Condition-Specific Growth Charts for Children With Alagille Syndrome

Abstract

QuestionWhat do condition-specific growth charts look like for children with Alagille syndrome (ALGS)?FindingsIn this case series of 1204 children with ALGS, growth charts developed for boys and girls using modern statistical techniques based on 9855 weight and 8463 height observations showed markedly different growth patterns when overlaid with US growth charts for children with typical development.MeaningThese findings suggest that condition-specific growth charts may provide references for the growth of children with ALGS and how the condition responds to new therapies. This case series examines weight and height growth patterns in children with Alagille syndrome and uses modern statistical approaches to develop condition-specific growth charts for these children. ImportanceDifferent degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.ObjectiveTo develop condition-specific growth charts for ALGS using modern statistical approaches.Design, Setting, and ParticipantsThis case series used data from the international, multicenter Global Alagille Alliance (GALA) study accrued between May 14, 2018, and March 20, 2023. Children born at full term between January 1, 1997, and August 31, 2019, with a clinically and/or genetically confirmed ALGS diagnosis and their native liver were included. Data from children with a known history of prematurity were excluded for the development of the growth charts. Data were analyzed from March 25, 2023, to December 30, 2024.ExposureGrowth of children with Alagille syndrome.Main Outcomes and MeasuresGeneralized additive models for location scale and shape were fitted to generate percentile plots for weight and height relative to age and superimposed on US Centers for Disease Control and Prevention (CDC) growth charts to illustrate differences in growth patterns compared with children with typical development.ResultsData from 1204 children with ALGS in overlapping cohorts (median [IQR] gestational age, 38 [37-39] weeks) were analyzed (1204 in the weight cohort; 695 boys [57.7%]; 9855 weight observations; 995 with neonatal cholestasis [82.6%]; 306 receiving a liver transplant [25.4%]; 98 deaths [8.1%] and 1106 in the height cohort, 635 boys [57.4%]; 8464 height observations; 906 with neonatal cholestasis [81.9%]; 287 receiving a liver transplant [25.9%]; 86 deaths [7.8%]) were included for the modeling of the weight-for-age and height-for-age charts, respectively. The median birth weight was 2.8 kg (IQR, 2.5-3.0 kg) for boys and 2.6 kg (IQR, 2.4-2.9 kg) for girls. The median birth length was 48.0 cm (IQR, 46.0-50.0 cm) for boys and 47.0 cm (IQR, 45.0-49.0 cm) for girls. The weight-for-age and height-for-age growth charts for boys and girls with AGLS differed significantly from CDC growth charts. The estimated height at age 18 years corresponded to the 50th percentile was 171.5 cm for boys and 156.5 cm for girls on the condition-specific charts vs 176 cm and 163 cm, respectively, on the CDC growth charts.Conclusions and RelevanceThese findings suggest that condition-specific growth charts for ALGS may provide a crucial tool for clinicians to evaluate growth and aid in decision-making around listing children for liver transplant.