Hospital for Sick Children, Toronto, Ontario, Canada, We excluded observations with extreme values, including women aged <12 years or >49 years at the date of delivery. The term NAS has been principally used to describe neonatal symptoms and signs occurring … Data curation, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada, The mean duration of follow-up was 8.4 years (England) and 7.2 years (Ontario) for NAS mothers and 8.2 years (England) and 8.6 years (Ontario) for controls. In our study, the high rate of premature mortality among the mothers of infants with NAS was mirrored by high rates for the mothers of control infants discharged to social services and for mothers with a history of hospitalization for addiction. We restricted the cohort to singleton births, and if a woman had more than 1 live birth delivery during the study period, 1 delivery was chosen at random as the focus of the study, i.e., a delivery date was selected at random and used as the entry point for the mother (referred to as the index delivery), and all other deliveries were ignored. 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. None of these studies address long-term all-cause mortality for mothers of NAS-affected infants as we have done. Our study cohort may also include the rare cases of NAS related to withdrawal from other substances [56] or from postnatal opioid use (“iatrogenic NAS”) [57], but data on these other exposures were not available. However, these figures may not reflect the much higher cumulative risk of foster care placements occurring later in childhood [53]. PLoS Med 16(11): Yes Yes https://doi.org/10.1371/journal.pmed.1002974.t003. Ten-year cumulative incidence of death was calculated for each cause of death category with consideration of other causes of death as competing risk events using Gray’s test for the homogeneity of 2 or more cumulative incidence functions. Yes While public health programs such as nurse home visits tend to focus on pregnancy and the early postpartum period [15], it is largely unknown whether this is the only period of risk for poor outcomes for mothers who use opioids in pregnancy. This research benefits from and contributes to, but was not commissioned by, the National Institute for Health Research Children and Families Policy Research Unit. Overall social disadvantage and opioid use are inextricably linked, and many women who misuse these drugs are at greater risk of adversity, including deprivation, violence and abuse, and use of other substances [13]. Opioids are now a leading cause of death of young and middle-aged people in North America, and rates of use and misuse are also increasing in the United Kingdom. 2020 Webinar Series: Improving Care for Moms and Babies in Virginia ; Antibiotic Stewardship in the Newborn Nursery and NICU; Community Events; Past Events; Home. Is the Subject Area "Infants" applicable to this article? Webinars. Over the last few decades a significant increase in the infants undergoing NAS has been noted. Statistical analyses were performed using Stata version 15 for England data and SAS version 9.4 statistical software for Ontario data in a Unix environment. NAS, The decline in survival of mothers of infants with NAS over time was steady in both jurisdictions, with no clear inflection point or distinct period of risk. This work was supported by Health Data Research UK, an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. Cause-specific deaths were classified as avoidable (defined as preventable, amenable to care, or both), unavoidable (as specified by the UK’s Office for National Statistics) [35], or cancer (avoidable and unavoidable). Search results. Investigation, Mothers with missing values for maternal age at delivery were excluded from the adjusted models. We hypothesized that NAS mothers would have significantly higher rates of mortality than control mothers. Author information: (1)Department of Epidemiology, University of Washington, Seattle, WA, USA. At 10 years after giving birth, 5.1% of English mothers with infants with NAS and 4.6% of Ontarian ones had died, compared with 0.4% of mothers whose infants did not have NAS in both countries. https://doi.org/10.1371/journal.pmed.1002974.s001, https://doi.org/10.1371/journal.pmed.1002974.s002, https://doi.org/10.1371/journal.pmed.1002974.s003, https://doi.org/10.1371/journal.pmed.1002974.s004. In this large population-based study across 2 countries, 1 in 20 mothers of infants with NAS died within 10 years of delivery—a mortality risk that was 11–12 times higher than for control mothers. Neonatal abstinence syndrome in methadone-exposed infants is altered by level of prenatal … Researchers need to test which models of care can best be used to improve the health of these mothers and reduce the risks they face that may cause them to die early. Neonatal therapy: An update. Other population-based studies report increased perinatal maternal mortality in mothers using opioids [5,16,17] and longer-term risk in mothers with alcohol or drug misuse during pregnancy [20,22] (Table 1). Women whose infants have NAS are at much higher risk of dying in the years following birth than mothers whose infants did not have NAS. The cohorts used longitudinal