Infant Mortality Associated With Prenatal Opioid Exposure.

Importance: Knowledge of health outcomes among opioid-exposed infants is limited, particularly for those not diagnosed with neonatal opioid withdrawal syndrome (NOWS). Objectives: To describe infant mortality among opioid-exposed infants and identify how mortality risk differs in opioid-exposed infants with and without a diagnosis of NOWS compared with infants without opioid exposure. Design, Setting, and Participants: A retrospective cohort study of maternal-infant dyads was conducted, linking health care claims with vital records for births from January 1, 2010, to December 31, 2014, with follow-up of infants until age 1 year (through 2015). Maternal-infant dyads were included if the infant was born in Texas at 22 to 43 weeks' gestational age to a woman aged 15 to 44 years insured by Texas Medicaid. Data analysis was performed from May 2019 to October 2020. Exposure: The primary exposure was prenatal opioid exposure, with infants stratified by the presence or absence of a diagnosis of NOWS during the birth hospitalization. Main Outcomes and Measures: Risk of infant mortality (death at age <365 days) was examined using Kaplan-Meier and log-rank tests. A series of logistic regression models was estimated to determine associations between prenatal opioid exposure and mortality, adjusting for maternal and neonatal characteristics and clustering infants at the maternal level to account for statistical dependence owing to multiple births during the study period. Results: Among 1 129 032 maternal-infant dyads, 7207 had prenatal opioid exposure, including 4238 diagnosed with NOWS (mean [SD] birth weight, 2851 [624] g) and 2969 not diagnosed with NOWS (mean [SD] birth weight, 2971 [639] g). Infant mortality was 20 per 1000 live births for opioid-exposed infants not diagnosed with NOWS, 11 per 1000 live births for infants with NOWS, and 6 per 1000 live births in the reference group (P < .001). After adjusting for maternal and neonatal characteristics, mortality in infants with a NOWS diagnosis was not significantly different from the reference population (odds ratio, 0.82; 95% CI, 0.58-1.14). In contrast, the odds of mortality in opioid-exposed infants not diagnosed with NOWS was 72% greater than the reference population (odds ratio, 1.72; 95% CI, 1.25-2.37). Conclusions and Relevance: In this study, opioid-exposed infants appeared to be at increased risk of mortality, and the treatments and supports provided to those diagnosed with NOWS may be protective. Interventions to support opioid-exposed maternal-infant dyads are warranted, regardless of the perceived severity of neonatal opioid withdrawal.

Neonatal Abstinence Syndrome and Associated Neonatal and Maternal Mortality and Morbidity.

OBJECTIVES: We examined demographic characteristics and birth outcomes of infants with neonatal abstinence syndrome (NAS) and their mothers in Canada. METHODS: This retrospective, population-based, descriptive cross-sectional study of mother-infant dyads included all singleton live births in Canada (excluding Quebec), from 2005-2006 to 2015-2016 (N = 2 881 789). Demographic characteristics, NAS, and neonatal and maternal morbidities were identified from delivery hospitalization data (including diagnostic codes). The main composite outcomes were maternal and neonatal mortality and/or severe morbidity, including death and potentially life-threatening conditions in the mother and the infant, respectively. Logistic regression yielded adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: The study included 10 027 mother-infant dyads with NAS. The incidence of NAS increased from 0.20% to 0.51%. Maternal mortality was 1.99 vs 0.31 per 10 000 women in the NAS group versus the comparison group (aOR = 6.53; 95% CI: 1.59 to 26.74), and maternal mortality and/or severe morbidity rates were 3.10% vs 1.35% (aOR = 2.21; 95% CI: 1.97 to 2.49). Neonatal mortality was 0.12% vs 0.19% (aOR = 0.28; 95% CI: 0.15 to 0.53), and neonatal mortality and/or severe morbidity rates were 6.36% vs 1.73% (aOR = 2.27; 95% CI: 2.06 to 2.50) among infants with NAS versus without NAS. CONCLUSIONS: NAS incidence increased notably in Canada between 2005-2006 and 2015-2016. Infants with NAS had elevated severe morbidity, and their mothers had elevated mortality and severe morbidity. These results highlight the importance of implementing integrated care services to support the mother-infant dyad during childbirth and in the postpartum period.

Rural and Appalachian Disparities in Neonatal Abstinence Syndrome Incidence and Access to Opioid Abuse Treatment.

