October 11, 2016
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Infant microcephaly caused by Zika virus infection during pregnancy

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Congenital Zika virus infection correlated strongly as a causal link with the microcephaly epidemic in Brazilian infants, according to preliminary study findings.

“Since the hypothesis that the microcephaly epidemic in Brazil is caused by congenital Zika virus infection was first proposed, there has been an accumulation of evidence supporting the association,” Thalia Velho Barreto de Araújo, PhD, from the department of social medicine at Federal University of Pernambuco in Recife, Brazil, and colleagues, wrote. “The relation between Zika virus and birth defects is strong enough to be deemed causal, but the argument would be stronger if confirmed by at least one case-control study and a cohort study.”

By request of the Brazilian Ministry of Health, Araújo and colleagues conducted the first prospective, case-control study to investigate the association between in utero Zika virus infection and microcephaly. The multisite study included 32 microcephalic neonates and 62 control neonates without microcephaly matched by expected delivery date and residential area. The patients were observed from Jan. 15 to May 2.

The investigators interviewed mothers and referred eligible neonates for brain CT immediately after delivery, collected cerebrospinal fluid from infants with microcephaly and collected blood from the umbilical cord in all study infants. Real-time PCR was applied to RNA samples of all mothers and neonates, and cerebrospinal fluid samples were scanned for African and Asian Zika virus genomes. In addition, serum samples were analyzed for immunoglobulin M and IgG antibodies for toxoplasmosis, rubella and cytomegalovirus.

Analysis concluded associations between IgM serum and cerebrospinal fluid test results in scanning for Zika genomes (kappa, 0.91, 95% CI, 0.74-1), and 24 of 30 mothers of microcephalic neonates tested positive for Zika infection compared with 39 of 61 mothers of infants in the control group. Laboratory-confirmed cases of Zika included 13 of 32 microcephalic infants and no cases among the 62 controls. Among the 27 microcephalic infants investigated by CT imaging, 11 had at least one brain abnormality; these included calcifications (n = 7), ventriculomegaly (n = 5), lissencephaly (n = 1) and six infants had other abnormalities. The OR for the seven cases with brain abnormalities was 113.3 (95% CI, 14.5-∞), while the overall crude OR for microcephaly and laboratory-confirmed Zika virus infection was 55.5 (95% CI, 8.6-∞).

“Our results showed that the association between laboratory-confirmed Zika virus infection and microcephaly was present in cases who had normal findings on brain imaging, suggesting that congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” the researchers wrote. “In view of these findings, patients with microcephaly and normal brain imaging findings should not be excluded from surveillance and diagnosis of congenital Zika virus infection.”

In an accompanying commentary, Patricia Brasil, PhD, of Fiocruz RJ, in Rio de Janeiro, and Karin Nielsen-Saines, MD, MPH, clinical professor in the pediatrics department at the Geffen School of Medicine at UCLA, wrote that the early results from Araújo and colleagues “might be a missing piece to the puzzle” in explaining the relationship between microcephaly and Zika virus infection.

“Their results highlight the striking magnitude of the association between microcephaly and laboratory-confirmed Zika virus infection: the risk is 50 times higher in all microcephaly cases and more than 100 times higher in cases with brain abnormalities detected by imaging,” they said. “More data are needed to refine gestational age-specific risk estimates for microcephaly and other adverse outcomes related to Zika virus infection.” – by Kate Sherrer

Disclosure: The researchers report no relevant financial disclosures.