Exclusion of pregnant and lactating persons from breast cancer clinical trials: a review of active trials registered on ClinicalTrials.gov.

INTRODUCTION: Treatment of pregnancy-associated breast cancer is complex, as providers try to balance risks to the pregnant person and the developing fetus. Given increased case fatality and increasing incidence, there is a pressing need understand the efficacy and safety of different treatment regimens in this population; however, pregnant and lactating people have traditionally been excluded from participating in randomized controlled trials (RCTs). Given recent efforts to expand the inclusion criteria for oncology RCTs, this study aimed to review the inclusion/exclusion criteria of current breast cancer RCTs to assess what proportion of trials permitted enrollment of pregnant and lactating persons. MATERIAL AND METHODS: We conducted a comprehensive search of ClinicalTrials.gov in January 2022 to identify interventional studies of breast cancer in adults that were actively recruiting. The primary outcomes were the exclusion of pregnant and lactating people. RESULTS: The search identified 1706 studies, of which 1451 met eligibility criteria. Overall, 69.4% and 54.8% of studies excluded pregnant and lactating people, respectively. The exclusion of pregnant and lactating persons differed by study characteristics but extended across all trial designs, locations, phases and interventions. Exclusion of pregnant and lactating persons was most common in trials where the intervention was biological (86.3%), drug (83.5%) or radiation (81.5%). CONCLUSIONS: The exclusion of pregnant and lactating people from clinical trials contributes to evidence gaps in how to treat this population. A paradigm shift is needed that focuses on how research can be used to protect pregnant people from future harms, instead of protecting pregnant people from research-related risks.

Long-term Mortality in Individuals Diagnosed With Cancer During Pregnancy or Postpartum.

Importance: Outcomes among patients with pregnancy-associated cancers (diagnosed during pregnancy or 1-year postpartum) other than breast cancer have received relatively little research attention. High-quality data from additional cancer sites are needed to inform the care of this unique group of patients. Objective: To assess mortality and survival in premenopausal women with pregnancy-associated cancers, with a particular focus on cancers other than those of the breast. Design, Setting, and Participants: This population-based retrospective cohort study included premenopausal women (aged 18-50 years) living in 3 Canadian provinces (Alberta, British Columbia, and Ontario) diagnosed with cancer between January 1, 2003, and December 31, 2016, with follow-up until December 31, 2017, or date of death. Data analysis occurred in 2021 and 2022. Exposures: Participants were categorized as being diagnosed with cancer during pregnancy (from conception to delivery), during the postpartum period (up to 1 year after delivery), or during a time that was remote from pregnancy. Main Outcomes and Measures: Outcomes were overall survival at 1 and 5 years and time from diagnosis to death due to any cause. Cox proportional hazard models were used to estimate mortality adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), adjusting for age at cancer diagnosis, cancer stage, cancer site, and days from diagnosis to first treatment. Meta-analysis was used to pool results across all 3 provinces. Results: During the study period there were 1014, 3074, and 20 219 participants diagnosed with cancer during pregnancy, postpartum, and periods remote from pregnancy, respectively. One-year survival was similar across the 3 groups, but 5-year survival was lower among those diagnosed with cancer during pregnancy or postpartum. Overall, there was a greater risk of death due to pregnancy-associated cancer among those diagnosed during pregnancy (aHR, 1.79; 95% CI, 1.51-2.13) and postpartum (aHR, 1.49; 95% CI, 1.33-1.67); however, these results varied across cancer sites. Increased hazard of mortality was observed for breast (aHR, 2.01; 95% CI, 1.58-2.56), ovarian (aHR, 2.60; 95% CI, 1.12-6.03), and stomach (aHR, 10.37; 95% CI, 3.56-30.24) cancers diagnosed during pregnancy, and brain (aHR, 2.75; 95% CI, 1.28-5.90), breast (aHR, 1.61; 95% CI, 1.32-1.95), and melanoma (aHR, 1.84; 95% CI, 1.02-3.30) cancers diagnosed postpartum. Conclusions and Relevance: This population-based cohort study found that pregnancy-associated cancers had increased overall 5-year mortality, though not all cancer sites presented the same risk.