hospital discharge records for mothers (back to April 1, 1997, for some covariates) linked to hospitalization records for the infant. Treating neonatal abstinence syndrome (NAS) as a marker of opioid use during pregnancy, this study reports long-term maternal mortality among mothers with a birth affected by NAS in relation to that of mothers without a NAS-affected birth in 2 high-prevalence jurisdictions, England and Ontario, Canada. Both have similar healthcare systems, including universal access to healthcare and similar postnatal public health programs that focus predominantly on the year after birth. Polydrug-and methadone-addicted newborns: a continuum of impairment? Tennessee Department of Health . Funding acquisition, (AAP, 2012) The symptoms of NAS vary based on maternal and neonatal factors but may include irritability, … Physiology. Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada, Funding: Ontario: This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Writing – original draft, This is primarily because our data reflect maternal opioid use at a single time point (delivery). Morbidity and Mortality Weekly Report. Citation: Guttmann A, Blackburn R, Amartey A, Zhou L, Wijlaars L, Saunders N, et al. Writing – original draft, ICES, Toronto, Ontario, Canada, Yes Large-scale linkage of health and social care administrative data would facilitate ongoing research, program evaluation, and surveillance. We found no differences in neonatal mortality between infants with NAS and controls in Ontario, but a marginally higher rate among infants with NAS in England (0.3% versus 0.2% p = 0.01). England: This study/project was funded by the National Institute for Health Research (NIHR) Policy Research Programme and supported by the Administrative Data Research Centre for England by the Economic and Social Research Council (grant reference number ES/L007517/1) [https://esrc.ukri.org/research/our-research/administrative-data-research-uk/]; the Farr Institute of Health Informatics Research London [http://farrinstitute.org/], funded by the Medical Research Council and 7 other funders (grant no MR/K006584/1); RB for a UKRI Innovation Fellowship [https://www.ukri.org/] funded by the Medical Research Council (Grant No: MR/S003797/1). Canadian datasets were linked using unique coded identifiers common across all aforementioned datasets and analyzed at ICES in Toronto, Ontario, Canada. An estimated 7%–20% of NAS-affected infants do not return home with their mother at the time of postnatal discharge from hospital [49–52], which is similar to the percentage in our study (10%–15%). We compared mothers with an infant affected by NAS and controls within each jurisdiction. Methodology, According to hospital discharge data, during 2010 to 2015 in Delaware, 1,172 cases of NAS were identified with an incidence of 18.6 cases per 1,000 births. Education Material for Medication-Assisted Treatment (MAT) Providers . No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, https://doi.org/10.1371/journal.pmed.1002974, https://www.ices.on.ca/DAS/Submitting-your-request, https://esrc.ukri.org/research/our-research/administrative-data-research-uk/, https://www.150.statcan.gc.ca/n1/daily-quotidien/190530/dq190530d-eng.htm, https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2018/INCB-Narcotics_Drugs_Technical_Publication_2018.pdf, https://www.hcup-us.ahrq.gov/reports/Trends_NeonatalAbstinenceSyndrome_Births_UnitedStates.pdf, https://www.ons.gov.uk/aboutus/whatwedo/statistics/consultationsandsurveys/allconsultationsandsurveys/reviewofavoidablemortalitydefinition, https://www.policyalternatives.ca/sites/default/files/uploads/publications/Manitoba%20Office/2015/12/Mothering_Project.pdf, http://www.mothercraft.ca/index.php?q=837, http://bccewh.bc.ca/wp-content/uploads/2012/05/2000_Evaluation-Report-of-the-Sheway-Project.pdf. The adjusted survival curve for the England controls is a 10% sample of the full control population. Most current home-visiting programs target only families with children and only for a short period of time. Neonatal Abstinence Syndrome and Associated Neonatal and Maternal Mortality and Morbidity Sarka Lisonkova, MD, PhD,a,b Lindsay L. Richter, MSc, aJoseph Ting, MBBS, MPH,c Giulia M. Muraca, PhD, MPH, Qi Wen, MSc,d Azar Mehrabadi, PhD,e Sheona Mitchell-Foster, MD, MPH,a,f Eugenia Oviedo-Joekes, PhD,b,g Janet Lyons, MD, MPHa OBJECTIVES: We examined demographic characteristics … In both jurisdictions, the majority of mothers had no previous recorded hospital birth (lookback to April 1, 1997) and lived in urban areas. Crude and adjusted survival curves were plotted to estimate the absolute risk of mortality at 5 and 10 years after birth. Infant discharge to care by social services was much more common among infants with NAS than among control infants in both England (9.7% versus 0.1%; p < 0.001) and Ontario (15.2% versus 0.1%; p < 0.001). Investigation, Conceptualization, No, Is the Subject Area "Medical risk factors" applicable to this article? Projects conducted under section 45, by definition, do not require review by a research ethics board. Across all of these jurisdictions, there is increasing opioid use by pregnant women, and while little is known