Exploration of Medicine

From: Obstetric implications of maternal chronic hepatitis B virus infection

Table 1. Factors which could influence the likelihood of any demonstrable effect of chronic HBV infection on obstetric outcome

No.	Factors influencing obstetric effects of chronic HBV infection
1.	Endemicity in the general population, or prevalence in the study population
2.	Reason for diagnosis of maternal HBV infection, and whether HBsAg screening is a routine antenatal test
3.	Presence of antiviral treatment before and/or during pregnancy
4.	Genotype of HBV infection in the population
5.	Age of acquiring the infection and immune phase of chronic HBV infection in the majority of the pregnant women, viral activity (HBV DNA level)
6.	Presence of co-morbidities
7.	Presence of chronic inflammation and/or hepatic inflammation
8.	Presence of co-infections

Return to article view

Declarations

Author contributions

The author contributes solely to this manuscript.

Conflicts of interest

The author declares that he has no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Beasley RP, Hwang LY, Lee GC, Lan CC, Roan CH, Huang FY, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983;2:1099–102. [DOI] [PubMed]

Wong VC, Ip HM, Reesink HW, Lelie PN, Reerink-Brongers EE, Yeung CY, et al. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HbeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study. Lancet. 1984;1:921–6. [DOI] [PubMed]

Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences. Antivir Ther. 2010;15 Suppl 3:25–33. [DOI] [PubMed]

Suen SS, Lao TT, Sahota DS, Lau TK, Leung TY. Implications of the relationship between maternal age and parity with hepatitis B carrier status in a high endemicity area. J Viral Hepat. 2010;17:372–8. [DOI] [PubMed]

Lao TT, Sahota DS, Law LW, Cheng YK, Leung TY. Age-specific prevalence of hepatitis B virus infection in young pregnant women, Hong Kong Special Administrative Region of China. Bull World Health Organ. 2014;92:782–9. [DOI] [PubMed] [PMC]

Lao TT, Sahota DS. Pregnancy and maternal chronic hepatitis B infection–evidence of reproductive advantage? Am J Reprod Immunol. 2017;77:e12667. [DOI] [PubMed]

Lao TT, Tse KY, Chan LY, Tam KF, Ho LF. HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women. Diabetes Care. 2003;26:3011–6. [DOI] [PubMed]

Tse KY, Ho LF, Lao T. The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study. J Hepatol. 2005;43:771–5. [DOI] [PubMed]

Lao TT, Chan BC, Leung WC, Ho LF, Tse KY. Maternal hepatitis B infection and gestational diabetes mellitus. J Hepatol. 2007;47:46–50. [DOI] [PubMed]

10.

Lao TT, Chung MK, Cheung TK, Law LW. Antenatal hepatitis B and increased risk of gestational diabetes mellitus—implications for obstetric care. J Infect. 2016;72:625–6. [DOI] [PubMed]

11.

Connell LE, Salihu HM, Salemi JL, August EM, Weldeselasse H, Mbah AK. Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int. 2011;31:1163–70. [DOI] [PubMed]

12.

Saleh Gargari S, Hantoushzadeh S, Zendehdel N, Jamal A, Aghdam H. The association of maternal HBsAg carrier status and perinatal outcome. Hepat Mon. 2009;9:180–4.

13.

Sirilert S, Traisrisilp K, Sirivatanapa P, Tongsong T. Pregnancy outcomes among chronic carriers of hepatitis B virus. Int J Gynaecol Obstet. 2014;126:106–10. [DOI] [PubMed]

14.

Tan J, Liu X, Mao X, Yu J, Chen M, Li Y, et al. HBsAg positivity during pregnancy and adverse maternal outcomes: a retrospective cohort analysis. J Viral Hepat. 2016;23:812–9. [DOI] [PubMed]

15.

Peng S, Wan Z, Lin X, Li X, Du Y. Maternal hepatitis B surface antigen carrier status increased the incidence of gestational diabetes mellitus. BMC Infect Dis. 2019;19:147. [DOI] [PubMed] [PMC]

16.

Zhao Y, Chen YL, Song HQ, Huang PY, Wang LY, Liu W, et al. Effects of maternal hepatitis B surface antigen positive status on the pregnancy outcomes: a retrospective study in Xiamen, China, 2011–2018. PLoS One. 2020;15:e0229732. [DOI] [PubMed] [PMC]

17.

Tan J, Mao X, Zhang G, Wang W, Pan T, Liu X, et al. Hepatitis B surface antigen positivity during pregnancy and risk of gestational diabetes mellitus: a systematic review and meta-analysis. J Viral Hepat. 2018;25:1372–83. [DOI] [PubMed]

18.

