Over the past twenty-five years, opioid-related morbidity and mortality surged in the United States (U.S.) (Lyden and Binswanger, 2019), including diagnosed maternal opioid use disorder (OUD) during pregnancy (Desai et al., 2014; Krans and Patrick, 2016). Indeed, the national prevalence of maternal OUD escalated from 1.5 cases to 8.2 cases per 1000 delivery hospitalizations from 1999 to 2017 (Haight et al., 2018; Hirai et al., 2021). Maternal OUD is associated with adverse infant health outcomes, including preterm birth, low birth weight, respiratory complications, and neonatal opioid withdrawal syndrome (NOWS) (Tobon et al., 2019). Because these conditions are risk factors for infant mortality (death within 365 days post-birth) (Almli et al., 2020; Behrman and Butler, 2007; Witt et al., 2017), maternal OUD may exacerbate such risk.

The link between maternal OUD and infant mortality has only recently been studied. In Ontario, Canada during 2002–2014, the infant mortality incidence among prenatally opioid-exposed infants was approximately three-times greater than that of Ontario's full population of births (Brogly et al., 2017). A study of Texas Medicaid births spanning 2010–2014 found that maternal OUD was associated with a doubled odds of infant mortality, and this association was stronger for infants without a NOWS diagnosis (Leyenaar et al., 2021). The authors speculated that services provided at discharge to NOWS-diagnosed infants may prevent mortality. However, a subsequent Tennessee-based study found that the association between maternal OUD and post‑neonatal mortality (death between 28 and 365 days post-birth) did not notably vary by NOWS diagnosis (Grossarth et al., 2023). With clinical guidelines recommending medication for opioid use disorder (MOUD) to manage OUD during pregnancy (American College of Obstetricians and Gynecologists, 2017; Rodriguez and Klie, 2019; Substance Abuse and Mental Health Services Administration, 2018), a study of NOWS-diagnosed infants born in North Carolina during 2016–2018 found that infant mortality was slightly lower with maternal MOUD receipt (1.0%) relative to no treatment (1.3%) (Austin et al., 2022).

Prior work is limited in several dimensions. The Ontario and North Carolina studies described differences in infant mortality in relatively small cohorts (<5000 infants) without adjustment for demographic confounders of opioid use and infant mortality (Austin et al., 2022; Brogly et al., 2017; Mohamoud et al., 2019; Nguyen et al., 2023). Additionally, differential survival time may explain heterogeneity in the association between maternal OUD and infant mortality by NOWS diagnosis, as infants may die before presenting NOWS symptoms (Jansson et al., 2009). To address these gaps, our study investigates associations between maternal OUD and infant mortality using data from Wisconsin, U.S. during 2010–2018. Further, we examine whether associations vary by NOWS diagnosis and by MOUD receipt during pregnancy.