Eye Abnormalities May Be First Sign of Congenital Zika Virus Infection

Abnormalities of the eye may be the only early sign of congenital Zika virus (ZIKV) infection in neonates and may be present in the absence of central nervous system (CNS) manifestations, according to a study from Brazil published online in JAMA Pediatrics.¹ Screening criteria are currently predicated on the presence of CNS abnormalities, which the researchers determined are inadequate to capture all cases of infantile Zika infection.

A multinational team of investigators examined the results of ophthalmic examinations performed in 112 infants born in 2015 to mothers in Rio de Janiero, Brazil, who had confirmed ZIKV infection during pregnancy. First examinations of the neonates conducted at a median of 31 days (range, 0-305 days) after birth revealed 24 cases of eye abnormalities (21.4%). Microencephalopathy, the current indication in Brazil for ophthalmic screening, was identified in only 14 (58%) of those infants. In addition, 16 (66.7%) of the 24 infants had other CNS findings, 7 (29.2%) had arthrogryposis, and most important, 8 (33.3%) showed no signs of CNS impairment. By current ophthalmic screening standards, the investigators calculated that diagnosis of 3 of the infants with CNS findings but without microencephalopathy would have been missed.

Among the mothers, ZIKV infection occurred most frequently in the second trimester (49.1%), followed by 28.6% in the first and 22.3% in the third. Higher risks for eye abnormalities in the newborns were also associated with first trimester infections (odds ratio [OR], 5.1; 95% CI, 1.9-13.2) compared with infections in the second and third trimesters (OR, 0.5 [95% CI, 0.2-1.2] and 0.3 [95% CI, 0.1-1.2], respectively).

“However, we have to interpret this finding with caution,” coauthor Andrea A. Zin, MD, PhD, from the Departamento de Pesquisa Clinica, Instituto Nacional de Saúde da Mulher, Rio de Janeiro, Brazil, told Infectious Disease Advisor. She pointed to a previous study published by her group in which adverse outcomes “were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester).”²

The team concluded that current guidelines for ophthalmic screening in Zika-exposed infants are inadequate to identify all cases, as eye abnormalities indicative of congenital ZIKV infection were not limited to newborns with microencephalopathy. “Zika infection is asymptomatic in 80% of cases, so it is difficult to define screening criteria,” Dr Zin said. “In epidemic areas, it seems reasonable to examine all babies born to mothers with ZIKV infection confirmed during pregnancy (blood, urine, amniotic fluid RT-PCR+), those with any symptoms compatible with ZIKV infection, or infants who presented any CNS abnormalities or development delay.”

Dr Zin suggested that infants exposed to Zika should be examined soon after birth. “My advice would be that caregivers should watch carefully any sign or visual development delay. If [such a sign or delay is observed], babies should be examined again, even if the eyes were normal at first exam,” she said.

Study limitations included a referral bias in which approximately half the cohort was enrolled through a Brazilian Ministry of Health center for high-risk pregnancies and infectious diseases in children. The study lacked a control group, and was also conducted at a tertiary care center, so the results could not be extrapolated to the general population.

References

1. Zin AA, Tsui I, Rossetto J, et al. Screening criteria for ophthalmic manifestations of congenital Zika virus infection [published online July 17, 2017]. JAMA Pediatr. doi: 10.1001/jamapediatrics.2017.1474
2. Brasil P, Pereira JP, Moreira ME, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med. 2016;375:2321-2334. doi: 10.1056/NEJMoa1602412