Association Between Residential Proximity to Hydraulic Fracturing Sites and Adverse Birth Outcomes.

Importance: The association between hydraulic fracturing and human development is not well understood. Several studies have identified significant associations between unconventional natural gas development and adverse birth outcomes; however, geology and legislation vary between regions. Objective: To examine the overall association between residential proximity to hydraulic fracturing sites and adverse birth outcomes, and investigate whether well density influenced this association. Design, Setting, and Participants: This population-based retrospective cohort study of pregnant individuals in rural Alberta, Canada, took place from 2013 to 2018. Participants included reproductive-aged individuals (18-50 years) who had a pregnancy from January 1, 2013, to December 31, 2018, and lived in rural areas. Individuals were excluded if they lived in an urban setting, were outside of the age range, or were missing data on infant sex, postal code, or area-level socioeconomic status. Exposures: Oil and gas wells that underwent hydraulic fracturing between 2013 to 2018 were identified through the Alberta Energy Regulator (n = 4871). Individuals were considered exposed if their postal delivery point was located within 10 km of 1 or more wells that was hydraulically fractured during 1 year preconception or during pregnancy. Main Outcomes and Measures: Outcomes investigated were spontaneous and indicated preterm birth, small for gestational age, major congenital anomalies, and severe neonatal morbidity or mortality. Results: After exclusions, the sample included 26 193 individuals with 34 873 unique pregnancies, and a mean (SD) parental age of 28.2 (5.2) years. Small for gestational age and major congenital anomalies were significantly higher for individuals who lived within 10 km of at least 1 hydraulically fractured well after adjusting for parental age at delivery, multiple births, fetal sex, obstetric comorbidities, and area-level socioeconomic status. Risk of spontaneous preterm birth and small for gestational age were significantly increased in those with 100 or more wells within 10 km. Conclusions and Relevance: Results suggest that individuals who were exposed to hydraulic fracturing within pregnancy may be at higher risk of several adverse birth outcomes. These results may be relevant to health policy regarding legislation of unconventional oil and gas development in Canada and internationally.

Maternal, Fetal, and Neonatal Outcomes of Elective Fetal Reduction Among Multiple Gestation Pregnancies: A Systematic Review.

OBJECTIVE: To review the existing literature on fetal and maternal health outcomes following elective pregnancy reduction. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Trials Register. STUDY SELECTION: Studies involving women pregnant with dichorionic twins, trichorionic triplets, or quadra-chorionic quadruplets who underwent elective fetal reduction of 1 or more fetuses to reduce the risks associated with multiple gestation pregnancies. DATA EXTRACTION: The main fetal health outcomes measured were gestational age at delivery, preterm birth, miscarriage, birth weight, and small for gestational age at delivery. The main maternal health outcomes measured were gestational diabetes, hypertensive disorders of pregnancy, and cesarean delivery. DATA SYNTHESIS: Of 7678 studies identified, 24 were included (n = 425 dichorionic twin pregnancies, n = 2753 trichorionic triplet pregnancies, and n = 111 quadra-chorionic quadruplet pregnancies). Fifteen studies (62.5%) did not report maternal health outcomes, while every study reported at least 1 fetal health outcome. Fetal reduction was associated with higher gestational age at birth, lower preterm birth, higher birth weight, and lower rates of small for gestational age infants and intrauterine growth restriction. No consistent pattern was observed for miscarriage and neonatal mortality rates. Following fetal reduction, cesarean delivery rates were lower in most studies. There were no appreciable trends with respect to gestational diabetes or hypertensive disorders of pregnancy. CONCLUSION: Fetal reduction reliably optimizes gestational age at birth and neonatal birth weight. Miscarriage rates and other adverse procedural outcomes did not increase following transabdominal reduction. Further research on maternal outcomes is needed given a paucity of information in the literature.

