Identifying possible inaccuracy in reported birth head circumference measurements among infants in the US Zika Pregnancy and Infant Registry

The US Zika Pregnancy and Infant Registry (USZPIR) monitors infants born to mothers with confirmed or possible Zika virus (ZIKV) infection during pregnancy. The surveillance case definition for Zika-associated birth defects includes microcephaly based on head circumference (HC). We assessed birth and follow-up data from infants with birth HC measurements <3rd percentile and birthweight ≥10th percentile to determine possible misclassification of microcephaly.We developed a schema informed by literature review and expert opinion to identify possible HC measurement inaccuracy using HC growth velocity and neuroimaging results. Two or more HC measurements between 2-12 months of age were required for assessment. Inaccuracy in birth HC measurement was suspected if growth velocity was >3 centimeters/month in the first three months or HC was consistently >25th percentile during follow-up. Normal neuroimaging was considered supportive of HC measurement inaccuracy. Of 6,799 infants, 351 (5.2%) had Zika-associated birth defects, of which 111 had birth HC measurements <3rd percentile and birthweight ≥10th percentile. Of 84/111 infants with sufficient follow-up, 38/84 (45%) were classified as having possible inaccuracy of birth HC measurement, 19/84 (23%) had HC ≥3rd percentile on follow-up without meeting criteria for possible inaccuracy, and 27/84 (32%) had continued HC <3rd percentile. After excluding possible inaccuracies, the proportion of infants with Zika-associated birth defects including microcephaly decreased from 5.2% to 4.6%.About one-third of infants with Zika-associated birth defects had only microcephaly, but indications of possible measurement inaccuracy were common. Implementation of this schema in ZIKV infection during pregnancy studies can reduce misclassification of microcephaly.