about associated maternal mortality, a recent study using data from 22 US states and the District of Columbia reports a higher than 3-fold increase from 2007 to 2017 in opioid-related deaths in women during or within the first year after pregnancy [5]. Neonatal abstinence syndrome is a drug withdrawal syndrome that may result from chronic maternal opioid use during pregnancy and is an expected and treatable condition seen in 30–80% of infants born to women taking opioid agonist therapies 43 85. Most studies of NAS focus on the child’s health, with very few about the mother’s health. The primary exposure was a live birth of an infant with NAS, and the main outcome was all deaths among mothers following their date of delivery. Red, neonatal abstinence syndrome (NAS) mothers; blue, controls. You may … Thus we are unable to examine the direction of effect for key factors such as mental illness or socioeconomic status that may either confound the association between opioid use and death or lie on the causal pathway. Ko JY Patrick SW Tong VT, et al. In both jurisdictions, rates of death were higher among mothers of infants with NAS compared to controls across most risk groups. PLOS Medicine publishes research and commentary of general interest with clear implications for patient care, public policy or clinical research agendas. The majority of deaths in mothers with infants with NAS were from avoidable causes such as intentional and unintentional injuries. All of these factors impact negatively on maternal health and may diminish parenting capacity [14]. However, rigorous evidence on interventions promoting long-term support is limited and should be a research and policy priority. Intentional and unintentional injuries (e.g., transport injuries, unintentional falls) made up the majority of avoidable mortality in the mothers of infants with NAS in both jurisdictions. S1 and S2 Tables list diagnostic codes and provide definitions for neighbourhood income quintile and urban or rural residence. Neonatal abstinence syndrome (NAS) is coded in the infant birth hospitalization record and offers a widely used but imperfect proxy measure of maternal opioid use during pregnancy. here. Data curation, The syndrome most commonly occurs in the context of antepartum opiate use, although other drugs have also been implicated. Yes Methodology, There is a dearth of information about long-term health outcomes for women—particularly mothers—with opioid use, which is an important knowledge gap given rising rates of prescription and illicit opioid use. NAS severity depends on multiple factors including genetics, type, number, dose and duration of drug exposure. In particular, unintentional injury deaths (which include those related to victimization) predominate and may result from social vulnerability or misclassification of injuries that are intentional [42–46]. Evidence on mortality for mothers who use opioids in pregnancy is limited but consistently shows increased rates around the time of delivery (Table 1) [5,16–18]. OBJECTIVES: We examined demographic characteristics and birth outcomes of infants with neonatal abstinence syndrome (NAS) and their mothers in Canada. We chose the Deyo version of the Charlson comorbidity index as it has been most widely used in maternal mortality studies and, unlike other indices, has been validated on longer-term mortality, although not in pregnant women [36,37]. The data set from this study is held securely in coded form at ICES. The majority of deaths were by avoidable causes, defined as those that are preventable, amenable to care, or both. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI) and the Ontario Office of the Registrar General (ORG), the original source of which is ServiceOntario. Increased Infant mortality Rates; Associated with family and social issues Neonatal Abstinence Syndrome (NAS)/ NAS- like Syndrome NAS is an array of signs and neuro-behaviours experienced by the newborn that occur after abrupt discontinuation of pregnancy exposure to substances taken by the mother. Although several mechanisms have been proposed … We included P04.4 as it is often used for opioid withdrawal in both jurisdictions. Public Health Burden of Neonatal Abstinence Syndrome. Visualization, Cleveland serves on numerous committees to influence policy change and administers more than $25M in grants focused on addiction, overdose prevention, recovery housing, first responder training, and maternal opioid related mortality. Limitations include potential linkage error, misclassification of mothers using opioids whose babies did not develop NAS, and lack of direct measures of maternal opioid use or treatment, or other substance misuse, which may underestimate the burden of mortality in mothers with opioid use within our study or make findings less generalizable to opioid-using mothers whose infants do not have NAS or who live in other jurisdictions with other approaches to treatment and available supportive services. We derived 95% confidence intervals for mortality at 5 and 10 years after delivery through log–log transformation of the survival function and computed p-values using the z test [38]. Writing – original draft, • Drug withdrawal syndrome in newborns