#Neurodevelopmental #Abnormalities in #Children With In Utero #Zika Virus Exposure Without Congenital Zika Syndrome (JAMA Pediatr., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

JAMA Pediatr. 2020 Jan 6. doi: 10.1001/jamapediatrics.2019.5204. [Epub ahead of print]

Neurodevelopmental Abnormalities in Children With In Utero Zika Virus Exposure Without Congenital Zika Syndrome.

Mulkey SB1,2,3, Arroyave-Wessel M1, Peyton C4, Bulas DI1,5, Fourzali Y6, Jiang J1, Russo S1, McCarter R1, Msall ME7, du Plessis AJ1,2,3, DeBiasi RL1,2,8, Cure C9.

Author information: 1 Children’s National Hospital, Washington, DC. 2 Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC. 3 Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC. 4 Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, Illinois. 5 Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, DC. 6 Sabbag Radiologos, Barranquilla, Colombia. 7 Kennedy Research Center on Neurodevelopmental Disabilities, University of Chicago Comer Children’s Hospital, Chicago, Illinois. 8 Department of Tropical Medicine and Infectious Disease, The George Washington University School of Medicine and Health Sciences, Washington, DC. 9 BIOMELAB, Barranquilla, Colombia.

 

Abstract

IMPORTANCE:

The number of children who were born to mothers with Zika virus (ZIKV) infection during pregnancy but who did not have apparent disability at birth is large, warranting the study of the risk for neurodevelopmental impairment in this population without congenital Zika syndrome (CZS).

OBJECTIVE:

To investigate whether infants without CZS but who were exposed to ZIKV in utero have normal neurodevelopmental outcomes until 18 months of age.

DESIGN, SETTING, AND PARTICIPANTS:

This cohort study prospectively enrolled a group of pregnant women with ZIKV in Atlántico Department, Colombia, and in Washington, DC. With this cohort, we performed a longitudinal study of infant neurodevelopment. Infants born between August 1, 2016, and November 30, 2017, were included if they were live born, had normal fetal brain findings on magnetic resonance imaging and ultrasonography, were normocephalic at birth, and had normal examination results without clinical evidence of CZS. Seventy-seven infants born in Colombia, but 0 infants born in the United States, met the inclusion criteria.

EXPOSURES:

Prenatal ZIKV exposure.

MAIN OUTCOMES AND MEASURES:

Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) at 1 or 2 time points between 4 and 18 months of age. The WIDEA and AIMS scores were converted to z scores compared with normative samples. Longitudinal mixed-effects regression models based on bootstrap resampling methods estimated scores over time, accounting for gestational age at maternal ZIKV infection and infant age at assessment. Results were presented as slope coefficients with 2-tailed P values based on z statistics that tested whether the coefficient differed from 0 (no change).

RESULTS:

Of the 77 Colombian infants included in this cohort study, 70 (91%) had no CZS and underwent neurodevelopmental assessments. Forty infants (57%) were evaluated between 4 and 8 months of age at a median (interquartile range [IQR]) age of 5.9 (5.3-6.5) months, and 60 (86%) underwent assessment between 9 and 18 months of age at a median (IQR) age of 13.0 (11.2-16.4) months. The WIDEA total score (coefficients: age = -0.227 vs age2 = 0.006; P < .003) and self-care domain score (coefficients: age = -0.238 vs age2 = 0.01; P < .008) showed curvilinear associations with age. Other domain scores showed linear declines with increasing age based on coefficients for communication (-0.036; P = .001), social cognition (-0.10; P < .001), and mobility (-0.14; P < .001). The AIMS scores were similar to the normative sample over time (95% CI, -0.107 to 0.037; P = .34). Nineteen of 57 infants (33%) who underwent postnatal cranial ultrasonography had a nonspecific, mild finding. No difference was found in the decline of WIDEA z scores between infants with and those without cranial ultrasonography findings except for a complex interactive relationship involving the social cognition domain (P < .049). The AIMS z scores were lower in infants with nonspecific cranial ultrasonography findings (-0.49; P = .07).

CONCLUSIONS AND RELEVANCE:

This study found that infants with in utero ZIKV exposure without CZS appeared at risk for abnormal neurodevelopmental outcomes in the first 18 months of life. Long-term neurodevelopmental surveillance of all newborns with ZIKV exposure is recommended.

PMID: 31904798 DOI: 10.1001/jamapediatrics.2019.5204

Keywords: Zika Virus; Zika Congenital Infection; Psychiatry; Neurology.

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#Neurodevelopment of Nonmicrocephalic #Children, After 18 Months of Life, Exposed Prenatally to #Zika Virus (J Child Neurol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Child Neurol. 2019 Dec 26:883073819892128. doi: 10.1177/0883073819892128. [Epub ahead of print]

Neurodevelopment of Nonmicrocephalic Children, After 18 Months of Life, Exposed Prenatally to Zika Virus.

Gerzson LR1, de Almeida CS2, da Silva JH3, Feitosa MMA4, de Oliveira LN5, Schuler-Faccini L6.

