Vital Signs

Update on Zika Virus–Associated Birth Defects and Evaluation of All U.S. Infants With Congenital Zika Virus Exposure — U.S. Zika Pregnancy Registry, 2016

Megan R. Reynolds, MPH; Abbey M. Jones, MPH; Emily E. Petersen, MD; Ellen H. Lee, MD; Marion E. Rice, MPH; Andrea Bingham, PhD; Sascha R. Ellington, MSPH; Nicole Evert, MS; Sarah Reagan-Steiner, MD; Titilope Oduyebo, MD; Catherine M. Brown, DVM; Stacey Martin, MSc; Nina Ahmad, MD; Julu Bhatnagar, PhD; Jennifer Macdonald, MPH; Carolyn Gould, MD; Anne D. Fine, MD; Kara D. Polen, MPH; Heather Lake-Burger, MPH; Christina L. Hillard, MA; Noemi Hall, PhD; Mahsa M. Yazdy, PhD; Karnesha Slaughter, MPH; Jamie N. Sommer, MS; Alys Adamski, PhD; Meghan Raycraft, MPH; Shannon Fleck-Derderian, MPH; Jyoti Gupta, MPH; Kimberly Newsome, MPH; Madelyn Baez-Santiago, PhD; Sally Slavinski, DVM; Jennifer L. White, MPH; Cynthia A. Moore, MD, PhD; Carrie K. Shapiro-Mendoza, PhD; Lyle Petersen, MD; Coleen Boyle, PhD; Denise J. Jamieson, MD; Dana Meaney-Delman, MD; Margaret A. Honein, PhD

Disclosures

Morbidity and Mortality Weekly Report. 2017;66(13)

Abstract and Introduction

Abstract

Background: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants.

Methods: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations.

Results: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus–associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%–7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%–14%]). Birth defects were reported in 15% (95% CI = 8%–26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%).

Conclusions and Implications for Public Health Practice: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

Introduction

In response to the outbreak of Zika virus in the World Health Organization Region of the Americas and concerns about birth defects linked to Zika virus infection during pregnancy, CDC issued a travel notice on January 15, 2016, advising pregnant women to consider postponing travel to areas with active transmission of Zika virus. As part of the initial phase of the emergency response, CDC collaborated with state, tribal, local, and territorial health departments to establish the U.S. Zika Pregnancy Registry (USZPR) as an enhanced national surveillance system to monitor pregnancy and fetal/infant outcomes among pregnancies with laboratory evidence of possible recent Zika virus infection.^[1] The USZPR includes data on pregnant women and their infants at birth and at ages 2, 6, and 12 months.

The USZPR includes data from all 50 states, DC, and all U.S. territories except Puerto Rico; pregnancies in Puerto Rico are monitored separately by the Zika Active Pregnancy Surveillance System.^[2] To be included in the USZPR, either the pregnant woman, placenta, or fetus/infant must have laboratory evidence of possible recent Zika virus infection. Pregnant women in the United States and U.S. territories (with the exception of Puerto Rico) with laboratory evidence of possible recent Zika virus infection (regardless of whether they have symptoms) and the periconceptionally,* prenatally, or perinatally exposed infants born to these women are eligible to be included. The USZPR also includes infants with laboratory evidence of possible congenital Zika virus infection (regardless of whether they have symptoms or findings at birth) and their mothers.

This report updates the previous report^[3] from the USZPR and provides data on pregnancies completed in the 50 U.S. states and DC from December 1, 2015 through December 27, 2016, reported to CDC from January 15, 2016, through March 14, 2017.^† Completed pregnancies include those of any length of gestation that end in a liveborn infant or a pregnancy loss. The baseline prevalence of defects consistent with those that have been observed with congenital Zika virus infection was approximately 2.9 per 1,000 live births in the pre-Zika years.^[4] The initial findings from the USZPR represent an approximate twentyfold increase in Zika virus–associated birth defects among pregnant women with laboratory evidence of possible recent Zika virus infection, with an approximate thirtyfold increase in brain abnormalities and/or microcephaly. Updated data in this report can also be compared with this benchmark.^[3,4]

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*Periconceptional exposure is defined as maternal Zika virus infection during the 8 weeks before conception (6 weeks before and 2 weeks after the first day of the last menstrual period).
^†Data on pregnancies reported to CDC by December 27, 2016; all data have been updated with additional information reported on these pregnancies through March 14, 2017. Completed pregnancies are limited to those with a pregnancy completion date on or before December 27, 2016.
^§First trimester is defined as last menstrual period +14 days to 13 weeks, 6 days (97 days).

