Definition of cases and controls used in study and by Ministry of Health in Brazil
| CZS/microcephaly cases | Controls/not microcephaly cases | Other disabilities included in controls | |
| Ministry of Health, Brazil | In the beginning of the microcephaly epidemic, the Brazilian Ministry of Health defined a more sensitive parameter (HC ≤33 cm, for both sex), but it changed in December 2015 (HC ≤32 cm), to reduce the number of false positive cases. In March of 2016, under WHO recommendation, it was modified to 31.5 cm for girls and 31.9 cm for boys, for full-term newborn. From August 2021, the Intergrowth standard was adopted, being even more specific, as the HC 30.24 cm for girls and 30.54 cm for boys, for those born at 37 weeks or more. Suspected microcephaly cases sent for investigation:
If <−3 SD classified as severe microcephaly | See changing case definition over time | n/a |
| Case–control study in Pernambuco | Severe CZS included children with head circumference at least −3 SD than the mean for sex and gestational age on the Fenton growth chart and mild/moderate if at least −2 SD. All cases had mothers with a laboratory confirmed ZIKV infection during pregnancy | Above −2 SD HC than the mean for sex and gestational age on the Fenton growth chart for children from the case–control study and compared with the Intergrowth standard in the cohort study | Excluded based on Denver II Developmental Screening Test conducted with caregivers of controls |
| Cohort study in Rio de Janeiro | Born to mothers that were ZIKV positive during pregnancy with microcephaly or significant developmental delays. Microcephaly was assessed as above, defining an HC of −3 SD as severe and of −2 SD as moderate (using Intergrowth standard) and other children were assessed using the Bayley Scale of Infant Development25) and/or by assessment by two paediatricians Severe: Bayley score of <70 Moderate: Bayley score of 70–<85 | A head circumference of above -2SD on the Intergrowth standard and a Bayley score of ≥85 between 6 months and 36 months of age | Included N=3, prevalence of 1.6% in control group. As comparison, the prevalence of at least one disability in the 0–9 year age group in the National Health Survey in 2013 was 1.6%28 |
CZS, congenital Zika Syndrome; HC, head circumference; SD, Standard Deviation; ZIKV, Zika virus.