Author information: 1 Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 2 Department of Physiotherapy, Physical Education and Dance, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 3 Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 4 Federal University of Amazonas, Manaus, Brazil. 5 Graduate Program in Science of Information, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 6 SIAT, Information Service on Teratogenic Agents, Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

 

Abstract

The aim of this work was to evaluate the cognitive, language, and motor development, after 18 months of life, of nonmicrocephalic children born to mothers with Zika virus infection during pregnancy. Participants were 37 children aged 18-29 months divided into 2 groups: 17 nonmicrocephalic children born to mothers who had Zika virus infection during pregnancy (ZIKVG) and 20 nonmicrocephalic children with no maternal history of infection matched by sex and age (control group). A semistructured interview and the Bayley Scale of Infant and Toddler Development (Bayley III) were used for their evaluation. One child in the ZIKVG presented low cognitive score, the same in the control group. There were no statistical differences between the 2 groups regarding cognitive, language, and motor development. This sample, although small, showed that a significant proportion of nonmicrocephalic children exposed prenatally to Zika virus had normal development. A longer follow-up is necessary to observe if no other adverse outcomes will appear in the future.

KEYWORDS: Bayley III; ZIKV; child development; physiotherapy

PMID: 31878830 DOI: 10.1177/0883073819892128

Keywords: Zika Virus; Pregnancy; Pediatrics; Neurology.

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#Epidemiology and clinical #outcomes of hospitalizations for acute respiratory or febrile illness and laboratory-confirmed #influenza among #pregnant women during six influenza seasons, 2010-2016 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Epidemiology and clinical outcomes of hospitalizations for acute respiratory or febrile illness and laboratory-confirmed influenza among pregnant women during six influenza seasons, 2010-2016

Fatimah S Dawood, Shikha Garg, Rebecca V Fink, Margaret L Russell, Annette K Regan, Mark A Katz, Stephanie Booth, Hannah Chung, Nicola P Klein, Jeffrey C Kwong, Avram Levy, Allison Naleway, Dan Riesel, Mark G Thompson, Brandy E Wyant, Deshayne B Fell on behalf of the PREVENT workgroup

The Journal of Infectious Diseases, jiz670, https://doi.org/10.1093/infdis/jiz670

Published: 26 December 2019

 

Abstract

Background

Pregnant women are at increased risk of seasonal influenza hospitalizations, but data about the epidemiology of severe influenza among pregnant women remain largely limited to pandemics.

Methods

To describe the epidemiology of hospitalizations for acute respiratory infection or febrile illness (ARFI) and influenza-associated ARFI among pregnant women, administrative and electronic health record data were analyzed from retrospective cohorts of pregnant women hospitalized with ARFI who had testing for influenza viruses by RT-PCR in Australia, Canada, Israel and the United States during 2010-2016.

Results

Of 18,048 ARFI-coded hospitalizations, 1,064 (6%) included RT-PCR testing for influenza viruses, of which 614 (58%) were influenza-positive. Of 614 influenza-positive ARFI hospitalizations, 35% were in women with low socioeconomic status, 20% with underlying conditions, and 67% in their third trimesters. The median length of influenza-positive hospitalizations was 2 days (IQR 1-4), 18% (95% confidence interval (CI) 15-21%) resulted in delivery, 10% (95% CI 8-12%) included a pneumonia diagnosis, 5% (95% CI 3-6%) required intensive care, 2% (95% CI 1-3%) included a sepsis diagnosis, and <1% (95% CI 0-1%) resulted in respiratory failure.

Conclusions

Our findings characterize seasonal influenza hospitalizations among pregnant women and can inform assessments of the public health and economic impact of seasonal influenza on pregnant women.

Influenza, Pregnant, Hospitalization

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Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Seasonal Influenza; Pregnancy; Pneumonia; Intensive care; Sepsis.

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#DNA #vaccination before #conception protects #Zika virus-exposed pregnant macaques against prolonged viremia and improves fetal outcomes (Sci Transl Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Transl Med. 2019 Dec 18;11(523). pii: eaay2736. doi: 10.1126/scitranslmed.aay2736.

DNA vaccination before conception protects Zika virus-exposed pregnant macaques against prolonged viremia and improves fetal outcomes.

Van Rompay KKA1,2, Keesler RI3, Ardeshir A3, Watanabe J3, Usachenko J3, Singapuri A2, Cruzen C3, Bliss-Moreau E3,4, Murphy AM3,4, Yee JL3, Webster H5, Dennis M5, Singh T5, Heimsath H5, Lemos D2, Stuart J2, Morabito KM6, Foreman BM7, Burgomaster KE7, Noe AT6, Dowd KA7, Ball E2, Woolard K2, Presicce P8, Kallapur SG8, Permar SR5, Foulds KE6, Coffey LL2, Pierson TC7, Graham BS9.

Author information: 1 California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA. kkvanrompay@ucdavis.edu bgraham@nih.gov. 2 Department of Pathology, Microbiology and Immunology, University of California, Davis, Davis, CA 95616, USA. 3 California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA. 4 Department of Psychology, University of California, Davis, Davis, CA 95616, USA. 5 Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. 6 Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. 7 Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA. 8 Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. 9 Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. kkvanrompay@ucdavis.edu bgraham@nih.gov.