OBJECTIVE: Incidence of neonatal abstinence syndrome (NAS) is increasing due to the rise in opioid use. Rural states like Kentucky have been disproportionally impacted by opioid abuse, and this study determines NAS burden nationally and in Kentucky while quantifying differences in access to care between Appalachian and non-Appalachian counties. METHODS: NAS rates were calculated using National (2013) and Kentucky (2008-2014) National Inpatient Sample discharge data. Births were identified using International Classification of Diseases v9 code 779.5 and live birth codes V30.x-V38.x. Counties were classified as rural, micropolitan, or metropolitan using census data. Proximity analysis was conducted via mapping from ZIP code centroid to nearest opioid treatment facility. Distance to treatment facilities was calculated and then compared using nonparametric testing for counties by rural and Appalachian status. RESULTS: NAS cases tripled from 2008 to 2014 in Kentucky counties, with a 2013 NAS rate more than double the national NAS rate. Rural and Appalachian counties experienced an NAS increase per 1,000 births that was 2-2.5 times higher than urban/non-Appalachian counties, with a greater number of NAS births overall in Appalachian counties. All opioid treatment facility types were further from rural patients than micropolitan/metropolitan patients (P < .001), as well as further for Appalachians versus non-Appalachians (P < .001, all facility types). CONCLUSIONS: NAS burden disparately affects rural and Appalachian Kentucky counties, while treatment options are disproportionately further away for these residents. Policy efforts to increase NAS prevention and encourage opioid abuse treatment uptake in pregnant women should address rural and Appalachian disparities.

Neonatal abstinence syndrome and early childhood morbidity and mortality in Washington state: a retrospective cohort study.

OBJECTIVE: The objective of the study was to evaluate the association between neonatal abstinence syndrome (NAS) and long-term childhood morbidity and infant mortality. STUDY DESIGN: We conducted a cohort study of infants born in Washington State during 1990 to 2008 who were diagnosed with NAS (n=1900) or were unexposed (n=12,283, frequency matched by birth year). 5-year hospital readmissions and infant mortality were ascertained. RESULTS: Children with history of NAS had increased risk of readmission during the first 5 years of life relative to unexposed children; this remained statistically significant after adjustment for maternal age, maternal education, gestational age and intrapartum smoking status (readmission rates: NAS=21.3%, unexposed=12.7%, adjusted relative risk (aRR) 1.54, 95% confidence interval (CI) 1.37 to 1.73). NAS was associated with increased unadjusted infant mortality risk, but this did not persist after adjustment (aRR 1.94, 95% CI 0.99 to 3.80). CONCLUSION: The observed increased risk for childhood hospital readmission following NAS diagnosis argues for development of early childhood interventions to prevent morbidity.Journal of Perinatology advance online publication,.

Are infants exposed to methadone in utero at an increased risk for mortality?

BACKGROUND: The prevalence of opioid abuse is increasing in North America. Opioid abuse during pregnancy can cause medical, obstetric and psychosocial complications. Neonates exposed to opioids in utero often develop the neonatal abstinence syndrome. Methadone maintenance therapy is the treatment of choice for maternal opioid dependency. There have been unsupported concerns that infants cared for by mothers treated with methadone have higher mortality rates during the first year of life than in the general population. OBJECTIVES: To compare the mortality rates of infants exposed to methadone in utero to those of general population in Ontario, Canada. METHODS: We utilized several provincial and national databases including those of the Office of the Chief Coroner of Ontario, the Canadian Institute for Health Information, and the Ontario Infant Mortality Rate Report. Reference organ weights were obtained from the peer reviewed literature. RESULTS: The Office of the Chief Coroner of Ontario has reported 8 deaths in children under one associated with in utero methadone exposure between January 1, 2006 and December 31, 2010. Over the same period there have been a total of 1103 cases of neonatal abstinence syndrome recorded in the province. The mean infant mortality rate in Ontario for children under the age of 1year over the same period was 5.2 per 1000 live births. The odds ratio for mortality among children with neonatal abstinence syndrome was not different from that in the general population [OR 1.45 (95% confidence interval 0.471-4.459)] (p=0.56). CONCLUSION: The available data do not support the concerns that children under the age of one year, born to mothers on methadone maintenance therapy (MMT) are at an increased risk for mortality.

French field experience with buprenorphine.

In most European countries, methadone treatment is provided to only 20-30% of opiate abusers who need treatment due to regulations and concerns about safety. To address this need in France, all registered medical doctors since 1995 have been allowed to prescribe buprenorphine (BUP) without any special education or licensing. This led to treating approximately 65,000 patients per year with BUP, about ten times more than with more restrictive methadone policies. French physician compensation mechanisms, pharmacy services, and medical insurance funding all minimized barriers to BUP treatment. About 20% of all physicians in France are using BUP to treat about half of the estimated 150,000 problem heroin users. Daily supervised dosing by a pharmacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use. Intravenous diversion of BUP may occur in up to 20% of BUP patients and has led to various infections and relatively rare overdoses in combination with sedatives. Opiate overdose deaths have declined substantially (by 79%) since BUP was introduced in 1995. Newborn opiate withdrawal in mothers treated with buprenorphine compared to methadone was reported to be less frequent, less severe, and of shorter duration. Although some of the public health benefits seen during the time of buprenorphine expansion in France might be contingent upon characteristics of the French health and social services system, the French model raises questions about the value of tight regulations on prescribing BUP imposed by many countries throughout the world.