Population‐based microcephaly surveillance in the United States, 2009 to 2013: An analysis of potential sources of variation

Abstract

Background Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. Methods Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. Results The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers <20 years (11.5) and ≥40 years (13.2). For gestational age and birth weight, the highest prevalence was among infants <32 weeks gestation and infants <1500 gm. Case definitions varied; 41.8% of cases had an HC ≥ the 10th percentile for sex and gestational age. Conclusion Differences in methods, population distribution of maternal/infant characteristics, and case definitions for microcephaly can contribute to the wide range of observed prevalence estimates across individual birth defects surveillance programs. Addressing these factors in the setting of Zika virus infection can improve the quality of prevalence estimates.

Pre‐Zika descriptive epidemiology of microcephaly in Texas, 2008–2012

“…Congenital microcephaly is characterized by a smaller‐than‐normal head circumference, with the most affected part of the brain being the forebrain (Bianchi & Crombleholme, ). Diagnosis at birth is determined by comparing an infant's head circumference (HC)—or occipitofrontal circumference—with that of infants of the same sex and gestational age (Bray, Shields, Wolcott, & Madsen, ; Cooke, Lucas, Yudkin, & Pryse‐Davies, ; Cragan, Isenburg, & Parker, ; McInerny et al, ). Those falling below a certain measurement, generally less than the 3 rd centile or >2 standard deviations below the reference population mean, are characterized as having severe microcephaly (Opitz & Holt, ; Woods, ), although opinions about the lower limit of HC vary (Bianchi & Crombleholme, ).…”

“…Microcephaly has a pre‐ZIKV prevalence range of approximately 2.9 (Europe) (EUROCAT, ) to 8.7/10,000 live births (U.S.) (Cragan et al, ). In 2009, before the emergence of ZIKV in the Americas, approximately 25,000 children were diagnosed with microcephaly in the U.S. (Metsky, Matranga, & Wohl, ).…”

“…A recent National Birth Defects Prevention Network (NBDPN) analysis found that certain demographic factors (e.g., maternal age (<20 and ≥40 years), race/ethnicity (non‐Hispanic (NH) Black and Hispanic), plural births) were associated with microcephaly using birth defects surveillance data from 30 U.S. programs, including Texas, for infants born during 2009–2013 (Cragan et al, ). Assessing risk factors for microcephaly has been problematic due to inconsistent parameters for defining and characterizing the defect such as differing cut‐points and references for microcephaly severity and differing ages at which microcephaly diagnoses are made, e.g., evident at birth vs. developed in the first year of life (Cragan et al, ).…”

Misclassification in defining and diagnosing microcephaly

“…In the two remaining studies, there is no further explanation of the criteria used to diagnose microcephaly beyond the head circumference cut‐off . Surveillance studies conducted throughout the US during a similar time period have emphasised the need for additional neuroimaging and clinical diagnosis, but the exact types of clinical evaluation were not always specified or consistent across these studies …”

Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult

“…This condition is multifactorial in nature, with genetic, infectious agent, and environmental factors linked to causing microcephaly 4,5,6,7,8,9 . Prior to the 2015 – 2016 ZIKV outbreak, 8 children out of 10,000 births were diagnosed with microcephaly in the United States according to the CDC 10 . On February 1 st of 2016 the World Health Organization declared the Zika virus a Public Health Emergency of International Concern due to the alarming increase in microcephaly diagnoses associated with ZIKV infection in mothers 11,12 .…”