Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study

Childhood Liver Disease Research Network (ChiLDReN)

doi:10.1016/j.jpeds.2017.12.048

Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study

Childhood Liver Disease Research Network (ChiLDReN)

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

41 Scopus citations

Abstract

Objectives: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. Study design: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ ² analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. Results: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P =.01) and low length z-scores at time of testing (OR, 0.70; P <.04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P =.001) and ascites (OR, 2.89; P =.01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P <.02) and mental/cognitive/language impairment (OR, 4.76; P =.02) at 2 years of age. Conclusion: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. Trial registration: Clinicaltrials.gov: NCT00061828 and NCT00294684.

Original language	English (US)
Pages (from-to)	139-147.e3
Journal	journal of pediatrics
Volume	196
DOIs	https://doi.org/10.1016/j.jpeds.2017.12.048
State	Published - May 2018

Funding

Supported by U01 grants from the National Institute of Diabetes and Digestive and Kidney Diseases ( DK 62445 [Mount Sinai School of Medicine], DK 62497 [Cincinnati Children's Hospital Medical Center], DK 62470 [Children's Healthcare of Atlanta], DK 62481 [The Children's Hospital of Philadelphia], DK 62456 [The University of Michigan], DK 84536 [Riley Hospital for Children], DK 84575 [Seattle Children's Hospital], DK 62500 [UCSF Children's Hospital], DK 62503 [Johns Hopkins School of Medicine], DK 62466 [Children's Hospital of Pittsburgh of UPMC], DK 62453 [Children's Hospital Colorado], DK 62452 [Washington University School of Medicine], DK 84538 [Children's Hospital Los Angeles], DK 62436 [Ann & Robert H Lurie Children's Hospital of Chicago], DK103149 [Texas Children's Hospital], DK103135 [The Hospital for Sick Children], DK103140 [University of Utah]), and by CTSA grants from the National Center for Advancing Translational Sciences : UL1TR000003 [The Children's Hospital of Philadelphia, Philadelphia, PA], UL1TR000077 [Cincinnati Children's Hospital Medical Center, Cincinnati, OH], UL1TR000130 [Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA], UL1TR000067 [Mount Sinai School of Medicine, New York, NY], U01DK062500 and UL1TR000004 [UCSF Benioff Children's Hospital, University of California, San Francisco, CA], UL 1TR000424 [Johns Hopkins School of Medicine, Baltimore, MD], UL1TR000005 [Children's Hospital Pittsburgh of UPMC, Pittsburgh, PA], UL1TR000448 [Washington University, St. Louis, MO], UL1TR000150 [Ann and Robert H. Lurie Children's Hospital and Northwestern University, Chicago, IL], and T32DK67009 , UL1TR001082 [University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO]. K.M. holds stock in Merck and received research support from Gilead, Merck, and Shire. B.H. holds stock in Merck and is employed by Merck. V.N. is a consultant for Albireo. B.S. is a consultant for Bristol Myers Squibb. P.R. is a consultant for Gilead, Abbvie, Intercept, Alexion, Retrophin, Albireo, Audentes, is on the speaker's bureau of Retrophin, and receives research support from Gilead, Abbvie, Bristol Myers Squibb, Roche/Genetech. K.S. is a consultant for Gilead, Roche, and Up to Date and receives research support from Gilead, Roche, BMS, Genentech, and NIDDK. R.S. is a consultant for Retrophin, Albireo, Shire, Alexion and receives research support from Shire. S.K. is a consultant for Regulus, Retrophin, Albireo, and Intercept. J.M. serves on the advisory board for Eli Lilly Co and receives research support from Abbie, Gillead, Shire, CF Foundation. J.B. receives research support from Gilead. The other authors declare no conflicts of interest. Supported by U01 grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK 62445 [Mount Sinai School of Medicine], DK 62497 [Cincinnati Children's Hospital Medical Center], DK 62470 [Children's Healthcare of Atlanta], DK 62481 [The Children's Hospital of Philadelphia], DK 62456 [The University of Michigan], DK 84536 [Riley Hospital for Children], DK 84575 [Seattle Children's Hospital], DK 62500 [UCSF Children's Hospital], DK 62503 [Johns Hopkins School of Medicine], DK 62466 [Children's Hospital of Pittsburgh of UPMC], DK 62453 [Children's Hospital Colorado], DK 62452 [Washington University School of Medicine], DK 84538 [Children's Hospital Los Angeles], DK 62436 [Ann & Robert H Lurie Children's Hospital of Chicago], DK103149 [Texas Children's Hospital], DK103135 [The Hospital for Sick Children], DK103140 [University of Utah]), and by CTSA grants from the National Center for Advancing Translational Sciences: UL1TR000003 [The Children's Hospital of Philadelphia, Philadelphia, PA], UL1TR000077 [Cincinnati Children's Hospital Medical Center, Cincinnati, OH], UL1TR000130 [Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA], UL1TR000067 [Mount Sinai School of Medicine, New York, NY], U01DK062500 and UL1TR000004 [UCSF Benioff Children's Hospital, University of California, San Francisco, CA], UL 1TR000424 [Johns Hopkins School of Medicine, Baltimore, MD], UL1TR000005 [Children's Hospital Pittsburgh of UPMC, Pittsburgh, PA], UL1TR000448 [Washington University, St. Louis, MO], UL1TR000150 [Ann and Robert H. Lurie Children's Hospital and Northwestern University, Chicago, IL], and T32DK67009, UL1TR001082 [University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO]. K.M. holds stock in Merck and received research support from Gilead, Merck, and Shire. B.H. holds stock in Merck and is employed by Merck. V.N. is a consultant for Albireo. B.S. is a consultant for Bristol Myers Squibb. P.R. is a consultant for Gilead, Abbvie, Intercept, Alexion, Retrophin, Albireo, Audentes, is on the speaker's bureau of Retrophin, and receives research support from Gilead, Abbvie, Bristol Myers Squibb, Roche/Genetech. K.S. is a consultant for Gilead, Roche, and Up to Date and receives research support from Gilead, Roche, BMS, Genentech, and NIDDK. R.S. is a consultant for Retrophin, Albireo, Shire, Alexion and receives research support from Shire. S.K. is a consultant for Regulus, Retrophin, Albireo, and Intercept. J.M. serves on the advisory board for Eli Lilly Co and receives research support from Abbie, Gillead, Shire, CF Foundation. J.B. receives research support from Gilead. The other authors declare no conflicts of interest.

