Detection of #Zika virus in mouse mammary #gland and #breast #milk (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Detection of Zika virus in mouse mammary gland and breast milk

Jose Angel Regla-Nava, Karla M. Viramontes, Teodora Vozdolska, Anh-Thy Huynh, Tom Villani, Graeme Gardner, Michael Johnson, Pamela J. Ferro, Sujan Shresta , Kenneth Kim

Published: February 11, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007080 / This is an uncorrected proof.

 

Abstract

Clinical reports of Zika Virus (ZIKV) RNA detection in breast milk have been described, but evidence conflicts as to whether this RNA represents infectious virus. We infected post-parturient AG129 murine dams deficient in type I and II interferon receptors with ZIKV. ZIKV RNA was detected in pup stomach milk clots (SMC) as early as 1 day post maternal infection (dpi) and persisted as late as 7 dpi. In mammary tissues, ZIKV replication was demonstrated by immunohistochemistry in multiple cell types including cells morphologically consistent with myoepithelial cells. No mastitis was seen histopathologically. In the SMC and tissues of the nursing pups, no infectious virus was detected via focus forming assay. However, serial passages of fresh milk supernatant yielded infectious virus, and immunohistochemistry showed ZIKV replication protein associated with degraded cells in SMC. These results suggest that breast milk may contain infectious ZIKV. However, breast milk transmission (BMT) does not occur in this mouse strain that is highly sensitive to ZIKV infection. These results suggest a low risk for breast milk transmission of ZIKV, and provide a platform for investigating ZIKV entry into milk and mechanisms which may prevent or permit BMT.

 

Author summary

Can Zika virus be transmitted from nursing mothers to their children via breast milk? Only 4 years have passed since the Zika virus outbreak in Brazil, and much remains to be understood about the transmission and health consequences of Zika infection. To date some case reports have detected Zika virus RNA in the breast milk of infected mothers, but the presence of a virus’ RNA does not mean that intact virus is present. Milk also contains many natural defense components against infection, so even intact virus carried in breast milk may not be infectious to a child. Here we used a mouse that is genetically engineered to be highly susceptible to Zika infection, and tested whether 1) we could find intact virus in mouse breast milk and 2) infection was passed from mother to pups. We found very low levels of intact Zika virus in mouse breast milk, and found none of the nursing pups to be infected. The model of Zika virus breast milk infection developed in this study establishes a system by which we may learn whether Zika RNA in human breast milk is truly infectious to children, and how Zika virus may enter the milk.

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Citation: Regla-Nava JA, Viramontes KM, Vozdolska T, Huynh A-T, Villani T, Gardner G, et al. (2019) Detection of Zika virus in mouse mammary gland and breast milk. PLoS Negl Trop Dis 13(2): e0007080. https://doi.org/10.1371/journal.pntd.0007080

Editor: David W.C. Beasley, University of Texas Medical Branch, UNITED STATES

Received: June 5, 2018; Accepted: December 14, 2018; Published: February 11, 2019

Copyright: © 2019 Regla-Nava 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 paper and its Supporting Information files.

Funding: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was funded by NIH grants (R01 AI116813 and R21 NS100477 to S.S.) and the Chiba-UCSD Center for Mucosal Immunology, Allergy and Vaccine Development. And the La Jolla Institute for Allergy and Immunology institutional support.

Competing interests: M.J. is CEO of Visikol.

Keywords: Zika Virus; Pregnancy; Animal models.

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#Clinical presentation of #pregnant women in #isolation units for #Ebola virus disease in #SierraLeone, 2014 (Int J Gynaecol Obstet., abstract)

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

Int J Gynaecol Obstet. 2019 Feb 1. doi: 10.1002/ijgo.12775. [Epub ahead of print]

Clinical presentation of pregnant women in isolation units for Ebola virus disease in Sierra Leone, 2014.

Mpofu JJ1,2, Soud F3, Lyman M4, Koroma AP5, Morof D1,2, Ellington S1, Kargbo SS5, Callaghan W1.

