Baseline Prevalence of Birth Defects Associated With Congenital Zika Virus Infection — Massachusetts, North Carolina, and Atlanta, Georgia, 2013–2014

Janet D. Cragan, MD; Cara T. Mai, DrPH; Emily E. Petersen, MD; Rebecca F. Liberman, MPH; Nina E. Forestieri, MPH; Alissa C. Stevens, MPH; Augustina Delaney, PhD; April L. Dawson, MPH; Sascha R. Ellington, MSPH; Carrie K. Shapiro-Mendoza, PhD; Julie E. Dunn, PhD; Cathleen A. Higgins; Robert E. Meyer, PhD; Tonya Williams, PhD; Kara N.D. Polen, MPH; Kim Newsome, MPH; Megan Reynolds, MPH; Jennifer Isenburg, MSPH; Suzanne M. Gilboa, PhD; Dana M. Meaney-Delman, MD; Cynthia A. Moore, MD, PhD; Coleen A. Boyle, PhD; Margaret A. Honein, PhD

Disclosures

Morbidity and Mortality Weekly Report. 2017;66(8):219-222. 

In This Article

Abstract and Introduction

Introduction

Zika virus infection during pregnancy can cause serious brain abnormalities, but the full range of adverse outcomes is unknown.[1] To better understand the impact of birth defects resulting from Zika virus infection, the CDC surveillance case definition established in 2016 for birth defects potentially related to Zika virus infection*[2] was retrospectively applied to population-based birth defects surveillance data collected during 2013–2014 in three areas before the introduction of Zika virus (the pre-Zika years) into the World Health Organization's Region of the Americas (Americas).[3] These data, from Massachusetts (2013), North Carolina (2013), and Atlanta, Georgia (2013–2014), included 747 infants and fetuses with one or more of the birth defects meeting the case definition (pre-Zika prevalence = 2.86 per 1,000 live births). Brain abnormalities or microcephaly were the most frequently recorded (1.50 per 1,000), followed by neural tube defects and other early brain malformations (0.88), eye abnormalities without mention of a brain abnormality (0.31), and other consequences of central nervous system (CNS) dysfunction without mention of brain or eye abnormalities (0.17). During January 15–September 22, 2016, the U.S. Zika Pregnancy Registry (USZPR) reported 26 infants and fetuses with these same defects among 442 completed pregnancies (58.8 per 1,000) born to mothers with laboratory evidence of possible Zika virus infection during pregnancy.[2] Although the ascertainment methods differed, this finding was approximately 20 times higher than the proportion of one or more of the same birth defects among pregnancies during the pre-Zika years. These data demonstrate the importance of population-based surveillance for interpreting data about birth defects potentially related to Zika virus infection.

Statewide data from birth defects surveillance programs in Massachusetts and North Carolina for 2013 and from a surveillance program in three counties in metropolitan Atlanta, Georgia, for 2013–2014 were chosen for analysis because these programs conducted population-based surveillance for all types of birth defects, used active multisource case-finding, and were rapidly able to provide individual-level data with sufficient detail to apply all inclusion and exclusion criteria.[4] Trained staff members in these surveillance programs routinely reviewed the medical records of infants and fetuses with birth defects and abstracted information about those defects, related diagnostic procedures, and demographic and pregnancy information. Included were all infants and fetuses who were identified through surveillance with a birth defect characterized by CDC subject matter experts as being consistent with those observed in cases of congenital Zika virus infection.[2] Additional data collected included the pregnancy outcome (live birth or pregnancy loss), maternal age, gestational age at delivery, and verbatim clinical descriptions of all birth defects, including genetic abnormalities. These verbatim descriptions were reviewed by CDC subject matter experts to verify the case definition and categorization. The earliest age that a birth defect meeting the definition was noted (i.e., prenatally, ≤28 days after delivery, 29 days to <3 months after delivery, ≥3 to <6 months after delivery, and ≥6 months after delivery) was available for data from Massachusetts and Atlanta.

Infants or fetuses with birth defects were aggregated into four mutually exclusive categories of defects characterized by CDC subject matter experts as being consistent with those observed with congenital Zika virus infection: 1) brain abnormalities or microcephaly (head circumference at delivery <3rd percentile for sex and gestational age);[5] 2) neural tube defects and other early brain malformations; 3) eye abnormalities without mention of a brain abnormality included in the first two categories; and 4) other consequences of CNS dysfunction, specifically joint contractures and congenital sensorineural deafness, without mention of brain or eye abnormalities included in another category. Baseline prevalence per 1,000 live births[6] and 95% confidence intervals (CIs) were estimated using Poisson regression.

The three birth defects surveillance programs identified 747 infants and fetuses during 2013 (North Carolina and Massachusetts) and 2013–2014 (Atlanta) with one or more defects that met the 2016 CDC Zika surveillance case definition (2.86 per 1,000 live births [CI = 2.65–3.07]) (Table). Brain abnormalities or microcephaly accounted for the largest number (392 [52%]) and highest prevalence (1.50 per 1,000), followed by neural tube defects and other early brain malformations (229 [31%]; 0.88). Eye abnormalities without mention of a brain abnormality (81 [11%]; 0.31) and consequences of CNS dysfunction without mention of brain or eye abnormalities (45 [6%]; 0.17) were less frequent. Pregnancy losses (48%) and preterm delivery (<37 weeks' gestation) (66%) occurred most frequently with neural tube defects and other early brain malformations. In contrast, all infants with eye abnormalities without mention of a brain abnormality were liveborn.

In general, the distribution by maternal age was similar across birth defect categories. Among 410 (55%) infants or fetuses with information on the earliest age a birth defect was recorded, 371 (90%) had evidence of a birth defect meeting the Zika definition before age 3 months. More than half of those with brain abnormalities or microcephaly or with neural tube defects and other early brain malformations had evidence of these defects noted prenatally (55% and 89%, respectively).

*The Zika surveillance case definition covers all birth defects that have been reported as potentially related to Zika virus infection and includes brain abnormalities such as microcephaly, intracranial calcifications, fetal brain disruption sequence, abnormal cortical formation, and porencephaly, among others; neural tube defects and other early brain malformations, such as anencephaly, spina bifida, encephalocele, and holoprosencephaly; eye abnormalities, such as microphthalmia/anophthalmia, cataracts, chorioretinal and optic nerve abnormalities, among others; and consequences of central nervous system dysfunction, such as joint contractures and congenital sensorineural deafness.
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 defects in the other categories.

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