Epidemiology of Macrocephaly in the Texas Birth Defects Registry, 1999-2019

Macrocephaly is a clinical observation denoted as an occipitofrontal head circumference exceeding two standard deviations above same age and sex norms. By its definition, macrocephaly occurs in approximately 3% of the population. Descriptive epidemiologic evaluations of macrocephaly are lacking in the literature. The primary objective of this study was to describe the prevalence of macrocephaly captured by the Texas Birth Defects Registry (TBDR) by infant sex, rural/urban residence, and select maternal characteristics.

Cases of TBDR between 1999 and 2019 with a six-digit Centers for Disease Control modified-British Pediatric Association (BPA) code of 742.400 (enlarged brain/head, large head, macrocephaly, megalencephaly) were identified. All pregnancy outcomes and diagnostic certainties were included. Prevalence (per 10,000 live births) and 95% confidence intervals (CIs) were calculated using a Poisson table by rural/urban residence, infant sex, maternal age, education, race/ethnicity, history of diabetes, and body mass index (BMI). Prevalence calculations were repeated across multiple sensitivity analyses including (1) definite, isolated cases excluding those with indication of being either "benign" or "familial", (2) definite, non-isolated cases, (3) definite non-isolated cases excluding chromosomal and syndromic cases, and (4) definite, proportionate (at birth) cases. A secondary objective was to describe the most common co-occurring congenital defects among definite, non-isolated cases.

Overall, between 1999 and 2019, 14,637 cases of macrocephaly were identified in the TBDR resulting in a prevalence of 18.12/10,000 live births (95% CI: 17.83-18.42). Most cases were live born (99%), had a definite diagnosis (87%), and were non-isolated (57%). Prevalence was significantly higher among males, among those with an urban residence, and among mothers who were older, Non-Hispanic White, who had greater than high school education, who had a history of diabetes, and who were obese. Prevalence patterns remained consistent across all sensitivity analyses. The most common co-occurring congenital defects among definite, non-isolated cases were minor and primarily included skull and facial bone anomalies (e.g., plagiocephaly [18%]).

To our knowledge, this is the first epidemiologic evaluation of macrocephaly in a birth defects registry. The long-term clinical impact of isolated macrocephaly is not well understood and should be the focus of future investigations.