with fetal exposure to substances –Opioid exposure: prescription pain relievers, illicit substances, opioid maintenance therapy • Withdrawal symptoms most commonly occur 48–72 hours after … Recent estimates of mortality from a meta-analysis of people with substance misuse disorder and homeless and prison populations reported a standardized mortality ratio for women of 11.9 (95% CI 10.4–13.3), which was higher than the equivalent figure for men (7.9; 95% CI 7.0–8.7) [21]. Estimated crude 10-year mortality based on Kaplan–Meier curves in mothers of infants with NAS was 5.1% (95% CI 4.7%–5.6%) in England and 4.6% (95% CI 3.8%–5.5%) in Ontario versus 0.4% (95% CI 0.41%–0.42%) in England and 0.4% (95% CI 0.38%–0.41%) in Ontario for controls (p < 0.001 for all comparisons). Crude and adjusted hazard ratios were produced that were adjusted only for maternal age group at delivery to describe the extent of the mortality gap between NAS mothers and controls. HES data are available from the NHS Digital Data Access Request Service team (enquiries@nhsdigital.nhs.uk) for researchers who meet the criteria for access to confidential data. Neonatal abstinence syndrome (NAS) results from physiological dependence secondary to in utero exposure to maternal illicit as well as prescription drugs. 2-5 In addition to NAS, illicit drug use (specifically opioid dependence) during pregnancy is associated with a significantly increased risk of adverse neonatal outcomes such as low birthweight (2500 g) and mortality. Some evaluations of programs supporting mothers with opioid use and their children suggest that multifaceted services addressing health, addiction, housing, and parenting needs can improve parenting capacity and attachment and reduce child apprehension [56,59–64]. Notably, 3 large-scale studies present crude mortality rates per 1,000 person-years of 6.5 (95% CI 6.1–6.9) in New South Wales [39], between 7.5 and 13.9 in opioid-using women aged 15–44 years in California [29], and 12.2 (95% CI 10.3–14.4) and 19.7 (95% CI 15–25.8), respectively, for female users of heroin and other opioids in Denmark [40]. For general information visit www.ices.on.ca/DAS or email das@ices.on.ca. Formal analysis, This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (S2 Text). Cause-specific mortality was available only up until December 31, 2014, for Ontario. Conceptualization, In conclusion, while much attention and research on NAS has focused on infant and child outcomes in isolation, our study is the first population-based analysis to our knowledge of long-term maternal mortality following the birth of an infant with NAS. Astrid Guttmann, 1982; 70 (2):210–213. UCL Great Ormond Street Institute of Child Health, London, United Kingdom, Affiliations e1002974. Investigation, Avoidable deaths were the most common cause of death among mothers of infants with NAS in both jurisdictions (accounting for >85% in England and 75% in Ontario), with a 10-year cumulative incidence risk of 42.9 deaths per 1,000 population (95% CI 38.4–47.9) among English mothers and 30.8 deaths per 1,000 population (95% CI 24.1–38.8) among Ontario mothers. The cumulative incidence of death was higher among NAS mothers than controls for almost all causes of death. The authors … Other countries such as England have seen similar rates of increase in prescription opioid use but not concomitant increases in mortality rates, likely related in part to better access to addiction treatment and more oversight of prescription opioids [4]. Neonatal drug dependency or withdrawal symptoms, known as neonatal abstinence syndrome (NAS), occur from maternal use of opiates such as heroin, methadone, and prescription pain medications. Writing – review & editing, Affiliations In England, de-identified data on inpatient admissions for all National Health Service (NHS) hospitals linked to Office for National Statistics mortality data were obtained from NHS Digital, linked between mother and infant using previously reported methods [30], and analyzed within the UCL Data Safe Haven, England [31]. However, we also describe mortality in mothers without an infant with NAS, but who received care for mental illness and addictions, thus broadening the scope for generalizability. Our study has implications for research, practice, and policy to improve maternal and, arguably, child outcomes related to prenatal opioid use. Competing interests: The authors have declared that no competing interests exist. Symptoms of NAS include fever, diarrhea, irritability, trembling, and increased muscle tone. In this study, we found that approximately 1 in 20 mothers of infants with NAS died within 10 years of delivery in both England and Canada—a mortality risk 11–12 times higher than for control mothers. We did not observe any particular time after birth that was associated with a high risk of death. Our findings suggest that interventions need to extend past the early postpartum period and include mothers whose children may not return home. The pathophysiology underlying NAS has not been fully understood. In this study, we capitalize on linked population-based maternal–infant healthcare records and mortality files in 2 jurisdictions (England and Ontario, Canada).