Bajema KL, Stankiewicz Karita HC, Tenforde MW, Hawes SE, Heffron R. Maternal hepatitis B infection and pregnancy outcomes in the United States: a population-based cohort study. Open Forum Infect Dis. 2018;5:ofy134. [DOI] [PubMed] [PMC]

19.

Reddick KL, Jhaveri R, Gandhi M, James AH, Swamy GK. Pregnancy outcomes associated with viral hepatitis. J Viral Hepat. 2011;18:e394–8. [DOI] [PubMed]

20.

Stokkeland K, Ludvigsson JF, Hultcrantz R, Ekbom A, Höijer J, Bottai M, et al. Pregnancy outcome in more than 5000 births to women with viral hepatitis: a population-based cohort study in Sweden. Eur J Epidemiol. 2017;32:617–25. [DOI] [PubMed] [PMC]

21.

Wong S, Chan LY, Yu V, Ho L. Hepatitis B carrier and perinatal outcome in singleton pregnancy. Am J Perinatol. 1999;16:485–8. [DOI] [PubMed]

22.

To WW, Cheung W, Mok KM. Hepatitis B surface antigen carrier status and its correlation to gestational hypertension. Aust N Z J Obstet Gynaecol. 2003;43:119–22. [DOI] [PubMed]

23.

Safir A, Levy A, Sikuler E, Sheiner E. Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome. Liver Int. 2010;30:765–70. [DOI] [PubMed]

24.

Mak SL, Leung KY. Hepatitis B carriers in Hong Kong: prevalence and pregnancy outcomes. Hong Kong J Gynaecol Obstet Midwifery. 2013;13:67–73.

25.

Cui AM, Cheng XY, Shao JG, Li HB, Wang XL, Shen Y, et al. Maternal hepatitis B virus carrier status and pregnancy outcomes: a prospective cohort study. BMC Pregnancy Childbirth. 2016;16:87. [DOI] [PubMed] [PMC]

26.

Cai Q, Liu H, Han W, Liu L, Xu Y, He Y, et al. Maternal HBsAg carriers and adverse pregnancy outcomes: a hospital-based prospective cohort analysis. J Viral Hepat. 2019;26:1011–8. [DOI] [PubMed]

27.

Zhang Y, Chen J, Liao T, Chen S, Yan J, Lin X. Maternal HBsAg carriers and pregnancy outcomes: a retrospective cohort analysis of 85,190 pregnancies. BMC Pregnancy Childbirth. 2020;20:724. [DOI] [PubMed] [PMC]

28.

Sun Q, Lao TT, Du M, Xie M, Sun Y, Bai B, et al. Chronic maternal hepatitis B virus infection and pregnancy outcome–a single center study in Kunming, China. BMC Infect Dis. 2021;21:253. [DOI] [PubMed] [PMC]

29.

Cosson E, Benchimol M, Carbillon L, Pharisien I, Pariés J, Valensi P, et al. Universal rather than selective screening for gestational diabetes mellitus may improve fetal outcomes. Diabetes Metab. 2006;32:140–6. [DOI] [PubMed]

30.

Griffin ME, Coffey M, Johnson H, Scanlon P, Foley M, Stronge J, et al. Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabet Med. 2000;17:26–32. [DOI] [PubMed]

31.

Qiu C, Sorensen TK, Luthy DA, Williams MA. A prospective study of maternal serum C-reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. Paediatr Perinat Epidemiol. 2004;18:377–84. [DOI] [PubMed]

32.

Lao TT, Tam KF. Maternal serum ferritin and gestational impaired glucose tolerance. Diabetes Care. 1997;20:1368–9. [DOI] [PubMed]

33.

Yarrington CD, Cantonwine DE, Seely EW, McElrath TF, Zera CA. The association of alanine aminotransferase in early pregnancy with gestational diabetes. Metab Syndr Relat Disord. 2016;14:254–8. [DOI]

34.

Leng J, Zhang C, Wang P, Li N, Li W, Liu H, et al. Plasma levels of alanine aminotransferase in the first trimester identify high risk Chinese women for gestational diabetes. Sci Rep. 2016;6:27291. [DOI] [PubMed] [PMC]

35.

Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Practice Res Clin Obstet Gynaecol. 2011;25:391–403. [DOI] [PubMed]

36.

Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005;330:565. [DOI] [PubMed] [PMC]

37.

Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335:974. [DOI] [PubMed] [PMC]

38.

Huang X, Tan H, Li X, Zhou S, Wen SW, Luo M. Maternal chronic HBV infection would not increase the risk of pregnancy-induced hypertension—results from pregnancy cohort in Liuyang rural China. PLoS One. 2014;9:e114248. [DOI] [PubMed] [PMC]

39.

