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Seroprevalence of Hepatitis B Virus Among Pregnant Women in India: A Systematic Review and Meta-Analysis

Published:August 26, 2022DOI:https://doi.org/10.1016/j.jceh.2022.08.005

      Objectives

      Hepatitis B virus (HBV) infection during pregnancy is associated with perinatal transmission contributing to the pool of HBV infection in the population. There is a wide variation in the reported data on the seroprevalence of HBV in pregnant patients from various parts of India. Hence, a systematic review and meta-analysis was conducted to determine the pooled seroprevalence of HBV and its associated demographic factors.

      Methods

      A comprehensive literature search of Medline, Scopus, and Google Scholar was conducted from January 2000 to April 2022 for studies evaluating the prevalence of HBV in pregnant patients from India.

      Results

      A total of 44 studies with data on 272,595 patients were included in the meta-analysis. The pooled prevalence of hepatitis B surface antigen (HBsAg) in pregnant women was 1.6% [95% confidence interval (CI), 1.4–1.8]. Among patients with HBsAg positivity, the pooled prevalence of hepatitis B e antigen was 26.0% (95%CI 17.4–34.7). There was no significant difference in the odds of HBV seroprevalence based on the age (<25 years vs. > 25 years) [odds ratio (OR) 1.07, 95%CI 0.74–1.55], parity (primipara vs. multipara) (OR 1.09, 95%CI 0.70–1.70) or area of residence (urban vs. rural) (OR 0.88, 95%CI 0.56–1.39). However, the odds of HBV seroprevalence in those with no or primary education was higher than in those with secondary level education or higher (OR 2.29, 95%CI 1.24–4.23). Prior history of risk factors was present in 13.5–22.7% of patients indicating a vertical mode of acquisition.

      Conclusion

      There is a low endemicity of HBV among pregnant women in India. Risk factors are seen in less than 25% of the cases, indicating vertical transmission as the predominant mode of acquisition, which can be reduced by improving vaccination coverage.

      Graphical abstract

      Keywords

      Abbreviations:

      CI (Confidence interval), HBV (Hepatitis B virus), HBeAg (Hepatitis B e antigen), HBsAg (Hepatitis B surface antigen), MTCT (Mother-to-child transmission), OR (Odds ratio)
      Hepatitis B virus (HBV) infection is a global health problem, and India has the second-highest number of people living with HBV infection globally.
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      • Nguyen M.H.
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      Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.
      ,
      • Custer B.
      • Sullivan S.D.
      • Hazlet T.K.
      • Iloeje U.
      • Veenstra D.L.
      • Kowdley K.V.
      Global epidemiology of hepatitis B virus.
      Infected mothers significantly contribute to the pool of HBV infection in the population through perinatal transmission.
      • Ayoub W.S.
      • Cohen E.
      Hepatitis B management in the pregnant patient: an update.
      Because of the heterogeneous geographic distribution of chronic HBV infection, the regions are divided into low (<2%), medium (2–8%), and high (>8%) prevalence areas, with India being in the intermediate zone.
      • Previsani N.
      • Lavanchy D.
      Hepatitis B. Geneva: department of communicable diseases surveillance and response.
      As a consequence of chronic infection, HBV contributes substantially to liver-related morbidity and mortality. About 15%–40% of patients with chronic HBV infection develop complications like cirrhosis and hepatocellular carcinoma contributing to 780,000 deaths yearly.
      • Gentile I.
      • Borgia G.
      Vertical transmission of hepatitis B virus: challenges and solutions.
      ,
      In India, the carrier rate of HBV varies in different regions.
      • Batham A.
      • Narula D.
      • TotejaT
      • Sreenivas V.
      • Puliyel J.
      Systematic review and meta-analysis of prevalence of hepatitis B in India.
      As reported in a meta-analysis by Batham A et al., the true prevalence of Hepatitis B in India ranges from 2.4% among non-tribal populations to 15.9% among tribal populations.
      • Batham A.
      • Narula D.
      • TotejaT
      • Sreenivas V.
      • Puliyel J.
      Systematic review and meta-analysis of prevalence of hepatitis B in India.
      Generally, in pregnant women, the prevalence of HBV is comparable to that in the general population of the respective geographic area. However, Batham et al. reported the prevalence of HBV infection in pregnant women as 3.09% [95% confidence interval (CI) 2.03–4.15], which was higher compared to the general population.
      • Batham A.
      • Narula D.
      • TotejaT
      • Sreenivas V.
      • Puliyel J.
      Systematic review and meta-analysis of prevalence of hepatitis B in India.
      Vertical transmission is still responsible for most chronic HBV infections despite mass vaccination programs against hepatitis B. There is a considerable difference in the risk of developing chronic infection between newborns (90%) and adults (5%).
      • McMahon B.J.
      Epidemiology and natural history of hepatitis B.
      In a meta-analysis, the risk of perinatal transmission after the first dose of hepatitis B vaccination at birth was 32.4–36.6% and 0.0% in infants born to hepatitis B e antigen (HBeAg) positive and negative mothers, respectively.
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      • Funk A.L.
      • Shimakawa Y.
      Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa.
      Though there is much data on the overall prevalence of HBV among the general population, the subgroup analysis on HBV seroprevalence in pregnant women in the previous meta-analysis included only a few studies.
      • Batham A.
      • Narula D.
      • TotejaT
      • Sreenivas V.
      • Puliyel J.
      Systematic review and meta-analysis of prevalence of hepatitis B in India.
      It is crucial for policymakers to obtain accurate estimates of the burden of HBV infection among pregnant women in India to allocate resources to prevent perinatal transmission and reduce the overall disease burden in the nation. The main objective of this meta-analysis was to evaluate the point prevalence and provide updated epidemiological data on HBV infection among pregnant women in India.

      Methods

      The present meta-analysis was conducted as per the Meta-analysis Of Observational Studies in Epidemiology (MOOSE)
      • Stroup D.F.
      • Berlin J.A.
      • Morton S.C.
      • et al.
      Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group.
      and the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      • Page M.J.
      • McKenzie J.E.
      • Bossuyt P.M.
      • et al.
      The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.

      Information Source and Search Strategy

      Electronic databases of MEDLINE, Scopus, and Google Scholar were searched from January 2000 to April 2022 for the title and abstracts of all relevant studies using a detailed search strategy described in Supplementary Table 1. Two independent reviewers (SG, ShS) screened the title and abstract of the retrieved studies and assessed the full texts for eligibility before including them. The bibliographies of the included studies were searched for any relevant studies. A third reviewer resolved any disagreement (SrS).

      Eligibility Criteria

      Studies included in this meta-analysis were prospective or retrospective studies fulfilling the following criteria: (a) Study population – Pregnant patients in India; (b) Diagnostic test – Hepatitis B surface antigen (HBsAg) and other markers of HBV infection [HBeAg, anti-HBe or HBV DNA]; (c) Outcomes – Seroprevalence of HBV and associated risk factors. Conference abstracts, case series, review articles, correspondences, and editorials were excluded.

      Data Extraction and Quality Assessment

      Data were entered into a structured data extraction form with the following parameters: first author, year of publication, location of study, number of patients, study population description, methods used for diagnosis, and risk factors. The quality of the included studies was assessed by two reviewers (SuA, ShA) using the Joanna Briggs Institute Critical Appraisal tools for use in systematic reviews
      • Munn Z.
      • Barker T.H.
      • Moola S.
      • et al.
      Methodological quality of case series studies: an introduction to the JBI critical appraisal tool.
      (Supplementary Table 2). A third independent individual (SrS) was consulted to determine the best score based on any discrepancy in the study quality assessment.

