Abstract
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.
Keywords: hepatitis B, pregnancy, epidemiology, meta-analysis, prevalence
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
Graphical abstract
There is a wide variation in the reported data on the seroprevalence of hepatitis B virus (HBV) in pregnant patients from various parts of India requiring a systematic review of current literature. The present meta-analysis of 44 studies on the prevalence of markers of HBV among Indian pregnant women showed a pooled prevalence of HBsAg as 1.6% (1.4–1.8), indicating low endemicity. Among patients with HBsAg positivity, the pooled prevalence of HBeAg, anti-HBe, and HBV DNA were 26.0% (17.4–34.7), 40.1% (28.6–51.6), and 57.6% (8.4–100.0), respectively. On analyzing the demographic factors, 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, 1.24–4.23). Risk factors were seen in less than 25% of the cases, indicating vertical transmission as the predominant mode of acquisition.
Hepatitis B virus (HBV) infection is a global health problem, and India has the second-highest number of people living with HBV infection globally.1,2 Infected mothers significantly contribute to the pool of HBV infection in the population through perinatal transmission.3 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.4 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.5,6 In India, the carrier rate of HBV varies in different regions.7 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.7
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.7 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%).8 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.9
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.7 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)10 and the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.11
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 reviews12 (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.13 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.14 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 studies15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 (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 studies33,36,39,54,55 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 studies28,30,33,36,37,39,42 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.
PRISMA flowchart for study selection and inclusion process.
Table 1.
Characteristics of Included Studies.
| Author | Study design | Study duration | Location | Total sample | HBsAg Positive | Method used | HBeAg positive | Study quality |
|---|---|---|---|---|---|---|---|---|
| Abass 200115 | Retrospective | 1999 | Delhi | 6910 | 70 | ELISA | – | 7 |
| Sahni 200416 | Prospective | 2001–2002 | Delhi | 987 | 22 | ELISA | – | 8 |
| Shenoy 200417 | Prospective | 2001 | Karnataka | 300 | 12 | Both | 1 | 5 |
| Varghese 200418 | Prospective | 2000 | Delhi | 6341 | 52 | ELISA | – | 6 |
| Banerjee 200519 | Prospective | 1998 | West Bengal | 400 | 15 | ELISA | 4 | 6 |
| Chakravarti 200520 | Prospective | 1999–2000 | Delhi | 400 | 17 | ELISA | – | 4 |
| Sandesh 200621 | Prospective | 2002–2004 | Kerala | 70659 | 180 | ELISA | – | 6 |
| Singla 200822 | Retrospective | 2003–2007 | Chandigarh | 2933 | 51 | ELISA | – | 6 |
| Chatterjee 200923 | Prospective | 2003–2006 | Multicentric | 36379 | 398 | Both | – | 8 |
| Paranjothi 200924 | Prospective | – | Tamil Nadu | 762 | 39 | ELISA | 15 | 5 |
| Dwivedi 201125 | Prospective | 2006–2007 | Uttar Pradesh | 4000 | 37 | ELISA | 21 | 8 |
| Pande 201126 | Prospective | 2004–2008 | Delhi | 20194 | 224 | ELISA | 42 | 9 |
| Bakthavatchalu 201227 | Prospective | 2011–2012 | Tamil Nadu | 500 | 39 | ELISA | 22 | 5 |
| Jindal 201228 | Prospective | 2004–2006 | Punjab | 500 | 12 | ELISA | – | 6 |
| Khakhkhar 201229 | Retrospective | 2001–2003 | Gujarat | 2050 | 63 | Both | 11 | 7 |
