Re: It is very important to understand the prevalence and clinical profile of microcephaly in South America pre-Zika
Sir,
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[1].
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[2], 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[5]. 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[8]. 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[9]. 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.
Rapid Response:
Re: It is very important to understand the prevalence and clinical profile of microcephaly in South America pre-Zika
Sir,
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[1].
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[2], 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[5]. 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[8]. 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[9]. 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.
References:
[1] 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
[2] World Health Organisation. Child growth standards – head circumference for age: http://www.who.int/childgrowth/standards/hc_for_age/en/ (accessed 28/11/17)
[3] The INTERGROWTH-21st Network – Newborn size: https://intergrowth21.tghn.org/newborn-size-birth/#ns1 (accessed 28/11/17)
[4] United States Centers for Disease Control, National Centre for Health Statistics, clinical growth charts: https://www.cdc.gov/growthcharts/clinical_charts.htm
[5] Central Intelligence Agency, The World Factbook: Brazil https://www.cia.gov/library/publications/the-world-factbook/geos/br.html
[6] 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)
[7] 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
[8] 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
[9] 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.