High Background Congenital Microcephaly in Rural Guatemala: Implications for Neonatal Congenital Zika Virus Infection Screening.

BACKGROUND

Congenital microcephaly is the result of a disturbance in early brain development and can have multiple etiologies. Establishing background prevalence of microcephaly in Zika virus (ZIKV)-affected areas is important for improving identification of ZIKV-affected newborns. However, to date, there is limited consistent guidance for the accurate identification of microcephaly in infants of unknown gestational age, a common concern in low- and middle-income countries.

METHODS

Occipital frontal head circumference (OFC) obtained from infants (0-13 days) of unknown gestational age at enrollment in a pregnancy registry in rural Guatemala from August 2014 to March 2016 were retrospectively reviewed. Trained community health nurses recorded anthropometry in an online database. In April 2015, ZIKV was identified in this population. Gestational age was approximated in 2 ways: presumed term and estimated using z-score of zero for height on modified Fenton growth curves. After which, z-scores for OFC and weight were obtained. Microcephaly and microcephaly background prevalence were estimated using 7 established microcephaly case definitions from national and international organizations and 3 proposed definitions using Fenton growth curves. Independent associations with microcephaly and OFC, including relationship with date of birth, were assessed with prevalence ratios and linear regression.

RESULTS

For 296 infants, the mean OFC was 33.1 cm (range, 29.5 to 37 cm) and the mean OFC z-score was -0.68. Depending on case definition, 13 to 125 infants were classified as having microcephaly (background prevalence 439 to 4,223 per 10,000 live births), and 1 to 9 infants were classified as having severe microcephaly (<-3 standard deviation [SD]) (34 to 304 per 10,000 live births). Five (1.7%) infants met all the microcephaly case definitions. Weight ≤-1 SD (prevalence rate [PR], 3.77; 95% confidence interval [CI]: 1.6 to 8.8; =.002) and small for gestational age (PR, 4.68; 95% CI, 1.8 to 12.3; =.002) were associated with microcephaly. Date of birth was not associated with OFC z-score or OFC after adjusting for gestational age and gender.

CONCLUSIONS

Estimated background microcephaly is high in rural Guatemala compared with reported rates in Latin America prior to ZIKV epidemic, which has important implications for neonatal screening programs for congenital ZIKV infection. Fenton growth curves offer a standardized approach to the identification of microcephaly in infants of unknown gestational age.