| Pai 201230 | Prospective | 2008–2009 | Maharashtra | 1002 | 5 | Both | – | 9 |
| Saraswathi 201231 | Prospective | 2010–2012 | Telangana | 2155 | 19 | Both | – | 5 |
| Alexander 201332 | Prospective | 2002–2007 | Tamil Nadu | 12037 | 190 | Rapid | – | 9 |
| Dhevahi 201333 | Prospective | – | Tamil Nadu | 5042 | 276 | – | 41 | 7 |
| Mehta 201334 | Prospective | 2010 | Gujarat | 1038 | 31 | ELISA | – | 8 |
| Ambade 201435 | Retrospective | 2010–2014 | Maharashtra | 1815 | 21 | ELISA | – | 5 |
| Mehta 201436 | Prospective | 2013 | Gujarat | 1810 | 15 | ELISA | – | 5 |
| Bansal 201537 | Retrospective | 2012–2015 | Uttar Pradesh | 1600 | 38 | Both | – | 6 |
| Parveen 201538 | Prospective | – | Telangana | 465 | 4 | Both | – | 7 |
| Bharathi 201639 | Prospective | 2015 | Andhra Pradesh | 6982 | 91 | ELISA | – | 6 |
| Malhotra 201640 | Retrospective | 2015 | Haryana | 10000 | 84 | Both | – | 5 |
| Sibia 201641 | Retrospective | 2013–2014 | Punjab | 3686 | 41 | ELISA | – | 5 |
| Sinha 201642 | Prospective | 2015–2016 | Bihar | 1150 | 45 | Both | 5 | 7 |
| Garg 201743 | Prospective | 2015–2016 | Uttar Pradesh | 2058 | 42 | – | – | 6 |
| Mishra 201744 | Retrospective | 2016 | Madhya Pradesh | 3567 | 39 | Rapid | – | 6 |
| Rajendiran 201745 | Prospective | 2014–2016 | Tamil Nadu | 1282 | 13 | ELISA | – | 5 |
| Shinde 201746 | Retrospective | 2015–2016 | Karnataka | 3800 | 64 | – | – | 5 |
| Bose 201847 | Prospective | 2016–2017 | West Bengal | 540 | 6 | ELISA | – | 7 |
| Palange 201848 | Prospective | 2015–2017 | Telangana | 1411 | 14 | Rapid | – | 6 |
| Sharma 201849 | Prospective | 2015–2017 | Rajasthan | 1011 | 13 | Both | – | 6 |
| Tinna 201850 | Prospective | – | Rajasthan | 2212 | 12 | Rapid | – | 5 |
| Devi 201951 | Prospective | 2016–2018 | Telangana | 27024 | 133 | Rapid | – | 5 |
| Samal 201952 | Prospective | 2017–2018 | Odisha | 3230 | 150 | ELISA | – | 8 |
| Sujatha 201953 | Prospective | 2016–2017 | Telangana | 12240 | 93 | ELISA | – | 8 |
| Apoorva 202054 | Prospective | 2019–2020 | Uttar Pradesh | 435 | 12 | Rapid | – | 4 |
| Goel 202055 | Retrospective | 2019 | Uttar Pradesh | 9628 | 70 | Both | – | 7 |
| Jahan 202056 | Prospective | 2017–2018 | Uttar Pradesh | 345 | 20 | – | – | 4 |
| Prakash 202057 | Prospective | 2018–2019 | Bihar | 1440 | 12 | ELISA | – | 6 |
| Pandey 202158 | Prospective | – | Bihar | 275 | 1 | Rapid | – | 6 |
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 studies15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 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.
Forest plot for pooled seroprevalence of HBV in pregnancy with subgroup analysis based on year of study.
Figure 3.
State-wise reported pooled prevalence of HBV from the included studies.
Prevalence of HBeAg in Patients with Positive HBsAg
Only 9 studies17,19,24, 25, 26, 27,29,33,42 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 studies19,25, 26, 27,29,33,42 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 studies19,25, 26, 27,29,33,42 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 studies19,25,26,33 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 studies25,27,29,34,35,39,41,47, 48, 49, 50,52,54,56 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 studies25,26,28,32,43,47,48,52 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 studies27,29,34,35,47,49,56 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 studies28,41,47,50,56 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 studies28,41,43,52 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.
Forest plot comparing the seroprevalence of HBV based on the educational status of the pregnant women.
Prior Risk Factors
Overall, 10 studies25, 26, 27,29,37,42,43,49,52,56 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.33 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.
Bubble 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 2.
