Population-based Surveillance of Birth Defects Potentially Related to Zika Virus Infection — 15 States and U.S. Territories, 2016

Augustina Delaney, PhD; Cara Mai, DrPH; Ashley Smoots, MPH; Janet Cragan, MD; Sascha Ellington, MSPH; Peter Langlois, PhD; Rebecca Breidenbach, MPA; Jane Fornoff, PhD; Julie Dunn, PhD; Mahsa Yazdy, PhD; Nancy Scotto-Rosato, PhD; Joseph Sweatlock, PhD; Deborah Fox, MPH; Jessica Palacios, MPH; Nina Forestieri, MPH; Vinita Leedom, MPH; Mary Smiley, MS; Amy Nance, MPH; Heather Lake-Burger, MPH; Paul Romitti, PhD; Carrie Fall, MS; Miguel Valencia Prado, MD; Jerusha Barton, MPH; J. Michael Bryan, PhD; William Arias, MPH; Samara Viner Brown, MS; Jonathan Kimura, MPH; Sylvia Mann, MS; Brennan Martin, MPH; Lucia Orantes, PhD; Amber Taylor, MPH; John Nahabedian, MS; Amanda Akosa, MPH; Ziwei Song, MPH; Stacey Martin, MSc; Roshan Ramlal, PhD; Carrie Shapiro-Mendoza, PhD; Jennifer Isenburg, MPH; Cynthia A. Moore, MD, PhD; Suzanne Gilboa, PhD; Margaret A. Honein, PhD

Disclosures

Morbidity and Mortality Weekly Report. 2018;67(3):91-96. 

In This Article

Abstract and Introduction

Introduction

Zika virus infection during pregnancy can cause serious birth defects, including microcephaly and brain abnormalities.[1] Population-based birth defects surveillance systems are critical to monitor all infants and fetuses with birth defects potentially related to Zika virus infection, regardless of known exposure or laboratory evidence of Zika virus infection during pregnancy. CDC analyzed data from 15 U.S. jurisdictions conducting population-based surveillance for birth defects potentially related to Zika virus infection.* Jurisdictions were stratified into the following three groups: those with 1) documented local transmission of Zika virus during 2016; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents; and 3) less than one case of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents. A total of 2,962 infants and fetuses (3.0 per 1,000 live births; 95% confidence interval [CI] = 2.9–3.2)[2] met the case definition. In areas with local transmission there was a non-statistically significant increase in total birth defects potentially related to Zika virus infection from 2.8 cases per 1,000 live births in the first half of 2016 to 3.0 cases in the second half (p = 0.10). However, when neural tube defects and other early brain malformations (NTDs)§ were excluded, the prevalence of birth defects strongly linked to congenital Zika virus infection increased significantly, from 2.0 cases per 1,000 live births in the first half of 2016 to 2.4 cases in the second half, an increase of 29 more cases than expected (p = 0.009). These findings underscore the importance of surveillance for birth defects potentially related to Zika virus infection and the need for continued monitoring in areas at risk for Zika.

In 2016, as part of the emergency response to the Zika virus outbreak in the World Health Organization's Region of the Americas, population-based birth defects surveillance systems monitored fetuses and infants with birth defects potentially related to Zika virus infection using a standard case definition and multiple data sources. Medical records were abstracted for data on birth defects, congenital infections, pregnancy outcome, head circumference, vital status, and Zika laboratory test results, irrespective of maternal Zika virus exposure or infection. Verbatim text describing the birth defects was reviewed to identify those that met the case definition. Infants and fetuses were aggregated into four mutually exclusive categories: those with 1) brain abnormalities or microcephaly; 2) NTDs; 3) eye abnormalities without mention of a brain abnormality included in the two previously defined categories; and 4) other consequences of central nervous system (CNS) dysfunction, specifically joint contractures and congenital sensorineural deafness without mention of brain or eye abnormalities included in another category. Because the evidence linking NTDs and congenital Zika virus infection is weak, prevalence estimates per 1,000 live births were calculated both overall and excluding NTDs for each quarter in 2016; CIs were calculated using Poisson regression.[1,2]

