The study was performed by scientists at the Federal University of São Paulo (UNIFESP) and Pernambuco’s Altino Ventura Foundation, a charity that offers free ophthalmic care to poor families in the state considered the epicenter of the Zika epidemic.
The group evaluated the case of a baby born at 38 weeks of gestation, weighing 3.5 kg, and with a head perimeter of 33 cm, considered normal for its age. The infant’s age at examination was 57 days.
“The boy appeared to be normal at birth and didn’t have microcephaly, so the parents took him home. He began convulsing after a few days. They brought him back to the hospital, where CT scans detected cerebral calcifications in the basal ganglia, ventriculomegaly (dilated cerebral ventricles), and a severe retinal lesion similar to those found in babies with microcephaly,” said Rubens Belfort, a professor at UNIFESP’s Medical School (EPM) and co-author of the study.
The mother had had no symptoms of Zika during pregnancy but, after other infections associated with congenital malformations were ruled out, analysis of the infant’s cerebral spinal fluid showed the presence of antibodies against Zika.
According to Belfort, the manifestations observed in this case match the condition now known as congenital Zika syndrome, which has a broad spectrum and presents in a variety of ways. It may or may not include microcephaly, as well as cerebral and ocular lesions, auditory impairment, spasms, and seizures.
“Infection by Zika can’t be ruled out just because microcephaly isn’t present,” he said. “Microcephaly is a risk factor for the presence of cerebral and ocular lesions, but not an absolute pre-condition. For this reason, mothers should be tested for Zika during antenatal care, and if the result is positive the baby should be kept under surveillance after birth, including a complete ocular examination.”
This examination is considered simple to perform and enables the ophthalmologist to observe the fundus of the eye – the interior surface of the eye opposite the lens, including the retina, optic disc, optic nerve, retinal vessels, and the central region of the retina called the macula.
Other cases with similar characteristics are being analyzed and should be confirmed soon. “We decided to publicize this one first so that the scientific information can circulate more quickly,” Belfort said.
In early 2016, the same group of researchers showed for the first time that infection by Zika virus during pregnancy can cause macular atrophy and even blindness in newborn infants. Their findings were also published in The Lancet.
In May, they published an article in JAMA Ophthalmology suggesting that the probability of severe ocular lesions may be greater in infants born to mothers who report symptoms of Zika during the first trimester of pregnancy. The study pointed to a clear association between microcephaly and ocular lesions.
“Babies with microcephaly are often blind, but the lesions found in the babies of women who reported symptoms of Zika during pregnancy are different and very specific,” Belfort said. “Even so, Zika virus had not been definitively shown to be the cause of this problem. In this study, we ruled out all other possible causes of blindness.”
In the study described by this article, infants were excluded if they had a cephalic circumference that exceeded 33 cm, evidence for another congenital infection such as toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis or HIV, or a familial history of microcephaly, or a maternal history of alcohol or illicit drug use during pregnancy.
Twenty-nine microcephalic infants aged 1-6 months born to mothers who reported symptoms of Zika during pregnancy were examined for ocular abnormalities.
The neonates were divided into two groups: with and without alterations detected in the ocular examination.
Of the 29 infants (58 eyes) examined (18 female), ocular abnormalities were present in 17 eyes (29.3%) of 10 children (34.5%).
IgM antibody capture (MAC)-ELISA for Zika virus was performed on the cerebral spinal fluid of 24 infants, with positive results. The test could not be performed on all 29, Belfort explained, because it was not available when the study began.
In the group with retinal abnormalities, results of the antibody capture test were positive for 63.6%, compared with 55% in the group without ocular alterations. The percentage would probably have been higher if they had all taken the serological test. “The data clearly showed that infection by Zika virus leads to microcephaly and blindness in most babies,” Belfort said.
All participating mothers answered a questionnaire on the main signs and symptoms experienced during pregnancy. The most frequent in both groups were cutaneous rash (65%), fever (22.5%), headache (22.5%) and joint pain (20%). No mothers reported conjunctivitis or other ocular symptoms.
More than 70% reported symptoms during the first trimester of pregnancy. “We found that retinal lesions were more severe in the babies of mothers who were infected in the first trimester. Most of the retina was absent in these cases. Our hypothesis is that the virus prevents development of the retina, just as it does with the brain,” Belfort said.
To deepen their understanding of the damage caused by Zika, the researchers continue to monitor children in Pernambuco as well as a group of babies in Bahia. They are also studying the placentas of women who have given birth to infants with microcephaly.
The article “Ocular Findings in Infants With Microcephaly Associated With Presumed Zika Virus Congenital Infection in Salvador, Brazil” (doi: 10.1001/jamaophthalmol.2016.0267) can be read at archopht.jamanetwork.com/article.aspx?articleid=2491896.
The article “Zika: neurological and ocular findings in infant without microcephaly” (doi: 10.1016/S0140-6736(16)30776-0) can be read at thelancet.com/journals/lancet/article/PIIS0140-6736(16)30776-0/abstract.