Skip to main content

Advertisement

Log in

Maternal hepatitis B infection status and adverse pregnancy outcomes: a retrospective cohort analysis

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the association between maternal HBsAg-positive status and pregnancy outcomes.

Methods

The study enrolled women with singleton pregnancies who delivered during January–December 2018. Data of maternal demographics and main adverse pregnancy outcomes were collected from the institutional medical records and analyzed by univariate and multivariate logistic regression models to determine the association between maternal HBV markers (HBsAg/HBeAg/HBV-DNA loads status) and adverse pregnancy outcomes.

Results

Total 1146 HBsAg-positive and 18,354 HBsAg-negative pregnant women were included. After adjusting for potential confounding variables, maternal HBsAg-positive status was associated with a high risk of gestational diabetes mellitus (GDM) [adjusted odds ratio (aOR) = 1.24; 95% confidence interval (CI) 1.07–1.43], intrahepatic cholestasis of pregnancy (ICP) (aOR = 3.83; 95% CI 3.14–4.68), preterm birth (aOR = 1.42; 95% CI 1.17–1.72), and neonatal asphyxia (aOR = 2.20; 95% CI 1.34–3.63). Further, higher risks of ICP and neonatal asphyxia remained with either HBeAg-positive status (aOR = 1.64; 95% CI 1.10–2.44; aOR = 3.08; 95% CI 1.17–8.00) or high HBV-DNA load during the second trimester (aOR = 1.52; 95% CI 1.06–2.35; aOR = 4.20; 95% CI 4.20–15.83) among HBsAg-positive pregnant women.

Conclusion

Women with maternal HBsAg-positive status may have increased risks of GDM, ICP, preterm birth, and neonatal asphyxia; furthermore, the risks of ICP and neonatal asphyxia were higher in women with HBeAg-positive status and a high HBV-DNA load during the second trimester among the HBsAg-positive pregnant women, implying that careful surveillance for chronic HBV infection during pregnancy is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Listed NA (2017) New hepatitis data highlight need for urgent global response. Saudi Med J 38(6):672–675

    Google Scholar 

  2. Ott JJ, Stevens GA, Groeger J, Wiersma ST (2012) Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 30(12):2212–2219. https://doi.org/10.1016/j.vaccine.2011.12.116

    Article  CAS  PubMed  Google Scholar 

  3. Borchardt SM, Kocharian A, Hopfensperger D, Davis JP (2016) Prevention of perinatal transmission of hepatitis B virus: assessment among wisconsin maternity hospitals. WMJ 115(2):74–79

    PubMed  Google Scholar 

  4. Xiao B, Liu A, Zhang M, Xue H, Zhu Y (2019) Observation of the effect of the pregnancy complicated with the hepatitis B infection on the lying-in women and neonates. Saudi J Biol Sci 26(8):1978–1981

    Article  Google Scholar 

  5. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y (2009) Epidemiological serosurvey of hepatitis B in China–declining HBV prevalence due to hepatitis B vaccination. Vaccine 27(47):6550–6557. https://doi.org/10.1016/j.vaccine.2009.08.048

    Article  Google Scholar 

  6. Tse KY, Ho LF, Lao T (2005) The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study. J Hepatol 43(5):771–775. https://doi.org/10.1016/j.jhep.2005.05.023

    Article  CAS  PubMed  Google Scholar 

  7. Reddick KL, Jhaveri R, Gandhi M, James AH, Swamy GK (2011) Pregnancy outcomes associated with viral hepatitis. J Viral Hepatitis 18(7):e394–398. https://doi.org/10.1111/j.1365-2893.2011.01436.x

    Article  CAS  Google Scholar 

  8. Lao TT, Chan BC, Leung WC, Ho LF, Tse KY (2007) Maternal hepatitis B infection and gestational diabetes mellitus. J Hepatol 47(1):46–50. https://doi.org/10.1016/j.jhep.2007.02.014

    Article  CAS  PubMed  Google Scholar 

  9. Safir A, Levy A, Sikuler E, Sheiner E (2010) Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome. Liver Int 30(5):765–770. https://doi.org/10.1111/j.1478-3231.2010.02218.x

    Article  PubMed  Google Scholar 

  10. Abu Freha N, Wainstock T, Poupko L, Yonat Shemer A, Sergienko R, Sheiner E (2020) Maternal hepatitis B or hepatitis C virus carrier status and long-term infectious morbidity of the offspring: a population-based cohort study. J Viral Hepatitis. https://doi.org/10.1111/jvh.13300

    Article  Google Scholar 

  11. A N, W T, M TN, S E (2020) Maternal hepatitis B virus or hepatitis C virus carrier status and long-term endocrine morbidity of the offspring-a population-based cohort study. J Clin Med. https://doi.org/10.3390/jcm9030796

    Article  Google Scholar 

  12. Y G-Y, T W, N A-F, E S (2019) Maternal hepatitis B virus and hepatitis C virus carrier status during pregnancy and long-term respiratory complications in the offspring. Early Hum Dev 140:104904. https://doi.org/10.1016/j.earlhumdev.2019.104904

