Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis

Summary

Background

Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women.

Methods

We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle–Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023.

Findings

From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0–3.2, I² = 100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6–11.7, I² = 79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1–4.6, I² = 10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported.

Interpretation

HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection.

Funding

None.

Research in context.

Evidence before this study

The prevalence of hepatitis C virus (HCV) among younger women of reproductive age is increasing; however, the microelimination of HCV in this population remains an unmet need. A reliable estimate of the prevalence, natural history, and treatment outcomes of pregnant women with HCV infection is crucial to identify gaps and coordinate efforts of global HCV micro-elimination. We searched PubMed, EMBASE, Scopus and Web of Science from study inception until March 1, 2024, using the keywords “hepatitis C,” “pregnancy,” “prevalence,” “vertical transmission,” “mother-to-child,” “preterm,” “intrauterine growth restriction,” “intrahepatic cholestasis,” “direct-acting antiviral,” “treatment,” “efficacy,” and “safety” and did not identify any systematic review and meta-analysis that specifically and comprehensively addressed the prevalence, natural history, along with the treatment outcomes in pregnant women with HCV infection.

Added value of this study

This meta-analysis including 311,905,738 pregnant women with HCV infection from 333 studies, 62 countries, and six continents provided an updated estimate on global burden of HCV in pregnant women and complications associated with this. Despite the significant prevalence in this population and early data supporting the safety of direct-acting antivirals among pregnant women, HCV treatment among pregnant women remains low.

Implications of all the available evidence

Given the global HCV prevalence in young women, maternal & child sequelae of untreated HCV, and suboptimal uptake of DAA, the utility of risk-based versus universal screening should be examined to be aligned with the current guidelines. Linkage of care remained an important unmet need to optimize treatment uptake among pregnant women and neonates with HCV infection.

Introduction

Hepatitis C virus (HCV) infection is a major global health challenge that affects up to 50 million people with only 36% of people diagnosed between 2015 and 2020, and 20% receiving curative treatment.¹ In 2016, the World Health Organization (WHO) global hepatitis strategy set a goal to eliminate HCV by 2030.² This was defined as an 80% reduction in incidence and 65% reduction in mortality relative to 2015. While the global HCV prevalence has declined from 71 million since the introduction of direct-acting antivirals (DAA),3, 4, 5, 6 both pregnant women and children aged 3 and under are left behind because the current DAA is not licensed in these populations. While the current guidelines suggest that DAA treatment in pregnant women can be discussed on a case-by-case basis, HCV prevalence continues to rise among women of childbearing age.^7,8 This increase was primarily attributed to the opioid epidemic, resulting in an increase in substance use in women of childbearing age and a higher risk of injection-related behavior among women.^9,10 Parallel to this was an increase in HCV infection among children, suggesting the vertical transmission of HCV through pregnant mothers. Prenatal diagnosis of HCV infection among pregnant mothers is a prerequisite for appropriate screening and treatment of HCV-exposed infants. Furthermore, HCV diagnosis is a key step in the linkage between care and treatment in the postpartum setting.¹¹

Pregnant women with HCV infection constitute a special patient population. Maternal-to-child transmission (MTCT) of HCV is an important route of transmission,¹² and HCV infection may negatively affect maternal and fetal health.¹³ However, screening and treatment remain limited in pregnant women with HCV infections. This is primarily driven by the lack of safety data on DAA use among pregnant women and poor linkage to care postpartum.¹⁴ However, prior studies were limited by either single-centre or single-country designs, or by small sample sizes.¹⁵ Using a systematic review and meta-analytic approach, we aimed to provide a comprehensive review of HCV infection among pregnant women in terms of HCV prevalence, MTCT rates, maternal and fetal clinical outcomes, as well as the treatment response rates and tolerability to DAA among pregnant women with HCV infection. The study findings will inform the management of pregnant women with HCV infection as well as public health planning to curtail MTCT and assist with HCV elimination.

Methods

Search strategy and selection criteria

This systematic review and meta-analysis was conducted according to the Cochrane Handbook and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.¹⁶ We searched PubMed, MEDLINE, EMBASE, Scopus, and Web of Science from their inception to 1st March 1, 2024. The details of the search strategy are summarised in Supplementary Table S1. Briefly, our search strategy was based on a combination of MeSH terms and keywords such as “hepatitis C,” “pregnancy,” “prevalence,” “vertical transmission,” “mother-to-child,” “preterm,” “intrauterine growth restriction,” “intrahepatic cholestasis,” “direct-acting antiviral,” “treatment,” “efficacy,” and “safety.” This meta-analysis was performed according to the recommendations of the Cochrane Handbook of Intervention.¹⁷ The study protocol and pre-specified outcomes were registered in PROSPERO (CRD42024500023). Ethic approval was not required since this is a meta-analysis of published literature.

Selection of studies

We included studies that reported relevant data on pregnant women with HCV infection for any of the study aims. We excluded editorials, case reports, review articles, guidelines, animal or pediatric studies, clinical trial registries, and conference abstracts older than three years. In the event of overlapping data from multiple studies within the same cohort, only the data from the largest study, the study with the most detailed data, and/or the most updated study were included. Two authors (JWEQ, ABBO) independently screened the titles and abstracts identified in the primary search for eligibility followed by a full-text review. Any discrepancies in the screening process were resolved by consensus and/or a third senior author (WYJ).

Risk of bias assessment

The risk of bias was assessed using a scale developed for this study based on the Newcastle–Ottawa Scale (NOS) as per our study protocol (Supplementary Tables S2–S6)¹⁸ and our previous studies.19, 20, 21 Studies with a score of 7–9, 4–6, and <4 were considered to have a low risk of bias, 4–6 had a moderate risk of bias, and high risk of bias, respectively. In addition, we performed a second risk of bias assessment using the Risk of Bias in Non-Randomised Studies of Interventions (ROBIN-I), as recommended by the Cochrane Handbook.²²

Data extraction

All data were extracted using a standardised data collection form using predefined definitions. Data items from the standardised template included study characteristics (publication date, study location, primary author, sample size, and study design), patient characteristics (seroprevalence and viremic prevalence of HCV infection, age, human immunodeficiency virus (HIV) co-infection, and intravenous drug user [IVDU]), and relevant clinical outcomes (MTCT and obstetric and fetal complications). Additionally, we extracted data on antiviral treatment and outcomes in pregnant women with HCV infections. The corresponding authors were contacted for additional data details, when required.

Outcomes assessed

The outcomes of interest included in this study were (1) seroprevalence and viremic prevalence of HCV infection in pregnant women, with a pre-specified subgroup analysis based on the WHO region²³; (2) MTCT rate in pregnant women with HCV infection; (3) maternal and fetal complications; and (4) efficacy and safety of antiviral treatment in pregnant mothers with HCV infection. MTCT was defined as two or more HCV viral load positivity on two occasions beyond 2 months postpartum, or HCV antibody positivity beyond 18 months postpartum.¹⁵

Statistics

Before proceeding from systematic review to meta-analysis, we first summarised the characteristics of all included studies to determine if they were similar enough for pooled-analysis.²⁴ Once sufficient similar studies were available for pooled analysis, we performed a meta-analysis to improve the precision of our estimates.¹⁷

For HCV prevalence, we used the Freeman-Tukey double arcsine transformation to stabilise the variance of different studies.²⁵ We then used a random-effects model to estimate the pooled estimate of global HCV prevalence, expressed as 95% confidence interval (CI). Heterogeneity was assessed using Cochran's Q test. The percentage of variability due to between-study heterogeneity was assessed using I². I² values of <25, 25–50, and >50% represented low, moderate, and high heterogeneity.²⁶ Furthermore, we assessed publication bias using the Egger's test for continuous variables and Harbord's test for categorical variables.^27,28 We inspected funnel plots for asymmetrical distribution of data points across the vertical treatment effect axis. To explore the reason for this heterogeneity, further subgroup analyses were performed for HCV prevalence according to the year of publication, patient population, study design, study level, WHO region, maternal age, sample size, and study quality. Sensitivity analyses were performed using meta-regression to explore the potential interaction between HCV prevalence and the proportion of patients with intravenous drug use (IVDU) and HIV.²⁹ To assess the potential “dominant study effect” on the pooled global seroprevalence of HCV, we performed sensitivity analyses to identify influential studies using the leave-one-out method. The odds of maternal and neonatal complications and MTCT were presented as odds ratios (ORs) with 95% confidence intervals (CI) in forest plots. All analyses were performed using Review Manager (version 5.3) and R version 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria) using the “metap” package.³⁰

Role of funding source

The authors have no funding sources to declare.

Results

The study selection process is summarised in the PRISMA flowchart (Fig. 1). Of the initial 8945 citations identified, 5761 were screened and 333 studies (311,905,738 persons) were finally included in this meta-analysis. The mean (±SD) study quality score was 8.0 (±1.0), indicating that most studies had a low-to-moderate risk of bias. The concordance of the risk of bias assessment between the NOS and ROBINS-I was excellent (93.7%, n = 312/333 studies). The study characteristics of all included studies are reported in Table 1.

Fig. 1.

PRISMA Flowchart. ∗Total number of studies is less than the sum of the number of studies in the subgroups as some studies provided more than one outcome.

Table 1.

Study characteristics of all included studies.

