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Familial clustering of intrahepatic cholestasis of pregnancy: A nationwide population-based study in Denmark

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Jiong Li
  • Jiawen Chen, Shanghai Jiao Tong University
  • ,
  • Priscilla Ming Yi Lee
  • Jun Zhang, Shanghai Jiao Tong University
  • ,
  • Fei Li, Shanghai Jiao Tong University
  • ,
  • Tai Ren, Shanghai Jiao Tong University, Department of Developmental and Behavioural Paediatric & Child Primary Care

Background and Aims: Genetics plays a role in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP); however, empirical evidence on familial clustering of ICP is scarce. We aimed to assess the extent of familial recurrence of ICP. Approach and Results: This population-based cohort study included all 668,461 primiparous women who gave birth between 1995 and 2018 in Denmark. Women diagnosed with ICP were included to the index cohort. Kinship with index women was determined with the Danish Civil Registration System. Log-binomial regression was used to calculate the relative recurrence risk (RRR) of ICP in relatives of index women. A total of 6722 (1.0%) primiparous women were diagnosed with ICP. In co-twins (n=57), first-degree (n=2279), second-degree (n=1373), and third-degree (n=1758) relatives of the index women, the incidence of ICP reached 5.3%, 2.6%, 0.7%, and 1.4%, respectively, corresponding to adjusted RRRs of 4.82 (95% CI, 1.60-14.48), 2.54 (1.98-3.26), 0.81 (0.44-1.51), and 1.15 (0.77-1.71), respectively. The first-degree relatives of women who had recurrent ICP or first-trimester ICP seemed to be at higher risks [RRR, 4.30 (2.85-6.48), 3.04 (1.93-4.77), respectively]. A minor increased risk was observed in nonbiological relatives [RRR, 1.35 (1.05-1.73); n=4274, including women's full-brothers' partner and women's husbands' full sisters]. Conclusions: Co-twins and first-degree relatives of ICP patients were at 5- and 2.5-fold increased risk of ICP, respectively. No increased risk was observed in second-degree and third-degree relatives. Recurrent ICP and first-trimester ICP might indicate a higher degree of family clustering. Further investigation is needed to investigate the increased risk of ICP in nonbiological relatives.

Sider (fra-til)389-396
Antal sider8
StatusUdgivet - aug. 2023

Bibliografisk note

Funding Information:
This study was supported by grants from the Danish Council for Independent Research (DFF-6110-00019B, DFF-9039-00010B, and DFF-1030-00012B), the Nordic Cancer Union (R275-A15770, R278-A15877, and R279-A15931), the Karen Elise Jensens Fond (2016), Novo Nordisk Fonden (NNF18OC0052029), and the National Nature Science Foundation of China (82073570, 82103716, and 82204048). The funders had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Publisher Copyright:
© 2023 John Wiley and Sons Inc.. All rights reserved.

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