      Data Synthesis

      The pooled proportions were computed using a random-effect method with an inverse variance approach.
      • DerSimonian R.
      • Laird N.
      Meta-analysis in clinical trials.
      Before statistical analysis, a continuity correction of 0.5 was applied when the incidence of an outcome was zero in a study. Dichotomous variables were analyzed using the odds ratio (OR) and Mantel–Haenszel test. The heterogeneity was assessed by I2 and the P-value of heterogeneity. A P-value of <0.10 was statistically significant, while I2 values of 25%, 50%, and 75% were considered cut-offs for low, moderate, and considerable heterogeneity, respectively.
      • Higgins J.P.
      • Thompson S.G.
      • Deeks J.J.
      • Altman D.G.
      Measuring inconsistency in meta-analyses.
      Meta-regression was used to explore heterogeneity induced by the relationship between moderators and study effect sizes. The publication bias was assessed by evaluating the asymmetry of the funnel plot and quantified using Egger's test. Sensitivity analysis was performed using prevalence data based on age, parity status, area of residence, and educational status. Leave-one-out meta-analysis was carried out to assess the robustness of the analysis. All statistical analyses were performed using STATA software (version 17, StataCorp., College Station, TX).

      Results

      The literature search identified 944 records, of which 638 were screened after removing duplicates. Overall, 44 studies
      • Abass F.
      • Thomas R.D.
      • Rajkumar A.
      • Gupta N.
      • Puliyel J.M.
      Controlling perinatally acquired hepatitis B.
      • Sahni M.
      • Jindal K.
      • Abraham N.
      • Aruldas K.
      • Puliyel J.M.
      Hepatitis B immunization: cost calculation in a community-based study in India.
      • Shenoy S.
      • Baliga S.
      • Prashanth H.V.
      • Dominic R.M.
      • Haridas S.
      Prevalence of hepatitis B surface antigen (HBsAG) in pregnant women in South Kanara district, Karnataka state, India.
      • Varghese R.M.
      • Abraham J.
      • James J.
      • Puliyel J.M.
      Determining the point of indifference--where costs of selective and universal immunization against hepatitis B are identical, in a cost-minimization exercise.
      • Banerjee A.
      • Chakravarty R.
      • Mondal P.N.
      • Chakraborty M.S.
      Hepatitis B virus genotype D infection among antenatal patients attending a maternity hospital in Calcutta, India: assessment of infectivity status.
      • Chakravarti A.
      • Rawat D.
      • Jain M.
      A study on the perinatal transmission of the hepatitis B virus.
      • Sandesh K.
      • Varghese T.
      • Harikumar R.
      • et al.
      Prevalence of Hepatitis B and C in the normal population and high risk groups in north Kerala.
      • Singla N.
      • Chander J.
      Seroprevalence of HBsAg in females in a North India tertiary care hospital, with special reference to pregnancy.
      • Chatterjee S.
      • Ravishankar K.
      • Chatterjee R.
      • Narang A.
      • Kinikar A.
      Hepatitis B prevalence during pregnancy.
      • Paranjothi S.
      • Vijayarani H.
      Prevalence of hepatitis b virus surface antigen in pregnant women attending a private hospital in Krishnagiri.
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      • Jindal N.
      • Arora U.
      • Singh S.
      • Devi B.
      Prevalence of sexually transmitted infections (HIV, hepatitis B, herpes simplex type 2 and syphilis) among asymptomatic pregnant women.
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      • Pai N.P.
      • Kurji J.
      • Singam A.
      • et al.
      Simultaneous triple point-of-care testing for HIV, syphilis and hepatitis B virus to prevent mother-to-child transmission in India.
      • Saraswasthi K.S.
      • Aljabri F.
      The study of prevalence of Hepatitis B surface antigen during pregnancy in a tertiary care hospital, South India.
      • Alexander A.M.
      • Prasad J.H.
      • Abraham P.
      • Fletcher J.
      • Muliyil J.
      • Balraj V.
      Evaluation of a programme for prevention of vertical transmission of hepatitis B in a rural block in southern India.
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      • Mehta K.D.
      • Antala S.
      • Mistry M.
      • Goswami Y.
      Seropositivity of hepatitis B, hepatitis C, syphilis, and HIV in antenatal women in India.
      • Ambade V.C.
      • Bhusan I.
      • Sinha R.
      Seroprevalence of Hepatitis B surface antigen among pregnant women in rural based teaching hospital of Northern Maharashtra, India.
      • Mehta K.
      • Garala N.
      • Garala R.
      • et al.
      The study of prevalence of Hepatitis B surface antigen during pregnancy.
      • Bansal V.
      • Bansal A.
      • Bansal A.R.
      • Kumar A.
      Seroprevalence of HBV in pregnant women and its coinfection with HCV & HIV.
      • Parveen S.S.
      • Madhavi S.
      Antenatal screening for HIV, hepatitis B and syphilis in a tertiary care hospital.
      • Bharathi M.
      • Sasikala A.
      • Bathala N.S.
      • Sasidhar M.
      • Bai S.K.
      A study on seroprevalence of hepatitis B surface antigen in antenatal women attending a tertiary care hospital.
      • Malhotra P.
      • Nanda S.
      • Malhotra V.
      • et al.
      Prevalence of HIV, hepatitis B, hepatitis C in pregnancy at tertiary care center of northern India.
      • Sibia P.
      • Mohi M.K.
      • Kumar A.
      Seroprevalence of hepatitis B infection among pregnant women in one of the Institute of northern India.
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      • Garg R.
      • Nigam A.
      • Singh S.
      • Singh R.
      • Singh S.
      • Rani R.
      Seroprevalence of hepatitis B surface antigen among pregnant women in a tertiary care health center of north India.
      • Mishra S.
      • Purandhare P.
      • Thakur R.
      • Agrawal S.
      • Alwani M.
      Study on prevalence of hepatitis B in pregnant women and its effect on maternal and fetal outcome at tertiary care centre.
      • Sathiyakala R.
      • Ushadevi G.
      • Karthika J.
      Seroprevalence of Hepatitis B infection among pregnant women in South India.
      • Shinde R.S.
      • Parande A.M.
      • Mantur B.G.
      • Parande M.V.
      Seroprevalence and effect of Hepatitis B and effect on pregnancy at a tertiary care hospital in North Karnataka.
      • Bose M.
      • Basu R.
      • Sarkar M.
      Seroprevalence of hepatitis B virus surface antigen in pregnant women attending ANC clinic in a tertiary care hospital in West Bengal.
      • Palange P.
      • Rao B.P.
      Seroprevalence of Hepatitis B surface antigen among pregnant women attending rural based tertiary care teaching hospital in Northern Telangana, India: a cross sectional study.
      • Sharma M.
      • Golia S.
      • Mehra S.K.
      • Jani M.V.
      Seroprevalence & risk factors of hepatitis B surface antigen among pregnant women attending a tertiary care hospital of southern Rajasthan, India.
      • Tinna G.
      • Pannu S.
      • Gupta A.
      • Kalla A.
      • Sharma B.P.