Seroprevalence
S/N	Author, year	Country	Region	Study design	Study period	Study population	IVDU (n)	HIV patients(n)	Total (n)	Seroprevalence (n)
1	AbdulQawi, 2010	Egypt	EMR	Prospective	2003–2008	All pregnant women who were admitted at the obstetric emergency department at Benha University Hospital	NA	NA	1224	105
2	Aboubakar, 2020	Ethiopia	AFR	Cross-sectional	2018	Pregnant women who attended one of the 4 centres (3 Government hospitals and 1 private obstetrics and gynaecology clinic) in Cotonou	0	5	253	3
3	Abu, 2019	Israel	EUR	Retrospective	1991–2014	NR	NA	NA	243,682	186
4	Abuku, 2023	Ghana	AFR	Cross-sectional	2018	Pregnant women who visited the Comboni Hospital for antenatal care	NA	NA	250	9
5	Ades, 2000	UK	EUR	Prospective	1997–1998	NR	NA	4	126,009	241
6	Adhikari, 2019	USA	AMR	Cross-sectional	2017–2018	Women presenting for prenatal care at a large regional healthcare system	NA	NA	4891	75
7	Afsheen, 2017	Pakistan	EMR	Cross-sectional	NR	Women attending antenatal clinics at district headquarter hospitals	NA	NA	750	44
8	Agboghoroma, 2020	Nigeria	AFR	Cross-sectional	2016	Women who attended the antenatal clinic of National Hospital Abuja	2	31	252	3
9	Ahmad, 2016	Pakistan	EMR	Cross-sectional	2013–2014	Pregnant women admitted to Molvi Jee Hospital	NA	NA	10,288	146
10	Ahmed, 1998	Malawi	AFR	Retrospective	1993–1995	Serum samples collected between 1993 and 1995 in the Shire Valley in rural Malawi.	NA	6	150	24
11	Ahrens, 2023	USAa	AMR	Cross-sectional	2016–2020	Restricted-use data from the 2003 revised version of the US Standard Certificate of Live Birth for births	NA	NA	18,905,314	90,764
12	Akhtar, 2014	Pakistan	EMR	Cross-sectional	2009	Pregnant women who attended a public or private hospital of Lahore metropolitan	9	NA	83	9
13	Al-Kubaisy, 2017	Iraq	EMR	Cross-sectional	2013	NR	NA	NA	154	18
14	Al-Mandeel, 2015	Saudi Arabia	EMR	Cross-sectional	2010–2011	All pregnant women attending antenatal clinics at a university hospital in Riyadh city	NA	0	3051	2
15	Altinbas, 2009	Turkey	EUR	Retrospective	2006	Pregnant women admitted to a reference hospital in Ankara	NA	NA	4700	6
16	Amgalan, 2019	USAa	AMR	Retrospective	2017–2018	NR	NA	NA	3067	44
17	Andreotti, 2014	Malawi	AFR	Prospective	2008–2009	Women enrolled in the SMAC (Safe Milk for African Children) study	NA	309	309	8
18	Apea-Kubi, 2006	Ghana	AFR	Prospective	2000–2001	Patients attending the gynecological and antenatal clinics of the Korle-Bu teaching hospital	NA	NA	294	15
19	Arditi, 2023	USAa	AMR	Cross-sectional	2000–2019	Delivery hospitalizations among patients with a diagnosis of HCV infection using the National Inpatient Sample (NIS) created by the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project	NA	NA	76,698,773	182,094
20	Asres, 2022	Ethiopia	AFR	Cross-sectional	2019	Women who attended the at Mizan Tepi University Teaching Hospital (MTUTH)	NA	15	300	2
21	Assefa 2023	Ethiopia	AFR	Cross-sectional	2022	Pregnant women who attended the Debre Tabor Comprehensive Specialised Hospital	NA	NA	422	2
22	Aziz, 2010	Indiaa	SEAR	Prospective	NR	Pregnant patients who attended the Civil Hospital Karachi (CHK) and Abbasi Shaheed Hospital (ASH)	NA	NA	18,000	1043
23	Bafa, 2020	Ethiopia	AFR	Cross-sectional	2017	NR	NA	4	222	4
24	Bahat, 2019	Turkey	EUR	Retrospective	2012–2018	Pregnant women presenting to University of Health Sciences Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Obstetrics and Gynecology of İstanbul University of Health Sciences	NA	NA	67,760	200
25	Baldo, 2000	Italy	EUR	Cross-sectional	1996	Pregnant women attending antenatal clinic (Department of Obstetrics and Gynaecology) of the University of Padua (North-East Italy).	18	NA	2059	40
26	Balogun, 2000	UKa	EUR	Cross-sectional	1996	Women who during 1996 attended one of 14 antenatal clinics in Greater London and 11 antenatal clinics in the Northern and Yorkshire region	NA	NA	42,615	123
27	Barros, 2018	Brazil	AMR	Retrospective	2006–2013	Pregnant women who attended the Prenatal Service of the Hospital Universitario Antonio Pedro (HUAP)	NA	NA	635	7
28	Bassey, 2009	Nigeria	AFR	Cross-sectional	2005–2006	At the Wuse General Hospital, Abuja among pregnant women aged between 15 and 5	NA	42	500	8
29	Batool, 2008	Pakistan	EMR	Cross-sectional	2006–2007	Women who attended PMRC, Research Centre, Fatima Jinnah Medical College and Sir Ganga Ram Hospital Lahore	NA	NA	2439	178
30	Benhammou, 2018	Francea	EUR	Prospective	2005–2013	Women enrolled in the French Perinatal Cohort (ANRS CO1/CO11-EPF)	33	4236	4236	112
31	Benjelloun, 1996	Moroccoa	EMR	Cross-sectional	NR	NR	NA	NA	676	7
32	Berkley, 2008	USAa	AMR	Retrospective	2000–2006	All pregnant women from the Milagro Clinic, a state-supported drug abuse and treatment program	95	NA	300	159
33	Bibi, 2010	India	SEAR	Cross-sectional	2010	Pregnant women in the Department of Obstetrics and Gynaecology Unit-I, Liaquat University Hospital (LUH), Hyderabad	NA	NA	3078	146
34	Blasig, 2011	Canadaa	AMR	Cross-sectional	NR	NR	NA	NA	22,369	553
35	Boa-Sorte, 2014	Brazil	AMR	Cross-sectional	2009–2010	Women who attended one of the 16 Primary Health-care Units (UBS) distributed across seven administrative sub-units in Lauro de Freitas	NA	0	692	0
36	Bohman, 1992	USA	AMR	Retrospective	1991	Obstetric patients at Parkland Memorial Hospital.	23	NA	1005	23
37	Boland, 2021	USA	AMR	Retrospective	2016–2018	NR	NA	NA	8080	128
38	Bouare, 2012	Mali	AFR	Prospective	2009–2010	Pregnant women attending six reference health centres in Bamako	NA	41	1000	2
39	Boudova, 2018	USAa	AMR	Retrospective	2016	Pregnant women presenting to University of Maryland Medical Centre (UMMC)	NA	NA	1426	100
40	Bourdon, 2021	Francea	EUR	Prospective	NR	Women with a chronic viral illness HIV, HBV or HCV	NA	114	235	20
41	Boxall, 1994	USA	EUR	Cross-sectional	1990–1991	Women attending an inner city hospital antenatal clinic known to have a high proportion of immigrant women	NA	NA	3522	5
42	Brogly, 2019	USA	AMR	Prospective	2015–2016	Pregnant women attending the Project RESPECT (Recovery-Empowerment-Social Services-Prenatal Care-Education-Community-Treatment) Clinic	113	NA	113	80
43	Brohi, 2013	Pakistan	EMR	Cross-sectional	2009–2010	Pregnant women who attended Isra University hospital Hyderabad	NA	NA	52	7
44	Buseri, 2010	Nigeria	AFR	Cross-sectional	2008–2009	Pregnant women attending the antenatal care unit of the Family Support Programme (FSP) Clinic, Yenagoa	NA	NA	1000	5
45	Bushman, 2020	USA	AMR	Retrospective	2014–2018	NR	NA	NA	7039	166
46	Chasela, 2012	Malawia	AFR	Cross-sectional	NR	Antiretroviral-naive, HIV-infected, pregnant (<30 weeks gestation) women collected at pre-inclusion screening for the Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study	NA	2041	2041	110
47	Checa Cabot, 2012	Argentinaa	AMR	Prospective	2002–2009	Women enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI) Perinatal and Longitudinal Study in Latin American Countries	11	739	739	67
48	Chen, 2022	USAa	AMR	Cross-sectional	2012–2018	Pregnancy or delivery-related admissions identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Disease Tenth Revision, Clinical Modification (ICD-10CM) diagnostics and procedure codes	NA	NA	28,681,980	131,695
49	Chen, 2023	USAa	AMR	Cross-sectional	1998–2018	Pregnancy or delivery-related admissions identified using ICD-9-CM and ICD-10CM diagnostics and procedure codes	NA	NA	70,038,267	137,259
50	Chibwe, 2019	Tanzania	AFR	Cross-sectional	2017	Pregnant women of known gestational age attending the Makongoro antenatal clinic in Mwanza city	NA	NA	333	1
51	Choy, 2003	USA	AMR	Cross-sectional	1997–1999	Pregnant patients receiving care at University Women's Health Centre, New Jersey Medical School, Newark who tested positive for one or more STDs during prenatal visits	4	7	106	7
52	Çınar, 2019	Turkey	EUR	Retrospective	2013–2016	Pregnant women who presented to a regional maternity hospital in East-ern Anatolia for antenatal follow-up or delivery	NA	NA	9709	6
53	Collenberg, 2006	Burkina Fasoa	AFR	Cross-sectional	NR	Pregnant women from rural (Nouna) and urban (Ouagadougou) Burkina Faso, West Africa	NA	23	492	7
54	Cortina-Borja, 2016	Brazil	EUR	Cross-sectional	2012	NR	NA	1	31,437	30
55	Costa, 2009	Benin	AFR	Cross-sectional	2004–2005	Pregnant women who attended prenatal clinics located in Goiania	NA	2	28,561	60
56	De Paschale, 2014	Austria	EUR	Cross-sectional	2011	Pregnant women attending Saint Jean de Dieu de Tanguieta Hospital in Benin	NA	2	283	21
57	Dema,2022	Moldovaa	EUR	Cross-sectional	2012	NR	NA	NA	24,599	25
58	Deseda, 1995	Ethiopia	AMR	Cross-sectional	1989–1990	Pregnant women attending four prenatal clinics in San Juan	NA	8	997	19
59	Diab-Elschahawi, 2013	Turkey	EUR	Retrospective	2007–2011	Pregnant women presenting for antenatal care at the Vienna University Hospital	53	NA	8591	121
60	Drobeniuc, 1999	UK	EUR	Prospective	1994	The first 100 pregnant women presenting to prenatal clinics in Moldova	NA	NA	1098	25
61	Dabsu, 2018	Ethiopia	AFR	Cross-sectional	2014	Pregnant women who attended randomly selected health facilities in East Wollega Zone, West Oromia, Ethiopia	NA	1	421	35
62	Duru, 2009	Nigeria	AFR	Cross-sectional	2003–2004	Pregnant women attending antenatal care clinic at Faith Medical Centre Benin City	NA	2	200	10
63	Dutta, 2010	India	SEAR	Cross-sectional	NR	Blood samples from pregnant women at Apollo Hospital, Bilaspur(C.G).	NA	11	100	7
64	El-Kamary, 2015	Egypt	EMR	Cross-sectional	2012–2013	All healthy pregnant women 21–45 years old in their third trimester and attending the Cairo University antenatal clinic.	NA	NA	1250	52
65	Eleje, 2021	Nigeriaa	AFR	Cross-sectional	2020	Pregnant women from antenatal clinics across six geopolitical zones in Nigeria	NA	NA	159	2
66	Elmagd, 2011	Egypt	EMR	Cross-sectional	NR	NR	NA	0	61	8
67	Elrazek, 2016	Egypt	EMR	Prospective	2015–2016	NR	NA	NA	3000	46
68	Elsheikh, 2007	Sudan	EMR	Cross-sectional	2006	Pregnant women who attended the Umdurman maternity hospital, Sudan	NA	NA	423	3
69	Enow-Tanjong, 2016	Cameroon	AFR	Cross-sectional	2010	Study participants were recruited from Antenatal Clinics (ANCs) in the Buea Health District of Cameroon	NA	34	407	30
70	Ephraim, 2015	Ghana	AFR	Cross-sectional	2012–2013	Pregnant women attending antenatal clinics at Agogo Presbyterian hospital	NA	NA	168	13
71	Esan, 2014	Nigeria	AFR	Cross-sectional	2012–2013	Pregnant women who attended the antenatal clinic of the Federal Medical Centre Ido-Ekiti,	NA	NA	649	9
72	Ezechi, 2014	Nigeria	AFR	Cross-sectional	2006–2011	HIV positive pregnant women on their first visit to the PMTCT clinic	NA	2392	2392	37
73	Fakunle, 1991	Saudi Arabiaa	EMR	Cross-sectional	NR	Saudi women who presented for delivery in Maternity & Children's Hospital	NA	NA	511	6
74	Farshadpour, 2021	Irana	EMR	Cross-sectional	2018–2019	Pregnant women attending the public health centres for periodical checkups using the multistage cluster sampling method.	NA	NA	1425	19
75	Faulques, 1999	France	EUR	Prospective	NR	Pregnant women who delivered at a hospital in the south of Reunion	1	NA	1455	2
76	Fernandes, 2014	Brazil	AMR	Retrospective	2005–2009	Pregnant women attending a public hospital in the city of Catalao in the state of Goias	NA	NA	1641	2
77	Figueiredo, 2009	Brazil	AMR	Cross-sectional	2005	Pregnant women who undertook their prenatal care in thirteen basic health units (BHU) in São Paulo city	NA	NA	2200	8
78	Figueiró-Filho, 2006	Italy	EUR	Cross-sectional	2002–2003	NR	NA	NA	32,512	30
79	Fiore, 2004	Italy	EUR	Cross-sectional	NR	NR	NA	49	49	21
80	Floreani, 1996	Italy	EUR	Cross-sectional	1991–1992	Pregnant women seen in the obstetric department of the University of Padova for high-risk pregnancies.	16	8	1700	29
81	Floridia, 2010	Italy	EUR	Cross-sectional	2001–2008	Data from the National Programme on Surveillance on Antiretroviral Treatment in Pregnancy	228	1240	1240	302
82	Fouelifack, 2018	Cameroon	AFR	Cross-sectional	2016	Pregnant women attending the Obstetrics and Gynecology Unit of the Yaoundé Central Hospital (YCH)	NA	NA	360	9
83	Freire, 2021	Brazil	AMR	Retrospective	2014–2017	Pregnant women with STI seen at the Climério de Oliveira Maternity Hospital–Federal University of Bahia (MCO-UFBA),	NA	NA	520	10
84	Frempong, 2019	Ghana	AFR	Cross-sectional	2012–2013	Pregnant women attending the antiretroviral therapy (ART) clinic of the St. Elizabeth Hospital, Hwidiem and the Holy Family Hospital	NA	6	248	18
85	Gamboa, 1994	Mexico	AMR	Cross-sectional	NR	Obstetrical population of the Nuevo Hospital Civil de Guadalajara.	NA	NA	244	5
86	García-Romero, 2019	Mexicoa	AMR	Retrospective	NR	NR	NA	NA	10,762	13
87	Gardenal, 2011	Brazil	AMR	Prospective	2002–2005	Pregnant women registered in the information system on the prenatal and birth humanization program	NA	2	31,187	58
88	Garner, 1997	Australia	WPR	Cross-sectional	1995	Pregnant women attending the Lyell McEwin Health Service	42	NA	1537	17
89	Gebretsadik, 2022	Ethiopia	AFR	Cross-sectional	2020	Pregnant women attending at Borumeda General Hospital	NA	NA	124	4
90	Ghazaryan, 2015	USA	AMR	Cross-sectional	2006	NR	NA	553	553	21
91	Giacchino, 1998	Italy	EUR	Prospective	NR	NR	NA	NA	7023	82
92	Giudice, 2021	Italy	EUR	Cross-sectional	2016–2019	Blood samples from pregnant women sent to the Virology Laboratory of the University Hospital of Messina	NA	NA	6896	28
93	Goins, 2023	USAa	AMR	Retrospective	2015–2018	Nationwide Readmissions Database (NRD), from the United States Agency for Healthcare Research and Quality's Healthcare Cost	1,230,773	NA	10,040,850	47,335
94	Goldberg, 2001	UK	EUR	Cross-sectional	1997	All women who were seen at the antenatal clinic in Ninewells Hospital and all women who were admitted for termination of pregnancy of the above hospital	7	NA	3548	23
95	Golnar, 2022	Iran	EMR	Cross-sectional	2018–2020	Pregnant women attending the SBC centre in Mazandaran province	NA	NA	1092	1
96	Gonçalves, 2010	Brazil	AMR	Cross-sectional	2006–2007	Pregnant women who had attended the high-risk pregnancy and fetal medicine unit of Hospital de Base	NA	NA	545	4
97	Gonzalez, 2004	Spain	EUR	Cross-sectional	NR	Pregnant women who attended the Cabueñes Hospital, Gijón	NA	NA	2287	33
98	Gul, 2009	Pakistan	SEAR	Cross-sectional	2006–2007	Pregnant females of all ages, ethnic groups and races belonging to Hazara Divisionat Ayub Teaching Hospital	NA	NA	500	43
99	Gulersen, 2023	USAa	AMR	Retrospective	2016–2021	Retrospective analysis of the US Centres for Disease Control and Prevention Natality Live Birth database	NA	NA	22,604,938	107,761
100	Gutiérrez- Zufiaurre, 2004	Spain	EUR	Cross-sectional	2001	NR	NA	NA	2929	12
101	Hajira,2022	Pakistan	EMR	Cross-sectional	2021–2022	Pregnant women in the department of Obstetrics and Gynaecology, Women and Children Hospital, Charsadda	NA	NA	300	26
102	Hao, 1993	China	WPR	Cross-sectional	1992	Pregnant women presenting to the Third Military Hospital	NA	NA	1436	16
103	Hashem, 2017	Egypt	EMR	Prospective	2012–2015	Pregnant women who attended the antenatal clinic of the Department of Obstetrics and Gynecology at Kasr Al-Aini Hospital, Faculty of Medicine, Cairo University	NA	NA	2514	97
104	Hassan, 1993	Egypt	EMR	Cross-sectional	NR	NR	NA	NA	1536	67
105	He, 2023	Chinaa	WPR	Cross-sectional	2019–2021	Pregnant women who were admitted to selected hospitals for delivery	NA	NA	137,901	152
106	Hibbert, 2023	UKa	EUR	Retrospective	2016–2023	All women receiving at least one anti-HCV test during an antenatal clinic attendance	337	NA	32,088	814
107	Hilda,2017	Nigeria	AFR	Cross-sectional	2014–2015	Pregnant women at the Bowen University Teaching Hospital	NA	NA	138	1
108	Hillemanns, 2000	Germany	EUR	Cross-sectional	1992–1996	Pregnant women attending the antenatal clinic of the Department of Obstetrics and Gynecology, Klinikum Grosshadern, University of Munich	7	1	3712	31
109	Holbrook, 2012	USA	AMR	Prospective	NR	Pregnant women enrolled in the MOTHER study's	131	NA	131	42
110	Hood, 2023	USAa	AMR	Cross-sectional	2017	US National Birth Certificate dataset from the National Centre for Health Statistics (NCHS)	NA	NA	1,428,184	4412
111	Huong, 2010	Thailanda	SEAR	Cross-sectional	1997–1999	Pregnant women at one of the 27 hospitals in Thailand	NA	1435	1883	74
112	Hutchinson, 2004	UKa	EUR	Cross-sectional	2000	Women who delivered live babies in Scotland	NA	NA	30,259	121
113	Ifeorah, 2020	Nigeria	AFR	Cross-sectional	2017	Antenatal and postnatal mothers attending the ANC clinics in Kogi State Health Institutions	NA	NA	176	8
114	Ishizaki, 2017	Vietnam	WPR	Cross-sectional	2007–2012	NR	NA	NA	200	1
115	Israr, 2021	Pakistan	EMR	Cross-sectional	2019–2020	Pregnant women attending antenatal care health facilities at Bacha Khan Medical Complex (BKMC) Shahmansoor and District Head Quarter (DHQ) Hospital Swabi	NA	NA	375	8
116	Jadoon, 2017	Pakistan	EMR	Cross-sectional	2015–2016	Pregnant Women in the Ayub Teaching Hospital, Abbottabad in the department of Obstetrics & Gynaecology	NA	NA	174	13
117	Jahan, 2019	India	SEAR	Cross-sectional	2019	Apparently healthy pregnant females (Outpatient, OP and indoor patients, IP) attending Antenatal clinic.	NA	NA	550	3
118	Jamieson, 2008	Thailand	SEAR	Retrospective	NR	Women previously enrolled in three vertical transmission studies in Bangkok, Thailand who had specimens available for HCV testing	27	1274	1771	54
119	Jarlenski, 2022	USA	AMR	Cross-sectional	2016–2019	Administrative data from six states in the Medicaid Outcomes Distributed Research Network (MODRN)	156	NA	23,780	10,463
120	Jensen 2003	Denmark	EUR	Cross-sectional	NR	NR	NA	NA	4098	3
121	Jilani, 2017	Pakistan	EMR	Cross-sectional	2016	Pregnant women at the Al-Tibri Medical College & Hospital (ATMC&H), Isra University Karachi Campus in Gynae & Obs (OPD)	NA	NA	400	27
122	Kabinda, 2015	Democratic Republic of Congo	AFR	Cross-sectional	2013	NR	NA	24	581	24
123	Kassem, 2000	Egypt	EMR	Prospective	1996	HIV-negative pregnant women aged 25–41 years, attending Alexandria University Maternity Hospital	NA	0	100	19
124	Khamduang, 2013	Thailand	SEAR	Cross-sectional	2001–2003	HIV-1–infected pregnant women who participated in a clinical trial conducted in Thailand	NA	1812	1812	75
125	Khamis, 2016	Egypta	EMR	Cross-sectional	NR	Pregnant women visiting the antenatal healthcare units in selected villages for regular follow-up	NA	NA	360	22
126	Khattak, 2009	Pakistan	EMR	Retrospective	2008	Pregnant women in the Obstetric/Gynaecology ward of Saidu Teaching Hospital	4120	NA	5607	141
127	Khokhar, 2004	Pakistan	EMR	Cross-sectional	2001–2002	All pregnant women presenting in the antenatal clinic of Shifa International Hospital Islamabad	NA	NA	503	24
128	Ko, 2022	USA	AMR	Retrospective	2014–2019	Retrospective chart review was completed using data from Tricore Laboratories of pregnant women at UMNH	NA	NA	9310	139
129	Kopilovié, 2015	Sloveniaa	EUR	Cross-sectional	1999–2013	Sera stored at the National Institute of Public Health that were obtained from pregnant women for syphilis screening purposes	NA	NA	31,849	41
130	Koseki, 1994	Japan	WPR	Prospective	NR	NR	NA	NA	4801	59
131	Krans, 2015	USA	AMR	Retrospective	2009–2012	All pregnant women with Opioid Use Disorder who delivered an infant at Magee-Womens hospital	369	NA	611	369
132	Kristiansen, 2009	Norway	EUR	Cross-sectional	2003–2004	All pregnant women from all hospitals and delivery rooms in northern Norway	NA	NA	1668	5
133	Kumar, 1997	Egypta	EMR	Cross-sectional	1994–1996	Apparently healthy asymptomatic parturient Egyptian women in the third trimester who attended the routine antenatal clinics of the UAE University teaching hospitals	NA	0	499	65
134	Kumar, 2007	India	SEAR	Cross-sectional	2004–2006	Healthy pregnant women at the antenatal clinic of Department of Obstetrics and Gynaecology of Maulana Azad Medical College and Lok Nayak Hospital	0	NA	8130	84
135	Kumari, 2015	Pakistan	EMR	Cross-sectional	2012	NR	NA	NA	300	40
136	Kushner, 2020	USA	AMR	Prospective	2018–2019	Labour and Delivery admissions at 2 hospital sites in New York's Mount Sinai Health System, Mount Sinai Hospital (MSH), and Mount Sinai West (MSW)	NA	NA	7373	56
137	Kushner, 2022	Canada	AMR	Retrospective	2000–2018	Data collected under universal healthcare coverage in Ontario, Canada and housed at the ICES administrative data repository	869	37	1,988,581	2170
138	Kuugbee, 2023	Ghana	AFR	Cross-sectional	NR	Pregnant women attending antenatal clinic at the St. Joseph Hospital	NA	NA	246	2
139	Laganà,2014	Italy	EUR	Prospective	2003–2013	Pregnant migrant women who had attended an outpatient clinic in Messina	NA	1	320	3
140	Lam, 1993	UK	EUR	Prospective	NR	Child-bearing women, identified as being at risk for infection with HCV and HIV from previous intravenous drug use	NA	48	79	56
141	Lambert, 2013	Ireland	EUR	Cross-sectional	2007–2008	NR	29	2	8976	67
142	Lashari, 2012	Pakistan	EMR	Prospective	2010	Pregnant women in the Department of Obstetrics and Gynaecology, Ghulam Mohammed Mahar Medical Teaching Hospital Khairpur	NA	NA	4938	108
143	Lassey, 2004	Ghana	AFR	Cross-sectional	2001	Pregnant women in the Maternity Unit of the Korle-Bu Teaching Hospital (KBTH).	NA	1	638	16
144	Laurent, 2001	Congo	AFR	Cross-sectional	1988	Commercial sex workers seen at the Women's health centre of project SIDA	NA	2	1092	47
145	Lazenby, 2019	USA	AMR	Retrospective	2007–2016	Data from the electronic medical record housed in the Medical University of South Carolina (MUSC) Clinical Data Warehouse (CDW)	104	2	180	63
146	Leikin, 1994	USA	AMR	Prospective	1991–1992	Obstetric clinic patients at Westchester County Medical Centre	28	12	1700	75
147	Lembo, 2017	Italy	EUR	Retrospective	2010–2015	Pregnant women consecutively admitted to the Division of Obstetrics and Gynaecology of the University Hospital	NA	NA	5184	10
