#Zika Virus and #Pregnancy: Association between Acute #Infection and #Microcephaly in #Newborns in the State of #Rio de Janeiro, #Brazil (Geburtshilfe Frauenheilkd, abstract)

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

Geburtshilfe Frauenheilkd. 2020 Jan;80(1):60-65. doi: 10.1055/a-0972-2052. Epub 2020 Jan 13.

Zika Virus and Pregnancy: Association between Acute Infection and Microcephaly in Newborns in the State of Rio de Janeiro, Brazil.

Pereira AM1, Araujo Júnior E2,3, Werner H4, Monteiro DLM1.

Author information: 1 Perinatal Unit, State University of Rio de Janeiro (UERJ), Rio de Janeiro-RJ, Brazil. 2 Department of Obstetrics, Paulista School of Medicine – Federal University of São Paulo (EPM-UNIFESP), São Paulo-SP, Brazil. 3 Medical course, Municipal University of São Caetano do Sul (USCS), São Paulo-SP, Brazil. 4 Department of Radiology, Clínica de Diagnóstico por Imagem (CPDI), Rio de Janeiro-RJ, Brazil.

 

Abstract in English, German

Introduction Aim of the study was to evaluate the association between microcephaly and acute infection with Zika virus (ZIKV) in pregnant women in the state of Rio de Janeiro, Brazil. Infection was confirmed by laboratory testing. Materials and Methods A cross-sectional retrospective study of pregnant women with symptoms occurring between 2015 and 2016 suggestive of acute ZIKV infection was carried out, with confirmation of infection done by blood or urine RT-PCR. The relative proportions of categorical variables were calculated for two distinct groups: pregnant women whose newborns had microcephaly and pregnant women who gave birth to infants without microcephaly. Confidence intervals with a 95% level of agreement were estimated for the relative ratios. Results A total of 1609 pregnant women with a mean age of 26.4 ± 6.5 years were evaluated. As regards the time of acute infection, 19.6% (316) of cases occurred in the first trimester of pregnancy. Nineteen (76%) of the 25 cases with microcephaly (1.5%) were associated with an infection contracted in the first trimester of pregnancy (p < 0.001, OR = 13.7, 95% CI: 5.6 - 37.7). 48% (12/25) of the newborns with microcephaly had a birth weight of < 2500 grams, while only 7% (116/1597) of the group of newborns without microcephaly had a similarly low birth weight (p < 0.001, OR = 11.7, 95% CI: 5.2 - 26.2). Logistic regression showed that a birth weight of < 2500 g (OR = 12.54) and ZIKV infection in the first trimester of pregnancy (OR = 14.05) were associated with microcephaly (area under ROC curve = 0.86). Conclusion Acute ZIKV infection in the first trimester of pregnancy and low birth weight are associated with microcephaly.

KEYWORDS: Zika virus; congenital infection; first trimester of pregnancy; low birth weight; microcephaly

PMID: 31949320 PMCID: PMC6957353 DOI: 10.1055/a-0972-2052

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Keywords: Zika Virus; Zika Congenital Infection; Microcephaly; Brazil; Pregnancy.

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#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

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

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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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#Subclinical in #utero #Zika virus #infection is associated with #interferon alpha #sequelae and sex-specific molecular #brain #pathology in asymptomatic porcine offspring (PLoS Pathog., abstract)

[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring

Ivan Trus , Daniel Udenze, Brian Cox , Nathalie Berube, Rebecca E. Nordquist, Franz Josef van der Staay, Yanyun Huang, Gary Kobinger, David Safronetz, Volker Gerdts, Uladzimir Karniychuk

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Published: November 14, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1008038

 

Abstract

Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical and not associated with evident birth defects. Potentially detrimental life-long health outcomes in asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae in offspring may provide valuable information. To induce subclinical infection, we inoculated selected porcine fetuses at the mid-stage of development. Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months. Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects. However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment. Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult. Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology. While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection. RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses. Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.