      Seroprevalence of hepatitis b surface antigen among pregnant women attending ante-natal clinics in North-Western zone of Rajasthan.
      • Kavitha Devi P.
      • Vijaya Laxmi P.
      • Santosh Kumar B.
      Seroprevalence of HBsAg among antenatal women attending tertiary care hospital, Telangana state.
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      • Sujatha A.
      • Shvetha K.
      Study on hepatitis B virus infection in pregnant women and its risk factors.
      • Apoorva B.
      • Manjhi M.
      • Mohan S.
      • Kakru D.K.
      Seroprevalence of hepatitis B infection among pregnant women at a tertiary care hospital.
      • Goel N.
      • Sharma R.
      • Agarwal R.
      Seroprevalence of Hepatitis B and Hepatitis C viral infections in pregnant women attending antenatal clinic in Tertiary care centre.
      • Jahan G.
      • Jahan N.
      • Rungta S.
      • Ahmad A.
      Seroprevalence and risk factors of hepatitis B and C infections among pregnant women.
      • Prakash V.
      • Prasad N.
      • prasad D.
      • Shahi S.K.
      Hepatitis B virus seroprevalence amongst pregnant women attending antenatal clinics of a tertiary care centre of Bihar.
      • Pandey S.
      • Lohani P.
      • Roy R.
      • et al.
      Prevalence and knowledge of hepatitis B infection in pregnant women in a primary health center of Patna district, Bihar.
      (Figure 1, PRISMA flow chart) were included, which provided data on the seroprevalence of HBV in pregnant women. The characteristics and quality of the included studies are summarized in Table 1. Coinfection with hepatitis C virus (HCV) was analyzed in five studies
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      ,
      • Mehta K.
      • Garala N.
      • Garala R.
      • et al.
      The study of prevalence of Hepatitis B surface antigen during pregnancy.
      ,
      • Bharathi M.
      • Sasikala A.
      • Bathala N.S.
      • Sasidhar M.
      • Bai S.K.
      A study on seroprevalence of hepatitis B surface antigen in antenatal women attending a tertiary care hospital.
      ,
      • Apoorva B.
      • Manjhi M.
      • Mohan S.
      • Kakru D.K.
      Seroprevalence of hepatitis B infection among pregnant women at a tertiary care hospital.
      ,
      • Goel N.
      • Sharma R.
      • Agarwal R.
      Seroprevalence of Hepatitis B and Hepatitis C viral infections in pregnant women attending antenatal clinic in Tertiary care centre.
      with 243 patients. The pooled prevalence of anti-HCV positivity in patients with HBsAg positivity was 1.3% (95%CI 0.0–2.9; I2 = 0.0%, P = 0.412). Human immunodeficiency virus (HIV) coinfection was reported in seven studies
      • Jindal N.
      • Arora U.
      • Singh S.
      • Devi B.
      Prevalence of sexually transmitted infections (HIV, hepatitis B, herpes simplex type 2 and syphilis) among asymptomatic pregnant women.
      ,
      • Pai N.P.
      • Kurji J.
      • Singam A.
      • et al.
      Simultaneous triple point-of-care testing for HIV, syphilis and hepatitis B virus to prevent mother-to-child transmission in India.
      ,
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      ,
      • Mehta K.
      • Garala N.
      • Garala R.
      • et al.
      The study of prevalence of Hepatitis B surface antigen during pregnancy.
      ,
      • Bansal V.
      • Bansal A.
      • Bansal A.R.
      • Kumar A.
      Seroprevalence of HBV in pregnant women and its coinfection with HCV & HIV.
      ,
      • Bharathi M.
      • Sasikala A.
      • Bathala N.S.
      • Sasidhar M.
      • Bai S.K.
      A study on seroprevalence of hepatitis B surface antigen in antenatal women attending a tertiary care hospital.
      ,
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      with 216 patients. The pooled prevalence of HIV positivity in patients with HBsAg positivity was 0.4% (95%CI 0.0–1.8; I2 = 0.0%, P = 0.837). Among the included studies, 16 were of high quality, 25 were of medium quality, and three were of low quality.
      Figure 1
      Figure 1PRISMA flowchart for study selection and inclusion process.
      Table 1Characteristics of Included Studies.
      AuthorStudy designStudy durationLocationTotal sampleHBsAg PositiveMethod usedHBeAg positiveStudy quality
      Abass 2001
      • Abass F.
      • Thomas R.D.
      • Rajkumar A.
      • Gupta N.
      • Puliyel J.M.
      Controlling perinatally acquired hepatitis B.
      Retrospective1999Delhi691070ELISA7
      Sahni 2004
      • Sahni M.
      • Jindal K.
      • Abraham N.
      • Aruldas K.
      • Puliyel J.M.
      Hepatitis B immunization: cost calculation in a community-based study in India.
      Prospective2001–2002Delhi98722ELISA8
      Shenoy 2004
      • Shenoy S.
      • Baliga S.
      • Prashanth H.V.
      • Dominic R.M.
      • Haridas S.
      Prevalence of hepatitis B surface antigen (HBsAG) in pregnant women in South Kanara district, Karnataka state, India.
      Prospective2001Karnataka30012Both15
      Varghese 2004
      • Varghese R.M.
      • Abraham J.
      • James J.
      • Puliyel J.M.
      Determining the point of indifference--where costs of selective and universal immunization against hepatitis B are identical, in a cost-minimization exercise.
      Prospective2000Delhi634152ELISA6
      Banerjee 2005
      • Banerjee A.
      • Chakravarty R.
      • Mondal P.N.
      • Chakraborty M.S.
      Hepatitis B virus genotype D infection among antenatal patients attending a maternity hospital in Calcutta, India: assessment of infectivity status.
      Prospective1998West Bengal40015ELISA46
      Chakravarti 2005
      • Chakravarti A.
      • Rawat D.
      • Jain M.
      A study on the perinatal transmission of the hepatitis B virus.
      Prospective1999–2000Delhi40017ELISA4
      Sandesh 2006
      • Sandesh K.
      • Varghese T.
      • Harikumar R.
      • et al.
      Prevalence of Hepatitis B and C in the normal population and high risk groups in north Kerala.
      Prospective2002–2004Kerala70659180ELISA6
      Singla 2008
      • Singla N.
      • Chander J.
      Seroprevalence of HBsAg in females in a North India tertiary care hospital, with special reference to pregnancy.
      Retrospective2003–2007Chandigarh293351ELISA6
      Chatterjee 2009
      • Chatterjee S.
      • Ravishankar K.
      • Chatterjee R.
      • Narang A.
      • Kinikar A.
      Hepatitis B prevalence during pregnancy.
      Prospective2003–2006Multicentric36379398Both8
      Paranjothi 2009
      • Paranjothi S.
      • Vijayarani H.
      Prevalence of hepatitis b virus surface antigen in pregnant women attending a private hospital in Krishnagiri.
      ProspectiveTamil Nadu76239ELISA155
      Dwivedi 2011
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      Prospective2006–2007Uttar Pradesh400037ELISA218
      Pande 2011
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      Prospective2004–2008Delhi20194224ELISA429
      Bakthavatchalu 2012
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      Prospective2011–2012Tamil Nadu50039ELISA225
      Jindal 2012
      • Jindal N.
      • Arora U.
      • Singh S.
      • Devi B.
      Prevalence of sexually transmitted infections (HIV, hepatitis B, herpes simplex type 2 and syphilis) among asymptomatic pregnant women.