148	Lemon, 2019	USA	AMR	Cross-sectional	2013–2015	Women receiving methadone or buprenorphine and delivering live-born infants at Magee-Womens Hospital	716	NA	716	93
149	Lima LH, 2009	Brazil	AMR	Prospective	1999	Postpartum and pregnant women from the maternity ward of the Vitória Mercy Hospital and the Carapina Outpatient Referral Unit	NA	0	202	1
150	Lima MP, 2000	Brazil	AMR	Prospective	1994–1998	Pregnant women who attended a 400-bed general university hospital in Campinas	NA	5	6991	54
151	Lin, 1995	Taiwana	WPR	Cross-sectional	1992–1994	NR	NA	NA	3400	43
152	Lito, 2013	Portugal	EUR	Cross-sectional	2004–2009	NR	NA	4	934	13
153	Liu, 2009	Australiaa	WPR	Cross-sectional	2000–2006	Pregnant women who attended one of two major metropolitan hospitals (in Penrith and Blacktown) that belong to the Sydney West Area Health Service or one rural hospital in New South Wales	295	NA	10,282	41
154	Locatelli, 1999	Italy	EUR	Prospective	1992–1997	Pregnant women managed at the Department of Obstetrics and Gynecology, Istituto di Scienze Biomediche San Gerardo	NA	0	16,271	63
155	Lopata, 2020	USA	AMR	Retrospective	2005–2014	Mother–infant dyads were included if the mother was between 15 and 44 years of age at the time of delivery and was enrolled in TennCare at least 30 days before delivery	NA	697	384,837	4072
156	Madzime, 2000	Zimbabwe	AFR	Prospective	NR	Indigent pregnant women admitted for labour and delivery at Harare Maternity Hospital	NA	NA	1591	25
157	Maia, 2015	Brazil	AMR	Cross-sectional	1998–2013	NR	NA	545	545	20
158	Malik, 2021	Pakistan	EMR	Cross-sectional	2020	Pregnant women who attended the Punjab rangers hospital, Rahbar medical and dental college in Gynae/Obs OPD	NA	NA	300	29
159	Marcellin, 1993	France	EUR	Prospective	1988	Pregnant women attending the outpatient ward of the Obstetric Department at H6pital Beaujon	NA	0	670	26
160	Marranconi, 1994	Italy	EUR	Cross-sectional	1992	Pregnant women in the Province of Vicenza in Northeast Italy	12	NA	5672	24
161	Marschall, 2013	Swedena	EUR	Prospective	1973–2009	All women with their first and consecutive births recorded in the Swedish Medical Birth Register between 1973 and 2009	NA	NA	10,067	72
162	Martins, 1995	Brazil	AMR	Cross-sectional	1990–1992	Pregnant women who attended the Child-Maternal Hospital in Goiania	2	NA	1273	12
163	Martyn, 2011	Ireland	EUR	Retrospective	2006–2007	NR	92	7	13,888	133
164	Mathur, 2020	India	SEAR	Cross-sectional	NR	Pregnant women who attended a tertiary care centre affiliated to Medical College in the capital city of Rajasthan	NA	NA	16,224	3
165	Mawouma, 2022	Cameroon	AFR	Cross-sectional	2020–2021	Pregnant women who attended one of seven health facilities in the health district of Mokolo.	NA	1	794	9
166	Mboto, 2010	Nigeria	AFR	Cross-sectional	2005	Antenatal care (ANC) patients seen at the General Hospital, Mary Slessor Avenue, Calabar	NA	NA	506	2
167	McCormick, 2022	Ireland	EUR	Cross-sectional	2016–2019	Blood samples fromthe National Maternity Hospital and the Rotunda Hospitalsin Dublin	NA	NA	4655	20
168	McNicholas, 2012	USA	AMR	Prospective	NR	Opioid-dependent pregnant women enrolled in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study.	91	NA	172	66
169	Mehta, 2013	India	SEAR	Cross-sectional	2010	Patients attending the antenatal clinic of P. D. U. Medical College and Hospital	3	NA	1038	2
170	Millbourn, 2020	Sweden	EUR	Cross-sectional	2015–2016	Pregnant women and their partners in Orebro County and in the southern part of Stockholm, Sweden	NA	NA	4108	25
171	Mohebbi, 2011	Iran	EMR	Cross-sectional	2007–2008	All pregnant women who attended the reproduction section of rural and urban health care centres in Lorestan province, west of Iran	NA	NA	827	2
172	Molla, 2015	Ethiopia	AFR	Cross-sectional	2013–2014	Pregnant women attending antenatal care centre of Felege Hiwot Referral Hospital	NA	NA	384	1
173	Monteith, 2014	Ireland	EUR	Retrospective	2009–2011	Pregnant women presenting to the Rotunda Hospital for antenatal care	NA	NA	26,451	199
174	Moriya, 1995	Japan	WPR	Prospective	1990–1993	Pregnant women who attended one of the 34 obstetric and pediatric departments in Hiroshima and Ehime prefectures, Japan	NA	NA	16,714	163
175	Mostafa, 2020	Egypt	EMR	Retrospective	2018	Available medical records of all pregnant women admitted to a university hospital for delivery	NA	NA	2177	22
176	Motor, 2010	Turkey	EMR	Cross-sectional	2009	Women in reproductive age group who were applied to the Hatay Maternity and Childeren's nursing home hospital	NA	NA	5410	16
177	Mudji, 2021	Democratic Republic of Congo	AFR	Cross-sectional	2019	Pregnant women who attended Vanga Evangelical Hospital	NA	NA	457	22
178	Muñoz-Almagro, 2002	Spain	EUR	Cross-sectional	1999	Pregnant women who attended the Hospital Sant Joan de Deu	NA	80	2615	37
179	Murad, 2013	Yemen	EMR	Cross-sectional	2011	Pregnant women at the Antenatal Care Clinic at Al-Thawra Hospital in Sana'a	NA	NA	400	34
180	Mutagoma, 2017	Rwanda	AFR	Cross-sectional	2011	Pregnant women attending antenatal clinics in 30 HIV sentinel surveillance sites in Rwanda	NA	429	12,903	335
181	Ndong-Atome GR, 2008	Gabona	AFR	Prospective	2005	Pregnant women who attended one of the five sentinel sites in Gabon	NA	NA	947	20
182	Ng'wamkai, 2019	Tanzania	AFR	Cross-sectional	2018	Pregnant women attending three rural antenatal clinics (Magu, Karume and Sengerema) in Mwanza region	NA	25	499	2
183	Njouom, 2003	Cameroon	AFR	Cross-sectional	2000–2001	Pregnant women presenting for antenatal care at the mother and child centre of the Chantal Biya Foundation (FCB) and the Etoudi Maternity ward	NA	NA	1494	28
184	Nwankwo, 2016	Nigeriaa	AFR	Cross-sectional	2013	Pregnant women who attended the Grimad Hospital Anyigba,	NA	NA	130	9
185	O'Connor, 2015	Australia	WPR	Retrospective	2009–2012	Computerised perinatal data collected by the Obstetrics and Gynaecology Clinical Care Unit at King Edward Memorial Hospital	NA	NA	570	213
186	Odagami, 2023	Japana	WPR	Cross-sectional	2018–2019	NR	NA	NA	2838	3
187	Ogunro, 2007	Nigeria	AFR	Prospective	2005–2006	Pregnant women attending Ladoke Akintola University of Technology Teaching Hospital,(LTH)	NA	NA	272	25
188	Ohto, 2010	Japana	WPR	Prospective	1990–2004	Pregnant patients attending one of Fifteen clinics in Fukushima Prefecture	1	0	22,664	103
189	Okamoto, 1999	Japan	WPR	Prospective	1992–1998	Pregnant women in the Tottori Prefecture, Japan	NA	NA	21,791	127
190	Okeke, 2012	Nigeria	AFR	Cross-sectional	2007–2009	Pregnant women seen at the Prevention of Mother to Child Transmission (PMTCT) clinics at UNTH Enugu	NA	401	401	4
191	Okusanya, 2013	Nigeria	AFR	Prospective	2010	Healthy pregnant women attending the antenatal booking clinic of Irrua Specialist Teaching Hospital	NA	1	205	8
192	Oliverio Souza, 2023	Brazil	AMR	Retrospective	2010–2019	Women assisted in a sexual violence assistance centre in Brazil	NA	NA	633	4
193	Oluremi, 2020	Nigeria	AFR	Cross-sectional	2019	Pregnant women attending antenatal clinic in AMTHI	NA	NA	904	9
194	Omatola, 2019	Nigeria	AFR	Cross-sectional	2017	Pregnant women, who were attendees of the antenatal clinic of KSUTH, Anyigba	NA	NA	200	1
195	Onakewhor, 2009	Nigeria	AFR	Cross-sectional	2005	NR	NA	NA	269	5
196	Opaleye, 2016	Nigeria	AFR	Cross-sectional	NR	Pregnant women attending the antenatal clinic of the Ladoke Akintola University Teaching Hospital Osogbo	NA	0	182	5
197	Orkin, 2016	UK	EUR	Retrospective	2013	Women over the age of 18 years who had attended antenatal clinics during 2013 at two London hospitals	NA	NA	1000	5
198	Osazuwa, 2012	Nigeria	AFR	Cross-sectional	2011	Pregnant women attending the antenatal clinic of the General hospital, Abaji	NA	NA	395	12
199	Owolabi, 2015	Nigeria	AFR	Cross-sectional	2013–2014	Pregnant women who attended the departments of Obstetrics and Gynaecology at the University of Ilorin Teaching Hospital	NA	NA	400	17
200	Paternoster, 2002	Italy	EUR	Prospective	1996–1999	Pregnant women who attended the Prenatal Department at the University of Padua	NA	NA	5840	105
201	Patrick, 2021	USAa	AMR	Retrospective	2009–2019	All US birth data obtained from natality files obtained from the National Centre for Health Statistics at the Centres for Disease Control and Prevention and from the Area Health Resource File (AHRF)	NA	NA	39,380,122	138,343
202	Peixoto, 2004	Brazil	AMR	Prospective	1998–1999	Pregnant women followed at the Prenatal Care Clinic at Hospital Nossa Senhora da Conceicao	NA	NA	1090	29
203	Pergam, 2008	USA	AMR	Retrospective	2003–2005	Data from the Comprehensive Hospital Abstract Reporting System (CHARS), created by the Washington State Department of Health	NA	6	240,131	506
204	Pfeiffer, 2023	USA	AMR	Cross-sectional	2015–2020	Perinatal patients with opioid use disorder across 8 hospitals	582	NA	582	226
205	Pheng, 2022	Ghana	AFR	Cross-sectional	2016	Antiretroviral therapy (ART) sites for People Living with HIV and AIDS and in Antenatal care clinics for pregnant women	NA	NA	510	5
206	Piffer, 2020	Italy	EUR	Retrospective	2015–2020	Patients 18 years and older with a live birth at one of the 8 delivery hospitals in Maine	32	2	45,493	177
207	Pinto, 2021	Brazil	AMR	Prospective	2014–2018	Pregnant women delivering at Conceicao Hospital	19	13	18,953	130
208	Pipan, 1996	Italy	EUR	Prospective	1991–1993	Pregnant women who attended the Department of Obstetrics and Gynecology, Udine Medical School and University Hospital	NA	NA	1388	36
209	Pirillo, 2007	Uganda	AFR	Retrospective	NR	HIV-1 positive pregnant women who had participated to a mother-to-child prevention trial carried out in urban settings	NA	494	494	10
210	Pokracka, 2017	Poland	EUR	Cross-sectional	2015–2016	NR	NA	NA	427	2
211	Pollock, 2023	USA	AMR	Retrospective	2017–2021	NR	189	NA	988	119
212	Prasad, 2007	Switzerland	EUR	Cross-sectional	1990–1991	Mothers during consecutive births in obstetric wards of public hospitals in 23 of 26 cantons in Switzerland	NA	NA	9057	64
213	Prasad, 2020	USAa	AMR	Prospective	2012–2015	Pregnant women attending one of 32 hospitals (28 academic, 4 non-academic) located in 14 states	69	NA	106,823	254
214	Prasad, 2023	USAa	AMR	Prospective	2012–2018	Pregnant women attending hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network's “An Observational Study of HCV in Pregnancy"	NA	NA	109,379	1224
215	Puro, 1992	Italy	EUR	Prospective	1990	Pregnant women in the Department of Obstetrics of St. Camillo Hospital and in the Service for Pre- and Perinatal Prevention of Infectious Diseases of L. Spallanzani Hospital	NA	NA	1142	10
216	Raghu, 2012	Indiaa	SEAR	Cross-sectional	2006–2007	Pregnant women in the age group 15–35 years attending out patient section and inpatients of Obstetrics and Gynaecology (OBG) department from Bapuji Hospital (BH) and Chigateri General Hospital (CGH) attached to JJM Medical College, Davangere	NA	NA	100	4
217	Raptopoulou-Gigi, 2001	Greece	EUR	Prospective	1996–1997	Pregnant women who attended the prenatal clinics of the four University Departments of Obstetrics and gynecology in Hippokration Hospital of Thessaloniki and Hospital of Kavala and Kikis	15	NA	2408	47
218	Rauf, 2024	Pakistan	EMR	Cross-sectional	2023	Pregnant women aged 18 years and older in the Muzaffarabad district of Azad Kashmir	NA	NA	402	26
219	Reiche, 2000	Brazil	AMR	Retrospective	1996–1998	Pregnant women treated at the HURNP Obstetric outpatient clinic	NA	NA	1006	8
220	Romero-Gómez, 1998	Spain	EUR	Prospective	NR	NR	34	11	6566	27
221	Ropponen, 2006	Finlanda	EUR	Retrospective	1972–2000	Women diagnosed with ICP were identified from the Finnish Hospital Discharge Register	NA	NA	10,504	29
222	Rossi, 2020	USAa	AMR	Retrospective	2009–2017	All live births with reported HCV infection status in the United States	NA	NA	31,207,898	94,824
223	Roudot, 1993	France	EUR	Cross-sectional	NR	Pregnant women attending three Parisian hospitals	10	NA	2367	41
224	Rouet 2004	Cöte d'Ivoire	AFR	Retrospective	1995–1998	Serum repository of two clinical trials, ANRS 049a and 049 b DITRAME and the open-label zidovudine cohort	NA	6	1002	10
225	Ruiz-Extremera, 2020	Spain	EUR	Prospective	2015	Pregnant women attending one of 8 hospitals in Madrid	9	2	7659	20
226	Sabatino, 1996	Italy	EUR	Prospective	1990–1991	NR	2	0	2980	30
227	Salihu, 2012	Florida	AMR	Retrospective	1998–2007	De-identified version of the Florida-linked hospital discharge linked to birth certificate data files	NA	NA	1,700,734	1023
228	Salmerón, 1998	Granda	EUR	Cross-sectional	1993–1995	Pregnant women of the south area of Granada	NA	NA	3003	16
229	Sami, 2009	Pakistan	EMR	Prospective	2005	Pregnant women at Unit-I, (Ward-08), Department of Obstetrics and Gynecology, Jinnah Postgraduate Medical Centre	1152	NA	5902	108
230	Sanson, 2018	Arce	AMR	Cross-sectional	2007–2015	Pregnant women living in the city of Rio Branco, Acre	NA	NA	62,102	19
231	Santiago, 2012	Spain	EUR	Cross-sectional	2007–2008	NR	NA	11	1391	13
232	Schillie, 2018	USAa	AMR	Cross-sectional	2015	Data from the Centres for Disease Control and Prevention's (CDC's) National Centre for Health Statistics (NCHS) and two large commercial laboratories	NA	NA	3,823,723	14,417
233	Sert, 2021	Turkey	EUR	Retrospective	2008–2018	Pregnant women who attended antenatal clinics at Zekai Tahir Burak Women's Health and Education and Research Hospital	NA	NA	62,997	114
234	Sfameni, 2000	Australia	WPR	Prospective	NR	Clinic patients attending for antenatal care at the Mercy Hospital for Women	10	NA	2000	29
235	Shams, 2010	Pakistan	EMR	Retrospective	2002–2008	Pregnant women who attended Maternal-child Health (MCH) Pakistan institute of Medical sciences (PIMS), Islamabad	NA	NA	75,777	5620
236	Shebl, 2009	Egypt	EMR	Prospective	1997–2001	Pregnant women during their third trimester residing in three villages in the Nile delta and receiving antenatal care at their village's Community Health Unit (CHU)	NA	NA	3410	329
237	Sheikh, 2009	Pakistan	EMR	Cross-sectional	2006	All pregnant women who registered in the antenatal clinic at Zainab Panjwani Memorial Hospital	NA	NA	2592	18
238	Shittu, 2023	Nigeria	AFR	Cross-sectional	NR	Pregnant women who attended the Obstetrics and Gynaecology department of University of Uto Teaching Hospital	35	NA	480	22
239	Silverman, 1993	USA	AMR	Cross-sectional	1990–1991	Women receiving prenatal care at Thomas Jefferson University Hospital	NA	3	599	26
240	Simavli, 2013	Turkey	EUR	Retrospective	2007–2012	Pregnant women in the northwestern region of Turkey	NA	NA	22,432	21
241	Simpore, 2006	Burkina Faso	AFR	Cross-sectional	2003–2005	Pregnant women attending the Centre Medical Saint Camille	NA	36	336	18
242	Skalsky, 1993	Cameroon	AFR	Prospective	1990–1992	Pregnant women who attended the Presbyterian General Hospital in Manyemen	NA	NA	410	24
243	Smid, 2019	USA	AMR	Retrospective	2009–2016	All livebirths more than or equal to 20 weeks gestation in Utah	NA	NA	411,936	595
244	Solís Sánchez, 2003	Spain	EUR	Prospective	2009–2011	Pregnant women who attended the maternity hospital Prof. José Maria Magalhães Netto	NA	NA	2442	30
245	Sood, 2012	India	SEAR	Prospective	2006–2007	Women in the third trimester of pregnancy attending the Department of Obstetrics and Gynecology at Dayanand Medical College and Hospital	NA	NA	488	8
246	Spencer, 2003	Australia	WPR	Cross-sectional	NR	Pregnant women were recruited from the population of IVDU on a methadone maintenance programme at the Royal Prince Alfred Hospital (RPAH)	NA	NA	1000	13
247	Stokkeland, 2017	Swedena	EUR	Retrospective	2001–2011	Identified patients through the Swedish Medical Birth Register and Patient Register	NA	NA	1,093,969	2056
248	Stoszek, 2006	Egypt	EMR	Prospective	1997–2003	Pregnant women were enrolled in their second or third trimester during initial visits to prenatal clinics in Ministry of Health and Population (MOHP) rural health centres in three rural villages in the Nile Delta	NA	NA	2587	408
249	Sugiyama, 2017	Japan	WPR	Cross-sectional	2010–2011	Pregnant women who gave birth at all delivery hospitals/clinics in Hiroshima prefecture	NA	NA	15,035	38
250	Surya, 2005	Indonesia	SEAR	Prospective	2003	Pregnant women, at major hospitals in the eight jurisdictions of Bali	NA	NA	2450	1
251	Tanzi, 1997	Italy	EUR	Prospective	1993	Parturients consecutively admitted to the Maternity clinic of the University of Parma	NA	31	1347	31
252	Taseer, 2010	Pakistan	EMR	Cross-sectional	2006–2007	Pregnant women who attended the Gynaecology and Obstetrics outpatient department, Nishtar Hospital Multan	NA	NA	500	35
253	Tesfu, 2022	Ethiopia	AFR	Cross-sectional	2019–2020	HBsAg positive delivering mothers who attended governmental hospitals in Addis Ababa	NA	9	265	3
254	Thompson, 2013	USA	AMR	Prospective	2000–2006	Pregnant women enrolled in the Thalassemia Clinical Research Network (TCRN)	NA	NA	72	10
255	Thompson, 2023	Canada	AMR	Cross-sectional	NR	Patients participating in the Alberta Prenatal screening programme	NA	NA	6033	34
256	Tiruneh, 2008	Ethiopia	AFR	Cross-sectional	2006	Pregnant women attending antenatal clinic at Gondar Health Centre	NA	57	480	6
257	Todd, 2008	Afghanistan	EMR	Cross-sectional	2006	Pregnant women who attended one of the three hospitals with highest delivery volumes in the previous quarter (Malalai, Rabia Balkhi, and Khair Khana) in Kabul	NA	0	4452	13
258	Tornatore, 2012	Brazil	AMR	Cross-sectional	2003–2008	Pregnant women who attended the HIV/AIDS service of Hospital Universitário Dr Miguel Riet Corrêa Jr, Federal University of Rio Grande (FURG)	NA	130	130	14
259	Towers, 2020	USA	AMR	Prospective	NR	NR	NA	NA	5317	658
260	Tuli, 2019	India	SEAR	Cross-sectional	2017–2018	Pregnant women who attended the antenatal clinic of a tertiary care hospital	NA	NA	3070	40
261	Uehara, 1993	Japan	WPR	Prospective	NR	NR	NA	NA	2015	12
262	Ugbebor, 2011	Nigeria	AFR	Cross-sectional	2009–2010	Pregnant women attending the antenatal clinic of the University of Benin Teaching Hospital	NA	NA	5760	206
263	Ugwu, 2022	Nigeria	AFR	Retrospective	2020–2021	Pregnant women who attended the 68 Nigerian Army Reference Hospital Yaba (68NARHY)	NA	1	329	6
264	Umoke, 2021	Nigeria	AFR	Retrospective	2020	Pregnant women who attended one of 8 AMURT (Ananda Marga Universal Relief Team)-supported rural primary health care facilities in Ebonyi state southeast Nigeria	NA	41	4657	189
265	Urbanus, 2011	Netherlands	EUR	Cross-sectional	2003–2009	Surveys of pregnant women in Amsterdam and Netherlands	NA	912	4563	17
266	Vargas, 2020	Brazil	AMR	Cross-sectional	2016–2017	Parturient women who attended two public maternity hospitals in Salvador, Bahia	350	33	2099	9
267	Völker, 2017	Ghana	AFR	Cross-sectional	2011–2012	Pregnant women from the Jomoro, Nzema East Municipal, Ahanta West, and Ellembelle district	NA	1	174	2
268	Waheed, 2013	Pakistan	EMR	Cross-sectional	2012	Pregnant women who attended the Department of Obstetrics and Gynaecology, Nawaz Sharif Social Security Teaching Hospital	NA	NA	1500	35
269	Wahl, 1994	Sweden	EUR	Cross-sectional	1982–1983	Pregnant women attending a university mother care clinic	NA	NA	755	6
270	Walewska-Zielecka, 2016	Polanda	EUR	Cross-sectional	2004–2014	Electronic medical records of a large countrywide outpatient managed care clinic's network	NA	NA	16,130	123
271	Ward, 2000	UK	EUR	Cross-sectional	1997–1999	Pregnant women who attended the antenatal clinics at St Mary's Hospital	16	NA	4729	38
272	Waruingi, 2015	USA	AMR	Prospective	2012	NR	NA	NA	419	4
273	Watts, 2017	USA	AMR	Retrospective	2011–2015	Wisconsin Medicaid encounter data for pregnant women who delivered one or more infants	NA	NA	146,267	608
274	Wingate, 2021	USA	AMR	Cross-sectional	2013–2017	Laboratory data from the Tennessee department of health, National Electronic Disease Surveillance System (NEDSS) Base System (NBS)	NA	NA	404,694	5751
275	Winter,2020	USA	AMR	Retrospective	NR	Pregnant and early parenting women receiving outpatient medication-assisted treatment for Opioid Use Disorder (OUD)	NA	NA	5616	48
276	Xiao, 2019	USA	AMRa	Prospective	2011–2015	Twin birth records extracted from the United States birth records reated by the Centres for Disease Control and Prevention	NA	NA	270,256	850
277	Xiong, 1998	Japana	WPR	Prospective	1990–1997	Nonpathological Japanese pregnant women aged 17 to 44 at Dokkyo University	NA	NA	1941	72
278	Yadav, 2022	Indiaa	SEAR	Retrospective	2020–2021	Pregnant females of any trimester who attended Antenatal clinic in Obstetrics and Gynecology Department of SMS Medical College, Jaipur	NA	NA	364	1
279	Yadav, 2022	Indiaa	SEAR	Retrospective	2018–2019	Pregnant women attending a tertiary care teaching hospital, Uttar Pradesh, India	NA	NA	4037	21
280	Yousfani, 2006	Pakistan	EMR	Cross-sectional	2003	Pregnant women attending the maternity units of Liaquat University Hospital (LUH)	NA	NA	103	17
281	Zafar, 2022	Pakistana	EMR	Cross-sectional	2016–2021	Women attending the antenatal clinic in Alkhidmat Raazi Hospital	67	40	31,911	478
282	Zahran, 2010	Egypt	EMR	Cross-sectional	NR	Pregnant women in Upper Egypt	NA	NA	500	37
283	Zanetti, 1995	Italy	EUR	Prospective	NR	Women consecutively admitted for labor at several antenatal clinics in the Lombardy (North Italy)	NA	22	21,516	250
284	Zeba, 2011	Burkina Faso	AFR	Cross-sectional	2009	Pregnant women attending the Saint Camille Medical Centre	NA	9	607	13
285	Zenebe, 2015	Ethiopia	AFR	Retrospective	2013	Pregnant women attending antenatal care in Bahir Dar health institutions	NA	NA	318	2
286	Zhong, 2022	Chinaa	WPR	Cross-sectional	2009–2018	Pregnant women attending antenatal care in Guangxi, Southwest China	NA	NA	23,879	46
287	Алиева, 2018	Russia	EUR	Cross-sectional	NR	NR	NA	NA	277	77