 

Abstract

Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PMID: 31852797 DOI: 10.1126/scitranslmed.aay2736

Keywords: Zika virus; Pregnancy; Vaccines; Animal models.

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#Maternal #vaccination and protective immunity against #Zika virus vertical transmission (Nat Commun., abstract)

[Source: Nature Communications, full page: (LINK). Abstract, edited.]

Maternal vaccination and protective immunity against Zika virus vertical transmission

Chao Shan, Xuping Xie, Huanle Luo, Antonio E. Muruato, Yang Liu, Maki Wakamiya, Jun-Ho La, Jin Mo Chung, Scott C. Weaver, Tian Wang & Pei-Yong Shi

Nature Communications, volume 10, Article number: 5677 (2019)

 

Abstract

An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3ʹUTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3ʹUTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3ʹUTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3ʹUTR-∆10-LAV may also be considered for maternal vaccination.

Keywords: Zika Virus; Pregnancy; Vaccines; Animal models.

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Persistent #Zika Virus #Infection Associated with Early #Fetal #Demise: A Case Report (Open J Obstet Gynecol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Open J Obstet Gynecol. 2019 May;9(5):698-706. doi: 10.4236/ojog.2019.95069.

Persistent Zika Virus Infection Associated with Early Fetal Demise: A Case Report.

Pérez-Padilla J1, Paz-Bailey G1, Meaney-Delman D2, Doyle K3, Gary J4, Rodriguez DM1, Bhatnagar J4, Pérez-Rodriguez NM5, Montalvo S5, Alvarado L5, Sharp TM1.

Author information: 1 Centers for Disease Control and Prevention (CDC), Dengue Branch, San Juan, Puerto Rico. 2 CDC, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA. 3 CDC, Division of HIV/AIDS Prevention, Atlanta, GA, USA. 4 CDC, Infectious Disease Pathology Branch, Atlanta, GA, USA. 5 Ponce Health Sciences University/Saint Luke’s Episcopal Hospital, Ponce, Puerto Rico.

 

Abstract

BACKGROUND:

Infection with Zika virus (ZIKV) during pregnancy is known to cause birth defects and could also be linked to pregnancy loss.

CASE:

A pregnant woman in Puerto Rico contracted ZIKV at 16 weeks gestation. ZIKV RNA persisted in serum from her initial test at 16 weeks through 24 weeks gestation, when fetal demise occurred, and was detected in placental tissue.

CONCLUSION:

Prolonged detection of ZIKV RNA in maternal serum was associated with ZIKV RNA detection in the placenta of a patient who experienced fetal demise. While detection of placenta ZIKV RNA does not establish that ZIKV conclusively caused the demise, these findings support emerging evidence that the placenta may serve as a reservoir for ZIKV, which may be associated with prolonged detection of ZIKV RNA in serum.

KEYWORDS: Pregnancy Outcomes; ZIKV Persistence; Zika

PMID: 31799062 PMCID: PMC6889876 DOI: 10.4236/ojog.2019.95069

Keywords: Zika Virus; Pregnancy.

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#Discordant #Zika virus findings in #twin #pregnancies complicated by antenatal Zika virus exposure: a prospective cohort (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Discordant Zika virus findings in twin pregnancies complicated by antenatal Zika virus exposure: a prospective cohort

Nasim C Sobhani, MD, Elyzabeth Avvad-Portari, MD PhD, Aline C M Nascimento, MD, Heloisa N Machado, PhD, Daniel S S Lobato, MD, Jose Paulo Pereira, Jr, MD PhD, Mikaela S Esquivel, Zilton C Vasconcelos, PhD, Andrea A Zin, MD PhD, Irena Tsui, MD, Kristina Adachi, MD, Elizabeth B Brickley, PhD, Susan J Fisher, PhD, Karin Nielsen-Saines, MD, Patricia Brasil, MD, PhD, Maria E Moreira, MD PhD, Stephanie L Gaw, MD PhD

The Journal of Infectious Diseases, jiz629, https://doi.org/10.1093/infdis/jiz629

Published: 27 November 2019

 

Abstract

Background

There is limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding inter-twin concordance of prenatal, placental, and infant outcomes.

Methods

This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. PCR testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment.

Results

Among 244 pregnancies, four twin gestations without co-infection were identified. ZIKV infection occurred at 16-33 weeks gestation. ZIKV PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the eight infants, three (38%) had an abnormal neonatal outcome. Of six infants with long-term follow-up, three (50%) have demonstrated ZIKV-related abnormalities.

Conclusion

Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

TORCH infection, twin, vertical transmission, congenital Zika syndrome, perinatal infection

Topic:  polymerase chain reaction – pregnancy – vertical disease transmission – infant – newborn – twins – placenta  – prenatal care – zika virus

Issue Section: Major Article

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Keywords: Zika Virus; Zika Congenital Infection; Pregnancy; Zika Congenital Syndrome.

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