    Article  Google Scholar 

  13. I Y, E S, N A-F, T W (2019) Maternal hepatitis B or C status and the long-term risk of gastrointestinal morbidity for offspring: a population-based cohort study. Liver Int 39(11):2046–2051. https://doi.org/10.1111/liv.14193

    Article  CAS  Google Scholar 

  14. Fan L, Owusu-Edusei K Jr, Schillie SF, Murphy TV (2016) Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection. Hepatology (Baltimore, MD) 63(5):1471–1480. https://doi.org/10.1002/hep.28310

    Article  Google Scholar 

  15. Xu YY, Liu HH, Zhong YW, Liu C, Wang Y, Jia LL, Qiao F, Li XX, Zhang CF, Li SL, Li P, Song HB, Li Q (2015) Peripheral blood mononuclear cell traffic plays a crucial role in mother-to-infant transmission of hepatitis B virus. Int J Biol Sci 11(3):266–273. https://doi.org/10.7150/ijbs.10813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wan Z, Zhou A, Zhu H, Lin X, Hu D, Peng S, Zhang B, Du Y (2018) Maternal Hepatitis B virus infection and pregnancy outcomes. J Clin Gastroenterol 52(1):73–78

    Article  Google Scholar 

  17. To WW, Cheung W, Mok KM (2003) Hepatitis B surface antigen carrier status and its correlation to maternal hypertension. Aust N Z J Obstet Gynaecol 43(2):119–122

    Article  Google Scholar 

  18. Stokkeland K, Ludvigsson JF, Hultcrantz R, Ekbom A, Höijer J, Bottai M, Stephansson O (2017) Pregnancy outcome in more than 5000 births to women with viral hepatitis: a population-based cohort study in Sweden. Eur J Epidemiol 32(7):617–625

    Article  Google Scholar 

  19. Cui A-M, Shao J-G, Li H-B, Shen Y, Chen Z-X, Zhang S, Bian Z-L, Qin G, Cheng X-Y (2017) Association of chronic hepatitis B virus infection with preterm birth: our experience and meta-analysis. J Perinat Med 45(8):933–940

    Article  CAS  Google Scholar 

  20. Kong D, Liu H, Wei S, Wang Y, Hu A, Han W, Zhao N, Lu Y, Zheng Y (2014) A meta-analysis of the association between gestational diabetes mellitus and chronic hepatitis B infection during pregnancy. BMC Res Notes 7:139. https://doi.org/10.1186/1756-0500-7-139

    Article  PubMed  PubMed Central  Google Scholar 

  21. Peng S, Wan Z, Lin X, Li X, Du Y (2019) Maternal hepatitis B surface antigen carrier status increased the incidence of gestational diabetes mellitus. BMC Infect Dis 19(1):147. https://doi.org/10.1186/s12879-019-3749-1

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tan J, Liu X, Mao X, Yu J, Chen M, Li Y, Sun X (2016) HBsAg positivity during pregnancy and adverse maternal outcomes: a retrospective cohort analysis. J Viral Hepatitis 23(10):812–819. https://doi.org/10.1111/jvh.12545

    Article  CAS  Google Scholar 

  23. Huang X, Tan H, Li X, Zhou S, Wen SW, Luo M (2014) Maternal chronic HBV infection would not increase the risk of pregnancy-induced hypertension–results from pregnancy cohort in Liuyang rural China. PLoS ONE 9(12):e114248. https://doi.org/10.1371/journal.pone.0114248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cai Q, Liu H, Han W, Liu L, Xu Y, He Y, Li Q, Zhang M, Hu A, Zheng Y (2019) Maternal HBsAg carriers and adverse pregnancy outcomes: A hospital-based prospective cohort analysis. J Viral Hepatitis 26(8):1011–1018. https://doi.org/10.1111/jvh.13105

    Article  CAS  Google Scholar 

  25. Lumley J (2003) Defining the problem: the epidemiology of preterm birth. BJOG 110(Suppl 20):3–7

    Article  Google Scholar 

  26. Cui AM, Cheng XY, Shao JG, Li HB, Wang XL, Shen Y, Mao LJ, Zhang S, Liu HY, Zhang L, Qin G (2016) Maternal hepatitis B virus carrier status and pregnancy outcomes: a prospective cohort study. BMC Pregnancy Childbirth 16:87. https://doi.org/10.1186/s12884-016-0884-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Smith DD, Rood KM (2020) Intrahepatic cholestasis of pregnancy. Clin Obstet Gynecol 63(1):134–151

    Article  Google Scholar 

  28. Rook M, Vargas J, Caughey A, Bacchetti P, Rosenthal P, Bull L (2012) Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort. PLoS ONE 7(3):e28343. https://doi.org/10.1371/journal.pone.0028343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Medina Lomelí JM, Jáuregui Meléndrez RA, Medina Castro N, Medina Castro D (2012) Intrahepatic cholestasis of pregnancy: review. Ginecol Obstet Mex 80(4):285–294

    PubMed  Google Scholar 

  30. Larson SP, Kovilam O, Agrawal DK (2016) Immunological basis in the pathogenesis of intrahepatic cholestasis of pregnancy. Exp Rev Clin Immunol 12(1):39–48. https://doi.org/10.1586/1744666x.2016.1101344

