The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births

<p><strong>BACKGROUND:</strong> In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the...

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Main Authors: Brady, OJ, Osgood-Zimmerman, A, Kassebaum, NJ, Ray, SE, De Araújo, VEM, Da Nóbrega, AA, Frutuoso, LCV, Lecca, RCR, Stevens, A, De Oliveira, B, De Lima, JM, Bogoch, II, Mayaud, P, Jaenisch, T, Mokdad, AH, Murray, CJL, Hay, S, Reiner, RC, Marinho, F
Format: Journal article
Language:English
Published: Public Library of Science 2019
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author Brady, OJ
Osgood-Zimmerman, A
Kassebaum, NJ
Ray, SE
De Araújo, VEM
Da Nóbrega, AA
Frutuoso, LCV
Lecca, RCR
Stevens, A
De Oliveira, B
De Lima, JM
Bogoch, II
Mayaud, P
Jaenisch, T
Mokdad, AH
Murray, CJL
Hay, S
Reiner, RC
Marinho, F
author_facet Brady, OJ
Osgood-Zimmerman, A
Kassebaum, NJ
Ray, SE
De Araújo, VEM
Da Nóbrega, AA
Frutuoso, LCV
Lecca, RCR
Stevens, A
De Oliveira, B
De Lima, JM
Bogoch, II
Mayaud, P
Jaenisch, T
Mokdad, AH
Murray, CJL
Hay, S
Reiner, RC
Marinho, F
author_sort Brady, OJ
collection OXFORD
description <p><strong>BACKGROUND:</strong> In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates.</p> <p><strong>METHODS AND FINDINGS:</strong> We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk &lt; 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data.</p> <p><strong>CONCLUSIONS:</strong> This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.</p>
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spelling oxford-uuid:d51ad0f9-d367-4f05-a79c-bd5e326608542022-03-27T08:23:36ZThe association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million birthsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d51ad0f9-d367-4f05-a79c-bd5e32660854EnglishSymplectic Elements at OxfordPublic Library of Science2019Brady, OJOsgood-Zimmerman, AKassebaum, NJRay, SEDe Araújo, VEMDa Nóbrega, AAFrutuoso, LCVLecca, RCRStevens, ADe Oliveira, BDe Lima, JMBogoch, IIMayaud, PJaenisch, TMokdad, AHMurray, CJLHay, SReiner, RCMarinho, F<p><strong>BACKGROUND:</strong> In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates.</p> <p><strong>METHODS AND FINDINGS:</strong> We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk &lt; 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data.</p> <p><strong>CONCLUSIONS:</strong> This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.</p>
spellingShingle Brady, OJ
Osgood-Zimmerman, A
Kassebaum, NJ
Ray, SE
De Araújo, VEM
Da Nóbrega, AA
Frutuoso, LCV
Lecca, RCR
Stevens, A
De Oliveira, B
De Lima, JM
Bogoch, II
Mayaud, P
Jaenisch, T
Mokdad, AH
Murray, CJL
Hay, S
Reiner, RC
Marinho, F
The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births
title The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births
title_full The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births
title_fullStr The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births
title_full_unstemmed The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births
title_short The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births
title_sort association between zika virus infection and microcephaly in brazil 2015 2017 an observational analysis of over 4 million births
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