Birth Defects Potentially Related to Zika Virus Infection During Pregnancy in the United States

Zika remains a health threat in the United States, and publichealthsystemsareessentialtomonitoringthefulleffect of congenital Zika virus infection on infants and children. Because some healthy infants born following pregnancies complicated by Zika may have developmental problems that become evident later, developmental milestones should be closely monitored throughout the child’s first years of life. Zika virus can cause serious damage to the developing fetal brain when infection occurs during pregnancy. In addition to causing brain abnormalities and microcephaly, Zika virus infection during pregnancy has been associated with eye abnormalities, joint contractures, and potentially other birth defects and disabilities.1 From January 2016 through December 2017, 7054 pregnancies with laboratory evidence of possible Zika virus infection in US states and territories were reported to the US Zika Pregnancy and Infant Registry coordinated by the US Centers for Disease Control and Prevention (CDC).2 However, the total number of mothers and infants in the United States affected by congenital Zika virus infection since the emergence of the virus in the Americas is likely much higher because many women with exposure to Zika virus in pregnancy were not tested or were not tested in a timeframe that allowed identification of the infection. Most Zika virus infections are asymptomatic and detecting Zika virus RNA is complicated by its transient presence in body fluids; thus, Zika virus infection during pregnancy cannot be ruled out by negative nucleic acid testing results. Serologic testing is affected by the timing of specimen collection, and interpretation of positive results is complicated by cross-reactivity, especially in persons previously infected with a related flavivirus. Birth defect surveillance systems are a vital component to detect increases independent of whether Zika virus exposure or infection is identified. On January 25, 2018, the CDC released the first report of population-based birth defect surveillance from 15 jurisdictions for birth defects potentially associated with congenital Zika virus infection.3 Existing systems were enhanced to identify fetuses and infants with selected birth defects in a timely fashion (Box). The report examines pregnancies completed in 2016, and it included 3 areas with local transmission of Zika virus and areas with higher and lower travel-associated Zika virus disease cases reported. Comparing the second half of 2016 with the first half, there was an increase in total birth defects potentially associated with Zika virus infection in jurisdictions with local transmission of Zika virus that was not statistically significant, and there were no increases noted in the other jurisdictions. However, when limited to the birth defects strongly linked to Zika virus infection (brain abnormalities, microcephaly, or both; eye abnormalities; and consequences of central nervous system dysfunction), which collectively represent more than 90% of the Zikaassociated birth defects in the US Zika Pregnancy and Infant Registry,4 there was a significant 21% increase in areas with local transmission (from 2.0 to 2.4 per 1000 live births) in the latter half of 2016 compared with the first half. No increase was observed for neural tube defects and other early brain malformations, consistent with the much more limited evidence of congenital Zika virus infection as a cause for these birth defects. Because the peak of local virus transmission in these jurisdictions occurred in the second half of 2016, and most exposed pregnancies were completed in 2017, it is critical that public health surveillance programs continue reporting the occurrence of these birth defects to monitor for trends following the Zika virus outbreak. The birth defects surveillance report identified increased prevalence of birth defects strongly linked to Zika virus infection in 2016 in US areas with local Zika virus transmission.3 Although these birth defects are not specific to congenital Zika virus infection and have other causes, only those defects found previously to be most closely aligned with congenital Zika infection had increased prevalence. Most of the fetuses and infants described in the birth defects surveillance report had no laboratory evidence of congenital Zika virus infection and no Zika virus testing performed. For some of these infants, Zika virus testing would not have been indicated because of lack of possible maternal exposure or identification of other etiologies. The significant increase in birth defects strongly linked to Zika virus infection is concerning, but it might represent just a portion of the full effect of congenital Zika virus infection. About 5% to 10% of pregnancies with laboratory evidence of possible Zika virus infection have been initially reported to have one of these birth defects.5,6 However, there are also case reports of infants born with normal head circumference who developed postnatal-onset microcephaly following congenital Zika virus infection.7 The full range of developmental disabilities and other adverse early childhood outcomes associated with congenital Zika virus infection in the United States can only be determined by following up the infants and children as they develop. Understanding what is happening with those infants might have far-reaching implications for other exposed infants whose congenital infection was not identified during pregnancy or at birth. Many infants with congenital Zika virus infection and severe microcephaly will have profound developmental delays and face significant challenges,8 but ongoing surveillance is needed to determine the extent to which congenitally exposed infants without apparent birth defects will experience similar or other developmental issues. VIEWPOINT