All 15 U.S. jurisdictions included in this report had existing birth defects surveillance systems that were rapidly adapted to monitor birth defects potentially related to Zika virus infection. These jurisdictions provided data on live births and pregnancy losses occurring from January 1–December 31, 2016. The jurisdictions were stratified into the following three groups: those with 1) confirmed local Zika virus transmission during 2016**; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents (i.e., "higher" Zika prevalence)††; and 3) less than one case per 100,000 residents of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC (i.e., "lower" [low or no travel-associated] Zika prevalence)§§.[3]

Overall, 2,962 infants and fetuses with birth defects potentially related to Zika virus infection were identified (3.0 per 1,000 live births; CI = 2.9–3.2) (Table), including 1,457 (49%) with brain abnormalities or microcephaly, 581 (20%) with NTDs, 262 (9%) with eye abnormalities without mention of a brain abnormality, and 662 (22%) with other consequences of CNS dysfunction without mention of brain or eye abnormalities. Among the 2,962 infants and fetuses with defects potentially related to Zika virus infection, there were 2,716 (92%) live births. Laboratory evidence of possible Zika virus infection in maternal, placental, infant, or fetal specimens was present in 45 (1.5%) cases; 96 (3.2%) had negative tests for Zika virus, and 2,821 (95.2%) either had no testing performed or no results available.

The prevalence of reported birth defects cases potentially related to Zika virus infection increased in jurisdictions with confirmed local transmission, from 2.8 per 1,000 live births (182 cases) during the first half of 2016 to 3.0 per 1,000 live births (211 cases) during the second half (CI = 2.4–3.2 and CI = 2.6–3.4, respectively; p = 0.10). In "higher" Zika prevalence jurisdictions, the monitored birth defects prevalence was 3.0 per 1,000 live births in both the first (753 cases) and second (775 cases) halves of 2016. In "lower" prevalence jurisdictions, the monitored birth defects prevalence declined significantly from 3.4 per 1,000 live births (549 cases) during the first half of 2016 to 3.0 (492 cases) per 1,000 live births during the second half (CI = 3.2–3.7 and CI = 2.8–3.3, respectively; p = 0.002) (Figure 1).

Figure 1.

Prevalence of birth defects cases potentially related to Zika virus infection, by Zika virus transmission characteristics and quarter —15 U.S. jurisdictions, 2016*,†,§
*Local transmission jurisdictions included Florida (selected southern counties), Puerto Rico, and Texas (Public Health Region 11).
Higher travel-related Zika prevalence jurisdictions had one or more case of confirmed symptomatic travel-associated Zika virus disease reported to CDC per 100,000 residents. These jurisdictions included Georgia (selected metropolitan Atlanta counties), Massachusetts, New Jersey, New York (excluding New York City), Rhode Island, South Carolina, Texas (Public Health Regions 1, 3, and 9), and Vermont.
§ Low or no travel-related Zika prevalence jurisdictions had less than one case of confirmed symptomatic travel-associated Zika virus disease reported to CDC per 100,000 residents. These jurisdictions included Hawaii, Illinois, Iowa, North Carolina (selected regions), and Utah.

When NTDs were excluded, the prevalence of birth defects potentially related to Zika virus infection in jurisdictions with local Zika transmission increased 21%, from 2.0 per 1,000 live births (CI = 1.7–2.4) to 2.4 (CI = 2.1–2.8) (Figure 2). This increase indicated there were 29 more infants and fetuses with birth defects than were expected in areas with local transmission in the second half of 2016 (169 observed cases compared with 140 expected, p = 0.009). The prevalence of birth defects excluding NTDs in "higher" prevalence jurisdictions did not change (2.4 per 1,000 live births) and the prevalence in the "lower" prevalence jurisdictions significantly decreased from 2.8 per 1,000 live births (CI = 2.5–3.0) to 2.4 (CI = 2.2–2.7). Among 393 infants and fetuses with birth defects potentially related to Zika virus infection in areas with local transmission, 32 (8.1%) had laboratory evidence of possible Zika virus infection in a maternal, placental, infant, or fetal sample, 59 (15.0%) had negative Zika virus test results, and 302 (76.81%) had no testing performed or no results available.

