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Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study

BMJ 2017; 359 doi: (Published 21 November 2017) Cite this as: BMJ 2017;359:j5018
  1. Iêda M Orioli, professor1 2,
  2. Helen Dolk, professor3,
  3. Jorge S Lopez-Camelo, researcher2 4,
  4. Daniel Mattos, postdoctoral researcher1 2,
  5. Fernando A Poletta, researcher2 4,
  6. Maria G Dutra, public health researcher2 5,
  7. Flavia M Carvalho, public health researcher2 5,
  8. Eduardo E Castilla, researcher2 4
  1. 1Latin American Collaborative Study of Congenital Malformations (ECLAMC) at Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, 21944-001, Rio de Janeiro, Brazil
  2. 2National Institute of Population Medical Genetics (INAGEMP), Porto Alegre, Brazil
  3. 3Maternal Fetal and Infant Research Centre, Institute of Nursing and Health Research, Ulster University, Newtownabbey, Northern Ireland, UK
  4. 4ECLAMC at Center for Medical Education and Clinical Research (CEMIC-CONICET), Buenos Aires, Argentina
  5. 5ECLAMC at Laboratory of Congenital Malformations Epidemiology, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
  1. Correspondence to: I M Orioli orioli{at}
  • Accepted 19 October 2017


Objective To describe the prevalence and clinical spectrum of microcephaly in South America for the period 2005-14, before the start of the Zika epidemic in 2015, as a baseline for future surveillance as the Zika epidemic spreads and as other infectious causes may emerge in future.

Design Prevalence and case-control study.

Data sources ECLAMC (Latin American Collaborative Study of Congenital Malformations) database derived from 107 hospitals in 10 South American countries, 2005 to 2014. Data on microcephaly cases, four non-malformed controls per case, and all hospital births (all births for hospital based prevalence, resident within municipality for population based prevalence). For 2010-14, head circumference data were available and compared with Intergrowth charts.

Results 552 microcephaly cases were registered, giving a hospital based prevalence of 4.4 (95% confidence interval 4.1 to 4.9) per 10 000 births and a population based prevalence of 3.0 (2.7 to 3.4) per 10 000. Prevalence varied significantly between countries and between regions and hospitals within countries. Thirty two per cent (n=175) of cases were prenatally diagnosed; 29% (n=159) were perinatal deaths. Twenty three per cent (n=128) were associated with a diagnosed genetic syndrome, 34% (n=189) polymalformed without a syndrome diagnosis, 12% (n=65) with associated neural malformations, and 26% (n=145) microcephaly only. In addition, 3.8% (n=21) had a STORCH (syphilis, toxoplasmosis, other including HIV, rubella, cytomegalovirus, and herpes simplex) infection diagnosis and 2.0% (n=11) had consanguineous parents. Head circumference measurements available for 184/235 cases in 2010-14 showed 45% (n=82) more than 3 SD below the mean, 24% (n=44) between 3 SD and 2 SD below the mean, and 32% (n=58) larger than −2 SD.

Conclusion Extrapolated to the nearly 7 million annual births in South America, an estimated 2000-2500 microcephaly cases were diagnosed among births each year before the Zika epidemic began in 2015. Clinicians are using more than simple metrics to make microcephaly diagnoses. Endemic infections are important enduring causes of microcephaly.


  • We thank the ECLAMC members, especially the 107 physicians who collected all the data and the ECLAMC staff including Mariana Piola and Alejandra Mariona.

  • Contributors: IMO, JSLC, HD, and EEC conceived the research question. HD wrote the draft of the manuscript with further modifications from all authors. JSLP did the statistical analysis, and HD and FAP advised on all statistical aspects. Clinical analysis was done by IMO. IMO, HD, JSLC, DM, FAP, MGD, FMC, and EEC contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. IMO and EEC are the guarantors.

  • Funding: This research was funded by the MRC Rapid Response Initiative ZK/16-075 Zika: Establishment of enhanced birth defect surveillance in South America, supported jointly by MRC, Newton Fund, and Wellcome Trust, and was also partially supported by MCTIC/FNDCT-CNPq/MEC-CAPES/MS-Decit/No 14/2016 - Prevenção e Combate ao vírus Zika, European Union Horizon 2020 ZikaPLAN grant agreement No 734584 and Bolsista CAPES/BRASIL. Funding sources had no role in the study design, data acquisition, or analyses or in the decision to submit the article for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the ethical committee in Rio de Janeiro, Brazil (CAAE: 59488716.1.1001.5269).

  • Data sharing: The data used in this study belong to the individual hospitals. Data are available on request from the corresponding author, who will ask the individual hospitals’ permission to use the data.

  • Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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