Infertility and the Risk of Cardiovascular Disease: Findings From the Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in women globally. In recent years, attention has turned to infertility and pregnancy-related events as potential markers for early mortality and future CVD. METHODS: The Study of Women's Health Across the Nation (SWAN) is an ongoing longitudinal cohort study of women's health. Women aged 42-52 years with a uterus and ≤ 1 intact ovary, a menstrual period, and no hormone medications within 3 months before enrollment were eligible. Infertility was self-reported and defined as the inability to achieve pregnancy after 12 months of trying to conceive, or use of fertility medications for > 1 month. Outcomes included development of metabolic syndrome over a 7-year follow-up, and any atherosclerotic CVD event (ie, stroke, angina, myocardial infarction) over a 10-year follow-up. Cox proportional hazards models were used to calculate hazard ratios (HRs) for metabolic syndrome and CVD events in participants with infertility, with adjustment for relevant covariates. Participants without infertility were used as the comparison group. RESULTS: We included 2370 participants in the analysis of metabolic syndrome risk, and 2809 participants were included in the analysis of CVD event risk. Participants with self-reported infertility did not have a higher risk of developing metabolic syndrome (HR, 0.91; 95% confidence interval, 0.71-1.15) or experiencing CVD events (HR, 0.79; 95% confidence interval, 0.52-1.21) after adjusting for relevant covariates. CONCLUSIONS: Infertility was not associated with development of metabolic syndrome or CVD events in women; further research is required to investigate the effects of specific causes of infertility and fertility treatments on CVD outcomes.

INTRODUCTION: Les maladies cardiovasculaires (MCV) sont la principale cause de décès chez les femmes dans le monde. Au cours de dernières années, l'infertilité et les complications de la grossesse ont retenu l'attention, à savoir qu'ils constituent des marqueurs potentiels de la mortalité précoce et des MCV futures. MÉTHODES: La Study of Women's Health Across the Nation (l'étude SWAN) qui constitue une étude de cohorte longitudinale sur la santé des femmes est en cours. Les femmes âgées de 42 à 52 ans qui ont un utérus et ≤ 1 ovaire intact, une période menstruelle et qui ne prenaient aucun médicament hormonal 3 mois avant le recrutement étaient admissibles. L'infertilité était autodéclarée et définie comme l'incapacité à être enceinte après 12 mois de tentatives de conception ou l'utilisation de médicaments pour traiter l'infertilité durant > 1 mois. L'issue était la suivante : la survenue du syndrome métabolique au cours du suivi de 7 ans ou de tout événement lié à la MCV athérosclérotique (c.-à-d. l'accident vasculaire cérébral, l'angine, l'infarctus du myocarde) au cours du suivi de 10 ans. Nous avons utilisé les modèles de risques proportionnels de Cox pour calculer les rapports de risque (RR) du syndrome métabolique et des événements liés aux MCV chez les participantes infertiles par l'ajustement des covariables pertinentes. Les participantes fertiles constituaient le groupe témoin. RÉSULTATS: Nous avons recruté 2 370 participantes pour l'analyse du risque de syndrome métabolique, et 2 809 participantes pour l'analyse du risque d'événements liés aux MCV. Les participantes qui avaient autodéclaré leur infertilité n'avaient pas de risque plus élevé de souffrir du syndrome métabolique (RR, 0,91 ; intervalle de confiance à 95 %, 0,71-1,15) ou de subir des événements liés aux MCV (RR, 0,79 ; intervalle de confiance à 95 %, 0,52-1,21) après l'ajustement des covariables pertinentes. CONCLUSIONS: L'infertilité n'était pas associée à la survenue du syndrome métabolique ou des événements liés aux MCV chez les femmes. D'autres recherches qui porteront sur les effets des causes particulières de l'infertilité et des traitements favorisant la fertilité sur l'évolution des MCV sont nécessaires.

Incidence of Pregnancy-Associated Cancer in Two Canadian Provinces: A Population-Based Study.

Pregnancy-associated cancer-that is diagnosed in pregnancy or within 365 days after delivery-is increasingly common as cancer therapy evolves and survivorship increases. This study assessed the incidence and temporal trends of pregnancy-associated cancer in Alberta and Ontario-together accounting for 50% of Canada's entire population. Linked data from the two provincial cancer registries and health administrative data were used to ascertain new diagnoses of cancer, livebirths, stillbirths and induced abortions among women aged 18-50 years, from 2003 to 2015. The annual crude incidence rate (IR) was calculated as the number of women with a pregnancy-associated cancer per 100,000 deliveries. A nonparametric test for trend assessed for any temporal trends. In Alberta, the crude IR of pregnancy-associated cancer was 156.2 per 100,000 deliveries (95% CI 145.8-166.7), and in Ontario, the IR was 149.4 per 100,000 deliveries (95% CI 143.3-155.4). While no statistically significant temporal trend in the IR of pregnancy-associated cancer was seen in Alberta, there was a rise in Ontario (p = 0.01). Pregnancy-associated cancer is common enough to warrant more detailed research on maternal, pregnancy and child outcomes, especially as cancer therapies continue to evolve.