      Prospective2004–2006Punjab50012ELISA6
      Khakhkhar 2012
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      Retrospective2001–2003Gujarat205063Both117
      Pai 2012
      • Pai N.P.
      • Kurji J.
      • Singam A.
      • et al.
      Simultaneous triple point-of-care testing for HIV, syphilis and hepatitis B virus to prevent mother-to-child transmission in India.
      Prospective2008–2009Maharashtra10025Both9
      Saraswathi 2012
      • Saraswasthi K.S.
      • Aljabri F.
      The study of prevalence of Hepatitis B surface antigen during pregnancy in a tertiary care hospital, South India.
      Prospective2010–2012Telangana215519Both5
      Alexander 2013
      • Alexander A.M.
      • Prasad J.H.
      • Abraham P.
      • Fletcher J.
      • Muliyil J.
      • Balraj V.
      Evaluation of a programme for prevention of vertical transmission of hepatitis B in a rural block in southern India.
      Prospective2002–2007Tamil Nadu12037190Rapid9
      Dhevahi 2013
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      ProspectiveTamil Nadu5042276417
      Mehta 2013
      • Mehta K.D.
      • Antala S.
      • Mistry M.
      • Goswami Y.
      Seropositivity of hepatitis B, hepatitis C, syphilis, and HIV in antenatal women in India.
      Prospective2010Gujarat103831ELISA8
      Ambade 2014
      • Ambade V.C.
      • Bhusan I.
      • Sinha R.
      Seroprevalence of Hepatitis B surface antigen among pregnant women in rural based teaching hospital of Northern Maharashtra, India.
      Retrospective2010–2014Maharashtra181521ELISA5
      Mehta 2014
      • Mehta K.
      • Garala N.
      • Garala R.
      • et al.
      The study of prevalence of Hepatitis B surface antigen during pregnancy.
      Prospective2013Gujarat181015ELISA5
      Bansal 2015
      • Bansal V.
      • Bansal A.
      • Bansal A.R.
      • Kumar A.
      Seroprevalence of HBV in pregnant women and its coinfection with HCV & HIV.
      Retrospective2012–2015Uttar Pradesh160038Both6
      Parveen 2015
      • Parveen S.S.
      • Madhavi S.
      Antenatal screening for HIV, hepatitis B and syphilis in a tertiary care hospital.
      ProspectiveTelangana4654Both7
      Bharathi 2016
      • Bharathi M.
      • Sasikala A.
      • Bathala N.S.
      • Sasidhar M.
      • Bai S.K.
      A study on seroprevalence of hepatitis B surface antigen in antenatal women attending a tertiary care hospital.
      Prospective2015Andhra Pradesh698291ELISA6
      Malhotra 2016
      • Malhotra P.
      • Nanda S.
      • Malhotra V.
      • et al.
      Prevalence of HIV, hepatitis B, hepatitis C in pregnancy at tertiary care center of northern India.
      Retrospective2015Haryana1000084Both5
      Sibia 2016
      • Sibia P.
      • Mohi M.K.
      • Kumar A.
      Seroprevalence of hepatitis B infection among pregnant women in one of the Institute of northern India.
      Retrospective2013–2014Punjab368641ELISA5
      Sinha 2016
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      Prospective2015–2016Bihar115045Both57
      Garg 2017
      • Garg R.
      • Nigam A.
      • Singh S.
      • Singh R.
      • Singh S.
      • Rani R.
      Seroprevalence of hepatitis B surface antigen among pregnant women in a tertiary care health center of north India.
      Prospective2015–2016Uttar Pradesh2058426
      Mishra 2017
      • Mishra S.
      • Purandhare P.
      • Thakur R.
      • Agrawal S.
      • Alwani M.
      Study on prevalence of hepatitis B in pregnant women and its effect on maternal and fetal outcome at tertiary care centre.
      Retrospective2016Madhya Pradesh356739Rapid6
      Rajendiran 2017
      • Sathiyakala R.
      • Ushadevi G.
      • Karthika J.
      Seroprevalence of Hepatitis B infection among pregnant women in South India.
      Prospective2014–2016Tamil Nadu128213ELISA5
      Shinde 2017
      • Shinde R.S.
      • Parande A.M.
      • Mantur B.G.
      • Parande M.V.
      Seroprevalence and effect of Hepatitis B and effect on pregnancy at a tertiary care hospital in North Karnataka.
      Retrospective2015–2016Karnataka3800645
      Bose 2018
      • Bose M.
      • Basu R.
      • Sarkar M.
      Seroprevalence of hepatitis B virus surface antigen in pregnant women attending ANC clinic in a tertiary care hospital in West Bengal.
      Prospective2016–2017West Bengal5406ELISA7
      Palange 2018
      • Palange P.
      • Rao B.P.
      Seroprevalence of Hepatitis B surface antigen among pregnant women attending rural based tertiary care teaching hospital in Northern Telangana, India: a cross sectional study.
      Prospective2015–2017Telangana141114Rapid6
      Sharma 2018
      • Sharma M.
      • Golia S.
      • Mehra S.K.
      • Jani M.V.
      Seroprevalence & risk factors of hepatitis B surface antigen among pregnant women attending a tertiary care hospital of southern Rajasthan, India.
      Prospective2015–2017Rajasthan101113Both6
      Tinna 2018
      • Tinna G.
      • Pannu S.
      • Gupta A.
      • Kalla A.
      • Sharma B.P.
      Seroprevalence of hepatitis b surface antigen among pregnant women attending ante-natal clinics in North-Western zone of Rajasthan.
      ProspectiveRajasthan221212Rapid5
      Devi 2019
      • Kavitha Devi P.
      • Vijaya Laxmi P.
      • Santosh Kumar B.
      Seroprevalence of HBsAg among antenatal women attending tertiary care hospital, Telangana state.
      Prospective2016–2018Telangana27024133Rapid5
      Samal 2019
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      Prospective2017–2018Odisha3230150ELISA8
      Sujatha 2019
      • Sujatha A.
      • Shvetha K.
      Study on hepatitis B virus infection in pregnant women and its risk factors.
      Prospective2016–2017Telangana1224093ELISA8
      Apoorva 2020
      • Apoorva B.
      • Manjhi M.
      • Mohan S.
      • Kakru D.K.
      Seroprevalence of hepatitis B infection among pregnant women at a tertiary care hospital.
      Prospective2019–2020Uttar Pradesh43512Rapid4
      Goel 2020
      • Goel N.
      • Sharma R.
      • Agarwal R.
      Seroprevalence of Hepatitis B and Hepatitis C viral infections in pregnant women attending antenatal clinic in Tertiary care centre.
      Retrospective2019Uttar Pradesh962870Both7
      Jahan 2020
      • Jahan G.
      • Jahan N.
      • Rungta S.
      • Ahmad A.
      Seroprevalence and risk factors of hepatitis B and C infections among pregnant women.
      Prospective2017–2018Uttar Pradesh345204
      Prakash 2020
      • Prakash V.
      • Prasad N.
      • prasad D.
      • Shahi S.K.
      Hepatitis B virus seroprevalence amongst pregnant women attending antenatal clinics of a tertiary care centre of Bihar.
      Prospective2018–2019Bihar144012ELISA6
      Pandey 2021
      • Pandey S.
      • Lohani P.
      • Roy R.
      • et al.
      Prevalence and knowledge of hepatitis B infection in pregnant women in a primary health center of Patna district, Bihar.
      ProspectiveBihar2751Rapid6
      ELISA: Enzyme linked immunosorbent assay; HBsAg, hepatitis B surface antigen; Both indicates initial testing by positive rapid HBsAg test kit and confirmed by enzyme-linked immunosorbent assay (ELISA).

