Long-term mortality risk in mothers of infants with neonatal abstinence syndrome: an international cohort study in England and Canada

Abstract

BackgroundOpioid addiction is a major public health issue, but little is known about long-term mortality for mothers with opioid use in pregnancy. The prevalence of neonatal abstinence syndrome is high in England and Ontario (Canada). We aimed to compare maternal mortality among mothers of infants with and without neonatal abstinence syndrome in these regions. MethodsIn this population-based study, we used administrative data to obtain parallel cohorts of linked mother–child records from singleton hospital births in England and Ontario between April 1, 2002, and Dec 31, 2012. Death records captured maternal mortality up to 10 years after delivery. We used neonatal abstinence syndrome as a marker of opioid-use during pregnancy. We modelled the association between neonatal abstinence syndrome and all-cause maternal mortality using Cox regression, and the cumulative incidence of cause-specific mortality within a competing risks framework. The primary exposure was neonatal abstinence syndrome among all mothers (aged 12–49 years) who had a live birth during the study period; mothers of infants without neonatal abstinence syndrome were controls. The main outcome was all deaths among mothers following index delivery. We estimated all-cause mortality rates, 10-year cumulative incidence risk of death, and crude and adjusted hazard ratios (HRs). FindingsThe study included 13 577 and 4 205 675 mothers of infants with neonatal abstinence syndrome in England and Ontario, respectively, and 4966 and 929 985 mothers of infants without neonatal abstinence syndrome in England and Ontario, respectively. 10-year mortality among mothers of infants with neonatal abstinence syndrome was 5·1% in England and 4·6% in Ontario compared with 0·4% in controls (both p<0·0001). Crude HRs for all-cause mortality were 12·1 (95% CI 11·1–13·2) in England and 11·4 (9·7–13·4) in Ontario. Compared with controls, the cumulative incidence of death was higher among mothers of infants with neonatal abstinence syndrome than mothers of infants without neonatal abstinence syndrome for almost all causes of death. Most deaths were due to avoidable causes. InterpretationApproximately one in 20 mothers of infants with neonatal abstinence syndrome died within 10 years of delivery in both England and Canada. Our study was limited by the paucity of direct measures of maternal opioid use and treatment. Policy responses to the current opioid epidemic require effective strategies for long-term support to improve the health and welfare of mothers who use opioids and their children. FundingInstitute for Clinical Evaluative Sciences, Ontario Ministry of Health and Long-Term Care.