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...
Main Authors: | , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
Public Library of Science
2019
|
_version_ | 1797097150565318656 |
---|---|
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 < 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> |
first_indexed | 2024-03-07T04:51:26Z |
format | Journal article |
id | oxford-uuid:d51ad0f9-d367-4f05-a79c-bd5e32660854 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T04:51:26Z |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | dspace |
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 < 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 |
work_keys_str_mv | AT bradyoj theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT osgoodzimmermana theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT kassebaumnj theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT rayse theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT dearaujovem theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT danobregaaa theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT frutuosolcv theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT leccarcr theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT stevensa theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT deoliveirab theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT delimajm theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT bogochii theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT mayaudp theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT jaenischt theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT mokdadah theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT murraycjl theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT hays theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT reinerrc theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT marinhof theassociationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT bradyoj associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT osgoodzimmermana associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT kassebaumnj associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT rayse associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT dearaujovem associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT danobregaaa associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT frutuosolcv associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT leccarcr associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT stevensa associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT deoliveirab associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT delimajm associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT bogochii associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT mayaudp associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT jaenischt associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT mokdadah associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT murraycjl associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT hays associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT reinerrc associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths AT marinhof associationbetweenzikavirusinfectionandmicrocephalyinbrazil20152017anobservationalanalysisofover4millionbirths |