Complexities of Zika Diagnosis and Evaluation in a U.S. Congenital Zika Program

Sarah B. Mulkey Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, District of Colombia;
Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;

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Emily Ansusinha Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, District of Columbia;

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Caitlin Cristante Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, District of Colombia;

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Stephanie M. Russo Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, District of Colombia;

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Cara Biddle Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of General and Community Pediatrics, Children's National Hospital, Washington, District of Columbia;

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Youssef A. Kousa Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Neurology, Children's National Hospital, Washington, District of Columbia;

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Lindsay Pesacreta Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, District of Colombia;

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Barbara Jantausch Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, District of Columbia;

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Benjamin Hanisch Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, District of Columbia;

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Nada Harik Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, District of Columbia;

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Rana F. Hamdy Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, District of Columbia;

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Andrea Hahn Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, District of Columbia;

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Taeun Chang Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Neurology, Children's National Hospital, Washington, District of Columbia;

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Mohamad Jaafar Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Ophthalmology, Children's National Hospital, Washington, District of Columbia;

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Tracey Ambrose Division of Audiology, Children's National Hospital, Washington, District of Columbia;

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Gilbert Vezina Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Radiology, Children's National Hospital, Washington, District of Columbia;

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Dorothy I. Bulas Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Radiology, Children's National Hospital, Washington, District of Columbia;

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David Wessel Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Chief Medical Officer, Children’s National Hospital, Washington, District of Columbia;

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Adre J. du Plessis Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, District of Colombia;
Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Neurology, Children's National Hospital, Washington, District of Columbia;

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Roberta L. DeBiasi Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia;
Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, District of Columbia;
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia

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Abstract.

The objective of the study was to describe the complexity of diagnosis and evaluation of Zika-exposed pregnant women/fetuses and infants in a U.S. Congenital Zika Program. Pregnant women/fetuses and/or infants referred for clinical evaluation to the Congenital Zika Program at Children’s National (Washington, DC) from January 2016 to June 2018 were included. We recorded the timing of maternal Zika-virus (ZIKV) exposure and ZIKV laboratory testing results. Based on laboratory testing, cases were either confirmed, possible, or unlikely ZIKV infection. Prenatal and postnatal imaging by ultrasound and/or magnetic resonance imaging (MRI) were categorized as normal, nonspecific, or as findings of congenital Zika syndrome (CZS). Of 81 women–fetus/infant pairs evaluated, 72 (89%) had confirmed ZIKV exposure; 18% of women were symptomatic; only a minority presented for evaluation within the time frame for laboratory detection. Zika virus could only be confirmed in 29 (40%) cases, was possible in 26 (36%) cases, and was excluded in 17 (24%) cases. Five cases (7%) had prenatal ultrasound and MRI findings of CZS, but in only three was ZIKV confirmed by laboratory testing. Because of timing of exposure to presentation, ZIKV infection could not be excluded in many cases. Neuroimaging found CZS in 7% of cases, and in many patients, there were nonspecific imaging findings that warrant long-term follow-up. Overall, adherence to postnatal recommended follow-up evaluations was modest, representing a barrier to care. These challenges may be instructive to future pediatric multidisciplinary clinics for congenital infectious/noninfectious threats to pregnant women and their infants.

Author Notes

Address correspondence to Sarah B. Mulkey, Children’s National Hospital, Prenatal Pediatrics Institute, 111 Michigan Ave., NW Washington, DC 20010. E-mail: sbmulkey@childrensnational.org

Disclosures: DeBiasi, Mulkey, and Biddle had a contract by U.S. Centers for Disease Control/Vysnova to provide Zika-related technical expertise; Mulkey (Awardee), DeBiasi, Biddle, and du Plessis (mentors) receive research support for neurodevelopmental follow-up of Zika-exposed infants from the Thrasher Research Fund.

Financial support: The Congenital Zika Program was established with support of internal Special Purpose Funds from Children’s National Hospital and the Ikaria Fund.

Authors’ addresses: Sarah B. Mulkey, Emily Ansusinha, Stephanie M. Russo¸Cara Biddle, Youssef A. Kousa, Lindsay Pesacreta, Barbara Jantausch, Benjamin Hanisch, Nada Harik, Rana F. Hamdy, Andrea Hahn, Taeun Chang, Mohamad Jaafar, Tracey Ambrose, Gilbert Vezina, Dorothy I. Bulas, David Wessel, Adre J. du Plessis, and Roberta L. DeBiasi, Children’s National Hospital, Washington, DC, E-mails: sbmulkey@childrensnational.org, eansusinha@childrensnational.org, smarierusso@gmail.com, cbiddle@childrensnational.org, ykousa@childrensnational.org, lpesacre@childrensnational.org, bjantaus@childrensnational.org, bhanisch@childrensnational.org, nharik@childrensnational.org, rhamdy2@childrensnational.org, alhahn@childrensnational.org, tchang@childrensnational.org, mjaafar@childrensnational.org, tambrose@childrensnational.org, gvezina@childrensnational.org, dbulas@childrensnational.org, dwessel@childrensnational.org, adupless@childrensnational.org, and rdebiasi@childrensnational.org. Caitlin Cristante, University of Chicago School of Medicine, Chicago, IL, E-mail: caitante@gmail.com.

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