Keywords

Kasai
chronic liver disease
cognitive
motor

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health

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10.1016/j.jpeds.2017.12.048

Cite this

@article{4ea5a3da62b749bc830e077da040427c,

title = "Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study",

abstract = " Objectives: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. Study design: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ 2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. Results: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P =.01) and low length z-scores at time of testing (OR, 0.70; P <.04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P =.001) and ascites (OR, 2.89; P =.01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P <.02) and mental/cognitive/language impairment (OR, 4.76; P =.02) at 2 years of age. Conclusion: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. Trial registration: Clinicaltrials.gov: NCT00061828 and NCT00294684.",

keywords = "Kasai, chronic liver disease, cognitive, motor",

author = "{Childhood Liver Disease Research Network (ChiLDReN)} and Ng, {Vicky L.} and Sorensen, {Lisa G.} and Alonso, {Estella M.} and Fredericks, {Emily M.} and Wen Ye and Jeff Moore and Karpen, {Saul J.} and Shneider, {Benjamin L.} and Molleston, {Jean P.} and Bezerra, {Jorge A.} and Murray, {Karen F.} and Loomes, {Kathleen M.} and Philip Rosenthal and Squires, {Robert H.} and Kasper Wang and Ronen Arnon and Schwarz, {Kathleen B.} and Turmelle, {Yumirle P.} and Haber, {Barbara H.} and Sherker, {Averell H.} and Magee, {John C.} and Sokol, {Ronald J.} and Hertel, {Paula M.} and Sanjiv Harpavat and Brandt, {Mary L.} and Leung, {Daniel H.} and Wikrom Karnsakul and Rebecca Torrance and Sherry Hall and Edward Doo and Hoofnagle, {Jay H.} and Peter Whitington and Lee Bass and Miethke, {Alexander G.} and Heubi, {James E.} and Kenneth Setchell and Bove, {Kevin E.} and Greg Tiao and Mack, {Cara L.} and Narkewicz, {Michael R.} and Feldman, {Amy G.} and Sundaram, {Shikha S.} and Suchy, {Frederick J.} and Karrer, {Frederick M.} and Mark Lovell and {Van Hove}, {Johan L.} and Rand, {Elizabeth B.} and Squires, {James E.} and Venkat, {Veena L.} and Rakesh Sindhi",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = may,

