Chronic hepatitis C virus infection is associated with increased risk of preterm birth: a meta-analysis of observational studies
Huang Q-T, et al.
Journal of Viral Hepatitis, 2015; 22: 1033–42 .

Several epidemiological studies reported that maternal chronic HCV infection had significantly increased risk of undergoing adverse obstetrical and perinatal outcomes such as gestational diabetes mellitus, premature rupture of membranes, low birthweight infants and stillbirth. However, studies on the relationship between HCV infection and risk of preterm birth (PTB) have yielded inconclusive and inconsistent results.

Therefore, a systematic review of the literature and a meta-analysis were conducted to investigate the association between HCV infection and PTB. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. PubMed and Embase databases were searched until 1 September 2014. Articles were included if they investigated the association between HCV infection before pregnancy and the risk of PTB among pregnant women vs non-HCV control groups. PTB diagnosis was defined as delivery before 37 weeks' gestation.

The pooled odds ratio (OR) with 95% confidence intervals (CIs) between HCV infection and PTB was used to estimate the effect sizes. The ORs were combined in a meta-analysis using a fixed-effects model when heterogeneity observed among studies was absent to moderate. When heterogeneity was high (I 2 > 50%), a random-effects model was used.

The publication bias was investigated.

Subgroup analysis was performed with respect to study type, maternal age, parity, smoking/alcohol abuse status, drug abuse status and coinfected viral diseases status in order to explore the influence of these factors on the association.

Statistical analysis was performed using REVMEN 5.3 and STATA 10.0.

Nine studies (7 cohort studies and 2 case–control studies) involving 4186698 participants and 5218 HCV infection cases evaluated the ORs of preterm birth. All studies were of intermediate or high quality.

A significant association between HCV infection and PTB was observed (odds ratio = 1.62, 95% CI 1.48–1.76, P < 0.001, fixed-effects model). Stratification according to maternal smoking/alcohol abuse, maternal drug abuse or coinfected with HBV and/or HIV matched groups still demonstrated that women with HCV infection have a high risk for PTB with no or mild heterogeneity observed. There was a low probability of publication bias.

Findings from this meta-analysis suggested that maternal HCV infection was significantly associated with an increased risk of PTB. In the future, pathophysiological studies are warranted to ascertain the causality and explore the possible biological mechanisms involved.

Expert's Perspective

« The association between chronic hepatitis C virus infection and the risk of preterm labor is still controversial. This meta-analysis found a positive relationship between HCV infection and preterm labor. However, other factors may influence pregnancy outcomes in HCV-infected women. Maternal drug abuse, alcohol abuse and tobacco use, as well as HIV and HBV coinfection were included in the multivariate statistical analysis. The results showed that these factors had no significant impact. Despite this, the meta-analysis has several limitations. HCV infection was diagnosed by the presence of anti-HCV antibodies and only few studies had HCV RNA determination. It is critical to identify HCV Infection by HCV RNA and compare the risk of preterm birth among HCV RNA positive and HCV RNA negative mothers. Other cofactors such as the immunovirological status of HIV coinfection and extrahepatic manifestations of HCV infection need also to be weighted. The finding that maternal HCV infection could be associated with an increased risk of preterm birth has to be confirmed in prospective cohort studies including HCV RNA determination, before counselling pregnant women about potential risks of preterm birth. If these results are confirmed, this would be a very strong argument to recommend therapy for HCV in young women planning pregnancy »

Pr Maria Butti, Hospital General Universitari Valle Hebron, Barcelona