Maternal-to-child transmission
S/N	Author, year	Country	Region	Study design	Study period	Diagnosis of Maternal-to-child transmission	Maternal HCV seroprevalence (n)	Maternal HCV Viremia (n)	Maternal HIV co-infection (n)	Mother-to-child transmission rate (n)
1	Ades, 2023	UK	EUR	Prospective	NR	Infants were regarded as infected if they were ever anti-HCV positive after 18 months and/or had at least 2 positive RNA tests at any age.	1749	543	270	96
2	Bell, 2019	USA	AMR	Retrospective	2013–2018	Infant HCV-positivity was determined by using a positive antibody screen result followed by a positive RNA test result.	257	NA	NA	7
3	Benaglia, 2000	Italy	EUR	Prospective	1996–1999	NR	97	66	3	5
4	Catalano, 1999	Italy	EUR	Prospective	NR	Test RIBA II to search for Ab anti-HCV, alanine transaminase (ALT) evaluation and HCV-RNA research by PCR.	22	NA	14	2
5	Ceci, 2001	Italy	EUR	Prospective	1995–1997	HCV RNA at birth, 4, 8, 12, 18, and 24 months	78	60	4	22
6	Croxson, 1997	New Zealand	WPR	Prospective	NR	All infants were tested at birth for hepatitis C virus (HCV) RNA.	54	30	NA	2
7	Dal Molin, 2002	Italy	EUR	Prospective	1994–2000	Testing for ALT, IgG anti-HCV, IgM, anti-HCV, and HCV RNA in at least three serum samples collected at 1 month, 3–4 months, and 8–12 months of life	105	93	NA	5
8	Della Bella, 2005	Italy	EUR	Prospective	NR	Children were deemed infected with persistent detection of HCV-RNA starting from 3 months of age and persistent anti-HCV antibody beyond 18 months of age.	NA	23	NA	3
9	Di Domenico, 2006	Italy	EUR	Prospective	1996–2002	Infants were prospectively followed by clinical and laboratory tests (ALT levels, anti HCV Ab and HCV RNA) every 3 or 6 months for 16 to-80 months	50	28	NA	3
10	Ferrero, 2003	Italy	EUR	Prospective	1990–2000	Children were considered infected when both anti-HCV antibodies were persistent beyond 18 months and/or polymerase chain reaction (PCR) tests were positive on at least two separate occasions	170	NA	37	5
11	Fioredda, 1996	Italy	EUR	Prospective	NR	Infection of children was defined by the persistence of antibodies past 18 months of age, or the presence of serum RNA associated with increased aminotransferases.	53	NA	28	6
12	Fischler, 1996	Sweden	EUR	Prospective	NR	HCV RNA analyses by the polymerase chain reaction (PCR) and alanine aminotransferase (ALT) were performed on consecutive blood samples from birth to 18 months of age (0, 3, 9 and 18 months).	55	40	2	0
13	Granovsky, 1998	USA	AMR	Prospective	1986–1991	Infants were considered HCV-seropositive when serum or plasma reacted with at least two HCV-specific antigens by RIBA2.0/3.0	147	122	NA	7
14	Jamieson, 2008	Thailand	SEAR	Retrospective	1992–2004	An HCV infected infant was defined as an infant who was anti-HCV positive (i.e EIA-positive with confirmatory RIBA) at 18 months of age or older or who had positive HCV RNA on two occasions.	54	43	1274	2
15	Jhaveri, 2015	Egypt	EMR	Prospective	2012–2014	Infants were observed at 12 months of age for HCV RNA testing as part of the study.	2514	54	NA	7
16	La Torre, 1998	Italy	EUR	Prospective	1993–1995	Babies born to anti-HCV positive mothers were tested for ALT levels, anti-HCV antibodies by ELISA III and RIBA III and HCV-RNA by RT-PCR	80	NA	NA	2
17	Mast, 2005	USA	AMR	Prospective	1993–1998	Serum from HCV-infected infants that was found to be anti- HCV negative by EIA 2.0 was retested by EIA 3.0.	567	NA	NA	7
18	Matsubara, 1995	Japan	WPR	Prospective	1989–1993	Babies were tested for serum ALT activity and anti-HCV by ELISA-2 at birth and approximately every 2 or 3 months	31	NA	NA	3
19	Mazza, 1998	Italy	EUR	Prospective	1994–1996	Mother-to-infant transmission of HCV infection was monitored by anti- HCV by ELISA and by serum HCV RNA at least twice during follow-up. Samples positive with anti-HCV were also tested by RIBA.	75	63	23	6
20	Money, 2014	Canada	AMR	Prospective	2000–2003	Diagnosis of HCV infection was based on two positive qualitative HCV RNA results taken at least three months apart, and if possible was confirmed by the persistence of antibody to HCV beyond 18 months	145	108	19	4
21	Muñoz-Almagro, 2002	Norway	EUR	Cross-sectional	1995–2000	Anti-HCV antibodies at birth, 12, 18 and 24 months. HCV RNA at birth, 3 and 6 months	2615	NA	NA	6
22	Huong, 2010	Thailand	SEAR	Prospective	1997–1999	EIA performed on samples at 18 months of age, if missing, HCV RNA was quantified for samples between 6 weeks and 6 months.	42	30	NA	4
23	Nordbø, 2002	Norway	EUR	Prospective	1991–2000	Children with persistent anti-HCV antibody titres longer than 18 months were considered to be infected.	61	37	NA	3
24	Oliver, 2022	USA	AMR	Retrospective	2016–2020	Detectable HCV RNA viral load in infants	218	218	NA	13
25	Paccagnini, 1995	Italy	EUR	Prospective	From 1995	Infants were evaluated for anti-HCV and HCV RNA at 0,3,6,9,12,15 and 18 months	70	NA	50	14
26	Polywka, 1997	Germany	EUR	Prospective	1991–1996	Children were tested for anti-HCV and HCV RNA at five-month intervals.	117	62	5	6
27	Prasad, 2012	USA	AMR	Prospective	2006–2011	Infants were considered to be HCV infected if they were HCV-RNA positive at 3 or 6 months or if they had persistence of anti-HCV beyond 18 months of age.	19	NA	NA	2
28	Prasad 2023	USA	AMR	Prospective	2012–2018	Children were followed for evidence of perinatal transmission at 2–6 months (HCV RNA testing) and at 18–24 months (HCV RNA and antibody testing) of life. The primary outcome was perinatal transmission, defined as positive test results at either follow-up time point.	11,224	548	NA	26
29	Resti, 1998	Italy	EUR	Prospective	NR	Children were considered infected when hepatitis C virus RNA was detected or when antibodies to the virus persisted beyond age 2 years or reappeared after having disappeared.	403	275	NA	13
30	Resti, 2002	Italy	EUR	Prospective	1993–1999	HCV RNA was detected in peripheral blood by reverse-transcriptase (RT)–polymerase chain reaction (PCR) or when anti-HCV persisted beyond age 2 years	1372	897	NA	98
31	Resti, 1995	Italy	EUR	Prospective	NR	HCV-RNA was determined in children at the 4th and 12th months.	22	12	NA	5
32	Roudot-Thoraval, 1993	France	EUR	Cross-sectional study	NR	Infants were tested every 2 months for a mean of 10.8 months with the ELISA-2 and RIBA-2 tests and ALT determination.	24	NA	NA	0
33	Ruiz-Extremera, 2013	Spain	EUR	Prospective	1991–2009	The diagnosis of HCV was based on detectable HCV-RNA in the peripheral blood by the polymerase chain reaction (PCR), defined as infants who presented HCV-RNA + ve in at least two subsequent blood samples.	122	89	NA	15
34	Saez, 2004	Spain	EUR	Prospective	1992–2000	HCV RNA was tested in blood from newborns at birth and after 6, 12, and 24 months. Additional yearly testing of serum. HCV RNA was only performed in viremic infants.	110	80	NA	2
35	Spencer, 1997	Australia	WPR	Prospective	NR	NR	125	75	NA	6
36	Syriopoulou, 2005	Greece	EUR	Prospective	1995–2002	Children were considered to be HCV infected when HCV RNA was detected in more than 2 serum samples after the third month of age and/or when anti-HCV persisted beyond the age of 18 months.	86	56	NA	2
37	Tajiri, 2001	Japan	WPR	Prospective	1993–1998	The babies were diagnosed as vertically infected with HCV when circulating HCV RNA was positive in a repeated assay.	108	76	0	9
38	Uehara, 1993	Japan	WPR	Prospective	From 1992	In newborns and infants, peripheral blood samples at various intervals after birth were also examined for the presence or absence of HCV-RNA.	12	NA	NA	4
39	Zanetti, 1998	Italy	EUR	Prospective	NR	Detection of HCV-RNA, persistence of anti-HCV beyond 18 months of age or ex novo production of antibody were assumed to represent evidence of infection.	291	175	40	17
40	Zuccotti, 1995	Italy	EUR	Prospective	1991–1993	Serum of all infants was tested for HCV and HIV antibodies, HCV RNA, and ALT at birth and at 1 month of age, and then every 3 months until 18 months.	37	21	20	6

