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Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy

Educational Objective
To understand the hazards of exposure to Zika virus infection during pregnancy.
1 Credit CME
Key Points

Question  What proportion of fetuses and infants of women in the United States with laboratory evidence of possible Zika virus infection during pregnancy have birth defects?

Findings  Based on preliminary data from the US Zika Pregnancy Registry, among 442 completed pregnancies, 6% overall had a fetus or infant with evidence of a Zika virus–related birth defect, primarily microcephaly with brain abnormalities, whereas among women with possible Zika virus infection during the first trimester, 11% had a fetus or infant with a birth defect.

Meaning  These findings support the importance of screening pregnant women for Zika virus exposure.

Abstract

Importance  Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10 000 live births.

Objective  To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms.

Design, Setting, and Participants  Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments.

Exposures  Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample.

Main Outcomes and Measures  Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences.

Results  Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters.

Conclusions and Relevance  Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.

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Article Information

Corresponding Author: Margaret A. Honein, PhD, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30333 (mrh7@cdc.gov).

Published Online: December 13, 2016. doi:10.1001/jama.2016.19006

Author Contributions: Dr Honein had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Honein, Ahmad, Shapiro-Mendoza, Fine, L. R. Petersen, Boyle, Meaney-Delman, Jamieson.

Acquisition, analysis, or interpretation of data: Honein, Dawson, E. E. Petersen, Jones, Lee, Yazdy, Ahmad, Macdonald, Evert, Bingham, Ellington, Shapiro-Mendoza, Oduyebo, Fine, Brown, Sommer, Gupta, Cavicchia, Slavinski, White, Owen, Boyle, Meaney-Delman, Jamieson.

Drafting of the manuscript: Honein, Ahmad, L. R. Petersen, Meaney-Delman.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Honein, Dawson, Jones, Ahmad, Ellington, Sommer, Meaney-Delman.

Administrative, technical, or material support: E. E. Petersen, Jones, Lee, Yazdy, Ahmad, Ellington, Shapiro-Mendoza, Oduyebo, Fine, Brown, Gupta, Cavicchia, Slavinski, Owen, L. R. Petersen, Boyle, Meaney-Delman, Jamieson.

