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

Abstract

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.

Spatiotemporal Analysis of the Population Risk of Congenital Microcephaly in Pernambuco State, Brazil

“…However, the prevalence in the current study is comparable to that found by de Oliveira et al on the national level [10]. In South America, causes of microcephaly prior to the Zika outbreak included chromosomal syndromes (e.g., Patau), monogenic syndromes (e.g., Meckel), associated neural malformations (e.g., encephalocele), and embryopathies, which were largely related to infections (e.g., cytomegalovirus and toxoplasmosis) and less frequently to alcohol [28]. However, as is the case with surveillance in the United States, for example [27], the majority of cases did not have a documented cause and, in the current study, individual etiological investigation is only partially available.…”

Measurement error, microcephaly prevalence and implications for Zika: an analysis of Uruguay perinatal data

“…In the era prior to the Zika virus outbreak in the Americas, population estimates of microcephaly were between 0.3 and 12 per 10 000, indicating that stricter definitions, or additional criteria, were being used in diagnosis 3 21–24. The Latin American Collaborative Study of Congenital Malformations examined baseline prevalence of microcephaly as reported within 10 South American countries in this surveillance system25; hospital-based prevalence was 4.4 per 10 000 births and population-based prevalence was 3.0 per 10 000. Twenty-nine per cent of these were perinatal deaths, and 57% were diagnosed as part of a syndrome or had multiple malformations,25 suggesting these were particularly severe cases.…”

“…The Latin American Collaborative Study of Congenital Malformations examined baseline prevalence of microcephaly as reported within 10 South American countries in this surveillance system25; hospital-based prevalence was 4.4 per 10 000 births and population-based prevalence was 3.0 per 10 000. Twenty-nine per cent of these were perinatal deaths, and 57% were diagnosed as part of a syndrome or had multiple malformations,25 suggesting these were particularly severe cases. A study of microcephaly in Ribeirão Preto and São Luis, Brazil prior to the Zika epidemic (2010), found that between 2% and 4% of children had head circumference measurements that were <2 SD, and 0.5%–0.9% had head circumference <3 SD (by various standards) 21.…”

Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids

“…5 Thousands of infants born from ZIKV-infected mothers in the Americas exhibited thinner cortical layers, the hallmark of microcephaly. 6,7 Human neural progenitor cells (hNPCs), which give rise to building blocks of human cortex, are readily identified as the major target cells of ZIKV by using cell cultures, brain organoids and fetal brain slices. [8][9][10][11][12][13] More importantly, ZIKV exhibits specific tropism to hNPCs, whereas the more differentiated immature or mature neurons are less susceptible to ZIKV infection.…”