Complications
S/N	Author, year	Country	Study design	Inclusion criteria	Study period	Total number of pregnant patients (n)	Maternal HCV seroprevalence (n, %)
1	Berkley, 2008	USA	Retrospective	All pregnant women from the Milagro Clinic, a state-supported drug abuse and treatment program	2000–2006	300	159 (53.0)
2	Cheedalla, 2023	USA	Retrospective	Pregnant women who participated in >3 visits in a co-located prenatal/addiction program	2013–2021	941	404 (42.9)
3	Chen, 2022	USA	Cross-sectional	Pregnancy or delivery-related admissions identified using ICD-9-CM and ICD-10CM diagnostics and procedure codes	2012–2018	28,681,980	131,695 (0.5)
4	Chen, 2023	USA	Cross-sectional	Pregnancy or delivery-related admissions identified using ICD-9-CM and ICD-10CM diagnostics and procedure codes	1998–2018	70,038,267	137,259 (0.2)
5	Gulersen, 2023	USA	Retrospective	Retrospective analysis of the US Centres for Disease Control and Prevention Natality Live Birth database	2016–2021	22,604,938	107,761 (0.5)
6	Hughes, 2023	USA	Cross-sectional	Multicentre prospective cohort study of pregnant people with HCV	NR	735	249 (33.9)
7	Kushner, 2022	Canada	Retrospective	Data collected under universal healthcare coverage in Ontario, Canada and housed at the ICES administrative data repository	2000–2018	1,988,581	2170 (0.1)
8	Locatelli, 1999	Italy	Prospective	Pregnant women managed at the Department of Obstetrics and Gynecology, Istituto di Scienze Biomediche San Gerardo	1992–1997	16,271	63 (0.4)
9	Nikolajuk-Stasiuk, 2021	Poland	Cross-sectional	NR	NR	330	53 (16.1)
10	Paternoster, 2002	Italy	Prospective	Pregnant women who attended the Prenatal Department at the University of Padua	1996–1999	5840	105 (1.8)
11	Pergam, 2008	USA	Retrospective	Data from the Comprehensive Hospital Abstract Reporting System (CHARS), created by the Washington State Department of Health	2003–2005	240,131	506 (0.2)
12	Reddick, 2011	USA	Retrospective	National Inpatient Sample (NIS) from the Agency for Healthcare Research and Quality was queried for all pregnancy-related discharge codes	1995–2005	297,664	555 (0.2)
13	Stokkeland, 2017	Sweden	Retrospective	Identified patients through the Swedish Medical Birth Register and Patient Register	2001–2011	1,093,969	2056 (0.2)

