Condition-Specific Growth Charts for Children With Alagille Syndrome

Koen Huysentruyt; Shannon M Vandriel; Mathieu Roelants; David A Piccoli; Kathleen M Loomes; Elizabeth B Rand; Noelle H Ebel; Jeffrey A Feinstein; Irena Jankowska; Piotr Czubkowski; Dorota Gliwicz-Miedzinska; Emmanuel M Gonzales; Emmanuel Jacquemin; Jérôme Bouligand; Saul J Karpen; Rene Romero; Henry C Lin; Björn Fischler; Henrik Arnell; Li-Ting Li; Jian-She Wang; Rima Fawaz; Silvia Nastasio; Kyung Mo Kim; Seak Hee Oh; Lorenzo D'Antiga; Emanuele Nicastro; Ryan T Fischer; Susan M Siew; Michael Stormon; Chatmanee Lertudomphonwanit; Winita Hardikar; Sahana Shankar; James E Squires; Shikha S Sundaram; Catherine Larson-Nath; Deirdre A Kelly; Jane Hartley; Pinar Bulut; M Kyle Jensen; Catalina Jaramillo; Amin J Roberts; Helen M Evans; Étienne M Sokal; Tanguy Demaret; Henkjan J Verkade; Richard J Thompson; Bettina E Hansen; Tim J Cole; Victorien M Wolters

doi:10.1001/jamanetworkopen.2025.45294

Condition-Specific Growth Charts for Children With Alagille Syndrome

Koen Huysentruyt
, Shannon M Vandriel
, Mathieu Roelants
, David A Piccoli
, Kathleen M Loomes
, Elizabeth B Rand
, Noelle H Ebel
, Jeffrey A Feinstein
, Irena Jankowska
, Piotr Czubkowski
, Dorota Gliwicz-Miedzinska
, Emmanuel M Gonzales
, Emmanuel Jacquemin
, Jérôme Bouligand
, Saul J Karpen
, Rene Romero
, Henry C Lin
, Björn Fischler
, Henrik Arnell
, Li-Ting Li

Jian-She Wang, Rima Fawaz, Silvia Nastasio, Kyung Mo Kim, Seak Hee Oh, Lorenzo D'Antiga, Emanuele Nicastro, Ryan T Fischer, Susan M Siew, Michael Stormon, Chatmanee Lertudomphonwanit, Winita Hardikar, Sahana Shankar, James E Squires, Shikha S Sundaram, Catherine Larson-Nath, Deirdre A Kelly, Jane Hartley, Pinar Bulut, M Kyle Jensen, Catalina Jaramillo, Amin J Roberts, Helen M Evans, Étienne M Sokal, Tanguy Demaret, Henkjan J Verkade, Richard J Thompson, Bettina E Hansen, Tim J Cole, Victorien M Wolters,

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.

OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches.

DESIGN, SETTING, AND PARTICIPANTS: This 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.

EXPOSURE: Growth of children with Alagille syndrome.

MAIN OUTCOMES AND MEASURES: Generalized 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.

RESULTS: Data 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 RELEVANCE: These 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.

Original language	English
Article number	e2545294
Journal	JAMA network open
Volume	8
Issue number	11
DOIs	https://doi.org/10.1001/jamanetworkopen.2025.45294
Publication status	Published - 3 Nov 2025

Keywords

Alagille Syndrome/physiopathology
Body Height
Body Weight
Child
Child, Preschool
Female
Growth Charts
Humans
Infant
Infant, Newborn
Male

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Huysentruyt, K., Vandriel, S. M., Roelants, M., Piccoli, D. A., Loomes, K. M., Rand, E. B., Ebel, N. H., Feinstein, J. A., Jankowska, I., Czubkowski, P., Gliwicz-Miedzinska, D., Gonzales, E. M., Jacquemin, E., Bouligand, J., Karpen, S. J., Romero, R., Lin, H. C., Fischler, B., Arnell, H. (2025). Condition-Specific Growth Charts for Children With Alagille Syndrome. JAMA network open, 8(11), Article e2545294. https://doi.org/10.1001/jamanetworkopen.2025.45294

@article{ae91e5a0e51747bfa95e8a89eeeefbb5,

title = "Condition-Specific Growth Charts for Children With Alagille Syndrome",

abstract = "IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches.DESIGN, SETTING, AND PARTICIPANTS: This 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.EXPOSURE: Growth of children with Alagille syndrome.MAIN OUTCOMES AND MEASURES: Generalized 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.RESULTS: Data 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 RELEVANCE: These 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.",

keywords = "Alagille Syndrome/physiopathology, Body Height, Body Weight, Child, Child, Preschool, Female, Growth Charts, Humans, Infant, Infant, Newborn, Male",