      Seroprevalence of HBV

      All 44 studies
      • Abass F.
      • Thomas R.D.
      • Rajkumar A.
      • Gupta N.
      • Puliyel J.M.
      Controlling perinatally acquired hepatitis B.
      • Sahni M.
      • Jindal K.
      • Abraham N.
      • Aruldas K.
      • Puliyel J.M.
      Hepatitis B immunization: cost calculation in a community-based study in India.
      • Shenoy S.
      • Baliga S.
      • Prashanth H.V.
      • Dominic R.M.
      • Haridas S.
      Prevalence of hepatitis B surface antigen (HBsAG) in pregnant women in South Kanara district, Karnataka state, India.
      • Varghese R.M.
      • Abraham J.
      • James J.
      • Puliyel J.M.
      Determining the point of indifference--where costs of selective and universal immunization against hepatitis B are identical, in a cost-minimization exercise.
      • Banerjee A.
      • Chakravarty R.
      • Mondal P.N.
      • Chakraborty M.S.
      Hepatitis B virus genotype D infection among antenatal patients attending a maternity hospital in Calcutta, India: assessment of infectivity status.
      • Chakravarti A.
      • Rawat D.
      • Jain M.
      A study on the perinatal transmission of the hepatitis B virus.
      • Sandesh K.
      • Varghese T.
      • Harikumar R.
      • et al.
      Prevalence of Hepatitis B and C in the normal population and high risk groups in north Kerala.
      • Singla N.
      • Chander J.
      Seroprevalence of HBsAg in females in a North India tertiary care hospital, with special reference to pregnancy.
      • Chatterjee S.
      • Ravishankar K.
      • Chatterjee R.
      • Narang A.
      • Kinikar A.
      Hepatitis B prevalence during pregnancy.
      • Paranjothi S.
      • Vijayarani H.
      Prevalence of hepatitis b virus surface antigen in pregnant women attending a private hospital in Krishnagiri.
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      • Jindal N.
      • Arora U.
      • Singh S.
      • Devi B.
      Prevalence of sexually transmitted infections (HIV, hepatitis B, herpes simplex type 2 and syphilis) among asymptomatic pregnant women.
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      • Pai N.P.
      • Kurji J.
      • Singam A.
      • et al.
      Simultaneous triple point-of-care testing for HIV, syphilis and hepatitis B virus to prevent mother-to-child transmission in India.
      • Saraswasthi K.S.
      • Aljabri F.
      The study of prevalence of Hepatitis B surface antigen during pregnancy in a tertiary care hospital, South India.
      • Alexander A.M.
      • Prasad J.H.
      • Abraham P.
      • Fletcher J.
      • Muliyil J.
      • Balraj V.
      Evaluation of a programme for prevention of vertical transmission of hepatitis B in a rural block in southern India.
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      • Mehta K.D.
      • Antala S.
      • Mistry M.
      • Goswami Y.
      Seropositivity of hepatitis B, hepatitis C, syphilis, and HIV in antenatal women in India.
      • Ambade V.C.
      • Bhusan I.
      • Sinha R.
      Seroprevalence of Hepatitis B surface antigen among pregnant women in rural based teaching hospital of Northern Maharashtra, India.
      • Mehta K.
      • Garala N.
      • Garala R.
      • et al.
      The study of prevalence of Hepatitis B surface antigen during pregnancy.
      • Bansal V.
      • Bansal A.
      • Bansal A.R.
      • Kumar A.
      Seroprevalence of HBV in pregnant women and its coinfection with HCV & HIV.
      • Parveen S.S.
      • Madhavi S.
      Antenatal screening for HIV, hepatitis B and syphilis in a tertiary care hospital.
      • Bharathi M.
      • Sasikala A.
      • Bathala N.S.
      • Sasidhar M.
      • Bai S.K.
      A study on seroprevalence of hepatitis B surface antigen in antenatal women attending a tertiary care hospital.
      • Malhotra P.
      • Nanda S.
      • Malhotra V.
      • et al.
      Prevalence of HIV, hepatitis B, hepatitis C in pregnancy at tertiary care center of northern India.
      • Sibia P.
      • Mohi M.K.
      • Kumar A.
      Seroprevalence of hepatitis B infection among pregnant women in one of the Institute of northern India.
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      • Garg R.
      • Nigam A.
      • Singh S.
      • Singh R.
      • Singh S.
      • Rani R.
      Seroprevalence of hepatitis B surface antigen among pregnant women in a tertiary care health center of north India.
      • Mishra S.
      • Purandhare P.
      • Thakur R.
      • Agrawal S.
      • Alwani M.
      Study on prevalence of hepatitis B in pregnant women and its effect on maternal and fetal outcome at tertiary care centre.
      • Sathiyakala R.
      • Ushadevi G.
      • Karthika J.
      Seroprevalence of Hepatitis B infection among pregnant women in South India.
      • Shinde R.S.
      • Parande A.M.
      • Mantur B.G.
      • Parande M.V.
      Seroprevalence and effect of Hepatitis B and effect on pregnancy at a tertiary care hospital in North Karnataka.
      • Bose M.
      • Basu R.
      • Sarkar M.
      Seroprevalence of hepatitis B virus surface antigen in pregnant women attending ANC clinic in a tertiary care hospital in West Bengal.
      • Palange P.
      • Rao B.P.
      Seroprevalence of Hepatitis B surface antigen among pregnant women attending rural based tertiary care teaching hospital in Northern Telangana, India: a cross sectional study.
      • Sharma M.
      • Golia S.
      • Mehra S.K.
      • Jani M.V.
      Seroprevalence & risk factors of hepatitis B surface antigen among pregnant women attending a tertiary care hospital of southern Rajasthan, India.
      • Tinna G.
      • Pannu S.
      • Gupta A.
      • Kalla A.
      • Sharma B.P.
      Seroprevalence of hepatitis b surface antigen among pregnant women attending ante-natal clinics in North-Western zone of Rajasthan.
      • Kavitha Devi P.
      • Vijaya Laxmi P.
      • Santosh Kumar B.
      Seroprevalence of HBsAg among antenatal women attending tertiary care hospital, Telangana state.
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      • Sujatha A.
      • Shvetha K.
      Study on hepatitis B virus infection in pregnant women and its risk factors.
      • Apoorva B.
      • Manjhi M.
      • Mohan S.
      • Kakru D.K.
      Seroprevalence of hepatitis B infection among pregnant women at a tertiary care hospital.
      • Goel N.
      • Sharma R.
      • Agarwal R.
      Seroprevalence of Hepatitis B and Hepatitis C viral infections in pregnant women attending antenatal clinic in Tertiary care centre.
      • Jahan G.
      • Jahan N.
      • Rungta S.
      • Ahmad A.
      Seroprevalence and risk factors of hepatitis B and C infections among pregnant women.
      • Prakash V.
      • Prasad N.
      • prasad D.
      • Shahi S.K.
      Hepatitis B virus seroprevalence amongst pregnant women attending antenatal clinics of a tertiary care centre of Bihar.
      • Pandey S.
      • Lohani P.
      • Roy R.
      • et al.
      Prevalence and knowledge of hepatitis B infection in pregnant women in a primary health center of Patna district, Bihar.
      with 272,595 patients reported the seroprevalence of HBV in pregnancy. The pooled prevalence of HBV in Indian pregnant women was 1.6% (95%CI, 1.4–1.8; I2 = 96.7%, P = 0.000) (Figure 2). On subgroup analysis, the pooled prevalence rate in studies conducted prior to 2010 (1.7%, 95%CI 1.3–2.1) and those after 2010 (1.6%, 95%CI 1.3–1.9) was comparable (P = 0.667). Figure 3 summarizes the pooled seroprevalence data from individual states in India.
      Figure 2
      Figure 2Forest plot for pooled seroprevalence of HBV in pregnancy with subgroup analysis based on year of study.
      Figure 3
      Figure 3State-wise reported pooled prevalence of HBV from the included studies.

      Prevalence of HBeAg in Patients with Positive HBsAg

      Only 9 studies
      • Shenoy S.
      • Baliga S.
      • Prashanth H.V.
      • Dominic R.M.
      • Haridas S.
      Prevalence of hepatitis B surface antigen (HBsAG) in pregnant women in South Kanara district, Karnataka state, India.
      ,
      • Banerjee A.
      • Chakravarty R.
      • Mondal P.N.
      • Chakraborty M.S.
      Hepatitis B virus genotype D infection among antenatal patients attending a maternity hospital in Calcutta, India: assessment of infectivity status.
      ,
      • Paranjothi S.
      • Vijayarani H.
      Prevalence of hepatitis b virus surface antigen in pregnant women attending a private hospital in Krishnagiri.
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      ,
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      ,
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      ,
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      with data on 750 HBsAg positive mothers reported the data on HBeAg positivity. The pooled prevalence of HBeAg was 26.0% (95%CI 17.4–34.7; I2 = 86.4, P = 0.000) (Supplementary Figure 1).

      Prevalence of Anti-HBe Antibody in Patients with Positive HBsAg

      Overall, 7 studies
      • Banerjee A.
      • Chakravarty R.
      • Mondal P.N.
      • Chakraborty M.S.
      Hepatitis B virus genotype D infection among antenatal patients attending a maternity hospital in Calcutta, India: assessment of infectivity status.
      ,
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      ,
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      ,
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      ,
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      with 699 HBsAg patients reported on anti-HBe positivity in patients with HBsAg positive status. The pooled prevalence of anti-HBe antibody was 40.1% (95%CI 28.6–51.6; I2 = 95.7, P = 0.000).

      HBsAg Positive Patients Negative for Both HBeAg and Anti-Hbe Antibody

      Overall, 7 studies
      • Banerjee A.
      • Chakravarty R.
      • Mondal P.N.
      • Chakraborty M.S.
      Hepatitis B virus genotype D infection among antenatal patients attending a maternity hospital in Calcutta, India: assessment of infectivity status.
      ,
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      ,
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      ,
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      ,
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      with 699 HBsAg patients reported on HBsAg positive patients who were negative for both HBeAg and anti-Hbe. The pooled prevalence of such patients was 33.2% (95%CI 22.2–44.1; I2 = 88.8, P = 0.000).