    Article  CAS  Google Scholar 

  31. Luo L, Wu J, Qu Y, Li J, Pan L, Li D, Wang H, Mu D (2015) Association between maternal HBsAg carrier status and neonatal adverse outcomes: meta-analysis. J Mater-Fetal Neonatal Med 28(11):1308–1317. https://doi.org/10.3109/14767058.2014.953475

    Article  Google Scholar 

  32. Wong S, Chan LY, Yu V, Ho L (1999) Hepatitis B carrier and perinatal outcome in singleton pregnancy. Am J Perinatol 16(9):485–488. https://doi.org/10.1055/s-1999-6802

    Article  CAS  PubMed  Google Scholar 

  33. Bai H, Zhang L, Ma L, Dou XG, Feng GH, Zhao GZ (2007) Relationship of hepatitis B virus infection of placental barrier and hepatitis B virus intra-uterine transmission mechanism. World J Gastroenterol 13(26):3625–3630. https://doi.org/10.3748/wjg.v13.i26.3625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Janičko M, Veselíny E, Leško D, Jarčuška P (2013) Serum cholesterol is a significant and independent mortality predictor in liver cirrhosis patients. Ann Hepatol 12(4):581–587

    Article  Google Scholar 

  35. Hu Y, Ding YL, Yu L (2014) The impact of intrahepatic cholestasis of pregnancy with hepatitis B virus infection on perinatal outcomes. Ther Clin Risk Manag 10:381–385. https://doi.org/10.2147/tcrm.s61530

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wood AM, Livingston EG, Hughes BL, Kuller JA (2018) Intrahepatic cholestasis of pregnancy: a review of diagnosis and management. Obstet Gynecol Surv 73(2):103–109. https://doi.org/10.1097/ogx.0000000000000524

    Article  PubMed  Google Scholar 

  37. Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM (2002) TNF-alpha is a predictor of insulin resistance in human pregnancy. Diabetes 51(7):2207–2213. https://doi.org/10.2337/diabetes.51.7.2207

    Article  CAS  PubMed  Google Scholar 

  38. Sheron N, Lau J, Daniels H, Goka J, Eddleston A, Alexander GJ, Williams R (1991) Increased production of tumour necrosis factor alpha in chronic hepatitis B virus infection. J Hepatol 12(2):241–245. https://doi.org/10.1016/0168-8278(91)90945-8

    Article  CAS  PubMed  Google Scholar 

  39. Fernández-Real JM, Ricart-Engel W, Arroyo E, Balançá R, Casamitjana-Abella R, Cabrero D, Fernández-Castañer M, Soler J (1998) Serum ferritin as a component of the insulin resistance syndrome. Diabetes Care 21(1):62–68. https://doi.org/10.2337/diacare.21.1.62

    Article  PubMed  Google Scholar 

  40. Gomes CP, Torloni MR, Gueuvoghlanian-Silva BY, Alexandre SM, Mattar R, Daher S (2013) Cytokine levels in gestational diabetes mellitus: a systematic review of the literature. Am J Reprod Immunol 69(6):545–557. https://doi.org/10.1111/aji.12088

    Article  CAS  PubMed  Google Scholar 

  41. Lao TT, Sahota DS, Suen SS, Law LW, Leung TY (2012) Maternal HBsAg status and infant size—a Faustian bargain? J Viral Hepatitis 19(7):519–524. https://doi.org/10.1111/j.1365-2893.2011.01575.x

    Article  CAS  Google Scholar 

  42. Hedderson M, Ehrlich S, Sridhar S, Darbinian J, Moore S, Ferrara A (2012) Racial/ethnic disparities in the prevalence of gestational diabetes mellitus by BMI. Diabetes Care 35(7):1492–1498. https://doi.org/10.2337/dc11-2267

    Article  PubMed  PubMed Central  Google Scholar 

  43. Strong C, Lee S, Tanaka M, Juon HS (2012) Ethnic differences in prevalence and barriers of HBV screening and vaccination among Asian Americans. J Community Health 37(5):1071–1080. https://doi.org/10.1007/s10900-012-9541-4

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work has been funded by Zhejiang Medical Health Science and Technology Project (No. 2017203230).

Author information

Authors and Affiliations

Authors

Contributions

KW: literature review, investigation, data collection and analysis, and writing (original draft). HW: literature review, investigation, data collection and analysis, writing (review/edits), and funding acquisition. SL: literature review, investigation, data collection, and writing (review/edits). HZ: literature review, investigation, data collection, and writing (review/edits). BZ: conceptualization, investigation, data collection and analysis, funding acquisition, supervision, validation, and writing (review/edits).

Corresponding author

Correspondence to Bo Zhu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Medical Ethics Committee of Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China (Approval number: IRB-20200063-R).

Informed consent

Not applicable for this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, K., Wang, H., Li, S. et al. Maternal hepatitis B infection status and adverse pregnancy outcomes: a retrospective cohort analysis. Arch Gynecol Obstet 302, 595–602 (2020). https://doi.org/10.1007/s00404-020-05630-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05630-2

Keywords

Navigation