilities in Ouagadougou, using secondary data. Immunochromatographic rapid test Duo detecting specific antibodies, immunoglobin M/G and /or dengue non structural antigen1 virus was used to diagnose dengue cases. RESULTS: Out of 399 (48%) women registered during the study period, 25 (6%) were pregnant. The average age of pregnant women was 30 years, with 18 and 45 years as extremes. The main symptoms were fever (92%) and headache (92%). Nine patients (36%) had severe dengue characterized by bleeding (16%), neurological symptoms (16%) and acute respiratory distress (8%). Eight (32%) of the 25 women had early miscarriage and 8 (32%) women gave birth to viable fetuses. Among those with viable babies, 5 (20%) presented post-partum hemorrhage and 3 (12%) presented early delivery. The main fetal complications included 3 cases of acute fetal distress (12%). One case of maternal death (4%) and 4 cases of neonatal mortality (44.5%) were notified. CONCLUSION: Dengue fever occurring during pregnancy increases maternal and neonatal mortality. Its severe complications require specific monitoring of pregnant women until delivery.

Spontaneous Abortion Associated with Zika Virus Infection and Persistent Viremia.

We report a case of spontaneous abortion associated with Zika virus infection in a pregnant woman who traveled from Spain to the Dominican Republic and developed a rash. Maternal Zika viremia persisted at least 31 days after onset of symptoms and 21 days after uterine evacuation.

Expected Duration of Adverse Pregnancy Outcomes after Zika Epidemic.

Evidence is increasing that Zika virus-related adverse outcomes can occur throughout pregnancy. Mathematical modeling analysis using reported outcome data suggests that surveillance for these outcomes should begin as soon as an outbreak is detected and should continue for 40 weeks after the outbreak ends.

A Novel Porcine Circovirus Distantly Related to Known Circoviruses Is Associated with Porcine Dermatitis and Nephropathy Syndrome and Reproductive Failure.

Porcine circovirus-associated disease (PCVAD) is clinically manifested by postweaning multisystemic wasting syndrome (PMWS), respiratory and enteric disease, reproductive failure, and porcine dermatitis and nephropathy syndrome (PDNS). Porcine circovirus 2 (PCV2) is an essential component of PCVAD, although an etiologic role in PDNS is not well established. Here, a novel circovirus, designated porcine circovirus 3 (PCV3), was identified in sows that died acutely with PDNS-like clinical signs. The capsid and replicase proteins of PCV3 are only 37% and 55% identical to PCV2 and bat circoviruses, respectively. Aborted fetuses from sows with PDNS contained high levels of PCV3 (7.57 × 107 genome copies/ml), and no other viruses were detected by PCR and metagenomic sequencing. Immunohistochemistry (IHC) analysis of sow tissue samples identified PCV3 antigen in skin, kidney, lung, and lymph node samples localized in typical PDNS lesions, including necrotizing vasculitis, glomerulonephritis, granulomatous lymphadenitis, and bronchointerstitial pneumonia. Further study of archived PDNS tissue samples that were negative for PCV2 by IHC analysis identified 45 of 48 that were PCV3 positive by quantitative PCR (qPCR), with 60% of a subset also testing positive for PCV3 by IHC analysis. Analysis by qPCR of 271 porcine respiratory disease diagnostic submission samples identified 34 PCV3-positive cases (12.5%), and enzyme-linked immunosorbent assay detection of anti-PCV3 capsid antibodies in serum samples found that 46 (55%) of 83 samples tested were positive. These results suggest that PCV3 commonly circulates within U.S. swine and may play an etiologic role in reproductive failure and PDNS. Because of the high economic impact of PCV2, this novel circovirus warrants further studies to elucidate its significance and role in PCVAD. IMPORTANCE: While porcine circovirus 2 (PCV2) was first identified in sporadic cases of postweaning multisystemic wasting syndrome in Canada in the early 1990s, an epidemic of severe systemic disease due to PCV2 spread worldwide in the ensuing decade. Despite being effectively controlled by commercial vaccines, PCV2 remains one of the most economically significant viruses of swine. Here, a novel porcine circovirus (PCV3) that is distantly related to known circoviruses was identified in sows with porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure. PCV2, which has previously been associated with these clinical presentations, was not identified. High levels of PCV3 nucleic acid were observed in aborted fetuses by quantitative PCR, and PCV3 antigen was localized in histologic lesions typical of PDNS in sows by immunohistochemistry (IHC) analysis. PCV3 was also identified in archival PDNS diagnostic samples that previously tested negative for PCV2 by IHC analysis. The emergence of PCV3 warrants further investigation.

Infection status of human parvovirus B19, cytomegalovirus and herpes simplex Virus-1/2 in women with first-trimester spontaneous abortions in Chongqing, China.