 

Author summary

A number of studies showed that Zika virus (ZIKV) can cause severe abnormalities in fetuses, e.g., brain lesions, and subsequently life-long developmental and cognitive impairment in children. However, the majority of infections in pregnant women are subclinical and are not associated with developmental abnormalities in fetuses and newborns. It is known that disruptions to the in utero environment during fetal development can program increased risks for disease in adulthood. For this reason, children affected in utero even by mild ZIKV infection can appear deceptively healthy at birth but develop immune dysfunction and brain abnormalities during postnatal development. Here, we used the porcine model of subclinical fetal ZIKV infection to determine health sequelae in offspring which did not show apparent signs of the disease. We demonstrated that subclinical fetal infection was associated with abnormal immunological responses in apparently healthy offspring under normal environmental conditions and during social stress. We also showed silent sex-specific brain pathology as represented by altered gene expression. Our study provides new insights into potential outcomes of subclinical in utero ZIKV infection. It also emphasizes that further attempts to better understand silent pathology and develop alleviative interventions in ZIKV-affected offspring should take into account interactions of host factors, like sex, and environmental insults, like social stress.

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Citation: Trus I, Udenze D, Cox B, Berube N, Nordquist RE, van der Staay FJ, et al. (2019) Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring. PLoS Pathog 15(11): e1008038. https://doi.org/10.1371/journal.ppat.1008038

Editor: Ted C. Pierson, NIH, UNITED STATES

Received: May 8, 2019; Accepted: August 21, 2019; Published: November 14, 2019

Copyright: © 2019 Trus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: Financial support was provided by Genome Canada, Emerging Issue Program grant #418402, the Public Health Agency of Canada and the Government of Saskatchewan through Innovation Saskatchewan #418836. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. https://www.genomecanada.ca/ https://innovationsask.ca/research/saskatchewan-advantage-innovation-fund

Competing interests: The authors have declared that no competing interests exist.

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

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#Maternal #Zika Virus #Infection: Association With Small-for-Gestational-Age #Neonates and Preterm #Birth (Obstet Gynecol., abstract)

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

Obstet Gynecol. 2019 Nov 4. doi: 10.1097/AOG.0000000000003577. [Epub ahead of print]

Maternal Zika Virus Infection: Association With Small-for-Gestational-Age Neonates and Preterm Birth.

Cooper HJ1, Iwamoto M, Lash M, Conners EE, Paladini M, Slavinski S, Fine AD, Kennedy J, Heinke D, Ciaranello A, Seage GR 3rd, Lee EH.

Author information: 1 Bureau of Communicable Disease, New York City Department of Health and Mental Hygiene, Queens, and the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene, New York, New York; and the Harvard T. H. Chan School of Public Health and the Medical Practice Evaluation Center, Division of Infectious Disease, Massachusetts General Hospital, Boston, Massachusetts.

 

Abstract

OBJECTIVE:

To evaluate whether antenatal Zika virus infection is associated with risk of having a small-for-gestational-age (SGA) neonate, risk of preterm birth, and lower mean birth weight of term neonates.

METHODS:

For this retrospective observational study, we linked birth record data for women who delivered liveborn singleton neonates in New York City in 2016 to data for pregnant women with Zika virus infection reported to the New York City Health Department. We restricted the analysis to nonsmoking, nonwhite women and adjusted for maternal characteristics. Among women with antenatal Zika virus infection, we used modified Poisson regression to assess risks of having an SGA neonate and of delivering preterm, and linear regression to assess the association of infection with mean birth weight of term neonates.

RESULTS:

Of 116,034 deliveries of singleton neonates in New York City in 2016, 251 (0.2%) were to women with antenatal Zika virus infection. A higher percentage of women with Zika virus infection delivered an SGA neonate compared with those without (11.2% vs 5.8%; adjusted relative risk [RR] 1.8; 95% CI 1.3-2.6). There was no difference in preterm birth prevalence for women with and without Zika virus infection (adjusted RR 1.0; 95% CI 0.69-1.6). Mean birth weight of term neonates born to women with Zika virus infection was 47 g less (95% CI -105 to 11 g); this difference was not statistically significant in crude or adjusted analyses.

