Maternal chronic hepatitis B virus (HBV) infection is associated with a 16% increase in risk of preterm birth (PTB), with substantial heterogeneity, according to an updated systematic review and meta-analysis in the Journal of Medical Virology.
The analysis also found that risk of PTB significantly increased by 21% in HBsAg-positive/HBeAg-positive pregnant women compared to pregnant women who were uninfected.
“Maternal viral infection is a frequent and important risk cause of preterm birth basically due to activation of the innate immune system,” wrote the Chinese authors.
A recent, large-sample Chinese study showed that maternal pre-pregnancy chronic HBV infection is independently associated with a high risk of PTB and early PTB, and that the association was similar among subgroups of patients with various baseline characteristics.
However, the authors of the current evaluation noted that the effects of chronic HBV infection on PTB are inconsistent, based on previous meta-analyses, ranging from no association to a weak association to being mostly at risk for spontaneous PTB.
Limitations of these previous reviews include few observational studies and lack of subgroup analysis and detailed heterogeneity analysis, as well as confounding factors in preterm labor and PTB.
Information for the current meta-analysis was collected on pregnant women from 22 observational studies, three prospective cohort studies, 15 retrospective cohort studies and four case-control studies.
Analysis of 11 relevant observational studies demonstrated that chronic HBV infection is associated with a 28% increase in incidence of preterm labor, in a random-effects model with substantial heterogeneity.
Likewise, analysis of 16 relevant observational studies showed a 16% higher incidence of PTB for maternal chronic HBV infection.
“Different subgroup analyses show similar heterogeneity among the included studies, but reveal the relative negative influence of chronic HBV infection on preterm birth only based on study design,” the authors wrote.
Sensitivity analyses also concluded that heterogeneity did not cease after excluding any study.
Moreover, meta-regression demonstrated that no significant factor contributed to heterogeneity, indicating that heterogeneity between studies cannot be well explained by any of the tested characteristics.
Regarding preterm labor, chronic HBV infection was found to be a significant influence only in the case-control studies, with large selection bias.
As for PTB, chronic HBV infection was observed as a relatively negative influence in studies from developed geographic regions, large sample studies or studies with adjusted covariates.
Some of the studies propose possible mechanisms that cause chronic HBV infection to increase risk of preterm labor and/or birth, including HBV interacting with the placental inflammatory response, which is a known contributor to PTB.
Risk factors linked to HBV infection like substance use and low socioeconomic status are also associated with PTB, which contribute to increased incidence of PTB in developed regions.
Moreover, HBeAg positivity is directly related to a greater number of viral copies, which might reflect a higher viral load in HBsAg-negative women versus HBsAg-positive women.
“In other words, the impact degree on pregnancy outcomes could be associated with the number of viral copies or load,” wrote the authors.
Despite several strengths of the study, including a broad search strategy and a large sample size, the authors did not identify unpublished reports, thus potentially skewing results. Also, the criterion for classifying developing and developed regions was not necessarily accurate.
Information about treatment of infection in mothers also was lacking, too.
Further, the conclusion that chronic HBV infection increases risks of preterm labor and birth, “should be interpreted with caution given the possibility of residual confounding, and be confirmed by well-designed studies in the future,” the authors wrote.