Sensitivity Analysis for Seroprevalence of Hepatitis B in Pregnant Women.
| Groups | No. of studies (no. of patients) | Prevalence | I2 |
|---|---|---|---|
| Overall | 43 studies (n = 267553) | 1.5% (1.3–1.7) | 96.1% |
| Age distribution | |||
| Less than 25 years | 14 studies (n = 16995) | 2.1% (1.4–2.8) | 94.1% |
| More than 25 years | 14 studies (n = 12243) | 1.6% (1.2–2.0) | 68.8% |
| Parity | |||
| Primipara | 8 studies (n = 18240) | 1.7% (1.0–2.4) | 94.9% |
| Multipara | 8 studies (n = 25443) | 1.4% (1.1–1.8) | 74.5% |
| Antenatal period | |||
| First trimester | 7 studies (n = 1645) | 1.8% (0.7–2.9) | 66.9% |
| Second trimester | 7 studies (n = 2629) | 3.0% (1.5–4.5) | 83.5% |
| Third trimester | 7 studies (n = 2994) | 2.3% (1.2–3.4) | 73.1% |
| Residence | |||
| Urban | 5 studies (n = 3220) | 1.3% (0.4–2.1) | 67.8% |
| Rural | 5 studies (n = 4063) | 1.4% (0.6–2.3) | 68.7% |
| Education | |||
| None or primary | 4 studies (n = 6562) | 3.8% (1.2–6.5) | 96.6% |
| Secondary or higher | 4 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.59
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.,52 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 2005.7 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.60 Pande et al.26 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.60
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.61 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%.7 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.62,63
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.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jceh.2022.08.005.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
References
- 1.Razavi-Shearer D., Gamkrelidze I., Nguyen M.H., et al. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3:383–403. doi: 10.1016/S2468-1253(18)30056-6. [DOI] [PubMed] [Google Scholar]
- 2.Custer B., Sullivan S.D., Hazlet T.K., Iloeje U., Veenstra D.L., Kowdley K.V. Global epidemiology of hepatitis B virus. J Clin Gastroenterol. 2004 Nov 1;38:S158–S168. doi: 10.1097/00004836-200411003-00008. [DOI] [PubMed] [Google Scholar]
- 3.Ayoub W.S., Cohen E. Hepatitis B management in the pregnant patient: an update. J Clin Transl Hepatol. 2016;4:241–247. doi: 10.14218/JCTH.2016.00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Previsani N., Lavanchy D. Organisation WH: World Health Organisation. 2002. Hepatitis B. Geneva: department of communicable diseases surveillance and response. [Google Scholar]
- 5.Gentile I., Borgia G. Vertical transmission of hepatitis B virus: challenges and solutions. Int J Womens Health. 2014;6:605–611. doi: 10.2147/IJWH.S51138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.WHO | Hepatitis B [Internet] WHO. World Health Organization; May 22, 2020. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b Available from: [Google Scholar]
- 7.Batham A., Narula D., TotejaT, Sreenivas V., Puliyel J. Systematic review and meta-analysis of prevalence of hepatitis B in India. Indian Pediatr. 2007;44:663–674. [PubMed] [Google Scholar]
- 8.McMahon B.J. Epidemiology and natural history of hepatitis B. InSeminars in liver disease. 2005 Feb;25:3–8. doi: 10.1055/s-2005-915644. Published in 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. [DOI] [PubMed] [Google Scholar]
- 9.Keane E., 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. Aliment Pharmacol Ther. 2016;44:1005–1017. doi: 10.1111/apt.13795. [DOI] [PubMed] [Google Scholar]
- 10.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. JAMA. 2000;283:2008–2012. doi: 10.1001/jama.283.15.2008. [DOI] [PubMed] [Google Scholar]
- 11.Page M.J., McKenzie J.E., Bossuyt P.M., et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Munn Z., Barker T.H., Moola S., et al. Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. JBI Evid Synth. 2020;18:2127–2133. doi: 10.11124/JBISRIR-D-19-00099. [DOI] [PubMed] [Google Scholar]
- 13.DerSimonian R., Laird N. Meta-analysis in clinical trials. Contr Clin Trials. 1986;7:177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
