NF1-specific growth charts for head circumference over the first three years of life.

Background and objectives: Macrocephaly is among the most common findings in neurofibromatosis type 1 (NF1) and may be associated with other clinical manifestations of the genetic syndrome. NF1-specific growth charts that account for expected macrocephaly may increase sensitivity to detect atypical growth. We aimed to produce NF1-specific growth charts of head circumference for the age range of 0 to 3 years and to assess their potential clinical impact. Methods: Using electronic health records from the Children's Hospital of Philadelphia, we collected head circumference measurements from children with NF1 and a community control cohort seen at scheduled well-child visits. We compared head circumference normed using Center for Disease Control (CDC) growth charts between these groups over time. We constructed NF1-specific growth charts using two independent methods. Finally, we used mixed-effects models to relate the resulting centile scores with developmental delay assessed with the Survey of Well-being of Young Children. Results: Our dataset contained 2180 observations from 305 individuals (167 male) with NF1, and 104,750 observations from 16,742 individuals (8809 male) in the community control cohort, all aged 0 to 3 years old. Head circumference was significantly elevated in NF1 throughout the age range ( Discussion: We present the first NF1-specific growth charts for head circumference covering ages 0 to 3 years. Macrocephaly in NF1 becomes more exaggerated over time as rate-of-growth is sustained compared to controls. Smaller head size relative to NF1 growth expectations is not captured by CDC charts yet nevertheless relates to developmental delay, suggesting that NF1-specific charts may increase sensitivity to clinically concerning patterns of growth in children with NF1.