Study supervision: Honein, Ahmad, L. R. Petersen, Boyle, Jamieson.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Group Information: Members of the US Zika Pregnancy Registry Collaboration were Miranda Daniels, MPH (Alabama Department of Public Health); Alabama Department of Public Health Bureaus of Communicable Diseases and Family Health Services; Hayley D. Belisle-Yaglom, MS, MPH (Arizona Department of Health Services); Irene Ruberto, PhD, MPH (Arizona Department of Health Services); Jennifer Adair, BSN, RN (Maricopa County Department of Public Health); Melissa Kretschmer, CVT, MA (Maricopa County Department of Public Health); Lucy Im, MPH (Arkansas Department of Health); Charsey Porse, PhD, MPH (California Department of Public Health); Sharon Messenger, PhD (California Department of Public Health); Jacklyn Wong, PhD (California Department of Public Health); Barbara Warmerdam (California Department of Public Health); Olga Barer, BS (California Department of Public Health); Brenda Hansen, MA, MS (California Department of Public Health); Richard Olney, MD, MPH (California Department of Public Health); Karen Ramstrom, DO, MSPH (California Department of Public Health); Devra Barter, MS (Colorado Department of Public Health and Environment); Jennifer House, DVM, MPH, DACVPM (Colorado Department of Public Health and Environment); Epidemiology and Emerging Infections Program, Connecticut Department of Public Health; Delaware Division of Public Health; District of Columbia Department of Health, Division of Epidemiology, Disease Surveillance & Investigation; Leah Eisenstein, MPH (Florida Department of Health); Nicole Kikuchi, MPH (Florida Department of Health); Janet J. Hamilton, MPH (Florida Department of Health); Amanda Feldpausch, MPH (Georgia Department of Public Health); Sarah Y. Park, MD, FAAP (Hawaii Department of Health); Sylvia Mann, MS, CGC (Hawaii Department of Health); Illinois Zika Response Team; Taryn Stevens, MPH (Indiana State Department of Health); Iowa Department of Public Health; Kansas Department of Health and Environment; Kentucky Department for Public Health Zika Pregnancy Registry Workgroup; Louisiana Department of Health’s Office of Public Health; Sara Robinson, MPH (Maine); Richard Brooks, MD, MPH (Maryland Department of Health and Mental Hygiene); Erin Jenkins, MPH (Maryland Department of Health and Mental Hygiene); Julie E. Dunn, PhD (Massachusetts Department of Public Health); Susan Soliva, MPH (Massachusetts Department of Public Health); Sarah Scotland, MPH (Massachusetts Department of Public Health); Cathleen A. Higgins (Massachusetts Department of Public Health); Gerlinde S. Munshi, MA (Massachusetts Department of Public Health); Angela E. Lin, MD (Massachusetts General Hospital for Children); Michigan Zika Pregnancy Registry Workgroup; Elizabeth Schiffman, MPH, MA (Minnesota Department of Health); Sheryl Hand, RN, BSN (Mississippi State Department of Health); Missouri Department of Health and Senior Services; Christine L. Mulgrew, PhD, MPH (Montana Department of Public Health & Human Services); Jeff Hamik, MS (Nebraska Department of Health and Human Services); Samir Koirala, MBBS, MSc (Nebraska Department of Health and Human Services); Office of Public Health Informatics and Epidemiology at the Nevada Division of Public and Behavioral Health; Carolyn Fredette, MPH (New Hampshire Department of Health and Human Services); Abigail Mathewson, DVM, MPH (New Hampshire Department of Health and Human Services); Joseph A. Sweatlock, PhD, DABTJ (New Jersey Department of Health); Karen Worthington (New Jersey Department of Health); Kara McGinnis Pilote, MA, MPH (New Jersey Department of Health); Kristin Garafalo, MPH, CHES (New Jersey Department of Health); Edward Lifshitz, MD, FACP (New Jersey Department of Health); Joy Rende, MSA, RNC-MN, NE-BC (New Jersey Department of Health); Mary Knapp, MSN, RN (New Jersey Department of Health); Regina Grazel, MSN, RN, BC, APN-C (New Jersey Department of Health); Nancy Nolet Mimm, DNP-C, MSN, APHN-BC (New Jersey Department of Health); Abubakar Ropri, MPH (New Mexico Department of Health); Lou C. Smith, MD, MPH (New York State Department of Health); Amy Robbins, MPH (New York State Department of Health); Lou Ann Lance, MSN, RN (New York State Department of Health); Helen M. Blanchette, RN, BSN (New York State Department of Health); Elizabeth Dufort, MD, FAAP (New York State Department of