CONCLUSION:

For a cohort of New York City women, antenatal Zika virus infection was associated with an increased risk of having an SGA neonate, but not preterm birth or lower mean birth weight of term neonates. This supports a putative association between Zika virus infection during pregnancy and SGA.

PMID: 31698388 DOI: 10.1097/AOG.0000000000003577

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

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Impact evaluation of #Zika #epidemic on #congenital #anomalies registration in #Brazil: An interrupted time series analysis (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Disease, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Impact evaluation of Zika epidemic on congenital anomalies registration in Brazil: An interrupted time series analysis

Enny S. Paixão  , Moreno S. Rodrigues , Luciana L. Cardim, Juliane F. Oliveira, Catharina L. C., Maria da Conceição N. Costa, Maurício L. Barreto, Laura C. Rodrigues, Liam Smeeth, Roberto F. S. Andrade, Wanderson K. Oliveira, Maria Glória Teixeira

Published: September 23, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007721 / This is an uncorrected proof.

 

Abstract

This study aimed to assess the impact of the Zika epidemic on the registration of birth defects in Brazil. We used an interrupted time series analysis design to identify changes in the trends in the registration of congenital anomalies. We obtained monthly data from Brazilian Live Birth Information System and used two outcome definitions: 1) rate of congenital malformation of the brain and eye (likely to be affected by Zika and its complications) 2) rate of congenital malformation not related to the brain or eye unlikely to be causally affected by Zika. The period between maternal infection with Zika and diagnosis of congenital abnormality attributable to the infection is around six months. We therefore used September 2015 as the interruption point in the time series, six months following March 2015 when cases of Zika started to increase. For the purposes of this analysis, we considered the period from January 2010 to September 2015 to be “pre-Zika event,” and the period from just after September 2015 to December 2017 to be “post-Zika event.” We found that immediately after the interruption point, there was a great increase in the notification rate of congenital anomalies of 14.9/10,000 live births in the brain and eye group and of 5.2/10,000 live births in the group not related with brain or eye malformations. This increase in reporting was in all regions of the country (except in the South) and especially in the Northeast. In the period “post-Zika event”, unlike the brain and eye group which showed a monthly decrease, the group without brain or eye malformations showed a slow but significant increase (relative to the pre-Zika trend) of 0.2/10,000 live births. These findings suggest an overall improvement in the registration of birth malformations, including malformations that were not attributed to Zika, during and after the Zika epidemic.

 

Author summary

Zika can be characterized as one of the most significant emerging arboviruses. The Zika epidemic in Brazil and the subsequent increase in the number of serious brain anomalies, such as microcephaly, has demonstrated the importance of analysing the impact of Zika infection on the rate of congenital anomalies in an affected population. From the analysis of the monthly data on the Live Birth Information System, the authors found that immediately after the Zika event there was a large increase in the notification rate of congenital anomalies reported as a complication of which infection (malformations of brain and eye) and also an increase in the rate of congenital malformations not related with Zika. This growth was seen throughout the country as a whole and in all regions (except in the South), especially in the Northeast where the infection rates were the highest. In the period post-Zika event, the group not related with brain or eye malformation there was an increase in the monthly notification rate while in the brain and eye group there was a decrease in the monthly notification rate. These findings suggest an overall growing awareness of health professionals to improve the registration of birth malformations trigged by the Zika epidemic.

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Citation: Paixão ES, Rodrigues MS, Cardim LL, Oliveira JF, L. C. C, Costa MdCN, et al. (2019) Impact evaluation of Zika epidemic on congenital anomalies registration in Brazil: An interrupted time series analysis. PLoS Negl Trop Dis 13(9): e0007721. https://doi.org/10.1371/journal.pntd.0007721

Editor: David Harley, University of Queensland, AUSTRALIA

Received: April 17, 2019; Accepted: August 19, 2019; Published: September 23, 2019

Copyright: © 2019 Paixão et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: ESP is funded by the Wellcome Trust (grant number 213589/Z/18/Z). The funders had no role in study design, analysis, decision to publish or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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Keywords: Zika Virus; Zika Congenital Infection; Brazil.