Author information: 1 Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA. 2 US Public Health Service Commissioned Corps, Rockville, MD, USA. 3 Zambia Country Office, Centers for Disease Control and Prevention, Lusaka, Zambia. 4 Epidemic Intelligence Service, Division of Scientific Education and Professional Development, Office of Public Health Scientific Services, Centers for Disease Control and Prevention, Atlanta, GA, USA. 5 Ministry of Health and Sanitation, Freetown, Sierra Leone.

 

Abstract

OBJECTIVES:

To examine Ebola virus disease (EVD) symptom prevalence and EVD status among pregnant women in Ebola isolation units in Sierra Leone.

METHODS:

In an observational study, data were obtained for pregnant women admitted to Ebola isolation units across four districts in Sierra Leone from June 29, 2014, to December 20, 2014. Women were admitted to isolation units if they had suspected EVD exposures or fever (temperature >38°C) and three or more self-reported symptoms suggestive of EVD. Associations were examined between EVD status and each symptom using χ2 tests and logistic regression adjusting for age/labor status.

RESULTS:

Of 176 pregnant women isolated, 55 (32.5%) tested positive for EVD. Using logistic regression models adjusted for age, EVD-positive women were significantly more likely to have fever, self-reported fatigue/weakness, nausea/vomiting, headache, muscle/joint pain, chest pain, vaginal bleeding, unexplained bleeding, or sore throat upon admission. In models adjusted for age/labor, only women with fever or vaginal bleeding upon admission were significantly more likely to be EVD-positive.

CONCLUSIONS:

Several EVD symptoms and complications increased the odds of testing EVD-positive; some of these were also signs and symptoms of labor/pregnancy complications. The study results highlight the need to refine screening for pregnant women with EVD.

This article is protected by copyright. All rights reserved.

KEYWORDS: Ebola virus disease; Ebola virus infection; Pregnancy; Sierra Leone; Signs and symptoms; Symptom assessment

PMID: 30706470 DOI: 10.1002/ijgo.12775

Keywords: Ebola; Pregnancy; Sierra Leone.

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SIMULTANEOUS CIRCULATION OF #ARBOVIRUSES AND OTHER #CONGENITAL #INFECTIONS IN #PREGNANT WOMEN IN #RIO DE JANEIRO, #BRAZIL (Acta Trop., abstract)

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

Acta Trop. 2019 Jan 24. pii: S0001-706X(18)31538-9. doi: 10.1016/j.actatropica.2019.01.020. [Epub ahead of print]

SIMULTANEOUS CIRCULATION OF ARBOVIRUSES AND OTHER CONGENITAL INFECTIONS IN PREGNANT WOMEN IN RIO DE JANEIRO, BRAZIL.

Carvalho FR1, Medeiros T2, de Oliveira Vianna RA3, Douglass-Jaimes G4, Guerra Nunes PC5, Salgado Quintans MD6, Fernandes C7, Baêta Cavalcanti SM8, Dos Santos FB9, de Oliveira SA10, Araújo Cardoso CA11, Silva AA12.

Author information: 1 Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: fabianarc@id.uff.br. 2 Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: thaliamedeiros@id.uff.br. 3 Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: renatavianna03@gmail.com. 4 Environmental Analysis Program, Pomona College, Claremont, CA, USA. Electronic address: guillermo.douglass-jaimes@pomona.edu. 5 Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address: pricgn@ioc.fiocruz.br. 6 Departamento Materno-Infantil, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: mdsquintans@id.uff.br. 7 Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: cinttiafs@yahoo.com.br. 8 Departamento de Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: silviacavalcanti67@gmail.com. 9 Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address: flaviab@ioc.fiocruz.br. 10 Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: sartimos@id.uff.br. 11 Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil; Departamento Materno-Infantil, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: claudetecardoso@id.uff.br. 12 Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil; Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: aasilva@id.uff.br.

 

Abstract

BACKGROUND:

Arboviruses (Zika, dengue and chikungunya) represent a major risk for pregnant women, especially because their vertical transmission can lead to neurological damage in newborns. Early diagnosis can be difficult due to similar clinical presentation with other congenital infections that are associated with congenital abnormalities.