Treatment with DAA
S/N	Author, year	Country	Study design and setting	Inclusion criteria	Study period	Total number of HCV pregnant patients (n)	IVDU (n, %)	HIV co-infection (n, %)	Treated with DAA (n, %)	Type of DAA	Duration of DAA (weeks)	Timing of DAA treatment initiation	Completed treatment (n, %)	SVR12 (fraction)
1	Chappell, 2020	Pittsburgh, PA, USA	Prospective cohort study–phase 1 open label study. Participants recruited from prenatal or substance use treatment providers	Age between 18 -39 and 23–24 weeks of gestation with chronic HCV genotype 1, 4, 5, or 6 and a singleton gestation with no known fetal abnormalities.	Oct 2016–Sep 2018	9	8	0	9	Sofosbuvir/ledipasvir	12	Between 23 and 24 weeks of gestation	9	9/9
2	Chappell, 2023	United States	Prospective cohort study–phase 4 open label study	–	Jul 2022–Sep 2023	26	0	0	26	sofosbuvir/velpatasvir	12	20 weeks of gestation	21	17/26 (ITT) 17/17 (PP)
3	Kushner, 2022	New York, USA	Retrospective cohort study in a obstetric clinic offering universal HCV screening	–	–	22	10	–	7	sofosbuvir/ledipasvir or sofosbuvir/velpatasvir	12	Intrapartum	4	3/7 (ITT) 3/4 (PP)
4	Mosquera, 2020	North Carolina, USA	Retrospective cohort study in a obstetric clinic offering universal HCV screening	Patients with HCV-related ICD codes who were referred to the “obstetrics” hepatology clinic	2015–2017	11	8	–	4	3 glecaprevir/pibrentasvir 1 sofosbuvir/ledipasvir	12	Intrapartum	4	3/4 (ITT) 3/3 (PP)
5	Yattoo, 2023	India	Prospective cohort study of 2 maternity hospital offering universal HCV screening	Pregnant women with chronic HCV	Mar 2016–Feb 2019	39	0	0	26	Sofosbuvir/ledispavir	12	15/26 in 2nd trimester, 11/26 in 3rd trimester	26	26/26
6	Zeng, 2022	Taiyuan, China	Prospective cohort study	Pregnant women with chronic HCV	–	2	–	–	2	1 Sofosbuvir/ledipasvir, 1 sofosbuvir/velpatasvir	12	31 and 26 weeks respectively	2	2/2

