• Patrícia Brasil, José P Pereira, M Elisabeth Moreira, Rita M Ribeiro Nogueira, Luana Damasceno, Mayumi Wakimoto, Renata S Rabello, Stephanie G Valderramos, Umme-Aiman Halai, Tania S Salles, Andrea A Zin, Dafne Horovitz, Pedro Daltro, Marcia Boechat, Claudia Raja Gabaglia, Patrícia Carvalho de Sequeira, José H Pilotto, Raquel Medialdea-Carrera, Denise Cotrim da Cunha, Liege M Abreu de Carvalho, Marcos Pone, André Machado Siqueira, Guilherme A Calvet, Ana E Rodrigues Baião, Elizabeth S Neves, Paulo R Nassar de Carvalho, Renata H Hasue, Peter B Marschik, Christa Einspieler, Carla Janzen, James D Cherry, Ana M Bispo de Filippis, and Karin Nielsen-Saines.
• From Fundação Oswaldo Cruz (P.B., J.P.P., M.E.M., R.M.R.N., L.D., M.W., R.S.R., T.S.S, A.A.Z., D.H., M.B., P.C.S., J.H.P., R.M.-C., D.C.C., L.M.A.C., M.P., A.M.S., G.A.C., A.E.R.B., E.S.N., P.R.N.C., A.M.B.F.); and Clinica de Diagnostico por Imagem (P.D.) - both in Rio de Janeiro; David Geffen UCLA School of Medicine, Los Angeles (S.G.V., U.-A.H., C.J., J.D.C., K.N.-S.), and Biomedical Research Institute of Southern California, Oceanside (C.R.G.) - both in California; Faculty of Medicine, University of São Paulo, São Paulo (R.H.H.); Medical University of Graz, Graz, Austria (P.B.M., C.E.), and Karolinska Institutet, Stockholm (P.B.M.).
• N. Engl. J. Med. 2016 Dec 15; 375 (24): 2321-2334.

BackgroundZika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants.MethodsWe enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes.ResultsA total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. 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).ConclusionsDespite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

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