Predicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy

Study Overview
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Brief Summary
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This study will be a 12-month prospective, genotype-blinded longitudinal observational study with current standard of clinical care. This study will enroll 100 pregnant women with OUD at UPMC with its high volumes. Because of the observational nature of the study, the anticipated dropout rate will be ≤ 20%. Investigators expect the effective sample size of evaluable patients will be 200 with longitudinal data.

Detailed Description
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Background: 7% of pregnant women in the U.S. use opioids and 21% of these women report misuse, making opioid use disorder (OUD) a major public health concern during pregnancy. The number of infants born with prenatal opioid exposure, neonatal opioid withdrawal syndrome (NOWS) and costly prolonged hospitalization has increased exponentially. The opioid epidemic is further worsened by the ongoing COVID-19 pandemic. Despite medication treatment for OUD with buprenorphine (BUP) or methadone (METH), these pregnant women continue to be at high risk for early relapse, polysubstance use, and depression. These infants are at risk for not only immediate NOWS and also poor long-term neurodevelopmental and behavioral outcomes. Genetic factors influence 30-60% of opioid adverse events (AEs). In pregnant women on medication management for OUD, and infants receiving opioids for NOWS treatment there is variability in dose required to prevent withdrawal symptoms and craving, likely related to physiological alterations, upregulation of metabolic and biological pathways, determined in part by opioid pharmacogenomics. Investigators have shown that in children and adults, opioid related poor clinical outcomes are related to opioid receptor genetic variations and resulting variations in their metabolism. Maternal depression and anxiety increase the risks for OUD, maternal relapse, NOWS and negatively impact pregnant women and their children. Thus, there is an urgent and unmet clinical need for a reliable tool to proactively predict maternal relapse, NOWS, and improve the safety of pregnant women with OUD and their children.

Official Title
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Predicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy

Conditions
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Opioid Use Disorder, Pregnancy Related

Intervention / Treatment
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* Drug: Buprenorphine/ Methadone exposure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women with OUD and their infant Currently on BUP/METH for OUD Enrolled in prenatal opioid maintenance program Age >18 years Singleton pregnancy Planned delivery at UPMC's Magee Womans Hospital Positive opioid urine screen results Exclusion Criteria: Serious maternal medical illness as deemed by the PI that would make it challenging to comply with study procedures HIV or AIDS Known major fetal congenital abnormalities

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant women with Opioid Use Disorder (OUD)<br>This study will enroll 100 pregnant women with OUD at UPMC with its high volumes | Drug: Buprenorphine/ Methadone exposure<br>* Validate candidate genes- and prenatal opioid exposure- related maternal relapse and NOWS outcome associations in pregnant women and their newborns.<br>* Other names: Opioid Use Disorder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of maternal opioid relapse | Measured via binary response, yes/no | Measured from enrollment to 3-months post delivery | 
| Incidence of NOWS | Clinical definition of NOWS: Substance withdrawal encompasses a continuum of variable clinical expression from neonate to neonate; the diagnosis is not limited only to neonates who require pharmacotherapy. Incidence of NOWS measured by binary response, yes/no | Measured at delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Maternal Opioid Relapse | Severity of maternal opioid relapse measured by requirement of medical treatment (binary response, yes/no) | Measured from enrollment to 3-months post delivery | 
| Severity of NOWs | Severity of NOWs measured by the need for >3 days of hospital stay (binary response, yes/no) | Measured at delivery |