Prematurity and biliary atresia: a 30-year observational study

Abstract

Aim of studyThe diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes?MethodsReview of a single-centre prospectively maintained database. Prematurity was defined as delivery < 37/40 gestation. PBA was compared with date-matched term biliary atresia controls on a 2:1 basis. Primary outcomes were clearance of jaundice (< 20 μmol/L) and native liver survival. A retrospective assessment of liver fibrosis was made on biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and term cohorts. Data are quoted as median (range) unless indicated. A P value of ≤ 0.05 was considered statistically significant.Results21 (female n = 14, 67%) premature infants with BA were treated in the period Jan. 1988–Dec. 2016 and compared with 41 contemporaneous term BA controls. Median gestation was 33 (29–36) weeks and birth weight 1930 (948–4230)g. Twin pregnancy (n = 10) was the leading cause for prematurity and significantly higher than the controls (48 vs. 0%; P < 0.0001). Maternal co-morbidity was high (n = 10, 48%) including pre-eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%) patients (all diagnostic) at a median of 57 (4–266) days. Delayed diagnosis (> 50 days) was seen in n = 13 but not associated with parenteral nutrition use (46 vs. 33%, P = 0.59) or phototherapy (50 vs. 83%, P = 0.19). Both BASM (33 vs. 7.5%; P = 0.01) and duodenal atresia (19 vs. 0%; P = 0.01) were seen more frequently in the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower in the premature group than the control group (2.71 vs. 3.53, P = 0.043) indicating less fibrosis but this equalized by time of subsequent KPE (P = 0.17). Primary surgery was Kasai portoenterostomy (n = 20) at an older median age than controls (65 vs. 56 days; P = 0.06). Liver transplantation was the primary procedure in one late-presenting child. There was an increased but non-significant clearance of jaundice in the PBA group [n = 12/20 (60%) vs 20/41 (48%); P = 0.23] post-KPE. Native liver survival and true survival were not different (P = 0.58 and 0.23).ConclusionsPBA infants have similar outcomes to term infants, despite delayed diagnosis and higher frequency of the syndromic form. The high incidence of discordant twins supports the theory that epigenetic modifications could contribute to the pathogenesis of BA.Level of evidenceIIIc Retrospective Matched Cohort Study.

Biliary Atresia: Clinical and Research Challenges for the Twenty‐First Century

“…An important debate has been whether BA arises during fetal life or only postnatally. In support of the postnatal nature of BA is the lack of reports of BA in stillborn or aborted fetuses and the limited association with prematurity, low birth weight, and poor Apgar scores; reports are conflicting on whether there are differences in the incidence of BA between premature and term newborns . In support of a prenatal etiology, instances of biliary atresia with cystic abnormalities have been recognized by second‐trimester and third‐trimester ultrasound examinations .…”

“…In support of the postnatal nature of BA is the lack of reports of BA in stillborn or aborted fetuses and the limited association with prematurity, low birth weight, and poor Apgar scores; reports are conflicting on whether there are differences in the incidence of BA between premature and term newborns. (6,7) In support of a prenatal etiology, instances of biliary atresia with cystic abnormalities have been recognized by second-trimester and third-trimester ultrasound examinations. (8) Furthermore, recent work, validated by a prospective study, reports that direct bilirubin levels were elevated in 34 of 34 BA patients at 24-72 hours, suggesting that the initial insult is prenatal and that direct bilirubin might be a means of screening for and identifying BA shortly after birth.…”

A case report of a challenging diagnosis of biliary atresia in a patient receiving total parenteral nutrition

“…A second question that emerges is when and how to evaluate patients with long-term TPN requirements for biliary atresia, which was especially challenging in our patient. Finally, it remains unclear from the literature whether the timeline for premature infants should include their corrected or chronological age [7].…”

“…PNAC is a diagnosis of exclusion and difficult to differentiate from BA on liver biopsy. Finally, the natural history of BA in premature infants (gestational age < 37 weeks) remains unclear, even though premature infants are often diagnosed at an older age than non-premature infants [7]. We present here a case of BA in a premature infant receiving TPN and the associated challenges in making the diagnosis and highlight the need for clinical judgement as well as new diagnostic testing tools.…”

Cholestatic jaundice in neonates: How common is biliary atresia? Experience at an Australian tertiary centre

“…Recent studies in BA in preterm have tended to highlight the importance of expedient and thorough investigations to avoid diagnostic delay; however, they do not adequately highlight the need of a more conservative approach to the vulnerable NICU neonates. 23,24 Based on our preliminary findings, we proposed an algorithm for the investigation of neonatal cholestasis in preterm neonate in the NICU setting with cholestatic jaundice with prolonged TPN exposure (Fig. 2).…”