Health); Bryon Backenson, MS (New York State Department of Health); Daniel Kuhles, MD, MPH (New York State Department of Health); Lauren Culver Barlow, MS, RD, RN (Suffolk County Department of Health Services); Maria I. Souto, MPH (Rockland County Department of Health); Debra Blog, MD, MPH (New York State Department of Health); Jemma Rowlands, MPH (New York State Department of Health); Stephanie E. Ostrowski, PhD (New York State Department of Health); Susan Wong, PhD (Wadsworth Center, New York State Department of Health); Kirsten St. George, PhD (Wadsworth Center, New York State Department of Health); Laura Kramer, PhD (Wadsworth Center, New York State Department of Health); Ronald Limberger, PhD (Wadsworth Center, New York State Department of Health); Al Dupuis, BS (Wadsworth Center, New York State Department of Health); Amy Dean, PhD (Wadsworth Center, New York State Department of Health); Kimberly Alvarez, MPH (New York State Department of Health); Julius N. Ade, MD, PhD, MPH (New York State Department of Health); Rachel Wester, MPH, RN (New York State Department of Health); Kadri Ajileye, MD, MPH (New York State Department of Health); Amy Burns, MS (New York State Department of Health); Brenda Naizby, BSN (New York State Department of Health); Patricia Many, MS, RN (New York State Department of Health); Christina Hidalgo, MPH (New York State Department of Health); Ann Sullivan-Frohm, BSE (New York State Department of Health); Hwa-Gan Chang, PhD (New York State Department of Health); Jacquelin Griffin, PMP, CSM (New York State Department of Health); MaryJo Polfleit (New York State Department of Health); Kimberley Seward, MPH (New York State Department of Health); Inderbir Sohi, MSPH (New York State Department of Health); Rene Hull, BS (Wadsworth Center, New York State Department of Health); Li Zheng, MS, BS (Wadsworth Center, New York State Department of Health); Meghan Fuschino, MS, BS (Wadsworth Center, New York State Department of Health); Chantelle Seaver, MS, BS (Wadsworth Center, New York State Department of Health); Tabassum Rahman, MS, BS (Wadsworth Center, New York State Department of Health); Greg Farrell, BS (Wadsworth Center, New York State Department of Health); Scott Brunt, BS (Wadsworth Center, New York State Department of Health); Michael Popowich, BS (Wadsworth Center, New York State Department of Health); Patrick Bryant, PhD (Wadsworth Center, New York State Department of Health); Daryl Lamson, BS (Wadsworth Center, New York State Department of Health); Karen Kulas, BS (Wadsworth Center, New York State Department of Health); William Lee, PhD (Wadsworth Center, New York State Department of Health); Valerie Demarest, BS (Wadsworth Center, New York State Department of Health); Timothy Rem (Wadsworth Center, New York State Department of Health); Randy Stone (Wadsworth Center, New York State Department of Health); Sharon Casterlin (Wadsworth Center, New York State Department of Health); Mary Marchewka (Wadsworth Center, New York State Department of Health); Andrea Furuya, PhD (Wadsworth Center, New York State Department of Health); Kyle Carson, BS (Wadsworth Center, New York State Department of Health); Steven Bush, MS, BS (Wadsworth Center, New York State Department of Health); Joel Ackelsberg, MD, MPH (New York City Department of Health and Mental Hygiene); Byron Alex, MD, MPH (New York City Department of Health and Mental Hygiene); Vennus Ballen, MD, MPH (New York City Department of Health and Mental Hygiene); Jennifer Baumgartner, MPH (New York City Department of Health and Mental Hygiene); Danielle Bloch, MPH (New York City Department of Health and Mental Hygiene); Sandhya Clark, MPH (New York City Department of Health and Mental Hygiene); Erin Conners, PhD (New York City Department of Health and Mental Hygiene); Alexander Davidson, MPH (New York City Department of Health and Mental Hygiene); Catherine Dentinger, FNP (New York City Department of Health and Mental Hygiene); Bisram Deocharan, PhD (New York City Department of Health and Mental Hygiene); Andrea DeVito, MPH (New York City Department of Health and Mental Hygiene); Kristen Forney, MPH (New York City Department of Health and Mental Hygiene); Jie Fu, PhD (New York City Department of Health and Mental Hygiene); Gili Hrusa, MPH (New York City Department of Health and Mental Hygiene); Maryam Iqbal, MPH (New York City Department of Health and Mental Hygiene); Lucretia