Development and Psychometric Evaluation of the Preconception Health Knowledge Questionnaire.

PURPOSE: To develop and psychometrically test a comprehensive measure of preconception health knowledge. DESIGN: Cross-sectional survey, in May and June, 2019. SETTING: Alberta, Ontario, and Québec, Canada. SAMPLE: One thousand seven hundred seventy-seven women and men with ≥1 children born in the last 5 years or planning a pregnancy in the next 5 years. MEASURES: Using prior literature and input from public health nurses and physicians, the Preconception Health Knowledge Questionnaire (PHKQ) was developed and comprised 25 multiple choice questions on reproductive history, sexual health, infectious diseases, chronic medical conditions, mental health, medications, immunizations, lifestyle behaviors, psychosocial stressors, and environmental exposures. ANALYSIS: Psychometric testing was undertaken to evaluate item difficulty, discrimination, quality of response alternatives, internal consistency, and construct validity. RESULTS: Participants had a mean total score of 15.8/25 (SD = 3.9); women and men had mean total scores of 16.2 (SD = 3.6) and 13.8 (SD = 4.7), respectively. Most items were neither too difficult nor too easy, discriminated well between participants with high and low knowledge, and had appropriate response alternatives. High internal consistency (KR-20 = 0.87) and construct validity, shown via significant correlations with education level and previous preconception care receipt, were demonstrated. CONCLUSION: The PHKQ is a reliable and valid tool for measuring preconception health knowledge and may be useful in identification of high-risk groups in need of preconception health education and evaluation of preconception health interventions.

Pilot Randomized Controlled Trial of an Interconception Intervention Provided by Public Health Nurses.

OBJECTIVES: Preconception health impacts perinatal outcomes, but the difficulty in engaging reproductive-aged individuals in health promotion activities is a barrier to effective implementation of preconception interventions. Since most women have more than one pregnancy and many risk factors repeat across pregnancies, the time between pregnancies-the interconception period-may be an opportune time to improve health. Our objective was to examine the feasibility and acceptability of an interconception intervention delivered by public health nurses. METHODS: We conducted a pilot randomized controlled trial in three small urban and rural public health units in Ontario, Canada, in 2017-2018 among women who were ≥ 18 years of age and between 2 and 12 months postpartum after a first birth. Women randomly allocated to the intervention group received a preconception risk assessment, tailored health education, and referral for clinical follow-up as needed, while those in the control group received standard care. Primary outcomes were intervention feasibility, adherence, and acceptability. RESULTS: Of 66 eligible women, 61% agreed to participate and were randomized to the intervention (n = 16) or control (n = 24) groups. The follow-up rate was 78% at 1 month and 71% at 3 months. Most women (83%) were satisfied with the intervention, including the number and length of sessions and content of recommendations. CONCLUSIONS FOR PRACTICE: Results demonstrate the potential feasibility and acceptability of an interconception intervention delivered in a public health setting. The short- and long-term impacts of the intervention on knowledge, behavior, and health should be tested in a larger sample.

Roles of the underlying cause of delivery and gestational age on long-term child health.

