Head Circumference as a Measure of In Utero Zika Virus Exposure and Outcomes

The spectrum of clinical outcomes for infants and children with prenatal Zika virus (ZIKV) exposure continues to widen. When the ZIKV epidemic emerged in 2015, we were struck by the severe congenital malformations that occurred in utero. The constellation of microcephaly, abnormal neurologic tone, vision and hearing abnormalities, and arthrogryposis was given the term congenital Zika syndrome (CZS).1,2 The severity and frequency of brain damage were alarming and included findings of fetal brain disruption sequence and arthrogryposis, which were unique to congenital infection associated with ZIKV.2 However, for the 90% to 95% of ZIKV-exposed infants who were not born with severe abnormalities at birth and were normocephalic, our hope was that these children would have normal neurodevelopmental outcomes. Unfortunately, this has not been the case.3,4 Cranston et al5 provide detailed clinical follow-up of a large cohort of children from Rio de Janeiro, Brazil, with antenatal ZIKV exposure. To assess whether birth head circumference (HC) was associated with a difference in neurodevelopmental outcomes, the authors stratified infants as having normocephaly or microcephaly by their birth HC. Not surprisingly, there was a high burden of neurologic and other clinical abnormalities, including failure to thrive, ophthalmologic and audiologic abnormalities, and congenital heart defects in the children born with microcephaly, and none of the children with microcephaly at birth were able to complete the Bayley Scales of Infant and Toddler Development, Third Edition, (Bayley-III) assessment owing to their level of disability.5 However, of considerable concern was the 68% of infants who had normocephaly at birth and had neurologic abnormalities on follow-up examination.5 This high rate, in part, reflects the initial reason for referral and is higher than would be expected in a general ZIKV-exposed child cohort. Nevertheless, this study describes a wide range of clinical outcomes for ZIKV-exposed children and supports the recommendation for continued longitudinal neurodevelopmental follow-up for all ZIKV-exposed infants.3 An important finding by Cranston et al5 was that birth HC among infants who had normocephaly with in utero ZIKV exposure was associated with neurodevelopmental scores at follow-up evaluation. Infants with a larger birth HC, within the normocephalic range (±2 SDs), had higher overall neurodevelopmental scores on the Bayley-III assessment, whereas infants with a smaller birth HC within the normocephalic range had lower scores in the domains of cognitive and language functions. Although the authors did not report a specific HC z score that increased this risk, having a z score lower than 0 may be a way to stratify infants into highand low-risk categories among infants with normal birth HC z scores. Combining HC with other early clinical data, such as the results of neuroimaging or a neurologic examination, can then further stratify infants for risk of subsequent abnormal neurologic outcomes. This finding of HC has not been shown in other ZIKV-exposed cohorts, possibly owing to the higher burden of abnormal neurologic outcomes in this cohort. However, this finding provides a practical tool to help determine risk for adverse clinical outcomes in a ZIKV-exposed infant at birth that can be widely used in a variety of follow-up settings. Although birth HC is an important initial measurement, the HC growth trajectory is key. Cranston et al5 stratified outcomes based only on HC at birth, not on HC at follow-up. Of 162 infants with normocephaly at birth, 17 (10.5%) developed postnatal microcephaly;5 thus, the trajectory of head growth is critical. The neurologic outcome of a child who develops postnatal microcephaly would be very concerning compared with an infant who is born with normocephaly and maintains a steady HC percentile over time. Occipital frontal circumference correlates with intracranial volume. A small head size can be familial, but evaluations for genetic, infectious, or other etiologies are often + Related article