BACKGROUND: Infection with Parvovirus B19 (B19V), Cytomegalovirus (CMV) and Herpes Simplex Virus-1/2 (HSV-1/2) may cause fetal loses including spontaneous abortion, intrauterine fetal death and non-immune hydrops fetalis. Few comprehensive studies have investigated first-trimester spontaneous abortions caused by virus infections in Chongqing, China. Our study intends to investigate the infection of B19V, CMV and HSV-1/2 in first-trimester spontaneous abortions and the corresponding immune response. METHODS: 100 abortion patients aged from 17 to 47 years were included in our study. The plasma samples (100) were analyzed qualitatively for specific IgG/IgM for B19V, CMV and HSV-1/2 (Virion\Serion, Germany) according to the manufacturer's recommendations. B19V, CMV and HSV-1/2 DNA were quantification by Real-Time PCR. RESULTS: No specimens were positive for B19V, CMV, and HSV-1/2 DNA. By serology, 30.0%, 95.0%, 92.0% of patients were positive for B19V, CMV and HSV-1/2 IgG respectively, while 2% and 1% for B19V and HSV-1/2 IgM. CONCLUSION: The low rate of virus DNA and a high proportion of CMV and HSV-1/2 IgG for most major of abortion patients in this study suggest that B19V, CMV and HSV-1/2 may not be the common factor leading to the spontaneous abortion of early pregnancy.

Effect of human papilloma virus infection on in-vitro fertilization outcome: systematic review and meta-analysis.

OBJECTIVES: To identify, appraise and summarize the available data concerning the impact of human papilloma virus (HPV) infection on reproductive outcome following in-vitro fertilization (IVF). METHODS: We searched for studies in PubMed, EMBASE, Scopus, Lilacs and the Cochrane Central Register of Controlled Trials from inception to March 2017. Any type of HPV infection assessed through polymerase chain reaction, subfertility factors and IVF indications and protocols were considered. Our primary outcomes were live birth/ongoing pregnancy and miscarriage, while secondary outcomes included clinical and laboratory parameters. We planned subgroup analyses according to the status of cervical cytology and presence of infection in the male partner. We assessed the relative risk (RR), using a random-effects model; heterogeneity was assessed using the I2 statistic. Quality of the evidence was evaluated using the recommendations of the GRADE Working Group. RESULTS: From the 14 studies eligible for inclusion, quantitative data from 10, evaluating 299 women with HPV infection and 2049 women without HPV infection, were included in the analysis. The pooled results showed no significant difference between HPV-infected and non-infected women in rates of live birth/ongoing pregnancy (RR, 1.16 (95% CI, 0.88-1.53); I2 = 0%; six studies, 983 women), clinical pregnancy (RR, 1.06 (95% CI, 0.74-1.54); I2 = 61%; eight studies, 1173 women) or miscarriage (RR, 1.58 (95% CI, 0.93-2.69); I2 = 8%; six studies, 290 clinical pregnancies). The overall quality of the evidence was very low, downgraded two levels because of serious limitations of the included studies (observational studies) and imprecision. In contrast, pooled results in the subgroup analysis based on the presence of infection in the male partner showed significant differences in rates of live birth/ongoing pregnancy (RR, 0.43 (95% CI, 0.23-0.82); I2 = 0%; three studies, 429 participants; P = 0.01) and miscarriage (RR, 3.70 (95% CI, 1.94-7.05); I2 = 0%; two studies, 90 participants; P < 0.0001). CONCLUSIONS: The available evidence is still inadequate to enable us to draw firm conclusions regarding the effect of HPV infection in women on the most important reproductive outcomes following IVF; however, it suggests that the effect is not large for rates of live birth/ongoing pregnancy and clinical pregnancy. When infection is present in the male partner, it seems that there is a negative effect on live birth/ongoing pregnancy rate and an increase in miscarriage rate, a finding that should be interpreted with caution, owing to the very low quality of evidence supporting it. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Human papillomavirus in foetal and maternal tissues from miscarriage cases.

Early miscarriage is still a concern, and viral infections are recognised as one of the causes of this adverse outcome. The causal relationship between HPV and miscarriage remains controversial. The aim of the study was to evaluate whether HPV infection indeed may occur in both the maternal and placental tissue in cases of miscarriage. Decidual and chorionic villi fragments (n = 118) were dissected from 81 miscarriage cases, 68 spontaneous and 13 intentional. HPV DNA was detected using the consensus primers MY09/11; in eight cases (9.9%, 8/81), seven of which (10.3%) were from spontaneous miscarriages and one (7.7%), was from an intentional miscarriage. The deciduas (4/8) and chorionic villi (5/8) were both infected with HPV. A reverse line blot was used to genotype HPV positive samples and revealed HPV6, 11, 58, 66 and 82. Although the results obtained cannot infer an association between HPV and pregnancy loss, it cannot be ruled out. Impact Statement What is already known on this subject? Miscarriages are considered to be the most common complication in pregnancy. Several possible causes of miscarriage have been considered, and the role of infections as one of those is confirmed, especially during the second trimester of pregnancy. The prevalence of HPV in conception products is still questionable. However, an HPV infection should not be ignored and its association with miscarriage must be considered. What the results of this study add? The present study reveals the presence of HPV in the foetal and maternal tissues of conception. What the implications are of these findings for clinical practice and/or further research? This issue deserves further investigation aiming to clarify the role of HPV in miscarriage cases; which are mainly related to the specific type and grade of tissues' abnormalities found co-topographically with a virus presence.