BACKGROUND: Clinical conditions leading to delivery are heterogeneous. However, most studies examining the short- and long-term consequences of birth on child health only consider gestational age at delivery, not the underlying cause. OBJECTIVE: To examine the effect of both gestational age at delivery and underlying cause of delivery on child health outcomes. METHODS: This population-based retrospective cohort study of singleton infants born in Alberta (April 2004-March 2005) used linked administrative and perinatal data to identify birth subtypes by underlying cause (infection/inflammation (I/I), placental dysfunction (PD), both, or neither), gestational age at delivery, and child health outcomes (neonatal morbidity and mortality, paediatric complex chronic conditions, and neurodevelopmental disorders and disabilities). Poisson regression with robust variance was used to assess differences in the (adjusted) risk ratio (RR) of each outcome by gestational age, and by cause of delivery. The roles of gestational age and cause of delivery were examined using mediation analysis methods. RESULTS: A total of 38,192 children were included, with 66.7% experiencing neither I/I nor PD (I/I: 4.0%, PD: 27.5%, both: 1.8%). Infants born preterm had higher risk of all outcomes compared to those born at term and late-term. Infants with exposure to both causes had higher risk of all outcomes (neonatal morbidity, RR 8.96, 95% confidence interval [CI] 7.55, 10.63; paediatric complex chronic conditions, RR 3.94, 95% CI 3.08, 5.05; and neurodevelopmental disorders, RR 1.58, 95% CI 1.37, 1.84). The effect of underlying cause of delivery on child health outcomes was partially explained by gestational age, more in cases involving I/I than in those involving PD alone. CONCLUSIONS: Short- and long-term child health outcomes differ by the underlying cause leading to delivery, as well as the gestational age at delivery. Having a clearer prognosis for infants may promote the use of clinical interventions earlier for children at increased risk.

Prepregnancy Diabetes and Perinatal Mental Illness: A Population-Based Latent Class Analysis.

We examined the risk of any perinatal mental illness associated with prepregnancy diabetes and identified how diabetes duration, complexity, and intensity of care affect this risk. We performed a population-based study of women aged 15-49 years with (n = 14,186) and without (n = 843,818) prepregnancy diabetes who had a singleton livebirth (Ontario, Canada, 2005-2015) and no recent mental illness. Modified Poisson regression estimated perinatal mental illness risk between conception and 1 year postpartum in women with versus without diabetes and in diabetes groups, defined by a latent class analysis of diabetes duration, complexity, and intensity-of-care variables, versus women without diabetes. Women with diabetes were more likely than those without to develop perinatal mental illness (18.1% vs. 16.0%; adjusted relative risk = 1.11, 95% confidence interval: 1.07, 1.15). Latent classes of women with diabetes were: uncomplicated and not receiving regular care (59.7%); complicated, with longstanding diabetes, and receiving regular care (16.4%); and recently diagnosed, with comorbidities, and receiving regular care (23.9%). Perinatal mental illness risk was elevated in all classes versus women without diabetes (adjusted relative risks: 1.09-1.12), but results for class 2 were nonsignificant after adjustment. Women with diabetes could benefit from preconception and perinatal strategies to reduce their mental illness risk.

Measurement of Preconception Health Knowledge: A Systematic Review.

OBJECTIVE: Preconception health is an important determinant of maternal, paternal, and infant outcomes. Knowledge is commonly used to evaluate the effectiveness of interventions to promote preconception health. Our objective was to examine how preconception health knowledge has been measured in the existing literature and to identify measurement gaps, biases, and logistical challenges. DATA SOURCE: MEDLINE, EMBASE, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and gray literature were searched from database inception to January 2018. STUDY INCLUSION AND EXCLUSION CRITERIA: Studies were included if they measured preconception or interconception health knowledge and included reproductive-aged women and/or men. DATA EXTRACTION: Two independent reviewers completed data extraction and quality appraisal using standardized instruments. DATA SYNTHESIS: Due to measurement heterogeneity, a narrative synthesis was performed. RESULTS: The review included 34 studies from 14 countries with data collected in 2000 to 2017. Most studies used cross-sectional (n = 24) or prepost designs (n = 7). Studies primarily sampled women (n = 25), and methodological quality was rated largely as weak (n = 18) or moderate (n = 14). Preconception health knowledge tools focused on fertility, folic acid, and alcohol, with few questions pertaining to men's health, mental health, or the interconception period. Only 19 (56%) studies reported psychometric properties of their knowledge tools. CONCLUSIONS: This systematic review revealed the need for a valid and reliable knowledge tool that reflects a holistic conceptualization of preconception health.

Relation between opioid-related harms and socioeconomic inequalities in Ontario: a population-based descriptive study.