      HBV DNA Detection in Patients with Positive HBsAg

      Overall, 4 studies
      • Banerjee A.
      • Chakravarty R.
      • Mondal P.N.
      • Chakraborty M.S.
      Hepatitis B virus genotype D infection among antenatal patients attending a maternity hospital in Calcutta, India: assessment of infectivity status.
      ,
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      ,
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      ,
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      with 496 HBsAg positive patients reported on the detectable HBV DNA status. The pooled prevalence of HBV DNA positivity was 57.6% (95%CI 8.4–100.0; I2 = 99.5, P = 0.000). Genotype D was the commonest HBV genotype reported.

      HBV Prevalence and Odds Ratios by Sociodemographic Characteristics

      Age Distribution

      Fourteen studies
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      ,
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      ,
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      ,
      • Mehta K.D.
      • Antala S.
      • Mistry M.
      • Goswami Y.
      Seropositivity of hepatitis B, hepatitis C, syphilis, and HIV in antenatal women in India.
      ,
      • Ambade V.C.
      • Bhusan I.
      • Sinha R.
      Seroprevalence of Hepatitis B surface antigen among pregnant women in rural based teaching hospital of Northern Maharashtra, India.
      ,
      • Bharathi M.
      • Sasikala A.
      • Bathala N.S.
      • Sasidhar M.
      • Bai S.K.
      A study on seroprevalence of hepatitis B surface antigen in antenatal women attending a tertiary care hospital.
      ,
      • Sibia P.
      • Mohi M.K.
      • Kumar A.
      Seroprevalence of hepatitis B infection among pregnant women in one of the Institute of northern India.
      ,
      • Bose M.
      • Basu R.
      • Sarkar M.
      Seroprevalence of hepatitis B virus surface antigen in pregnant women attending ANC clinic in a tertiary care hospital in West Bengal.
      • Palange P.
      • Rao B.P.
      Seroprevalence of Hepatitis B surface antigen among pregnant women attending rural based tertiary care teaching hospital in Northern Telangana, India: a cross sectional study.
      • Sharma M.
      • Golia S.
      • Mehra S.K.
      • Jani M.V.
      Seroprevalence & risk factors of hepatitis B surface antigen among pregnant women attending a tertiary care hospital of southern Rajasthan, India.
      • Tinna G.
      • Pannu S.
      • Gupta A.
      • Kalla A.
      • Sharma B.P.
      Seroprevalence of hepatitis b surface antigen among pregnant women attending ante-natal clinics in North-Western zone of Rajasthan.
      ,
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      ,
      • Apoorva B.
      • Manjhi M.
      • Mohan S.
      • Kakru D.K.
      Seroprevalence of hepatitis B infection among pregnant women at a tertiary care hospital.
      ,
      • Jahan G.
      • Jahan N.
      • Rungta S.
      • Ahmad A.
      Seroprevalence and risk factors of hepatitis B and C infections among pregnant women.
      with 29238 patients reported on the age distribution of included patients. The pooled seroprevalence of HBV in women <25 years of age was 2.1% (1.4–2.8; I2 = 94.1%, P = 0.000) while in those with age >25 years, it was 1.6% (1.2–2.0; I2 = 68.8%, P = 0.000). However, there was no significant difference in the odds of HBV seroprevalence between women with age <25 years and >25 years (OR 1.07, 95%CI 0.74–1.55; I2 = 68.0%, P = 0.000) (Supplementary Figure 2).

      Parity

      The parity of the included patients was reported in 8 studies
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      ,
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      ,
      • Jindal N.
      • Arora U.
      • Singh S.
      • Devi B.
      Prevalence of sexually transmitted infections (HIV, hepatitis B, herpes simplex type 2 and syphilis) among asymptomatic pregnant women.
      ,
      • Alexander A.M.
      • Prasad J.H.
      • Abraham P.
      • Fletcher J.
      • Muliyil J.
      • Balraj V.
      Evaluation of a programme for prevention of vertical transmission of hepatitis B in a rural block in southern India.
      ,
      • Garg R.
      • Nigam A.
      • Singh S.
      • Singh R.
      • Singh S.
      • Rani R.
      Seroprevalence of hepatitis B surface antigen among pregnant women in a tertiary care health center of north India.
      ,
      • Bose M.
      • Basu R.
      • Sarkar M.
      Seroprevalence of hepatitis B virus surface antigen in pregnant women attending ANC clinic in a tertiary care hospital in West Bengal.
      ,
      • Palange P.
      • Rao B.P.
      Seroprevalence of Hepatitis B surface antigen among pregnant women attending rural based tertiary care teaching hospital in Northern Telangana, India: a cross sectional study.
      ,
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      with 43443 patients. The pooled seroprevalence of HBV in primipara was 1.7% (1.0–2.4; I2 = 94.9%, P = 0.000) while in multipara, it was 1.4% (1.1–1.8; I2 = 74.5%, P = 0.000). There was no significant difference in the odds of HBV seroprevalence with respect to parity (OR 1.09, 95%CI 0.70–1.70; I2 = 78.2%, P = 0.000) (Supplementary Figure 3).

      Trimester

      Seven studies
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      ,
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      ,
      • Mehta K.D.
      • Antala S.
      • Mistry M.
      • Goswami Y.
      Seropositivity of hepatitis B, hepatitis C, syphilis, and HIV in antenatal women in India.
      ,
      • Ambade V.C.
      • Bhusan I.
      • Sinha R.
      Seroprevalence of Hepatitis B surface antigen among pregnant women in rural based teaching hospital of Northern Maharashtra, India.
      ,
      • Bose M.
      • Basu R.
      • Sarkar M.
      Seroprevalence of hepatitis B virus surface antigen in pregnant women attending ANC clinic in a tertiary care hospital in West Bengal.
      ,
      • Sharma M.
      • Golia S.
      • Mehra S.K.
      • Jani M.V.
      Seroprevalence & risk factors of hepatitis B surface antigen among pregnant women attending a tertiary care hospital of southern Rajasthan, India.
      ,
      • Jahan G.
      • Jahan N.
      • Rungta S.
      • Ahmad A.
      Seroprevalence and risk factors of hepatitis B and C infections among pregnant women.
      with 7268 patients reported the prevalence based on the trimester in which the women were tested. The pooled seroprevalence of HBV was 1.8% (0.7–2.9; I2 = 66.9%, P = 0.006) in first trimester, 3.0% (1.5–4.5; I2 = 83.5%, P = 0.000) in second trimester, and 2.3% (1.2–3.4; I2 = 73.1%, P = 0.001) in third trimester, without any heterogeneity between the groups (P = 0.435) (Supplementary Figure 4).

      Location

      Residential location was defined as the region where the pregnant woman is staying for a certain period. The difference in prevalence based on residential location was reported by 5 studies
      • Jindal N.
      • Arora U.
      • Singh S.
      • Devi B.
      Prevalence of sexually transmitted infections (HIV, hepatitis B, herpes simplex type 2 and syphilis) among asymptomatic pregnant women.
      ,
      • Sibia P.
      • Mohi M.K.
      • Kumar A.
      Seroprevalence of hepatitis B infection among pregnant women in one of the Institute of northern India.
      ,
      • Bose M.
      • Basu R.
      • Sarkar M.
      Seroprevalence of hepatitis B virus surface antigen in pregnant women attending ANC clinic in a tertiary care hospital in West Bengal.
      ,
      • Tinna G.
      • Pannu S.
      • Gupta A.
      • Kalla A.
      • Sharma B.P.
      Seroprevalence of hepatitis b surface antigen among pregnant women attending ante-natal clinics in North-Western zone of Rajasthan.
      ,
      • Jahan G.
      • Jahan N.
      • Rungta S.
      • Ahmad A.
      Seroprevalence and risk factors of hepatitis B and C infections among pregnant women.
      with 7283 patients. The pooled seroprevalence of HBV in women from urban areas was 1.3% (0.4–2.1; I2 = 67.8%, P = 0.006) while prevalence in women from rural areas was 1.4% (0.6–2.3; I2 = 68.7%, P = 0.005). There was no significant difference in the odds of HBV seroprevalence with respect to residential location (OR 0.88, 95%CI 0.56–1.39; I2 = 0.0%, P = 0.601) (Supplementary Figure 5).

