Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control studyBMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j5018 (Published 21 November 2017) Cite this as: BMJ 2017;359:j5018
All rapid responses
The proposition presented in the article that the diagnosis of microcephaly should move towards a pathology-based criteria instead of the measurement approach might be problematic, considering the obstacles it would pose against the establishment of a worldwide standardised diagnostic procedure. Moreover, to gather consistent and reliable data for comparative research, the diagnosis of microcephaly must be assessed objectively.
Considering there is worldwide awareness of Zika nowadays, paediatricians might overestimate, willingly or unconsciously, microcephaly diagnosis proportionally to the degree of subjectivity which is granted. This process is known in Behavioural Economics as bounded rationality, meaning that people tend to believe that the probability of an event to occur is higher if they have experienced similar situations lately, and vice-versa . Additionally, there is a constraint for comparative studies between the current and the pre-epidemic period , as microcephaly diagnosis was not so critical prior to the latter, which could have led to its underrepresentation.
Furthermore, not all hospitals have the resources to perform a comprehensive individual assessment for borderline microcephaly cases, especially CT and MRI imaging. This could partially explain the higher microcephaly rate found in Southeast Brazil and in metropolitan Chile, considering these regions host reference health care centres. It could also explain the high incidence of microcephaly cases in the United States showed in other studies which analysed the pre-epidemic period .
Just for clarification, the signs in the chained inequalities in Table 3 are in the wrong direction. This might have been due to how the data was translated (e.g., “head size less than −2 SD”), which leads to a dubious interpretation. Perhaps an expression such as “more than 2 SD below the mean” would be more precise.
Nevertheless, the research is a valuable contribution towards the discussion of universally applicable and valid criteria for the diagnosis of microcephaly and particularly useful for comparative research of microcephaly prevalence.
1 Jolls C, Sunstein CR, Thaler R. A Behavioral Approach to Law and Economics. Stanford Law Review 1998;50:1471–550. doi:10.2307/1229304
2 Gulland A. Zika virus is a global public health emergency, declares WHO. BMJ 2016;352. doi:10.1136/bmj.i657
3 Cragan JD, Isenburg JL, Parker SE, et al. Population-based microcephaly surveillance in the United States, 2009 to 2013: An analysis of potential sources of variation. Birth Defects Research Part A: Clinical and Molecular Teratology 2016;106:972–82. doi:10.1002/bdra.23587
Competing interests: No competing interests
Re: It is very important to understand the prevalence and clinical profile of microcephaly in South America pre-Zika
The work by Orioli et al analysing the ECLAMC (Latin American Collaborative Study of Congenital Malformations) surveillance data to establish a baseline prevalence of microcephaly in South America before the 2015-17 Zika virus pandemic is invaluable to our understanding of the impact of Zika virus on congenital disease.
As the authors point out, a major challenge to anyone trying to understand the association between Zika virus and microcephaly is a lack of an internationally agreed definition of microcephaly. ECLAMC uses an ICD-8 definition, but “…does not specify the growth chart to be used by hospitals...”. The lack of an international consensus is surprising and unfortunate. We urge the international medical community to reach a consensus definition of microcephaly in order to facilitate public health surveillance, research and eventually, interventions. We note that the World health Organisation has growth charts and these would be a good international standard, but other such charts exist[3, 4].
One of the interesting points highlighted by Orioli et al is that even before Zika virus arrived in South America, there was regional variation in microcephaly across that continent. For example, the authors found that Brazil already had a relatively high prevalence of microcephaly between 2005-14, as did the Metropolitana region of Chile.
In contrast, Uruguay had no cases of microcephaly detected and Paraguay had only one case of microcephaly detected in the study period, albeit with only 3 ECLAMC centres between them.
The reasons for the significant regional variations are not yet known. Clearly there is scope for more research to understand the reasons for these variations.
The authors reported possible risk factors like maternal age, congenital infections and consanguinity in detail. However, some factors which could be relevant were not reported in this study, including ethnicity, maternal pre-conception and early pregnancy alcohol use and maternal smoking.
Brazil has an ethnically diverse population, which includes people of African, European and Asian descent. It would be interesting to see what if any effect ethnicity has on the prevalence of microcephaly in Brazil and South America.
Maternal alcohol use and smoking are both associated with reduced fetal head circumference and microcephaly[6,7]. Recently, there has been a suggestion that paternal pre-conception smoking may be associated with microcephaly. These are possible confounding factors which future research could address.
The arrival of Zika virus in Brazil in 2015 and concern over an excess incidence of microcephaly shortly after led to the declaration of a public health emergency of international concern by WHO. This study shows that before Zika virus arrived, Brazil already had a relatively high prevalence of microcephaly, higher than most other South American nations. Furthermore, it demonstrated significant but unexplained regional variations across the continent. Studies like this help our understanding of the effect of emergent teratogenic threats like Zika virus.
 Prevalence and clinical profile of microcephaly in South America pre-Zika 20015-14: prevalence and case-control study. Orioli IM et al. BMJ 2017;359:j5018 doi: https://doi.org/10.1136/bmj.j5018
 World Health Organisation. Child growth standards – head circumference for age: http://www.who.int/childgrowth/standards/hc_for_age/en/ (accessed 28/11/17)
 The INTERGROWTH-21st Network – Newborn size: https://intergrowth21.tghn.org/newborn-size-birth/#ns1 (accessed 28/11/17)
 United States Centers for Disease Control, National Centre for Health Statistics, clinical growth charts: https://www.cdc.gov/growthcharts/clinical_charts.htm
 Central Intelligence Agency, The World Factbook: Brazil https://www.cia.gov/library/publications/the-world-factbook/geos/br.html
 Relationship between head circumference, brain volume and cognition in children with prenatal alcohol exposure. Treit S et al. PLoS One 2016 https://doi.org/10.1371/journal.pone.0150370 (accessed 28/11/17)
 Prenatal tobacco exposure, biomarkers for tobacco in meconium and neonatal growth outcomes. Himes SK et al. J Pediatr. 2013 162(5):970-975 doi: https://dx.doi.org/10.1016%2Fj.jpeds.2012.10.045
 Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother Child Study (MoBa). Zuccolo L et al. SciRep 2016 doi: https://dx.doi.org/10.1038%2Fsrep39535
 Zika virus is a global public health emergency, declares WHO. Gulland A. BMJ 2016;352:i657 doi: https://doi.org/10.1136/bmj.i657
Competing interests: The views expressed are our own and not those of our employers.