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#Postnatal #Zika virus #infection of #NHP #infants born to mothers infected with homologous #Brazilian Zika virus (Sci Rep., abstract)

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

Sci Rep. 2019 Sep 5;9(1):12802. doi: 10.1038/s41598-019-49209-7.

Postnatal Zika virus infection of nonhuman primate infants born to mothers infected with homologous Brazilian Zika virus.

Maness NJ1,2, Schouest B3,4, Singapuri A5, Dennis M6, Gilbert MH3, Bohm RP3, Schiro F3, Aye PP3, Baker K3, Van Rompay KKA5,7, Lackner AA3, Bonaldo MC8, Blair RV3, Permar SR6,9, Coffey LL5, Panganiban AT10,3, Magnani D11.

Author information: 1 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA. nmaness@tulane.edu. 2 Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA. nmaness@tulane.edu. 3 Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA. 4 Biomedical Sciences Training Program, Tulane University School of Medicine, New Orleans, Louisiana, USA. 5 Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, USA. 6 Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA. 7 California National Primate Research Center, University of California, Davis, California, USA. 8 Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil. 9 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA. 10 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA. 11 MassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA.

 

Abstract

Recent data in a nonhuman primate model showed that infants postnatally infected with Zika virus (ZIKV) were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. In this pilot study, we addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding antibodies remained detectable until viral infection at 5 months. Acute serum viremia was comparatively lower than adults infected with the same Brazilian isolate of ZIKV (n = 11 pregnant females, 4 males, and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute and our study lacks an important comparison with postnatally infected infants born to naïve dams, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.

PMID: 31488856 DOI: 10.1038/s41598-019-49209-7

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Keywords: Zika Virus; Zika Congenital Infection; Pregnancy; Animal models.

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#International prospective observational cohort #study of #Zika in #infants and #pregnancy (#ZIP study): study protocol (BMC Pregnancy Childbirth, abstract)

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

BMC Pregnancy Childbirth. 2019 Aug 7;19(1):282. doi: 10.1186/s12884-019-2430-4.

International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

Lebov JF1, Arias JF2, Balmaseda A3, Britt W4, Cordero JF5, Galvão LA6, Garces AL7, Hambidge KM8, Harris E9, Ko A10,11, Krebs N8, Marques ETA12,13, Martinez AM14, McClure E15, Miranda-Filho DB16, Moreira MEL17, Mussi-Pinhata MM18, Ochoa TJ19, Osorio JE20, Scalabrin DMF10,11, Schultz-Cherry S2, Seage GR 3rd21, Stolka K15, Ugarte-Gil CA19, Vega CMV22, Welton M5, Ximenes R23, Zorrilla C24.

Author information: 1 Social, Statistical and Environmental Sciences, RTI International, Durham, NC, USA. jlebov@rti.org. 2 Department of Infectious Diseases, St Jude Children’s Research Hospital, Memphis, TN, 38105, USA. 3 Centro Nacional de Diagnostico y Referencia, Complejo Nacional de Salud, Managua, Nicaragua. 4 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA. 5 Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, USA. 6 Center for Global Health – CRIS, FIOCRUZ, Rio de Janeiro, Brazil. 7 Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP), Guatemala City, Guatemala. 8 Section of Nutrition, Pediatrics, University of Colorado, Aurora, CO, USA. 9 Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA. 10 Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. 11 Instituto Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Brazil. 12 School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. 13 Instituto Aggeu Magalhães, Department of Virology and Experimental Therapeutics, FIOCRUZ, Pernambuco, Brazil. 14 Director of Research Institute at Imbanaco Medical Center, Cali, Colombia. 15 Social, Statistical and Environmental Sciences, RTI International, Durham, NC, USA. 16 Programa de Pós-Graduação em Ciências da Saúde (PPGCS) da Universidade de Pernambuco, Microcephaly Epidemic Research Group, Recife, Brazil. 17 Instituto Fernandes Figueira – FIOCRUZ, Rio de Janeiro, Brazil. 18 Ribeirão Preto Medical School, Ribeirão Preto, Brazil. 19 Instituto de Medicina Tropical Alexander von Humboldt and Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru. 20 Department of Pathobiological Sciences, University of Wisconsin, Madison, WI, USA. 21 Department of Epidemiology, Harvard Chan School of Public Health, Boston, MA, USA. 22 University of Puerto Rico, San Juan, Puerto Rico. 23 Departamento de Medicina Tropical da Universidade Federal de Pernambuco, Microcephaly Epidemic Research Group, Recife, Brazil. 24 Maternal-Infant Studies Center (CEMI), San Juan, Puerto Rico.