      Educational Status

      Four studies
      • Jindal N.
      • Arora U.
      • Singh S.
      • Devi B.
      Prevalence of sexually transmitted infections (HIV, hepatitis B, herpes simplex type 2 and syphilis) among asymptomatic pregnant women.
      ,
      • Sibia P.
      • Mohi M.K.
      • Kumar A.
      Seroprevalence of hepatitis B infection among pregnant women in one of the Institute of northern India.
      ,
      • Garg R.
      • Nigam A.
      • Singh S.
      • Singh R.
      • Singh S.
      • Rani R.
      Seroprevalence of hepatitis B surface antigen among pregnant women in a tertiary care health center of north India.
      ,
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      with 9474 patients reported the HBV prevalence based on the patients' educational status. The pooled seroprevalence of HBV in women who were illiterate or had primary education was 3.8% (1.2–6.5; I2 = 96.6%, P = 0.000) and in those with secondary level or higher education, it was 1.5% (0.9–2.0; I2 = 34.8%, P = 0.203). There were significantly higher odds of HBV seroprevalence in those with education less than secondary level (OR 2.29, 95%CI 1.24–4.23; I2 = 62.4%, P = 0.046) (Figure 4).
      Figure 4
      Figure 4Forest plot comparing the seroprevalence of HBV based on the educational status of the pregnant women.

      Prior Risk Factors

      Overall, 10 studies
      • Dwivedi M.
      • Misra S.P.
      • Misra V.
      • et al.
      Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission.
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      • Bakthavatchalu D.
      Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission.
      ,
      • Khakhkhar V.M.
      • Bhuva P.J.
      • Bhuva S.P.
      • Patel C.P.
      • Cholera M.S.
      Sero-prevalence of hepatitis B amongst pregnant women attending the antenatal clinic of a tertiary care hospital, Jamnagar (Gujarat).
      ,
      • Bansal V.
      • Bansal A.
      • Bansal A.R.
      • Kumar A.
      Seroprevalence of HBV in pregnant women and its coinfection with HCV & HIV.
      ,
      • Sinha A.
      • Sharan M.
      • Shahi S.K.
      Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India.
      ,
      • Garg R.
      • Nigam A.
      • Singh S.
      • Singh R.
      • Singh S.
      • Rani R.
      Seroprevalence of hepatitis B surface antigen among pregnant women in a tertiary care health center of north India.
      ,
      • Sharma M.
      • Golia S.
      • Mehra S.K.
      • Jani M.V.
      Seroprevalence & risk factors of hepatitis B surface antigen among pregnant women attending a tertiary care hospital of southern Rajasthan, India.
      ,
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      ,
      • Jahan G.
      • Jahan N.
      • Rungta S.
      • Ahmad A.
      Seroprevalence and risk factors of hepatitis B and C infections among pregnant women.
      with 671 HBsAg positive patients reported on the presence of risk factors. Prior history of tattooing was present in 22.7% (6.2–39.2; I2 = 95.5%, P = 0.000) (Supplementary Figure 6), history of surgery was present in 20.9% (11.4–30.5; I2 = 92.3%, P = 0.000) (Supplementary Figure 7) while history of blood transfusion was present in 13.5% (8.0–19.0; I2 = 81.7%, P = 0.000) (Supplementary Figure 8) of women, with significant heterogeneity among the studies.

      Publication Bias, Heterogeneity, Meta-regression, and Sensitivity Analysis

      Assessment of publication bias was done by visual inspection of the funnel plot asymmetry (Supplementary Figure 9). There was significant publication bias for all the outcomes except for the difference in seroprevalence with age (Supplementary Figure 9C), parity (Supplementary Figure 9D), and area of residence (Supplementary Figure 9F). There was significant heterogeneity between the studies for all the outcomes. Meta-regression showed that the sample size of the studies was an important source of heterogeneity for the seroprevalence of HBV (Figure 5). In the leave-one-out meta-analysis, the study by Dhevahi et al.
      • Dhevahi E.S.
      • Nayak H.K.
      • Malathi S.
      • Thiagarajan S.P.
      Hepatitis B virus infection in asymptomatic pregnant women - a report from Chennai South India.
      was a significant outlier, and with its omission, the HBV DNA positivity increased to 72.0% (95%CI 43.8–100.0). Table 2 shows the sensitivity analysis for the seroprevalence of HBV in various subgroups of pregnant women.
      Figure 5
      Figure 5Bubble plot for assessment of source of heterogeneity in the HBV seroprevalence in pregnant women with respect to (A) Publication year, (B) Sample size, and (C) Study quality.
      Table 2Sensitivity Analysis for Seroprevalence of Hepatitis B in Pregnant Women.
      GroupsNo. of studies (no. of patients)PrevalenceI2
      Overall43 studies (n = 267553)1.5% (1.3–1.7)96.1%
      Age distribution
       Less than 25 years14 studies (n = 16995)2.1% (1.4–2.8)94.1%
       More than 25 years14 studies (n = 12243)1.6% (1.2–2.0)68.8%
      Parity
       Primipara8 studies (n = 18240)1.7% (1.0–2.4)94.9%
       Multipara8 studies (n = 25443)1.4% (1.1–1.8)74.5%
      Antenatal period
       First trimester7 studies (n = 1645)1.8% (0.7–2.9)66.9%
       Second trimester7 studies (n = 2629)3.0% (1.5–4.5)83.5%
       Third trimester7 studies (n = 2994)2.3% (1.2–3.4)73.1%
      Residence
       Urban5 studies (n = 3220)1.3% (0.4–2.1)67.8%
       Rural5 studies (n = 4063)1.4% (0.6–2.3)68.7%
      Education
       None or primary4 studies (n = 6562)3.8% (1.2–6.5)96.6%
       Secondary or higher4 studies (n = 2912)1.5% (0.9–2.0)34.8%

