EPIDEMIOLOGY, NATURAL HISTORY, AND TREATMENT OUTCOMES OF PREGNANT WOMEN WITH HCV INFECTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 227 STUDIES AND 255,862,858 WOMEN

INTRODUCTION: Pregnant women with HCV represent a special population where
treatment access remains limited despite the availability of effective DAA. We sought to
determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal
complication rates, and DAA treatment outcomes of CHC in pregnant women.

METHOD: We performed a systematic review and meta-analysis using 5 databases
(PubMed, MEDLINE, EMBASE, Scopus, Web of Science) to estimate the pooled HCV
prevalence during pregnancy, and the pooled odds of complications and treatment outcomes
in pregnant women with HCV infection using a random effects model.

RESULTS: From a total of 225,862,858 pregnant women from 227 studies as identified by
our search strategies and systematic review of the initial group of 8876 articles, the pooled
global seroprevalence and viraemic prevalence of HCV in pregnant women were 3.9%
(95%CI: 2.6-5.4) and 1.3% (95%CI: 0.5-2.36), respectively. We observed a wide regional
variation in HCV viraemic prevalence: highest in the American region (3.3%, 95%CI: 0-11.8)
and lowest in the Western Pacific region (0.32%, 95%CI: 0.18-0.49) (Figure 1). HCV
seroprevalence among pregnant women also increases with the proportion of intravenous
drug users in each study. The pooled MTCT rate in HCV viraemic mothers was 8.8%
(95%CI: 6.1-11.9). MTCT rate was not influenced by the mode of delivery (Natural versus
Cesarean section: OR: 1.04, 95%CI: 0.6-1.7, I² =26%).

HCV pregnant women had more maternal complications with higher odds of intrahepatic
cholestasis, preterm delivery, and antepartum hemorrhage but lower odds of pre-eclampsia
(Figure 2). Neonates from HCV mothers also had significantly higher odds of neonatal
jaundice and were small for gestational age. The pooled rate of SVR12 using DAA in
pregnant women with HCV (6 studies, n=60 [25 with sofosbuvir/ledipasvir, 7
sofosbuvir/daclatasvir, 2 sofosbuvir/velpatasvir, and 26 unknown), was 100% by per protocol
analysis and 87% by intention-to-treat analysis due to a loss to follow-up in 22%. No
treatment-related adverse event among pregnant mothers or in neonates requiring treatment
cessation.

CONCLUSION: HCV prevalence in pregnant women varies by geographic region, while
MCTC occurs in almost one in ten viremic mothers and without significant differences in
delivery methods. Importantly, both maternal and neonatal complications are significantly
higher in the setting of HCV infection. Limited data suggest that DAA is safe among pregnant
women with HCV infection. HCV screening during pregnancy should be offered for all
women in endemic areas, in those with risk factors such as illicit drug use, and where
universal screening is deemed cost-effective.