Abbreviations: HCV, hepatitis C virus; DAA, Direct-acting antivirals; SVR12, Sustained virological response; ITT, Intention-to-treat; PP, Per-protocol; IVDU: Intravenous Drug Use, HIV, Human Immunodeficiency Virus.

AFR: Africa; AMR: Americas; SEAR: Southeast Asia; EUR: Europe; EMR: Eastern Mediterranean; WPR: Western Pacific; USA: United States of America; UK: United Kingdom.

^aIndicates national studies (i.e studies that include multiple cities).

Prevalence of HCV infection in pregnant women

A total of 287 studies from 62 countries reported the prevalence of HCV infection in 311,597,108 pregnant mothers (Supplementary Figures S8 & S9). The overall seroprevalence and viremic prevalence of HCV in pregnant women were 2.6% (95% CI: 2.0–3.2, I² = 100%) and 1.3% (95% CI: 0.7–2.2, I² = 99%), respectively, with substantial heterogeneity observed. Subgroup analysis by region showed that the highest seroprevalence of HCV infection among pregnant women was found in the Eastern Mediterranean region (4.7%, 95% CI: 3.4–6.2, I² = 99%, 47 studies, 182,585 persons), followed by the Americas (3.4%, 95% CI: 1.7–5.6, I² = 100%; 70 studies, 308,867,714 persons), Africa (2.4%, 95% CI: 1.9–2.9, I² = 88%, 62 studies, 60,846 persons), Southeast Asia (1.6%, 95% CI: 0.8–2.7, I² = 99%, 17 studies, 63,295 persons), and the Western Pacific region (1.6%, 95% CI: 0.4–3.5, I² = 99%, 19 studies, 278,501 persons). The lowest HCV seroprevalence was observed in Europe (1.5%, 95% CI: 0.8–2.4, I² = 99%, 72 studies, 2,144,167 persons) (Fig. 2). HCV seroprevalence among pregnant women increased with the proportion of IVDU and HIV in individual studies (Fig. 3). There was no significant association between HCV seroprevalence in pregnant women and year of publication, study design, or study quality (Table 2). From 244 studies reported the types of HCV screening methods, the commonest screening method was universal screening (81.1%, 198 studies), followed by electronic databases (9.8%, 24 studies) and finally risk-based screening (9.0%, 22 studies).

Fig. 2.

Hepatitis C virus seroprevalence among pregnant women, by WHO region. Abbreviations: WHO: World Health Organization, CI: Confidence Interval.

Fig. 3.

a) Meta-regression of HCV prevalence by proportion of mothers with intravenous drug use, b) Meta-regression of HCV prevalence by proportion of mothers with HIV co-infection. Abbreviations: IVDU: Intravenous drug use; HIV: Human Immunodeficiency Virus; HCV: Hepatitis C virus.

Table 2.

Subgroup analyses on pooled HCV seroprevalence among pregnant women.

	No. of studies	Total	Seropositive women	Pooled mean prevalence (95% CI)	I2	p-value for subgroup analysis
Year of publication
Before 2010	99	770,486	5256	2.43 (1.63–3.37)	98.7	0.12
2010–2015	71	2,064,529	11,575	3.74 (2.30–5.36)	99.8
2016–2024	117	308,762,093	983,244	2.10 (1.39–2.95)	99.9
Patient population
General	270	311,534,288	987,806	1.93 (1.60–2.29)	99.8	<0.0001
OUD	17	62,820	12,269	22.48 (10.94–36.67)	99.9
Study design
Retrospective cohort	55	107,923,606	406,915	2.25 (1.02–3.95)	99.9	0.35
Prospective cohort	64	2,884,443	10,056	3.56 (2.05–5.47)	99.6
Cross-sectional	168	200,789,059	583,104	2.34 (1.81–2.95)	99.9
Study level
National	56	304,881,043	958,108	1.63 (0.91–2.53)	100.0	0.03
Sub-national	231	6,716,065	41,967	2.85 (2.20–3.58)	99.8
WHO regions
Africa	62	60,846	1678	2.41 (1.92–2.94)	87.8	0.0005
America	70	308,867,714	980,145	3.40 (1.74–5.57)	100.0
Eastern Mediterranean	47	182,585	8540	4.67 (3.37–6.17)	99.2
Europe	72	2,144,167	6870	1.49 (0.79–2.40)	98.9
Southeast Asia	17	63,295	1567	1.60 (0.76–2.72)	99.3
Western Pacific	19	278,501	1275	1.60 (0.40–3.54)	99.0
Maternal agea
<30 years	167	283,580,849	856,280	2.52 (1.85–3.29)	99.9	0.03
≥30 years	37	2,898,899	6096	1.42 (0.74–2.30)	99.4
Sample size
<1000	121	48,109	3029	5.58 (4.11–7.25)	97.7	<0.0001
1000–10,000	105	361,701	6450	1.56 (1.20–1.97)	98.6
>10,000	61	311,187,298	990,596	0.67 (0.33–1.13)	100.0
Study quality score (NOS)
<7	23	30,330,827	135,684	3.86 (1.04–8.27)	99.7	0.41
≥7	264	281,266,281	864,391	2.48 (1.96–3.05)	99.9
Screening typea
Universal Screening	198	246,364,969	75,0703	2.61 (1.97–3.33)	99.9	0.54
Risk-based screening	22	29,586,767	138,788	1.76 (0.91–2.87)	99.7
Electronic Database	24	33,397,760	98,713	2.74 (0.78–5.79)	99.6

^aNote: Seroprevalence by maternal age was reported in 204 studies; seroprevalence by screening type was reported in 244 studies.

The study characteristics reporting HCV viremia was summarized in Supplementary Table S7. For HCV viremic prevalence, the highest prevalence among pregnant women was reported in the Americas (4.6%, 95% CI: 0.6–11.7, I² = 100%, 11 studies, 253,393 persons), followed by the Eastern Mediterranean region (1.9%, 95% CI: 0.8–3.3, I² = 96%; 9 studies, 10,559 persons), Southeast Asia (1.5%, 95% CI: 0.5–3.2, I² = 97%, 3 studies, 11,784 persons), Africa (0.9%, 95% CI: 0.2–1.9, I² = 93%, 8 studies, 7008 persons), and Europe (0.4%, 95% CI: 0.2–0.6, I² = 97%, 19 studies, 196,802 persons). The Western Pacific region had the lowest HCV viremic prevalence (0.3%, 95% CI: 0.1–0.4, I² = 88%, 2 studies, 44,455 persons) (Fig. 4).

Fig. 4.

Pooled prevalence of Hepatitis C viremia among pregnant women, by WHO region. Abbreviations: WHO: World Health Organization, CI: Confidence Interval.

Maternal-to-child transmission (MTCT)

Forty studies (13,422 persons) reported MTCT rates among pregnant mothers with HCV infection. Over a median (interquartile range) follow-up of 12 (11–24) months post-partum, the pooled MTCT rate among mothers with HCV viremia was 9.0% (95% CI: 6.6–11.7, I² = 79%, 28 studies, 3838 persons) (Fig. 5). Sensitivity analyses by restricting studies with larger sample sizes (>100 patients) showed a lower MTCT rate of 7.8% (95% CI: 5.2–10.9%, I² = 88%, 8 studies, 2800 persons) (Supplementary Figure S1). HIV co-infection was associated with higher odds of MTCT among viremic HCV pregnant mothers (OR: 3.1, 95% CI: 2.1–4.6, I² = 10%, 16 studies, 3328 persons). The MTCT rate did not differ significantly according to the mode of delivery (cesarean section vs. vaginal delivery: OR, 1.0; 95% CI: 0.7–1.6, I² = 27%; 17 studies, 3342 persons) or breastfeeding (breastfeeding: OR: 1.3, 95% CI: 1.0–1.8, I² = 0%; 16 studies, 3190 persons) (Fig. 6). The rates of HCV diagnosis in HCV-exposed children were similar among mothers with IVDU (p = 0.283) and across different post-partum periods (p = 0.697).

Fig. 5.

Maternal-to-child-transmission amongst pregnant mothers with HCV viremia. Abbreviations: HCV: Hepatitis C virus; CI: Confidence Interval.

Fig. 6.

Maternal-to-child-transmission amongst HCV viremia mothers according to (a) mode of delivery and (b) breastfeeding. Abbreviations: HCV: Hepatitis C virus; CI: Confidence Interval.