- 14.Higgins J.P., Thompson S.G., Deeks J.J., Altman D.G. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560. doi: 10.1136/bmj.327.7414.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Abass F., Thomas R.D., Rajkumar A., Gupta N., Puliyel J.M. Controlling perinatally acquired hepatitis B. Indian J Pediatr. 2001;68:365. doi: 10.1007/BF02721853. [DOI] [PubMed] [Google Scholar]
- 16.Sahni M., Jindal K., Abraham N., Aruldas K., Puliyel J.M. Hepatitis B immunization: cost calculation in a community-based study in India. Indian J Gastroenterol. 2004;23:16–18. [PubMed] [Google Scholar]
- 17.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. Trop Doct. 2004;34:98–99. doi: 10.1177/004947550403400215. [DOI] [PubMed] [Google Scholar]
- 18.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. Indian J Gastroenterol. 2004;23:154–156. [PubMed] [Google Scholar]
- 19.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. Southeast Asian J Trop Med Public Health. 2005;36:203–206. [PubMed] [Google Scholar]
- 20.Chakravarti A., Rawat D., Jain M. A study on the perinatal transmission of the hepatitis B virus. Indian J Med Microbiol. 2005;23:128–130. doi: 10.4103/0255-0857.16055. [DOI] [PubMed] [Google Scholar]
- 21.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. Trop Gastroenterol. 2006;27:80–83. [PubMed] [Google Scholar]
- 22.Singla N., Chander J. Seroprevalence of HBsAg in females in a North India tertiary care hospital, with special reference to pregnancy. N Z Med J. 2008;121:105–106. [PubMed] [Google Scholar]
- 23.Chatterjee S., Ravishankar K., Chatterjee R., Narang A., Kinikar A. Hepatitis B prevalence during pregnancy. Indian Pediatr. 2009;46:1005–1008. [PubMed] [Google Scholar]
- 24.Paranjothi S., Vijayarani H. Prevalence of hepatitis b virus surface antigen in pregnant women attending a private hospital in Krishnagiri. Adv Biotech. 2009;9:38–40. [Google Scholar]
- 25.Dwivedi M., Misra S.P., Misra V., et al. Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission. Indian J Gastroenterol. 2011;30:66–71. doi: 10.1007/s12664-011-0083-y. [DOI] [PubMed] [Google Scholar]
- 26.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. J Med Virol. 2011;83:962–967. doi: 10.1002/jmv.22017. [DOI] [PubMed] [Google Scholar]
- 27.Bakthavatchalu D. Hepatitis B surface antigen carrier state among asymptomatic pregnant women and its correlation with vertical transmission. Int J Res Pharm Sci. 2012;2:111–120. [Google Scholar]
- 28.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. J Obstet Gynaecol India. 2012;62:158–161. doi: 10.1007/s13224-012-0164-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.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) Natl J Med Res. 2012;2:362–365. [Google Scholar]
- 30.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. Int J STD AIDS. 2012;23:319–324. doi: 10.1258/ijsa.2011.011139. [DOI] [PubMed] [Google Scholar]
- 31.Saraswasthi K.S., Aljabri F. The study of prevalence of Hepatitis B surface antigen during pregnancy in a tertiary care hospital, South India. Der Pharm Lett. 2012;4:983–985. [Google Scholar]
- 32.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. Indian J Med Res. 2013;137:356–362. [PMC free article] [PubMed] [Google Scholar]
- 33.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. Glob Res Analysis. 2013;4:210–211. [Google Scholar]
- 34.Mehta K.D., Antala S., Mistry M., Goswami Y. Seropositivity of hepatitis B, hepatitis C, syphilis, and HIV in antenatal women in India. J Infect Dev Ctries. 2013;7:832–837. doi: 10.3855/jidc.2764. [DOI] [PubMed] [Google Scholar]
- 35.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. Int J Med Sci Publ Health. 2014;3:1439–1441. [Google Scholar]
- 36.Mehta K., Garala N., Garala R., et al. The study of prevalence of Hepatitis B surface antigen during pregnancy. J Res Med Dent Sci. 2014;2:17–19. [Google Scholar]
- 37.Bansal V., Bansal A., Bansal A.R., Kumar A. Seroprevalence of HBV in pregnant women and its coinfection with HCV & HIV. Int J Rec Sci Res. 2015;6:3590–3593. [Google Scholar]
- 38.Parveen S.S., Madhavi S. Antenatal screening for HIV, hepatitis B and syphilis in a tertiary care hospital. Int J Curr Microbiol App Sci. 2015;4:318–322. [Google Scholar]