OBJECTIVES:

To investigate the circulation of arboviruses and other pathogens responsible for congenital infections, reporting clinical aspects and geographic distribution of maternal rash in a metropolitan region of Rio de Janeiro (Brazil).

METHODS:

Cross-sectional study with pregnant women presenting rash attended at the Exanthematic Diseases Unit (Niterói, Rio de Janeiro) from 2015 to 2018. Diagnosis of arboviruses was performed by real-time PCR (RT-qPCR) and laboratorial screening for syphilis, toxoplasmosis, rubella, cytomegalovirus and HIV was assessed. Demographic data was used for georeferencing analysis.

FINDINGS:

We included 121 pregnant women, of whom Zika virus was detected in 45 cases (37.2%), chikungunya in 33 (27.3%) and dengue in one (0.8%). Five patients presented syphilis, and we observed one case each of listeria, cytomegalovirus, and a syphilis-toxoplasmosis case. Similarity of clinical symptoms was observed in all groups; however, 84.8% of patients with chikungunya presented arthralgia. Following the decline of Zika cases, chikungunya infection was mostly observed during 2017-2018. Considering pregnant women infected with arboviruses and other infections, 41% resided in urban slums, mostly in Niterói.

MAIN CONCLUSIONS:

Simultaneous circulation of arboviruses and other agents responsible for congenital infections were observed; however, we did not identify co-infections between arboviruses. In this scenario, we emphasize the importance of adequate prenatal care to provide an accurate diagnosis of maternal rash.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: arboviruses; pregnancy; vertical transmission of infectious disease

PMID: 30685232 DOI: 10.1016/j.actatropica.2019.01.020

Keywords: Arbovirus; Zika Virus; Chikungunya Fever; Dengue fever; Pregnancy; Brazil.

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#Influenza associated #outcomes among #pregnant, #postpartum, and non-pregnant women of reproductive age (J Infect Dis., abstract)

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

Influenza associated outcomes among pregnant, post-partum, and non-pregnant women of reproductive age

Namrata Prasad, MPH, Q Sue Huang, PhD, Tim Wood, MSc, Nayyereh Aminisani, PhD, Colin McArthur, MBChB, Michael G Baker, MBChB, Ruth Seeds, Mark G Thompson, PhD, Marc-Alain Widdowson, VetMB, MSc, MA, E Claire Newbern, PhD, MPH

The Journal of Infectious Diseases, jiz035, https://doi.org/10.1093/infdis/jiz035

Published: 23 January 2019

 

Abstract

Background

Pregnant women are prioritised for seasonal influenza vaccination however, evidence on influenza risk during pregnancy used to inform these policies is limited.

Methods

Individual-level administrative datasets and active surveillance data were joined to estimate influenza-associated hospitalisation and outpatient visit rates by pregnancy, post-partum and trimester status.

Results

During 2012-2015, 46 (17.7%) of 260 influenza-confirmed acute respiratory hospitalisations and 13 (4.4%) of 294 influenza-confirmed outpatient visits were among pregnant and post-partum women. Pregnant and post-partum women experienced higher rates of influenza hospitalisation compared with non-pregnant women overall (Rate Ratio [RR] 3.4; 95% Confidence Interval [CI] 2.5-4.7) and by trimester (1st: 2.5; 95%CI 1.2-5.4; 2nd: 3.9; 95%CI 2.4-6.3; 3rd: 4.8; 95%CI 3.0-7.7; post-partum: 0.7; 95%CI 3.0-7.7). Influenza A viruses were associated with increased risk (A(H1N1)pdm09: 5.3; 95%CI 3.2-8.7 and A(H3N2): 3.0; 95%CI 1.8-5.0), but not influenza B (1.8; 95%CI 0.7-4.6). Influenza hospitalisation rates in pregnancy were significantly higher for Māori women (RR 3.2; 95% CI 1.3-8.4) compared with women of European/Other ethnicity. Similar risks for influenza-confirmed outpatient visits were not observed.