 

Abstract

BACKGROUND:

Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes.

METHODS:

At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained.

DISCUSSION:

With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure.

TRIAL REGISTRATION: NCT02856984 . Registered August 5, 2016. Retrospectively registered.

KEYWORDS: Latin America; Microcephaly; Pregnancy; Zika virus

PMID: 31391005 DOI: 10.1186/s12884-019-2430-4

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Keywords: Zika Virus; Pregnancy; Zika Congenital Infection.

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Association Between #Neonatal #Neuroimaging and #Clinical Outcomes in #Zika-Exposed #Infants From #Rio de Janeiro, #Brazil (JAMA Netw Open., abstract)

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

JAMA Netw Open. 2019 Jul 3;2(7):e198124. doi: 10.1001/jamanetworkopen.2019.8124.

Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil.

Pool KL1, Adachi K1, Karnezis S1, Salamon N1, Romero T1, Nielsen-Saines K1, Pone S2, Boechat M2, Aibe M2, Gomes da Silva T2, Ribeiro CTM2, Boechat MI1, Brasil P2, Zin A2, Tsui I1, Gaw SL3, Daltro P4, Ribeiro BG4, Fazecas T4, Hygino da Cruz LC4, Nogueira R4, Vasconcelos Z2, Pereira JP Jr2, Saad Salles T2, Barbosa CN2, Chen W5, Foo SS5, Jung J5, Moreira ME2, Pone M2.

Author information: 1 David Geffen School of Medicine, University of California, Los Angeles. 2 Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 3 University of California San Francisco School of Medicine. 4 Clinica de Diagnostico por Imagem CDPI, Rio de Janeiro, Brazil. 5 University of Southern California School of Medicine, Los Angeles.

 

Abstract

IMPORTANCE:

Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings.

OBJECTIVE:

To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection.

DESIGN, SETTING, AND PARTICIPANTS:

This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children’s hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic. Neuroimaging from March 1, 2016, to June 30, 2017, was evaluated to determine whether findings were associated with clinical outcomes and the timing of maternal ZIKV infection. Data were analyzed from July 1, 2017, to August 30, 2018.

EXPOSURES:

Neuroimaging (computed tomography and/or magnetic resonance imaging) was performed on ZIKV-exposed infants after birth. Blood and/or urine specimens from mothers and infants were tested for ZIKV by polymerase chain reaction assay.

MAIN OUTCOMES AND MEASURES:

Neuroimaging studies were evaluated for structural abnormalities and other forms of brain injury.

RESULTS:

A total of 110 infants with a mean (SD) gestational age of 38.4 (2.1) weeks had neuroimaging and clinical outcome data reviewed. Of these, 71 (65%) had abnormal neuroimaging findings, with the majority (96%) classified as having severe ZIKV infection at birth. The most common neuroimaging abnormalities were structural abnormalities including brain calcifications, especially at the cortico-subcortical white matter junction, cortex malformations, ventriculomegaly, and reduced brain volumes, followed by brainstem hypoplasia, cerebellar hypoplasia, and corpus callosum abnormalities. Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%). Four of 39 infants (10%) without initial evidence of severe ZIKV infection and normal findings on neurologic evaluation at birth had abnormal neuroimaging findings. Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging abnormalities. The odds of abnormal neuroimaging were 7.9 times greater for infants with first trimester ZIKV exposure compared with other trimesters combined (odds ratio, 7.9; 95% CI, 3.0-20.4; P < .001).

