Study (year)Representativeness of the exposed cohortSelection of the non-exposed cohortAscertainment of exposureDemonstration that outcome of interest was not present at baselineComparability of cohorts on the basis of the design or analysisAssessment of outcomesWas follow up long enough for outcomes to occurAdequacy of follow up of cohortsTotal number of stars (risk of bias)a
Greenup AJ (2014)☆ At least somewhat representative of the average HBV-infected pregnant woman☆ Drawn from the same community (same inclusion and exclusion criteria also)☆ Reporting on adherence within the paper, reduction of viral load used to assess women’s response to treatment☆ Always the case☆☆ Comparable for HBV DNA level and comparable HBeAg positive. Same regimen for infant immunoprophylaxis and confirmation that all infants received itNo details given on laboratory methods for infants, and no details of which assay was used for testing HBsAg☆ Yes> 20% LFU in control group, although <20% LFU in two treatment groups7 (low)
Zhang H (2014)☆ At least somewhat representative of the average HBV-infected pregnant woman☆ Drawn from the same community (same inclusion and exclusion criteria also)☆ Monthly HBV DNA level testing was done to check maternal adherence☆ Always the case☆☆ Comparable for HBV DNA level and comparable HBeAg positive. Same regimen for infant immunoprophylaxis☆ Describes testing done and refers to a central laboratory employed for this study☆ Yes☆ LFU reported and <20% LFU in all treatment and control groups9 (low)
Jackson V (2015)☆ At least somewhat representative of the average HBV-infected pregnant woman☆ Drawn from the same community (same inclusion and exclusion criteria also)☆ Mentions good treatment compliance in all but one patient, and measures decrease in viral load in 35/36 women taking treatment just prior to delivery and saw a significant decrease in most patients (also show these results in a figure in the paper)☆ Always the caseHBV DNA level and HBeAg not described in control group. Mentions that all infants received the same regimen for infant immunoprophylaxis; however, in the control group, many women defaulted from care/moved to other maternities, so this does not seem well verified☆ Laboratory assays described, with indication of record linkage (results viewed retrospectively in medical records)☆ Yes<80% retention in both treated and control groups6 (high)
Liu CP (2015)☆ At least somewhat representative of the average HBV-infected pregnant womanMany more women included in the control group (highly disproportionate, which could indicate non-similarity with the treated)Some limited data presented on decrease of maternal viral load, but no mention of linking this with compliance/adherence/time on treatment, and no detailed results provided☆ Always the caseHBV DNA level and/or HBeAg not described for both treated and control groups. Similar infant prophylaxis between treated and control groups☆ Laboratory assays described, with indication of record linkage (results viewed retrospectively in medical records)☆ YesNo loss to follow up described because it was a retrospective cohort study (or listed as such) where the infants needed to have had test results at the testing time-point (this is therefore misclassified as a cohort study, and has a high risk of bias for loss to follow up)5 (high)
Pan CQ (2017)☆ At least somewhat representative of the average HBV-infected pregnant womanSame population and criteria, however, no indication of how this group was chosen (usually says “unwillingness”, for example)Some data presented on decrease of maternal viral load, but no mention of linking this with compliance/adherence/time on treatment. Additionally, because of study design (retrospective) there is low/no chance of adherence monitoring☆ Always the case☆☆ Comparable for HBV DNA level and comparable HBeAg positive. Same regimen for infant immunoprophylaxis☆ Reference to the hospital’s centralized laboratory and linkage to medical records for assessing infant outcome☆ YesNo loss to follow up described because it was a retrospective cohort study (or listed as such) where the infants needed to have had test results at the testing time-point (this is therefore misclassified as a cohort study, and has a high risk of bias for loss to follow up)6 (high)
He T (2018)☆ At least somewhat representative of the average HBV infected pregnant woman☆ Drawn from the same community with same inclusion and exclusion criteria☆ Detailed information on reduction of viral load given, including specific data for each woman (every one had a −6 to −8 log reduction)☆ Always the case☆☆ Comparable for HBV DNA level and comparable HBeAg positive. Same regimen for infant immunoprophylaxis☆ Linkage to medical records☆ YesRetrospective cohort mentioned but no loss to follow up described, no mention of how there was perfect retention8 (low)
Wakano Y (2018)Not representative of the general population (women who have had a child infected previously)☆ Drawn from the same community with same inclusion and exclusion criteria☆ >2 log reduction of HBV DNA levels in all treated women☆ Always the case☆ Comparable for HBV DNA level and comparable HBeAg positive. Different immunoprophylaxis regimens mixed among the groups of treated and non-treatedLaboratory assays not well described☆ Yes☆ 100% retention6 (high)
Foaud HM (2019)☆ Truly representative of the average HBV-infected pregnant womanControl group comprised women who were not candidates for lamivudine (likely to be quite different from those who received it)☆ States that women were given lamivudine monthly and were questioned regarding compliance at each visit☆ Always the case☆ HBeAg proportion not comparable, and HBV DNA at baseline not given. Same regimen for infant immunoprophylaxis☆ Lab testing done centrally as part of the study, laboratory assays for defining infant outcome described☆ Yes<80% follow up at 6–12 months in control group, though ~86% follow up in treated group at that time-point. (Note: at later time-point that study defined, there was >80% follow up)6 (high)
a

Risk of bias assessments should be classified as being either low (≥7) or high (<7) by the Newcastle–Ottawa scale

From: Web Annex A, Systematic review of the efficacy and safety of antiviral therapy during pregnancy

Cover of Prevention of Mother-to-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy
Prevention of Mother-to-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy.
Geneva: World Health Organization; 2020 Jul.
© World Health Organization 2020.

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