- 39.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. Ind J Med Res Phar Sci. 2016;3:57–61. [Google Scholar]
- 40.Malhotra P., Nanda S., Malhotra V., et al. Prevalence of HIV, hepatitis B, hepatitis C in pregnancy at tertiary care center of northern India. Adv Res Gastroenterol Hepatol. 2016;1:1–3. [Google Scholar]
- 41.Sibia P., Mohi M.K., Kumar A. Seroprevalence of hepatitis B infection among pregnant women in one of the Institute of northern India. J Clin Diagn Res. 2016;10 doi: 10.7860/JCDR/2016/20614.8299. QC08-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Sinha A., Sharan M., Shahi S.K. Seroprevalence of hepatitis B virus in pregnant women at a tertiary care hospital of eastern India. Natl J Lab Med. 2016;5:1–4. [Google Scholar]
- 43.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. J S Asian Fed Obst Gynecol. 2017;9:164–168. [Google Scholar]
- 44.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. Int J Reprod Contracept Obstet Gynecol. 2017;6:2238–2240. [Google Scholar]
- 45.Sathiyakala R., Ushadevi G., Karthika J. Seroprevalence of Hepatitis B infection among pregnant women in South India. Int J Reprod Contracept Obstet Gynecol. 2017;6:249–251. [Google Scholar]
- 46.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. Indian J Microbiol Res. 2017;4:270–273. [Google Scholar]
- 47.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. J Evolution Med Dent Sci. 2019;7:2977–2981. [Google Scholar]
- 48.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. Pers Med Res. 2018;1:26–29. [Google Scholar]
- 49.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. Int Arc Biomed Cli Res. 2018;4:77–79. [Google Scholar]
- 50.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. Int J App Res. 2018;4:189–191. [Google Scholar]
- 51.Kavitha Devi P., Vijaya Laxmi P., Santosh Kumar B. Seroprevalence of HBsAg among antenatal women attending tertiary care hospital, Telangana state. Int J Sci Res. 2019;8:33–34. [Google Scholar]
- 52.Samal N., Padhi S., Burman L. Seroprevalence of hepatitis B infection among pregnant women in southern Odisha. Indian J Med Specialities. 2019;10:207–209. [Google Scholar]
- 53.Sujatha A., Shvetha K. Study on hepatitis B virus infection in pregnant women and its risk factors. Int J Contemp Med Res. 2019;6:C1–C6. [Google Scholar]
- 54.Apoorva B., Manjhi M., Mohan S., Kakru D.K. Seroprevalence of hepatitis B infection among pregnant women at a tertiary care hospital. Int J Curr Microbiol App Sci. 2020;9:2164–2166. [Google Scholar]
- 55.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. Int J Med Microbiol Trop Dis. 2020;6:86–89. [Google Scholar]
- 56.Jahan G., Jahan N., Rungta S., Ahmad A. Seroprevalence and risk factors of hepatitis B and C infections among pregnant women. Int J Res Med Sci. 2020;8:1718–1723. [Google Scholar]
- 57.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. Scholars J Appl Med Sci. 2020;8:409–412. [Google Scholar]
- 58.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. J Fam Med Prim Care. 2021;10:3675–3681. doi: 10.4103/jfmpc.jfmpc_731_21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59.World Health Organization . 2020. Prevention of Mother-To-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy. Geneva. [PubMed] [Google Scholar]
- 60.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. Lancet Infect Dis. 2021 Jan 1;21:85–96. doi: 10.1016/S1473-3099(20)30593-4. [DOI] [PubMed] [Google Scholar]
- 61.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. BMC Pregnancy Childbirth. 2019 Dec;19:1–9. doi: 10.1186/s12884-019-2473-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Badfar G., Shohani M., Nasirkandy M.P., et al. Epidemiology of hepatitis B in pregnant Iranian women: a systematic review and meta-analysis. Arch Virol. 2018;163:319–330. doi: 10.1007/s00705-017-3551-6. [DOI] [PubMed] [Google Scholar]
- 63.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. PLoS One. 2021;16 doi: 10.1371/journal.pone.0259218. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.