Biliary atresia : growth, bone health and neurocognitive and motor outcome in childhood and adolescence

Background: Biliary atresia (BA) is a rare cholangiopathy of infancy. Without treatment, inflammation and obstruction of the biliary tracts leads to liver cirrhosis and death within the first 2 years of life. BA is treated with portoenterostomy (PE), in which an exit for bile from the liver is created by attaching a jejunal loop to the porta hepatis. If PE fails, the next treatment option is liver transplantation (LT). Since the development of LT programs in the late 1980s, the long-term outcome for BA has improved. Patients with BA may survive until adulthood with their native livers (NL). The aims: The long-term effects of BA on the general health of patients in childhood and adolescence are not well-known. The aims of this study were to assess three aspects of BA patients’ health: growth, bone health and the neurocognitive and motor developmental outcome. Methods: To investigate the early childhood growth of BA patients, the growth data as well as the dosage of post-surgical corticosteroid treatment were evaluated for a cohort of 28 BA patients diagnosed in Finland between 1987–2017 alive with their NL. To analyze bone health, a cohort of 49 patients diagnosed between 2000–2017 who had survived at least ≥ 1 year of age was evaluated. Medical records were reviewed for histories and diagnoses of rickets and fractures and for dual-energy X-ray absorptiometry (DXA) measurements. A prospective cross-sectional cohort of 39 patients aged 1–20 years followed up at the Helsinki University Children’s Hospital during 2019 were studied to determine their neurocognitive and motor developmental outcomes. Participants in this prospective study underwent age-appropriate neurocognitive and motor test assessments. Results: BA patients were born shorter than the national reference population with a median height of −0.6 (interquartile range [IQR] −1.3 to −0.1 standard deviation scores [SDS], p<0.001). The height gain of BA patients decelerated during the first 3 months and accelerated between 3 to 6 months of age. Between 2–6 years-of-age, height gain was stable. A high (>50 mg/kg of prednisolone) cumulative corticosteroid dosage caused a 0.18 (β −0.18, SE 0.04, p<0.001) SDS lower height per treatment week compared to low dosage. Fourteen percent of BA patients were diagnosed with rickets based on radiographic findings. The majority (75%) of fractures in BA patients occurred in infancy in patients with rickets. The number of fractures in children with BA in later childhood and in adolescence did not differ from normal population. DXA measurements showed normal bone mineral content (BMC) and areal bone mineral density (aBMD) between 5 to 10 years of age in NL and LT patients. The mean total intelligent quotient (IQ) of BA patients was 91 (SD ±15), lower than in the normal population (100±15, p<0.01). Out of 30 patients tested, 43.3% were either at risk or fulfilled criteria for motor impairment. Guardians reported elevated rates of functional problems affecting everyday life of BA patients in 5/8 domains assessed with a validated questionnaire. Conclusions: Post-PE corticosteroids have a measurable impact on height gain post-PE. This effect does not continue after 6 months of age. BA patients have a clearly heightened risk for metabolic bone disease in the form of rickets in infancy. BA patients with NL and LT have BMC and aBMD measurements within the normal range during later childhood. Total IQ and motor developmental outcome among BA patients are compromised and early structured evaluation to identify individuals in need of additional support could enhance everyday functionality.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2021

Author dc:creator

• Ruuska, Satu

• lääketiede

Statement dc:rights

• Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
• This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
• Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden.

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/335661

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F335661