author = "Koen Huysentruyt and Vandriel, \{Shannon M\} and Mathieu Roelants and Piccoli, \{David A\} and Loomes, \{Kathleen M\} and Rand, \{Elizabeth B\} and Ebel, \{Noelle H\} and Feinstein, \{Jeffrey A\} and Irena Jankowska and Piotr Czubkowski and Dorota Gliwicz-Miedzinska and Gonzales, \{Emmanuel M\} and Emmanuel Jacquemin and J{\'e}r{\^o}me Bouligand and Karpen, \{Saul J\} and Rene Romero and Lin, \{Henry C\} and Bj{\"o}rn Fischler and Henrik Arnell and Li-Ting Li and Jian-She Wang and Rima Fawaz and Silvia Nastasio and Kim, \{Kyung Mo\} and Oh, \{Seak Hee\} and Lorenzo D'Antiga and Emanuele Nicastro and Fischer, \{Ryan T\} and Siew, \{Susan M\} and Michael Stormon and Chatmanee Lertudomphonwanit and Winita Hardikar and Sahana Shankar and Squires, \{James E\} and Sundaram, \{Shikha S\} and Catherine Larson-Nath and Kelly, \{Deirdre A\} and Jane Hartley and Pinar Bulut and Jensen, \{M Kyle\} and Catalina Jaramillo and Roberts, \{Amin J\} and Evans, \{Helen M\} and Sokal, \{{\'E}tienne M\} and Tanguy Demaret and Verkade, \{Henkjan J\} and Thompson, \{Richard J\} and Hansen, \{Bettina E\} and Cole, \{Tim J\} and Wolters, \{Victorien M\}",

note = "Publisher Copyright: {\textcopyright} 2025 Huysentruyt K et al.",

year = "2025",

month = nov,

day = "3",

doi = "10.1001/jamanetworkopen.2025.45294",

language = "English",

volume = "8",

journal = "JAMA network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "11",

}

Huysentruyt, K, Vandriel, SM, Roelants, M, Piccoli, DA, Loomes, KM, Rand, EB, Ebel, NH, Feinstein, JA, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, EM, Jacquemin, E, Bouligand, J, Karpen, SJ, Romero, R, Lin, HC, Fischler, B, Arnell, H, Li, L-T, Wang, J-S, Fawaz, R, Nastasio, S, Kim, KM, Oh, SH, D'Antiga, L, Nicastro, E, Fischer, RT, Siew, SM, Stormon, M, Lertudomphonwanit, C, Hardikar, W, Shankar, S, Squires, JE, Sundaram, SS, Larson-Nath, C, Kelly, DA, Hartley, J, Bulut, P, Jensen, MK, Jaramillo, C, Roberts, AJ, Evans, HM, Sokal, ÉM, Demaret, T, Verkade, HJ, Thompson, RJ, Hansen, BE, Cole, TJ, Wolters, VM 2025, 'Condition-Specific Growth Charts for Children With Alagille Syndrome', JAMA network open, vol. 8, no. 11, e2545294. https://doi.org/10.1001/jamanetworkopen.2025.45294

TY - JOUR

T1 - Condition-Specific Growth Charts for Children With Alagille Syndrome

AU - Huysentruyt, Koen

AU - Vandriel, Shannon M

AU - Roelants, Mathieu

AU - Piccoli, David A

AU - Loomes, Kathleen M

AU - Rand, Elizabeth B

AU - Ebel, Noelle H

AU - Feinstein, Jeffrey A

AU - Jankowska, Irena

AU - Czubkowski, Piotr

AU - Gliwicz-Miedzinska, Dorota

AU - Gonzales, Emmanuel M

AU - Jacquemin, Emmanuel

AU - Bouligand, Jérôme

AU - Karpen, Saul J

AU - Romero, Rene

AU - Lin, Henry C

AU - Fischler, Björn

AU - Arnell, Henrik

AU - Li, Li-Ting

AU - Wang, Jian-She

AU - Fawaz, Rima

AU - Nastasio, Silvia

AU - Kim, Kyung Mo

AU - Oh, Seak Hee

AU - D'Antiga, Lorenzo

AU - Nicastro, Emanuele

AU - Fischer, Ryan T

AU - Siew, Susan M

AU - Stormon, Michael

AU - Lertudomphonwanit, Chatmanee

AU - Hardikar, Winita

AU - Shankar, Sahana

AU - Squires, James E

AU - Sundaram, Shikha S

AU - Larson-Nath, Catherine

AU - Kelly, Deirdre A

AU - Hartley, Jane

AU - Bulut, Pinar

AU - Jensen, M Kyle

AU - Jaramillo, Catalina

AU - Roberts, Amin J

AU - Evans, Helen M

AU - Sokal, Étienne M

AU - Demaret, Tanguy

AU - Verkade, Henkjan J

AU - Thompson, Richard J

AU - Hansen, Bettina E

AU - Cole, Tim J

AU - Wolters, Victorien M

PY - 2025/11/3

Y1 - 2025/11/3

N2 - IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches.DESIGN, SETTING, AND PARTICIPANTS: This 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.EXPOSURE: Growth of children with Alagille syndrome.MAIN OUTCOMES AND MEASURES: Generalized 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.RESULTS: Data 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 RELEVANCE: These 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.

AB - IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches.DESIGN, SETTING, AND PARTICIPANTS: This 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.EXPOSURE: Growth of children with Alagille syndrome.MAIN OUTCOMES AND MEASURES: Generalized 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.RESULTS: Data 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 RELEVANCE: These 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.

KW - Alagille Syndrome/physiopathology

KW - Body Height

KW - Body Weight

KW - Child

KW - Child, Preschool

KW - Female

KW - Growth Charts

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

U2 - 10.1001/jamanetworkopen.2025.45294

DO - 10.1001/jamanetworkopen.2025.45294

M3 - Article

C2 - 41284294

SN - 2574-3805

VL - 8

JO - JAMA network open

JF - JAMA network open

IS - 11

M1 - e2545294

ER -

Condition-Specific Growth Charts for Children With Alagille Syndrome

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Keywords

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