doi = "10.1016/j.jpeds.2017.12.048",

language = "English (US)",

volume = "196",

pages = "139--147.e3",

journal = "journal of pediatrics",

issn = "0022-3476",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver

T2 - Results from the ChiLDReN Study

AU - Childhood Liver Disease Research Network (ChiLDReN)

AU - Ng, Vicky L.

AU - Sorensen, Lisa G.

AU - Alonso, Estella M.

AU - Fredericks, Emily M.

AU - Ye, Wen

AU - Moore, Jeff

AU - Karpen, Saul J.

AU - Shneider, Benjamin L.

AU - Molleston, Jean P.

AU - Bezerra, Jorge A.

AU - Murray, Karen F.

AU - Loomes, Kathleen M.

AU - Rosenthal, Philip

AU - Squires, Robert H.

AU - Wang, Kasper

AU - Arnon, Ronen

AU - Schwarz, Kathleen B.

AU - Turmelle, Yumirle P.

AU - Haber, Barbara H.

AU - Sherker, Averell H.

AU - Magee, John C.

AU - Sokol, Ronald J.

AU - Hertel, Paula M.

AU - Harpavat, Sanjiv

AU - Brandt, Mary L.

AU - Leung, Daniel H.

AU - Karnsakul, Wikrom

AU - Torrance, Rebecca

AU - Hall, Sherry

AU - Doo, Edward

AU - Hoofnagle, Jay H.

AU - Whitington, Peter

AU - Bass, Lee

AU - Miethke, Alexander G.

AU - Heubi, James E.

AU - Setchell, Kenneth

AU - Bove, Kevin E.

AU - Tiao, Greg

AU - Mack, Cara L.

AU - Narkewicz, Michael R.

AU - Feldman, Amy G.

AU - Sundaram, Shikha S.

AU - Suchy, Frederick J.

AU - Karrer, Frederick M.

AU - Lovell, Mark

AU - Van Hove, Johan L.

AU - Rand, Elizabeth B.

AU - Squires, James E.

AU - Venkat, Veena L.

AU - Sindhi, Rakesh

PY - 2018/5

Y1 - 2018/5

N2 - Objectives: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. Study design: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ 2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. Results: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P =.01) and low length z-scores at time of testing (OR, 0.70; P <.04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P =.001) and ascites (OR, 2.89; P =.01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P <.02) and mental/cognitive/language impairment (OR, 4.76; P =.02) at 2 years of age. Conclusion: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. Trial registration: Clinicaltrials.gov: NCT00061828 and NCT00294684.

AB - Objectives: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. Study design: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ 2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. Results: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P =.01) and low length z-scores at time of testing (OR, 0.70; P <.04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P =.001) and ascites (OR, 2.89; P =.01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P <.02) and mental/cognitive/language impairment (OR, 4.76; P =.02) at 2 years of age. Conclusion: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. Trial registration: Clinicaltrials.gov: NCT00061828 and NCT00294684.

KW - Kasai

KW - chronic liver disease

KW - cognitive

KW - motor

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UR - http://www.scopus.com/inward/citedby.url?scp=85043331672&partnerID=8YFLogxK

U2 - 10.1016/j.jpeds.2017.12.048

DO - 10.1016/j.jpeds.2017.12.048

M3 - Article

C2 - 29519540

AN - SCOPUS:85043331672

SN - 0022-3476

VL - 196

SP - 139-147.e3

JO - journal of pediatrics

JF - journal of pediatrics

ER -

Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study

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