Conclusion

Seasonal influenza poses higher risks of hospitalisation on pregnant women in all trimesters when compared with non-pregnant women. Hospitalisation rates vary by influenza type and ethnicity among pregnant women.

seasonal influenza, pregnancy

Issue Section: Major Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Seasonal Influenza; Pregnancy.

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#Zika virus #infection at mid- #gestation results in #fetal #cerebral cortical injury and fetal death in the olive baboon (PLoS Pathogens, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

Sunam Gurung, Nicole Reuter, Alisha Preno, Jamie Dubaut, Hugh Nadeau, Kimberly Hyatt, Krista Singleton, Ashley Martin, W. Tony Parks, James F. Papin, Dean A. Myers

Published: January 18, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1007507 / This is an uncorrected proof.

 

Abstract

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5–7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs.

 

Author summary

Zika virus is endemic in the Americas, primarily spread through mosquitos and sexual contact. Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome (CZS), with the most severe pathology being fetal microcephaly. Developing model organisms that faithfully recreate Zika infection in humans is critical for future development of treatments and preventions. In our present study, we infected Olive baboons at mid-gestation with Zika virus and studied the acute period of viremia and transfer of Zika virus to the fetus during the first three weeks after infection to better understand the timing and mechanisms of transfer of ZIKV across the placenta, leading to CZS. We observed Zika virus transfer to fetuses resulting in fetal death in one pregnancy and in a second pregnancy, significant damage to the frontal cortex of the fetal brain at a critical period of neurodevelopment in primates. Thus, the baboon provides a promising new non-human primate model to further compare and contrast the consequences of Zika virus infection in pregnancy to humans and other non-human primates.

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Citation: Gurung S, Reuter N, Preno A, Dubaut J, Nadeau H, Hyatt K, et al. (2019) Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. PLoS Pathog 15(1): e1007507. https://doi.org/10.1371/journal.ppat.1007507

Editor: Carolyn B. Coyne, University of Pittsburgh, UNITED STATES

Received: October 10, 2018; Accepted: December 5, 2018; Published: January 18, 2019

Copyright: © 2019 Gurung 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: These studies were supported in part by the National Institutes of Health, NS103772 (DAM) and OD01988 (JFP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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

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

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#Zika Virus #Epidemic in #Pregnant Women, #Dominican Republic, 2016–2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 2—February 2019 / CME ACTIVITY – Synopsis

Zika Virus Epidemic in Pregnant Women, Dominican Republic, 2016–2017

Farah Peña, Raquel Pimentel, Shaveta Khosla, Supriya D. Mehta, and Maximo O. Brito

Author affiliations: Ministry of Health, Santo Domingo, Dominican Republic (F. Peña, R. Pimentel); University of Illinois at Chicago, Chicago, Illinois, USA (S. Khosla, S.D. Mehta, M.O. Brito)

 

Abstract

Zika virus infection during pregnancy may result in birth defects and pregnancy complications. We describe the Zika virus outbreak in pregnant women in the Dominican Republic during 2016–2017. We conducted multinomial logistic regression to identify factors associated with fetal losses and preterm birth. The Ministry of Health identified 1,282 pregnant women with suspected Zika virus infection, a substantial proportion during their first trimester. Fetal loss was reported for ≈10% of the reported pregnancies, and 3 cases of fetal microcephaly were reported. Women infected during the first trimester were more likely to have early fetal loss (adjusted odds ratio 5.9, 95% CI 3.5–10.0). Experiencing fever during infection was associated with increased odds of premature birth (adjusted odds ratio 1.65, 95% CI 1.03–2.65). There was widespread morbidity during the epidemic. Our findings strengthen the evidence for a broad range of adverse pregnancy outcomes resulting from Zika virus infection.

Keywords: Zika Virus; Pregnancy; Zika Congenital Infection; Dominical Republic.

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Association of #Prenatal #Ultrasonographic Findings With Adverse #Neonatal Outcomes Among #Pregnant Women With Zika Virus Infection in #Brazil (JAMA Netw Open., abstract)

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

JAMA Netw Open. 2018 Dec 7;1(8):e186529. doi: 10.1001/jamanetworkopen.2018.6529.