CONCLUSIONS AND RELEVANCE:

Neuroimaging abnormalities of computed tomography and/or magnetic resonance imaging scans were common in ZIKV-exposed infants. While neuroimaging abnormalities were seen in 10% of infants without clinically severe ZIKV, most occurred almost exclusively among those with clinically severe ZIKV, especially among those with a history of ZIKV exposure in the first trimester.

PMID: 31365112 DOI: 10.1001/jamanetworkopen.2019.8124

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Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Neurology; Neuroimaging.

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Alterations in #visual acuity and visual #development in #infants 1-24 months old either exposed to or infected by #Zika virus during #gestation, with and without #microcephaly (J AAPOS., abstract)

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

J AAPOS. 2019 Jun 20. pii: S1091-8531(19)30137-5. doi: 10.1016/j.jaapos.2019.03.005. [Epub ahead of print]

Alterations in visual acuity and visual development in infants 1-24 months old either exposed to or infected by Zika virus during gestation, with and without microcephaly.

Baran LCP1, da Costa MF2, Vidal KS2, Damico FM3, Barboni MTS4, da S Lima D2, de C R de M França V5, Martins CMG2, Tabares HS2, Dias SL5, Silva LA2, Decleva D2, Hamer RD6, Zatz M7, Bertozzi APAP8, Gazeta RE8, Passos SD8, Ventura DF2.

Author information: 1 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil. Electronic address: baranejbio@gmail.com. 2 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil. 3 Department of Ophthalmology, University of São Paulo College of Medicine, São Paulo, SP, Brazil. 4 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil; Department of Ophthalmology, Semmelweis University, Budapest, Hungary. 5 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil. 6 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil; Department of Psychology, Florida Atlantic University, Boca Raton, Florida. 7 Human Genome and Stem Cells Center, Bioscience Institute, University of São Paulo. 8 University of Jundiai Medical School, Jundiai, São Paulo, SP, Brazil.

 

Abstract

PURPOSE:

To evaluate visual acuity and visual acuity development in children from the state of São Paulo, Brazil, who were exposed to the Zika virus (ZIKV) gestationally.

METHODS:

Children who had been exposed to ZIKV during gestation and age-matched control subjects received visual acuity and funduscopic examination. ZIKV exposure was confirmed by maternal quantitative polymerase chain reaction testing or serology assay. The ZIKV group was divided into two subgroups: Zika-exposed (ZE), with only the mother having confirmed ZIKV-infection, and Zika-infected (ZI), with confirmed infection. Visual acuity development was compared with prior norms and quantified by measuring visual acuity correlation with age.

RESULTS:

A total of 110 children were included: 47 who had been exposed to ZIKV (ZE, 23; ZI, 24) and 63 controls. Abnormal visual acuity was found in 5 of 24 ZI children. Of the 4 children with microcephaly, only 2 had visual acuity loss (only 1 also had abnormal funduscopic findings). There was significant correlation between age and visual acuity in both the control group (R2 = 0.8; P < 0.0000) and the ZE subgroup (R2 = 0.6; P < 0.0000). However, visual acuity did not correlate with age in the ZI subgroup (R2 = 0.04; P = 0.38). Furthermore, the increment in octaves/month was much lower in the ZI subgroup.

CONCLUSIONS:

Our data indicates that visual acuity losses only occur in infants who suffered gestational-infection, not simply exposure. Lack of correlation between age and visual acuity in the ZI subgroup suggests a slowing of visual development even in the absence of microcephaly. This result may have broad implications for the deleterious effects of ZIKV on the central nervous system.

Copyright © 2019 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

PMID: 31229606 DOI: 10.1016/j.jaapos.2019.03.005

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Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Microcephaly; Pediatrics; Ophthalmology; Neurology.

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