Jones, DrPH, MPH (New York City Department of Health and Mental Hygiene); Hannah Kubinson, MPH (New York City Department of Health and Mental Hygiene); Maura Lash, RN, MPH (New York City Department of Health and Mental Hygiene); Marcelle Layton, MD (New York City Department of Health and Mental Hygiene); Christopher Lee, MD, MSc, MPH (New York City Department of Health and Mental Hygiene); Dakai Liu, MD, PhD (New York City Department of Health and Mental Hygiene); Natasha McIntosh, MPH (New York City Department of Health and Mental Hygiene); Emily McGibbon, MPH (New York City Department of Health and Mental Hygiene); Morgan Moy, MPH (New York City Department of Health and Mental Hygiene); Stephanie Ngai, MPH (New York City Department of Health and Mental Hygiene); Panagiotis Papadopoulos, MPH (New York City Department of Health and Mental Hygiene); Hilary Parton, MPH (New York City Department of Health and Mental Hygiene); Eric Peterson, MPH (New York City Department of Health and Mental Hygiene); Jose Poy, MPH (New York City Department of Health and Mental Hygiene); Amado Punsalang, PhD (New York City Department of Health and Mental Hygiene); Jennifer Rakeman, PhD (New York City Department of Health and Mental Hygiene); Altaf Shaikh, MSc (New York City Department of Health and Mental Hygiene); Alaina Stoute, MPH (New York City Department of Health and Mental Hygiene); Corinne Thompson, PhD (New York City Department of Health and Mental Hygiene); Anthony Tran, DrPH, MPH, D(ABMM) (New York City Department of Health and Mental Hygiene); Don Weiss, MD, MPH (New York City Department of Health and Mental Hygiene); Emily Westheimer, MPH (New York City Department of Health and Mental Hygiene); Eliza Wilson, BSMT (New York City Department of Health and Mental Hygiene); Ann Winters, MD (New York City Department of Health and Mental Hygiene); David Yang, BS (New York City Department of Health and Mental Hygiene); Mohammad Younis, MS, MPA (New York City Department of Health and Mental Hygiene); Jennifer MacFarquhar, MPH, RN, CIC (North Carolina Department of Health and Human Services); Laura Cronquist, BS (North Dakota Department of Health); Michele Feist, BS (North Dakota Department of Health); Martín F. Celaya (CDC, epidemiology field assignee); Ohio Department of Health; Lisa Caton, MS, RN (Oklahoma State Department of Health); Kristy Bradley, DVM, MPH (Oklahoma State Department of Health); Oregon Public Health Division Acute and Communicable Disease Program; Leah Lind, MPH (Pennsylvania Department of Health); Kumar Nalluswami, MD, MPH (Pennsylvania Department of Health); Center for Acute Infectious Disease Epidemiology, Rhode Island Department of Health; Daniel Drociuk (South Carolina Department of Health and Environmental Control); Vinita Leedom, MPH, CIC (South Carolina Department of Health and Environmental Control); Jan Bollock, RN (South Dakota Department of Health); Tennessee Department of Health; Kelly Broussard, MPH (Texas Department of State Health Services); Dallin Peterson (Utah Department of Health); Amy Nance, MPH (Utah Department of Health); Patsy Kelso, PhD (Vermont Department of Health); Katie Kurkjian (CDC, Career Epidemiology Field Officer Program); Virginia Department of Health, Office of Epidemiology, Division of Disease Surveillance and Investigation; Virginia Department of Health, Office of Community Health Services; Hanna Oltean, MPH (Washington State Department of Health); West Virginia Bureau for Public Health, Office of Maternal, Child and Family Health; Angela Rohan, PhD (CDC, Wisconsin Department of Health Services); Katie Bryan, MPH (Wyoming Department of Health); Alys Adamski, PhD, MPH (CDC); Jeanne Bertolli, PhD, MPH (CDC); Melissa L. Danielson, MSPH (CDC); Valerie Godoshian, MPH (CDC); Caitlin Green, MPH (CDC); Christina Hillard, MA (CDC); Amy Lambert, PhD (CDC); Andrea Neiman, PhD, MPH (CDC); Kimberly Newsome, BSN, MPH (CDC); Kara Polen, MPH (CDC); Ann Powers, PhD (CDC); Marion Rice, MPH (CDC); Regina M. Simeone, MS, MPH (CDC); Robyn A. Stoddard, DVM, PhD (CDC); Tonya Williams, PhD, MS (CDC); Kathryn E. Arnold, MD (CDC); Shannon Fleck-Derderian, MPH (CDC); Sumaiya Khan, MPH (CDC); Fleetwood Loustalot, FNP, PhD (CDC); Megan Reynolds, MPH, MDiv (CDC); Infectious Diseases Pathology Branch (CDC).

Disclaimer: The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the CDC.

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