Lao TT, Sahota DS, Cheng YK, Law LW, Leung TY. Maternal hepatitis B surface antigen status and incidence of pre-eclampsia. J Viral Hepat. 2013;20:343–9. [DOI] [PubMed]

40.

Huang QT, Chen JH, Zhong M, Hang LL, Wei SS, Yu YH. Chronic hepatitis B infection is associated with decreased risk of preeclampsia: a meta-analysis of observational studies. Cell Physiol Biochem. 2016;38:1860–8. [DOI] [PubMed]

41.

Stoop JN, van der Molen RG, Baan CC, van der Laan LJ, Kuipers EJ, Kusters JG, et al. Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology. 2005;41:771–8. [DOI] [PubMed]

42.

Bertoletti A, Gehring AJ. The immune response during hepatitis B virus infection. J Gen Virol. 2006;87:1439–49. [DOI] [PubMed]

43.

Peng G, Li S, Wu W, Sun Z, Chen Y, Chen Z. Circulating CD4⁺ CD25⁺ regulatory T cells correlate with chronic hepatitis B infection. Immunology. 2008;123:57–65. [DOI] [PubMed] [PMC]

44.

Jonsson Y, Rubèr M, Matthiesen L, Berg G, Nieminen K, Sharma S, et al. Cytokine mapping of sera from women with preeclampsia and normal pregnancies. J Reprod Immunol. 2006;70:83–91. [DOI] [PubMed]

45.

Laresgoiti-Servitje E, Gómez-López N, Olson DM. An immunological insight into the origins of pre-eclampsia. Hum Reprod Update. 2010;16:510–24. [DOI] [PubMed]

46.

Pinheiro MB, Martins-Filho OA, Mota AP, Alpoim PN, Godoi LC, Silveira AC, et al. Severe preeclampsia goes along with a cytokine network disturbance towards a systemic inflammatory state. Cytokine. 2013;62:165–73. [DOI] [PubMed]

47.

Pastorek JG 2nd, Miller JM Jr, Summers PR. The effect of hepatitis B antigenemia on pregnancy outcome. Am J Obstet Gynecol. 1988;158:486–9. [DOI]

48.

Wan Z, Zhou A, Zhu H, Lin X, Hu D, Peng S, et al. Maternal hepatitis B virus infection and pregnancy outcomes: a hospital-based case-control study in Wuhan, China. J Clin Gastroenterol. 2018;52:73–8. [DOI]

49.

Lobstein S, Faber R, Tillmann HL. Prevalence of hepatitis B among pregnant women and its impact on pregnancy and newborn complications at a tertiary hospital in the eastern part of Germany. Digestion. 2011;83:76–82. [DOI] [PubMed]

50.

Hu Y, Ding YL, Yu L. The impact of intrahepatic cholestasis of pregnancy with hepatitis B virus infection on perinatal outcomes. Ther Clin Risk Manag. 2014;10:381–5. [DOI] [PubMed] [PMC]

51.

Cui AM, Shao JG, Li HB, Shen Y, Chen ZX, Zhang S, et al. Association of chronic hepatitis B infection with preterm birth: our experience and meta-analysis. J Perinat Med. 2017;45:933–40. [DOI] [PubMed]

52.

Huang QT, Wei SS, Zhong M, Hang LL, Xu YY, Cai GX, et al. Chronic hepatitis B infection and risk of preterm labor: a meta-analysis of observational studies. J Clin Virol. 2014;61:3–8. [DOI] [PubMed]

53.

Elefsiniotis I, Tsoumakas K, Vezali E, Glynou I, Drakoulis N, Saroglou G. Spontaneous preterm birth in women with chronic hepatitis B virus infection. Int J Gynaecol Obstet. 2010;110:241–4. [DOI] [PubMed]

54.

Pavel A, Tîrşia E, Maior E, Cristea A. Detrimental effects of hepatitis B virus infection on the development of the product of conception. Virologie. 1983;34:35–40. [PubMed]

55.

Liu J, Zhang S, Liu M, Wang Q, Shen H, Zhang Y. Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm birth: a population-based cohort study. Lancet Glob Health. 2017;5:e624–32. [DOI] [PubMed]

56.

Luo L, Wu J, Qu Y, Li J, Pan L, Li D, et al. Association between maternal HBsAg carrier status and neonatal adverse outcomes: meta-analysis. J Matern Fetal Neonatal Med. 2015;28:1308–17. [DOI] [PubMed]

57.