Maternal outcomes

Maternal outcomes of HCV infection during pregnancy were reported in 122,695,298 women from 13 studies. The study characteristics and specific complications reported in the individual studies are summarised in Supplementary Table S8. The definition of maternal HCV infection was heterogeneous across different studies based on HCV seropositivity (4 studies), HCV viremia (3 studies), ICD-coding (4 studies), and was not specified in 2 studies (Supplementary Table S5). Pregnant women with HCV infection had higher odds of maternal complications, including preterm delivery (OR: 1.62, 95% CI: 1.45–1.81, I² = 98%, 12 studies, 122,673,313 persons), intrahepatic cholestasis (OR: 12.97, 95% CI: 4.01–41.99, I² = 86%, 5 studies, 25,316 persons), and antepartum hemorrhage (OR: 1.39, 95% CI: 1.15–1.68, I² = 50%; 4 studies, 28,930,458 persons) (Fig. 7). The odds of developing gestational diabetes (OR: 1.02, 95% CI: 0.82–1.27, I² = 99%, 9 studies, 122,671,943 persons) or preeclampsia (OR: 0.90, 95% CI: 0.78–1.05; I² = 98%, 5 studies, 122,667,932 persons) were not significantly different between mothers with or without HCV infection. In a sensitivity analysis based on the definition of HCV infection, preterm delivery was higher for HCV mothers regardless of whether active HCV viremia was detected. This was true for both the random-effects (OR: 2.53 vs OR: 1.52; Supplementary Figure S2) and fixed-effects model (OR: 1.86 vs OR: 1.86; Supplementary Figure S3).

Fig. 7.

Maternal and neonatal complications.

Fetal outcomes

The fetal outcomes of HCV-infected mothers were available for 23,706,176 neonates from 7 studies. Neonates from HCV-infected mothers had significantly higher odds of being small for gestational age (SGA) (OR, 1.74; 95% CI: 1.30–2.31, I² = 87%; 7 studies, 23,706,079 persons). The odds of developing neonatal jaundice were not significantly different between mothers with or without HCV infection (OR, 1.30; 95% CI: 0.95–1.78; I² = 55%; 3 studies, 6824 persons) (Fig. 7).

DAA treatment

A total of six studies (n = 109) reporting treatment outcome of DAA in pregnant women with HCV infection. The treatment rate using DAA was 67.9% (n = 74). The two main reasons for not receiving DAA treatment were safety concerns regarding DAA treatment (n = 15) and loss to follow-up before initiation (n = 12). The remaining 23% [8/35] of patients had planned DAA treatment in the postpartum setting. The most commonly prescribed DAA regimens were sofosbuvir/ledipasvir (50.0%, n = 37/74), followed by sofosbuvir/velpatasvir (36.5%, n = 27/74), glecaprevir/pibrentasvir (4.1%, n = 3/74), and was not specified in 7 patients (9.4%, n = 7/74). DAA treatment was initiated between the late second and third trimesters for all pregnant women.

The overall SVR12 was 98.4% (n = 60/61) based on the per-protocol analysis. Loss to follow-up before SVR12 assessment was reported in 17.6% (n = 13/74) of patients, resulting in a lower pooled rate of SVR12 based on intention-to-treat (ITT) analysis (81.1%, n = 60/74). Including patients who lost to follow-up, the SVR12 was similar between clinical trials and real-world settings (86.1% vs. 87.7%, p = 0.92). Common adverse events included nausea or vomiting (17.6%, n = 13/74), headaches (10.8%, n = 8/74), and fatigue (9.5%, n = 7/74). There were no treatment-related adverse events among the pregnant mothers with HCV infection who required treatment cessation. To date, no fetal adverse events related to DAA treatment have been reported.

Sensitivity analysis to identify the source of heterogeneity

To explore the possible reasons behind the asymmetric funnel plot, we performed a comprehensive subgroup analysis of HCV seroprevalence based on year of publication, patient population, study design, study level, WHO region, maternal age, sample size, and study quality (Table 2). Subgroup analysis based on maternal age showed a higher prevalence of HCV observed in younger women below 30 years old (vs ≥ 30 years old: 2.5% vs 1.4%, p = 0.03; 204 studies; 283,580,849 women), and among individuals with opioid use disorder than in the general population (22.5% vs. 1.9%, p < 0.0001; 287 studies, 311,597,108 women). Subgroup analysis showed similar seroprevalence between universal, risk-based or electronic database screening (2.6% vs. 1.8% vs. 2.7%, p = 0.54; Table 2). A sensitivity analysis by serial exclusion of individual studies did not detect any study with a dominant effect. The adjusted estimates of HCV seroprevalence using the trim-and-fill method were 0.29% (95% CI: 0.08–0.60%, I² = 99.9%), with no evidence of publication bias based on Eggar's test and graphical inspection of the funnel plot (Supplementary Figure S4).

Discussion

In this systematic review of 311,905,738 pregnant women, we found that the pooled overall global seroprevalence and viremic prevalence of HCV infection among pregnant women between 1990 and 2024 were 2.6% and 1.3%, respectively. This study has several key findings. First, the prevalence varied significantly according to the presence of IVDU and geographic distribution. Second, despite the decline in global HCV prevalence, HCV prevalence among pregnant women remains similar across time periods, highlighting an unmet need among pregnant women with HCV infection. Third, the pooled MTCT rate among HCV viremic pregnant women was 9.0%, which was significantly higher in patients with HIV co-infection. Fourth, the risk of MTCT does not differ between the modes of delivery and breastfeeding. Our findings suggest that the decision to perform cesarean section should be based on obstetric indications without being influenced by the diagnosis of HCV. Fifth, HCV infection in pregnant women was associated with significant adverse events in both mothers (intrahepatic cholestasis, preterm delivery, antepartum hemorrhage) and neonates (small for gestational age). Sixth, early data from approximately 61 treated mothers suggest that DAA treatment is efficacious and safe in pregnant women with HCV infection.

Despite the introduction of highly efficacious direct-acting antivirals (DAA), a recent study reported a rising HCV prevalence among pregnant women.¹⁵ Micro-elimination efforts among pregnant mothers with HCV have been hampered by the COVID-19 pandemic, as shown in our previous studies.^29,31,32 Following the recommendations of the Centres for Disease Control and Prevention (CDC) and U.S. Preventive Services Task Force (USPSTF), HCV screening among pregnant women in the USA has increased but remains suboptimal (16.6%–40.6%).³³ Screening for asymptomatic diseases such as HCV often competes with priority over basic necessities and obstetric care.²⁹ In addition to screening, there were multiple barriers linking pregnant women with HCV infection to care. As many patients also have complex social circumstances and limited access to healthcare postpartum, the default rate during the postpartum period is high.^34,35 In addition, there are potential legal implications and discrimination against patients, particularly in countries where IVDUs are heavily criminalized. Even after diagnosis, women with HCV had a longer delay in treatment initiation than male.³⁵ Given that HCV prevalence increases with the proportion of patients with IVDU, targeted screening focusing on the IVDU cohort has been proposed in resource-limited settings. However, the implementation of the risk-based approach could leave many potential patients undetected. Of the 244 studies that reported diagnostic criteria in this meta-analysis, we found that most diagnoses of HCV infection among pregnant mothers were made through universal screening (81.1%, 198 studies) and only a small proportion were diagnosed based on risk-based screening (9.0%, 22 studies) or large electronic databases (9.8%, 24 studies). Universal screening among pregnant women, followed by DAA treatment postpartum has been shown to be cost-effective.³⁶ Moreover, a recent survey demonstrated that 88% of pregnant women will consider DAA in pregnancy if approved for use.^37,38 These rationales support universal screening during pregnancy as a unique opportunity to engage affected mothers and children with appropriate HCV treatment.³⁹

Vertical transmission has been the most common cause of HCV infection in children since the introduction of HCV screening of blood products.⁴⁰ Despite recommendations from professional societies^11,41 the screening rate among children with HCV exposure remains low (∼30%).⁴² In this regard, perinatal diagnosis of HCV infection among pregnant mothers is a pivotal step in postpartum HCV screening and the treatment of children with HCV exposure. The pooled MTCT rate among the infected pregnant women with HCV viremia was 9.0 per 100 infants. Without treatment, cirrhosis can occur in 2% of chronically infected children by the age of 20.⁴³ Current guidelines recommend antibody-based testing in all HCV-exposed children after 18 months of age for two main reasons⁴⁴: First, spontaneous clearance of HCV may occur in up to 50% of HCV-infected infants¹¹ and second, transplacental maternal antibodies may persist in children for up to 18 months.⁴⁵ Since the current treatment was not approved for children under 3-years old, close collaboration between obstetricians and pediatricians is crucial to improve retention and screening of HCV-exposed children. Diagnosing pregnant mothers with HCV infection is the first step in identifying infants at a risk of HCV infection. HCV diagnosis among pregnant mothers must prompt follow-up HCV testing of infants because children with prenatal exposure to HCV develop cirrhosis at an earlier age⁴⁰

To date, no DAA have been approved for use in pregnancy¹¹ due of the lack of safety data in this population. The current guidelines for AASLD suggest that DAA treatment should be considered on a case-by-case basis after discussing its potential risks and benefits.¹¹ The rationale for DAA treatment during pregnancy is to achieve a maternal cure that potentially reduces MTCT and prevents HCV spread. Furthermore, pregnancy is an opportunistic window for patients to access health care. Our meta-analysis demonstrated that DAA treatment in pregnancy resulted in a high SVR12, with no severe maternal adverse events and or fetal adverse events. Meanwhile, the safety and efficacy data of DAA during pregnancy are rapidly expanding. The STORC study was an open-label, single-arm study of sofosbuvir/velpatasvir in pregnant women at around 20 weeks of gestation.⁴⁶ The TiP-HepC is a registry that seeks to collect real-world data on DAA treatment in pregnant women.⁴⁷ The results of these emerging studies are highly anticipated to guide treatment decisions in pregnant women with HCV infection and DAA.

The strength of the current meta-analysis depends on a comprehensive and systematic review of HCV infection in pregnant women based on high-quality studies, and most studies had a low-to-moderate risk of bias. The limitations of our study was that we were unable to perform sensitivity analyses based on HIV status without individual patient data. The definition of HCV is heterogeneous in studies evaluating complications in mothers with HCV. Finally, early treatment outcome data using DAA among pregnant women, while encouraging, remain limited.

In conclusion, the perinatal diagnosis of HCV infection in pregnant women has important implications for both patients and infants. Wide regional variations in HCV prevalence in pregnant women may influence the cost-effectiveness of universal HCV screening among pregnant women. Similar MTCT rates between delivery methods suggest that HCV infection alone should not influence the decision regarding delivery method and breastfeeding. Early data suggest that DAA are safe among pregnant women with HCV infection, although further studies are required to establish the safety and efficacy of DAA in pregnant women.

Contributors

Ethan Quek: Data curation, validation, writing (original draft), writing (review & editing); Jing Hong Loo: Formal analysis, investigation, validation, writing (review and editing); En Qi Lim: Data curation, writing (original draft), writing (review and editing); Hon-Lam Chung: Data curation, writing (original draft), writing (review and editing); Abu Bakar Bin Othman: Data curation, writing (original draft), writing (review and editing); Jie-Rae Tan: validation, writing (review and editing); Scott Barnett: Analysis,^: writing (review and editing); Mindie H Nguyen: supervision, methodology, writing (review & editing); Yu Jun Wong: Study conception, formal analysis, supervision, investigation, validation, methodology, writing (review & editing).

ALL authors approved the final version of the article, including the authorship list. The data were verified by JWEQ, JHL and YJW.

Data sharing statement

Data collected for the study has been included as supplementary materials along with publication. Additional related documents will be available from the corresponding author.

Editor note

The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.

Declaration of interests

MHN: Research support: Pfizer, Enanta, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation; Consulting and/or Advisory Board: Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine, Janssen; WYJ: Invited speaker: Gilead. All other authors declare no competing interests.