      Discussion

      The burden of HBV infection is high in low and middle-income countries. With perinatal transmission being the most important mode of infection in the neonate leading to chronicity, tackling this pathway is the most important means to reduce the prevalence of this infection. Antenatal screening of all pregnant mothers is paramount in reducing the prevalence of hepatitis B infection. Accordingly, WHO guidelines recommend testing all pregnant women as early as possible.
      World Health Organization
      Prevention of Mother-To-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy.
      In the present meta-analysis that analyzed the prevalence of hepatitis B infection in pregnancy in India, the pooled prevalence was 1.6% (95%CI, 1.4–1.8), with HBeAg positivity in 26.0% (95%CI 17.4–34.7), and anti-HBe antibody in 40.1% (95%CI 28.6–51.6). Further, on subgroup analysis, the pooled prevalence rate in studies conducted before 2010 (1.7%, 95%CI 1.3–2.1) and those after 2010 (1.6%, 95%CI 1.3–1.9) was comparable (P = 0.667). Thus, over the last two decades, the seroprevalence of HBV in pregnant women has remained the same, pointing toward inadequate adherence to the screening and vaccination protocols. There was a significant difference in the prevalence of hepatitis B infection in various states, with a low prevalence in the western and northern parts and a slightly higher prevalence in the eastern and southern parts of the country. The heterogeneous distribution across states can be due to multiple factors like differences in the native practice of body piercing and tattooing, the difference in literacy rate, the difference in coverage of vaccination programs, and the prevalence of migrant laborers in the community. In the study by Samal et al.,
      • Samal N.
      • Padhi S.
      • Burman L.
      Seroprevalence of hepatitis B infection among pregnant women in southern Odisha.
      60% of the included population were spouses of migrant laborers, of which 4.2% were HBsAg positive. Also, hospital-based studies were likely to have a higher prevalence than community-based studies due to referral bias.
      The reported prevalence rate of HBV infection in pregnant women in the previous meta-analysis by Batham et al. was 3.09%, compared to 1.6% in the present analysis. The significant difference in the pooled rate can be explained by the fact that the analysis by Batham et al. included data on only seven studies from 1987 to 2005.
      • Batham A.
      • Narula D.
      • TotejaT
      • Sreenivas V.
      • Puliyel J.
      Systematic review and meta-analysis of prevalence of hepatitis B in India.
      On the contrary, the present analysis included 44 studies from 2000 to 2022. The meta-regression analysis showed that effect size (pooled prevalence) decreased with an increase in sample size. Hence, a smaller number of studies with a small sample size may have been responsible for a higher prevalence rate in the previous analysis. Also, two studies in the analysis by Batham et al. were significant outliers, and a leave-one-out analysis conducted excluding those studies one at a time reduced the prevalence rate to 2.5%.
      Maternal HBeAg positivity is a significant risk factor for mother-to-child transmission (MTCT). A recent meta-analysis of 66 studies on the role of HBeAg reported a pooled sensitivity of 88·2% (83·9–91·5) in detecting maternal HBV DNA of 5·30 log10 IU/mL or greater and 99·5% (91·7–100) in predicting MTCT of HBV infection despite infant immunoprophylaxis.
      • Boucheron P.
      • Lu Y.
      • Yoshida K.
      • et al.
      Accuracy of HBeAg to identify pregnant women at risk of transmitting hepatitis B virus to their neonates: a systematic review and meta-analysis.
      Pande et al.
      • Pande C.
      • Sarin S.K.
      • Patra S.
      • et al.
      Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.
      also reported that the median HBV DNA levels were significantly higher in the HBeAg positive compared to the HBeAg negative group (6.6 × 107 IU/ml [range 145–4.6 × 108] vs. 1.7 × 104 IU/ml [range <10–2.4 × 108], P < 0.01). Only nine studies in the present analysis reported the data on HBeAg positivity, which points to the underutilization of such an important marker. In resource-poor settings, HBeAg positivity can be used as a surrogate for HBV DNA levels concerning deciding the need for antiviral prophylaxis.
      • Boucheron P.
      • Lu Y.
      • Yoshida K.
      • et al.
      Accuracy of HBeAg to identify pregnant women at risk of transmitting hepatitis B virus to their neonates: a systematic review and meta-analysis.
      The current meta-analysis showed that the prevalence of HBV infection has no association with age and parity. Though it is recommended to test all pregnant women for HBV infection in the first trimester of pregnancy, the pooled seroprevalence of HBV based on the trimester in which the women were tested was 1.8% (0.7–2.9) in the first trimester, 3.0% (1.5–4.5) in the second trimester, and 2.3% (1.2–3.4) in the third trimester. This higher proportion of women tested in the second and third trimesters could be due to underutilization of health care services and late pregnancy registration, especially in rural areas.
      • Kumar G.
      • Choudhary T.S.
      • Srivastava A.
      • et al.
      Utilisation, equity and determinants of full antenatal care in India: analysis from the National Family Health Survey 4.
      The current healthcare programs should be aimed at increasing the testing of women in the first or second trimester rather than in the third trimester or at delivery to initiate early therapy for transmission reduction. The previous meta-analysis a decade ago reported a significantly higher prevalence of HBV infection in tribal areas of India, 15.5%, compared to non-tribal regions, 2.4%.
      • Batham A.
      • Narula D.
      • TotejaT
      • Sreenivas V.
      • Puliyel J.
      Systematic review and meta-analysis of prevalence of hepatitis B in India.
      However, we could not perform a similar analysis due to data unavailability. The pooled seroprevalence of HBV in women from urban areas was 1.3% (0.4–2.1), while in women from rural areas was 1.4% (0.6–2.3) without any difference (OR 0.88, 95%CI 0.56–1.39). This indicates the increased penetration and access to health care services in rural areas along with increased awareness regarding proper antenatal care among women.
      Education plays a vital role in raising awareness among women regarding the need for HBV vaccination and antenatal care during pregnancy. Accordingly, the seroprevalence of HBV in women who were illiterate or had primary education was 3.8% (1.2–6.5), and in those with secondary level or higher education, it was 1.5% (0.9–2.0) with a significantly higher odds of HBV seroprevalence in those with education less than secondary level (OR 2.29, 95%CI 1.24–4.23). Previous two other meta-analyses have also shown that illiteracy was the only significant demographic factor associated with increased risk of HBsAg positivity.
      • Badfar G.
      • Shohani M.
      • Nasirkandy M.P.
      • et al.
      Epidemiology of hepatitis B in pregnant Iranian women: a systematic review and meta-analysis.
      ,
      • Olakunde B.O.
      • Adeyinka D.A.
      • Olakunde O.A.
      • et al.
      A systematic review and meta-analysis of the prevalence of hepatitis B virus infection among pregnant women in Nigeria.
      Risk factors for HBV infection include a history of blood transfusion and surgical procedures, among many others. Prior history of surgery was present in 20.9% (11.4–30.5), while a history of blood transfusion was present in 13.5% (8.0–19.0) women. Though blood donors are mandatorily screened for HBsAg in blood banks, HBsAg alone cannot definitively rule out the risk of transmission of HBV infection from donors who are in the window period, occult HBV infection, mutant genotypes with false-negative HBsAg status. Incorporating anti-HBc and HBV DNA testing overcomes this limitation but with an additional cost. The only plausible way to decrease the prevalence of HBV infection is to increase awareness regarding safe sexual practices, MTCT, providing access to health care in remote areas of the country along with vaccine coverage. Under the Universal immunization program, all infants receive the first dose of the HBV vaccine within 24 h of birth. However, only adults with high risk are advocated for the HBV vaccine. It is of utmost importance to include the HBV vaccine in adult immunization schedules and catch-up vaccination programs to decrease the prevalence of HBV infection in India.
      There are a few limitations to the present meta-analysis. Most of the studies were retrospective, associated with a high risk of selection bias and significant heterogeneity among the studies. Second, data were available from only 18/35 states or union territories; thus, the present figure may not be representative of the entire population. Third, most studies did not report on HBeAg status and HBV viral load, which are important markers and should be done at 28 weeks for deciding on antiviral therapy in pregnant women. Lastly, data on associated risk factors were available in only a few studies, and vaccination history was unavailable in the majority.
      To conclude, the pooled seroprevalence of HBV was low in Indian pregnant women compared to the previously reported data of intermediate prevalence in the general population. Better educational status may be associated with a lower prevalence of HBV, indicating the role of improving the education status of women. The present data may be helpful in the estimation of the HBV burden in pregnant women and for projecting the cost-benefits of immunization. In less than one-fourth of cases, risk factors were detected, indicating vertical transmission as the dominant mode of acquisition, which can be reduced by improving vaccination coverage.

      Credit authorship contribution statement

      Conceptualization: SG,ShS; Data curation: SG,SuA,ShA; Formal analysis: SG,SuA,ShA; Funding acquisition: N/A; Investigation: SG,ShS; Methodology: SG,ShS,SuA,ShA,SrS,SB; Project administration: SrS,SB; Resources: SG,ShS,SuA,ShA; Software: SG; Supervision; SrS,SB; Validation: SG,SrS; Visualization: SG; Roles/Writing - original draft: SG,ShS,SuA,ShA,SrS,SB; Writing - review & editing: SG,ShS,SuA,ShA,SrS,SB.

      Conflicts of interest

      The authors have none to declare.

      Acknowledgments

      None.

      Funding

      None.

      Appendix A. Supplementary data

      The following is the Supplementary data to this article:

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