Ma X, Sun D, Li C, Ying J, Yan Y. Chronic hepatitis B virus infection and preterm labor (birth) in pregnant women—an updated systematic review and meta-analysis. J Med Virol. 2018;90:93–100. [DOI] [PubMed]

58.

Zhuang X, Cui AM, Wang Q, Cheng XY, Shen Y, Cai WH, et al. Liver dysfunction during pregnancy and its association with preterm birth in China: a prospective cohort study. EBioMedicine. 2017;26:152–6. [DOI] [PubMed] [PMC]

59.

Romero R, Gómez R, Chaiworapongsa T, Conoscenti G, Kim JC, Kim YM. The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol. 2001;15 Suppl 2:41–56. [DOI] [PubMed]

60.

Zeng LN, Zhang LL, Shi J, Gu LL, Grogan W, Gargano MM, et al. The primary microbial pathogens associated with premature rupture of the membranes in China: a systemic review. Taiwan J Obstet Gynecol. 2014;53:443–51. [DOI] [PubMed]

61.

Huang QT, Chen JH, Zhong M, Xu YY, Cai CX, Wei SS, et al. The risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: a systematic review and meta-analysis. Placenta. 2014;35:539–45. [DOI] [PubMed]

62.

Gurol-Urganci I, Cromwell DA, Edozien LC, Smith GC, Onwere C, Mahmood TA, et al. Risk of placenta previa in second birth after first birth cesarean section: a population-based study and meta-analysis. BMC Pregnancy Childbirth. 2011;11:95. [DOI] [PubMed] [PMC]

63.

Pan CQ, Zou HB, Chen Y, Zhang X, Zhang H, Li J, et al. Cesarean section reduces perinatal transmission of hepatitis B virus infection from hepatitis B surface antigen-positive women to their infants. Clin Gastroenterol Hepatol. 2013;11:1349–55. [DOI] [PubMed]

64.

Hu Y, Chen J, Wen J, Xu C, Zhang S, Xu B, et al. Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus. BMC Pregnancy Childbirth. 2013;13:119. [DOI]

65.

Lao TT, Sahota DS, Cheng YK, Law LW, Leung TY. Advanced maternal age and postpartum hemorrhage—risk factor or red herring? J Matern Fetal Neonatal Med. 2014;27:243–6. [DOI] [PubMed]

66.

Ye F, Liu Y, Jin Y, Shi J, Yang X, Liu X, et al. The effect of hepatitis B virus infected embryos on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2014;172:10–4. [DOI] [PubMed]

67.

Salemi JL, Whiteman VE, August EM, Chandler K, Mbah AK, Salihu HM. Maternal hepatitis B and hepatitis C infection and neonatal neurological outcomes. J Viral Hepat. 2014;21:e144–53. [DOI] [PubMed]

68.

Lao TT, Sahota DS, Suen SS, Law LW, Leung TY. Maternal HBsAg status and infant size—a Faustian bargain? J Viral Hepat. 2012;19:519–24. [DOI] [PubMed]

69.

Yarrington CD, Cantonwine DE, Seely EW, Mcelrath TF, Zera CA. The association of early unexplained elevated alanine aminotransferase with large-for-gestational-age birthweight. Am J Obstet Gynecol. 2016;215:474.e1–5. [DOI] [PubMed]

70.

Atesci FC, Cetin BC, Oguzhanoglu NK, Karadag F, Turgut H. Psychiatric disorders and functioning in hepatitis B virus carriers. Psychosomatics. 2005;46:142–7. [DOI] [PubMed]

71.

Gupta R, Avasthi A, Chawla YK, Grover S. Psychiatric morbidity, fatigue, stigma and quality of life of patients with hepatitis B infection. J Clin Exp Hepatol. 2020;10:429–41. [DOI] [PubMed] [PMC]

72.

Zhou F, Li J, Lin K, Ji P, Sun Y. A cross-sectional study on anxiety and stress in pregnant women with chronic HBV infection in the People’s Republic of China. Neuropsychiatr Dis Treat. 2015;11:2225–32. [DOI] [PubMed] [PMC]

73.

Chen X, Chen J, Wen J, Xu C, Zhang S, Zhou YH, et al. Breastfeeding is not a risk factor for mother-to-child transmission of hepatitis B virus. PLoS One. 2013;8:e55303. [DOI] [PubMed] [PMC]

74.

Shi Z, Yang Y, Wang H, Ma L, Schreiber A, Li X, et al. Breastfeeding of newborns by mothers carrying hepatitis B virus: a meta-analysis and systematic review. Arch Pediatr Adolesc Med. 2011;165:837–46. [DOI] [PubMed]