Table 1. Pregnancy outcomes* for 972 women with completed pregnancies ^† with laboratory evidence of possible recent Zika virus infection, by maternal symptom status and timing of symptom onset or exposure — U.S. Zika Pregnancy Registry, United States, December 2015–December 2016
Characteristic	Brain abnormalities and/or microcephaly (No.)	NTDs and early brain malformations, eye abnormalities, or consequences of CNS dysfunction without brain abnormalities or microcephaly (No.)	Total with ≥1 birth defect (No.)	Completed pregnancies (No.)	Proportion affected by Zika virus–associated birth defects, % (95% CI^§)
Any laboratory evidence of possible recent Zika virus infection ^¶
Total	43	8	51	972	5 (4–7)
Maternal symptom status
Symptoms of Zika virus infection reported	18	3	21	348	6 (4–9)
No symptoms of Zika virus infection reported	24	4	28	599	5 (3–7)
Unknown	1	1	2	25	—
Timing of symptoms or exposure**
First trimester^††,§§	13	1	14	157	9 (5–14)
Multiple trimesters including first	22	6	28	396	7 (5–10)
Confirmed evidence of Zika virus infection ^¶¶
Total	18	6	24	250	10 (7–14)
Maternal symptom status
Symptoms of Zika virus infection reported	8	3	11	141	8 (4–13)
No symptoms of Zika virus infection reported	10	2	12	102	12 (7–19)
Unknown	1	0	1	7	—
Timing of symptoms or exposure**
First trimester^††,§§	8	1	9	60	15 (8–26)
Multiple trimesters including first	8	4	12	58	21 (12–33)

Abbreviations: CI = confidence interval; CNS = central nervous system; IgM= immunoglobulin M; NAT=nucleic acid test; NTD = neural tube defect; PRNT = plaque reduction neutralization test; RT-PCR = reverse transcription–polymerase chain reaction.
*Outcomes for multiple gestation pregnancies are counted once.
^†Includes live births, spontaneous abortions, terminations, and stillbirths.
^§95% CI for a binomial proportion using Wilson score interval.
^¶Includes maternal, placental, or fetal/infant laboratory evidence of possible recent Zika virus infection based on presence of Zika virus RNA by a positive NAT (e.g., RT-PCR) or similar test, serological evidence of a recent Zika virus infection, or serological evidence of a recent unspecified flavivirus infection.
**Estimates were not calculated for exposure in other trimesters because of small numbers. Pregnant women who did not have first trimester exposure might have had exposure in the periconceptional period only (8 weeks before conception or 6 weeks before and 2 weeks after the first day of the last menstrual period), second trimester, third trimester, both the second and third trimester; many women were missing information on trimester of exposure.
^††First trimester is defined as last menstrual period +14 days to 13 weeks, 6 days (97 days).
^§§First trimester exposure includes women with exposure limited to the first trimester and women with exposure limited to the first trimester and periconceptional period.
^¶¶Includes maternal, placental, or fetal/infant laboratory evidence of confirmed Zika virus infection based on presence of Zika virus RNA by a positive NAT (e.g., RT-PCR) or similar test or serological results of IgM positive/equivocal with Zika PRNT ≥10 and dengue PRNT <10.

Table 2. Postnatal neuroimaging* and infant Zika virus testing results for 895 liveborn infants in the U.S. Zika Pregnancy Registry — 50 U.S. states and the District of Columbia, 2016
Testing	No (%) liveborn infants
Testing	With birth defects	Without birth defects	Total
Total	45	850	895
Neuroimaging
Any neuroimaging reported to USZPR	29 (64)	192 (23)	221 (25)
Infant Zika virus testing
Positive test result on an infant specimen^†,§	25 (56)	69 (8)	94 (11)
Negative infant test results among infants with ≥1 infant specimen reported as tested	17 (38)	474 (56)	491 (55)
No infant specimen test results reported to USZPR	3 (7)	307 (36)	310 (35)

Abbreviations: IgM= immunoglobulin M; NAT=nucleic acid test; RT-PCR = reverse transcription–polymerase chain reaction; USZPR = U.S. Zika Pregnancy Registry.
*Neuroimaging includes any cranial ultrasound, computed tomography, or magnetic resonance imaging test reported to the USZPR.
^†Positive infant tests included the presence of Zika virus RNA by a positive NAT (e.g., RT-PCR) and/or serological results of IgM positive/equivocal.
^§Infant specimens include serum, urine, blood, cerebrospinal fluid, cord serum, and cord blood.