Association of Prenatal Ultrasonographic Findings With Adverse Neonatal Outcomes Among Pregnant Women With Zika Virus Infection in Brazil.

Pereira JP Jr1, Nielsen-Saines K2, Sperling J3, Maykin MM3, Damasceno L4, Cardozo RF1, Valle HA1, Dutra BRT1, Gama HD1, Adachi K2, Zin AA1, Tsui I5, Vasconcelos Z1, Brasil P4, Moreira ME1, Gaw SL3.

Author information: 1 Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 2 Division of Pediatric Infectious Diseases, Department of Pediatrics, University of California, Los Angeles. 3 Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco. 4 Laboratorio de Doenças Febris Agudas, Instituto de Infectologia Evandro Chagas-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 5 Jules Stein Eye Institute, Retina Division, UCLA (University of California, Los Angeles).

 

Abstract

IMPORTANCE:

Congenital Zika virus infection causes a spectrum of adverse birth outcomes, including severe birth defects of the central nervous system. The association of prenatal ultrasonographic findings with adverse neonatal outcomes, beyond structural anomalies such as microcephaly, has not been described to date.

OBJECTIVE:

To determine whether prenatal ultrasonographic examination results are associated with abnormal neonatal outcomes in Zika virus-affected pregnancies.

DESIGN, SETTING, AND PARTICIPANTS:

A prospective cohort study conducted at a single regional referral center in Rio de Janeiro, Brazil, from September 1, 2015, to May 31, 2016, among 92 pregnant women diagnosed during pregnancy with Zika virus infection by reverse-transcription polymerase chain reaction, who underwent subsequent prenatal ultrasonographic and neonatal evaluation.

EXPOSURES:

Prenatal ultrasonography.

MAIN OUTCOMES AND MEASURES:

The primary outcome measure was composite adverse neonatal outcome (perinatal death, abnormal finding on neonatal examination, or abnormal finding on postnatal neuroimaging). Secondary outcomes include association of specific findings with neonatal outcomes.

RESULTS:

Of 92 mother-neonate dyads (mean [SD] maternal age, 29.4 [6.3] years), 55 (60%) had normal results and 37 (40%) had abnormal results on prenatal ultrasonographic examinations. The median gestational age at delivery was 38.6 weeks (interquartile range, 37.9-39.3). Of the 45 neonates with composite adverse outcome, 23 (51%) had normal results on prenatal ultrasonography. Eleven pregnant women (12%) had a Zika virus-associated finding that was associated with an abnormal result on neonatal examination (adjusted odds ratio [aOR], 11.6; 95% CI, 1.8-72.8), abnormal result on postnatal neuroimaging (aOR, 6.7; 95% CI, 1.1-38.9), and composite adverse neonatal outcome (aOR, 27.2; 95% CI, 2.5-296.6). Abnormal results on middle cerebral artery Doppler ultrasonography were associated with neonatal examination abnormalities (aOR, 12.8; 95% CI, 2.6-63.2), postnatal neuroimaging abnormalities (aOR, 8.8; 95% CI, 1.7-45.9), and composite adverse neonatal outcome (aOR, 20.5; 95% CI, 3.2-132.6). There were 2 perinatal deaths. Abnormal findings on prenatal ultrasonography had a sensitivity of 48.9% (95% CI, 33.7%-64.2%) and a specificity of 68.1% (95% CI, 52.9%-80.1%) for association with composite adverse neonatal outcomes. For a Zika virus-associated abnormal result on prenatal ultrasonography, the sensitivity was lower (22.2%; 95% CI, 11.2%-37.1%) but the specificity was higher (97.9%; 95% CI, 88.7%-99.9%).

CONCLUSIONS AND RELEVANCE:

Abnormal results on prenatal ultrasonography were associated with adverse outcomes in congenital Zika infection. The absence of abnormal findings on prenatal ultrasonography was not associated with a normal neonatal outcome. Comprehensive evaluation is recommended for all neonates with prenatal Zika virus exposure.

PMID: 30646333 DOI: 10.1001/jamanetworkopen.2018.6529

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

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