Factors associated with pubertal growth outcomes in cystic fibrosis: Early Growth and Puberty in CF.

• Early weight-for-length (WFL)/body mass index (BMI) growth trajectories are not associated with pubertal outcomes in people with cystic fibrosis (CF), but height at age 2 years is. • Initiating CFTR modulator therapy in childhood is associated with taller adult height even after adjusting for early growth. • Future research should explore the evolving impact of highly effective modulator therapy (HEMT) use in early childhood on pubertal growth outcomes in CF. Pubertal delays in children with cystic fibrosis (CF) have historically been common. It is unclear to what degree puberty is affected in the new era of CF care or the role of early nutritional status. We hypothesized that more favorable early growth trajectories are associated with improved pubertal growth outcomes. We used data from the United States CF Foundation Patient Registry to analyze associations between early weight-for-length/body mass index (WFL-BMI) growth trajectories and pubertal outcomes, using peak height velocity (PHV) and age at PHV (APHV) as proxy measures for puberty in addition to adult height (defined as height at age 18 years). Our analysis consisted of shape invariant mixed modeling and multivariable linear regression. Our sample consisted of 9,186 people with CF aged 18 to 21 years between 2010-2019. APHV was earliest and PHV/adult height were highest in those with WFL-BMI always >50th percentile from 0-6 years. However, there was no difference after adjusting for key covariates. Receiving CF transmembrane conductance regulator (CFTR) modulator therapy in childhood was associated with being taller at 18 years, by 0.92 cm in males (p=0.048) and 1.02 cm in females (p=0.010) in adjusted models. Higher height z-score at 2 years was associated with improved APHV and PHV for males and improved adult height for both males and females (p<0.001) in adjusted models. Early height, but not early WFL-BMI trajectories, may be associated with pubertal growth outcomes. CFTR modulator therapy shows the potential to improve pubertal growth outcomes, but further research is necessary. [ABSTRACT FROM AUTHOR]