Figure 2.

Prevalence of birth defects cases* potentially related to Zika virus infection in U.S. jurisdictions with documented local transmission of Zika virus, by defect type and quarter, 2016
*Fetuses and infants were aggregated into the following four mutually exclusive categories: those with 1) brain abnormalities with or without microcephaly (head circumference at delivery <3rd percentile for sex and gestational age); 2) NTDs and other early brain malformations; 3) eye abnormalities among those without mention of a brain abnormality included in the first two categories; and 4) other consequences of central nervous system dysfunction, specifically joint contractures and congenital sensorineural deafness, among those without mention of brain or eye abnormalities included in another category.
Jurisdictions with local transmission of Zika virus included Florida (selected southern counties), Puerto Rico, and Texas (Public Health Region 11).

*With population-based surveillance for birth defects potentially related to Zika virus infection, information is collected on all infants who have birth defects that might be related to Zika virus infection. This includes infants who have not been exposed to Zika virus and might have the same birth defects for other reasons. This helps to identify the full spectrum of outcomes associated with Zika virus infection. https://www.cdc.gov/pregnancy/zika/research/birth-defects.html.
Brain abnormalities or microcephaly (congenital microcephaly [head circumference <3rd percentile for gestational age and sex], intracranial calcifications, cerebral atrophy, abnormal cortical gyral patterns [e.g., polymicrogyria, lissencephaly, pachygyria, schizencephaly, and gray matter heterotopia], corpus callosum abnormalities, cerebellar abnormalities, porencephaly, hydranencephaly, ventriculomegaly/hydrocephaly [excluding "mild" ventriculomegaly without other brain abnormalities], fetal brain disruption sequence [collapsed skull, overlapping sutures, prominent occipital bone, and scalp rugae], and other major brain abnormalities); neural tube defects and other early brain malformations (anencephaly/acrania, encephalocele, spina bifida, and holoprosencephaly); structural eye abnormalities (microphthalmia/anophthalmia, coloboma, cataract, intraocular calcifications, and chorioretinal anomalies [e.g., atrophy and scarring, gross pigmentary changes, excluding retinopathy of prematurity]; optic nerve atrophy, pallor, and other optic nerve abnormalities); consequences of central nervous system dysfunction (arthrogryposis, club foot with associated brain abnormalities, congenital hip dysplasia with associated brain abnormalities, and congenital sensorineural hearing loss).
§Neural tube defects and other early brain malformations are included as biologically plausible birth defects; however, they have been reported much less frequently with Zika virus infection than have defects in the other categories.
Participating jurisdictions included Florida (selected southern counties), Georgia (selected metropolitan Atlanta counties), Hawaii, Illinois, Iowa, Massachusetts, New Jersey, New York (excluding New York City), North Carolina (selected regions), Puerto Rico, Rhode Island, South Carolina, Texas (Public Health Regions 1, 3, 9, and 11), Utah, and Vermont.
**Jurisdictions with confirmed local Zika virus transmission during 2016 were as follows: southern Florida, Puerto Rico, and Texas Public Health Region 11.
††Jurisdictions with one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents (i.e., "higher" prevalence) included Georgia, Massachusetts, New Jersey, New York, Rhode Island, South Carolina, Texas Public Health Regions 1, 3, and 9, and Vermont.
§§Jurisdictions with less than one case per 100,000 residents of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC (i.e., "lower" prevalence) included Hawaii, Illinois, Iowa, North Carolina, and Utah.

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