The incidence of hepatitis C virus (HCV) infection in reproductive-aged adults in the United States has risen in parallel with injection drug use associated with the opioid crisis. (Centers for Disease Control and Prevention, 2023) Universal screening for hepatitis C is recommended during each pregnancy.(Schillie et al., 2020) There are limited and conflicting data regarding the impact of HCV infection on pregnancy and infant outcomes beyond perinatal transmission.

Among a surveillance cohort of people with HCV infection during pregnancy, we describe maternal demographics, pregnancy characteristics, complications, and birth outcomes. We compare these outcomes by maternal substance use.

Pregnant people with HCV infection who had a live birth during 2018–2021 were reported to the Surveillance for Emerging Threats to Pregnant People and Infants Network by three U.S. jurisdictions (New York State, excluding New York City; Allegheny and Washington Counties, Pennsylvania; and Tennessee). Inclusion criteria were people with a positive nucleic acid test for HCV ribonucleic acid during pregnancy or in the 12 months pre-pregnancy without evidence of subsequent negative testing or treatment, or those who gave birth to an infant with positive HCV test results. Substance use was ascertained through birth certificates, provider notes, ICD-10 codes, and urine drug screening reports. Substance use in pregnancy was defined as use of ≥ 1 categories of the following: tobacco, alcohol, cannabis, opioids obtained illicitly or used in a manner not prescribed, and other illicit substances (e.g., methamphetamines, cocaine). Outcomes included preterm birth (< 37 weeks gestation), small-for-gestational age (SGA), neonatal intensive care unit (NICU) admission, possible birth defects, and neonatal abstinence syndrome (NAS). Statistical analyses were conducted using SAS Version 9.4 (Cary, NC). This activity was reviewed by the Centers for Disease Control and Prevention and conducted consistent with applicable federal law and policy (45 C.F.R. part 46.102(l) and 102(e)(1); 42 U.S.C. Section 241(d); 5 U.S.C. Sect. 552a).

Three jurisdictions reported 1393 pregnancies among 1303 people (90 people had > 1 pregnancy) meeting inclusion criteria, with data reported as of September 15, 2023. Median age was 29 years (interquartile range [IQR] 26–33), and most pregnant people with HCV infection had public insurance (89%) (Table 1). Of those with available information on prenatal care (91%), 17% initiated care in the third trimester or had none. Any substance use during pregnancy was common (89%, with 63% using ≥ 2 categories of substances). The most frequently reported substances were tobacco (86%) and illicit opioids (41%). Of those with reported substance use during pregnancy, 50% also were treated with Medication for Opioid Use Disorder.

The 1393 pregnancies resulted in 1418 liveborn infants. The proportion of infants born preterm was 20% (15% 34–36 weeks, 5% <34 weeks) and 13% were SGA. Among term infants, 34% were admitted to a NICU. 6% of infants had a birth defect, and 35% had a diagnosis of NAS. Frequencies of infants born preterm were 21% among infants born to people with reported substance use and 13% without (Table 1). Infants born to people with reported substance use had a higher frequency of adverse outcomes than those without reported substance use. After controlling for insurance and trimester of prenatal care initiation, this difference remained significant for SGA (adjusted prevalence ratio [aPR] 1.9, 95% confidence interval [CI] 1.04, 3.60) and NICU admission among term infants (aPR 4.0, 95% CI 2.27, 7.10). Among infants born to people with reported substance use, frequency of NAS was 40%.

The proportion of infants born preterm within this cohort (20%) was higher than the general population of each of the three states in 2018–2021 (9.3, 9.3, and 11.1% in New York, Pennsylvania, and Tennessee respectively)(National Center for Health Statistics, 2022). Frequency of preterm birth among those without reported substance use was less pronounced (12.6%). Other reports have described increased risk of preterm birth and SGA among people with hepatitis C (Rossi et al., 2020) but often lacked the ability to control for substance use, which is common among people with HCV infection. However, an analysis of a population-based cohort in Sweden found that even after adjusting for tobacco and alcohol or other substance use, HCV infection during pregnancy was associated with an increased risk of preterm birth, though no increased risk of lower birth weight, SGA, or birth defects (Stokkeland et al., 2017). It is not clear if the association between HCV infection and adverse birth outcomes is related to unmeasured confounders (e.g., other exposures, social determinants of health) or infection; more data may help inform these relationships.

This analysis has several limitations. First, the analysis was limited to pregnancies resulting in a live birth, and we are unable to assess frequency of pregnancy loss. Second, comprehensive ascertainment of substance use is challenging due to stigma associated with substance use, especially during pregnancy. Third, birth defects were likely under-ascertained given reporting only at birth hospitalization.

Continuing to examine how screening for hepatitis C during pregnancy can increase maternal access to curative hepatitis C treatment, and the identification and treatment of comorbidities such as substance use disorder which contribute to adverse pregnancy and infant outcomes could help inform future research.