BACKGROUND: Negative health outcomes associated with the use of both prescribed and nonprescribed opioids are increasingly prevalent. We examined long-term trends in opioid-related harms in Ontario across a set of 6 indicators and the relation between harms and neighbourhood income in 2016. METHODS: We examined rates of neonatal abstinence syndrome, opioid poisoning (fatal and nonfatal) and nonpoisoning opioid-related events from 2003 to 2016 in Ontario using population-based health administrative databases. We conducted descriptive analyses for harm indicators across neighbourhood income quintiles in 2016 (2015 for death). We examined social inequalities in opioid-related harms on both relative (prevalence ratio) and absolute (potential rate reduction) scales. RESULTS: Rates of opioid-related harms increased dramatically between 2003 and 2016. In 2016, neonatal abstinence syndrome and opioid poisoning and nonpoisoning events showed a strong social gradient, with harm rates being lowest in higher-income neighbourhoods and highest in lower-income neighbourhoods. Prevalence ratios for the lowest-income neighbourhoods compared to the highest-income neighbourhoods ranged from 2.36 (95% confidence interval [CI] 2.15-2.58) for emergency department visits for opioid poisoning to 3.70 (95% CI 2.62-5.23) for neonatal abstinence syndrome. Potential rate reductions for opioid-related harms ranged from 34.8% (95% CI 29.1-40.1) to 49.9% (95% CI 36.7-60.5), which suggests that at least one-third of all harmful events could be prevented if all neighbourhoods had the same socioeconomic profile as the highest-income neighbourhoods. INTERPRETATION: Rates of opioid-related harms increased in Ontario between 2003 and 2016, and people in lower-income neighbourhoods experienced substantially higher rates of opioid-related harms than those in higher-income neighbourhoods. This finding can inform planning for opioid-related public health interventions with consideration of health equity.

Assessment of Long-term Follow-up of Randomized Trial Participants by Linkage to Routinely Collected Data: A Scoping Review and Analysis.

Importance: Follow-up of participants in randomized trials may be limited by logistic and financial factors. Some important randomized trials have been extended well beyond their original follow-up period by linkage of individual participant information to routinely collected data held in administrative records and registries. Objective: To perform a scoping review of randomized clinical trials extended by record linkage to characterize this literature and explore any additional insights into treatment effectiveness provided by long-term follow-up using record linkage. Data Sources: A literature search in Embase, CINAHL, MEDLINE, and the Cochrane Register of Controlled Trials was performed for the period January 1, 1945, through November 25, 2016. Study Selection: Various combinations of search terms were used, as there is no accepted terminology. Determination of study eligibility and extraction of information about trial characteristics and outcomes, for both original and extended trial reports, were performed in duplicate. Data Extraction and Synthesis: Assessment of study eligibility and data extraction were performed independently by 2 reviewers. All analyses were descriptive. Main Outcomes and Measures: Outcomes in the pairs of original and extended trials were categorized according to whether any benefits or harms from interventions were sustained, were lost, or emerged during long-term follow-up. Results: A total of 113 extended trials were included in the study. Linkage to administrative and registry data extended follow-up by between 1 and 55 years. The most common interventions were pharmaceuticals (47 [41.6%]), surgery (19 [16.8%]), and disease screening (19 [16.8%]). End points most frequently studied through record linkage included mortality (88 [77.9%]), cancer (41 [36.3%]), and cardiovascular events (37 [32.7%]). One hundred four trial extensions (92.0%) were analyzed according to the original trial randomization. The reports provided details of 155 analyses of study outcomes. Seventy-four analyses (47.7%) identified statistically significant benefits in the trial extension phase. In 21 of these (28.4%), benefits were significant only in this period. Null results in both the original and extended trials were seen in 34 of the analyses (21.9%). Loss of significant benefits of an intervention were seen in 12 analyses (7.7%). Statistically significant harms were seen in 16 trial extension analyses (10.3%), and in 14 of these (87.5%), the harms were significant only in the trial extension phase. Conclusions and Relevance: Trial extension by linkage to routinely collected data is a versatile underused approach that may add critical insights beyond those of the original trial. Some beneficial and harmful outcomes of interventions are captured only in the extension phase of randomized trials.

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents.

Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide (10panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia.