Eye abnormalities were observed in 55% of a small cohort of Brazilian infants with microcephaly associated with presumed congenital Zika infection, researchers reported.
In a cross-sectional analysis, risk factors for eye abnormalities included the mother reporting Zika-like symptoms in the first trimester of pregnancy and a smaller head size at birth, according to Rubens Belfort Jr., MD, PhD, of the Paulista School of Medicine in Sao Paulo, Brazil, and colleagues.
On the other hand, there were no links between fundus abnormalities and duration of pregnancy, type of delivery or maternal age, and none of the mothers reported ocular symptoms during pregnancy or when they were examined later, Belfort and colleagues reported online in JAMA Ophthalmology.
The pathogenesis of the abnormalities remains unclear, Belfort and colleagues noted, adding they could have arisen as a consequence of the microcephaly, the Zika infection, or both.
Earlier research by two groups of scientists, including Belfort and colleagues, had reported the existence of ocular abnormalities in children in Brazil whose mothers had reported Zika-like symptoms during their pregnancies.
To try to identify risk factors for such lesions, Belfort and colleagues studied 40 infants with microcephaly born from May through December 2015 in Brazil's Pernambuco state, which has the highest number of cases of microcephaly in the country.
They were included in the cohort if they met the Brazilian health ministry's definition of microcephaly -- an occipitofrontal circumference more two standard deviations lower than the average for age and sex -- and toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus could be ruled out.
An antibody test for Zika was not available when the first 16 infants were enrolled, but was used to test cerebrospinal fluids of the remaining 24. Both infants and mothers had ocular exams, and the babies were stratified according to presence of absence of eye abnormalities.
All 24 of the babies tested for antibodies were positive for Zika, Belfort and colleagues reported, including 14 of the 22 infants with ophthalmoscopic findings and 10 of the 18 without abnormalities.
The similarity of the distribution in the two groups "reinforces the clinical diagnosis of ZIKV congenital infection in all 40 infants," Belfort and colleagues argued.
On average, the infants' average cephalic perimeter was 29.5 centimeters at birth, but it was significantly less (at P=0.004) in the infants who had ocular abnormalities than in those with normal eyes -- 28.8 centimeters versus 30.3.
The investigators found that 28 babies were born at term, 11 were preterm, and one was post-term, while slightly more than half of the mothers -- 55.3% -- had a caesarean delivery. Neither characteristic was significantly different between the ocular groups.
Some 27 mothers reported Zika-like symptoms during pregnancy, mainly rash, fever, headache, and arthralgia. None of the women reported conjunctivitis or ocular symptoms during pregnancy, and all but one had normal ocular examinations after giving birth. The exception had decreased vision that was present before pregnancy.
When Belfort and colleagues compared specific symptoms reported by mothers of infants with fundus abnormalities and those with a normal ocular examination, the incidence rates were similar between groups.
On the other hand, they reported, the timing of symptoms was significantly different (at P=0.04) -- 10 of 14 mothers of infants with ocular findings had their symptoms in the first trimester and eight of the 13 mothers (61.5%) whose infants had a normal eye exam had symptoms in the second trimester.
The investigators cautioned that Zika infection was not confirmed by serology in all cases. As well, they noted data on the mothers' symptoms was based on self-report -- most could not recall their precise symptoms by weeks of gestational age.
The report comes as U.S. researchers said mathematical modeling suggests the risk of microcephaly is highest when mothers catch the disease in the first trimester and is negligible later in the pregnancy.
The issue is complicated by lack of solid data on infection rates in Brazil, possible over- or under-reporting of microcephaly, and an uncertain baseline rate for the condition, according to CDC investigators led by Michael Johansson, PhD.
But, in a Perspective article in the New England Journal of Medicine, they applied data derived from Zika outbreaks in Micronesia and French Polynesia to the outbreak in the Brazilian state of Bahia, assuming infection rates of between 10% and 80%.
The estimated baseline risk of microcephaly was about two cases per 10,000 births, they reported, but the estimated risk of the condition due to infection in the first trimester ranged from:
- 0.88% when the overall infection rates was assumed to be 80% with 100% over-reporting of microcephaly cases.
- To 13.2% when the infection rate was assumed to be 10% but there was no over-reporting.
Johansson and colleagues cautioned that there are "uncertainties and limitations" affecting all estimates of microcephaly risk associated with Zika.
"First, available data are very limited, especially in recently affected areas such as Bahia, where infection rates are unknown and microcephaly cases are still being reported and evaluated," they noted.
That information gap is "compounded by difficulty in the clinical confirmation of microcephaly," Johansson and colleagues wrote.
Belfort and colleagues did not report external support for the study and did not declare any potential conflicts of interest.
Johansson and colleagues are employees of the CDC.
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