This is a multi-center prospective comparative cohort study examining the safety, efficacy, pharmacokinetics, and pharmacogenomics of naltrexone for pregnant women with opioid use disorder. Pregnancy, delivery, and maternal and infant outcomes to 12 months post-delivery will be examined and compared with a cohort treated with buprenorphine/naloxone.
Name: Pharmacokinetic analysis
Name: Safety and Efficacy
Name: Genetic and epigenetic analysis
Name: Breast milk analysis
Description: Maternal relapse of illicit and/or unprescribed drug use from maternal/provider report and or from urine toxicology testing at any point during the pregnancy and up to 12 months after delivery
Measure: Maternal drug use relapse Time: up to 12 months post-deliveryDescription: Number and type of side effects or adverse events such as injection site reactions, gastrointestinal upset, syncope, headaches, or dizziness reported by participant or provider
Measure: Naltrexone side effects or adverse events Time: up to 12 months post-deliveryDescription: Mean fetal heart rate (FHR), FHR variability, and episodic accelerations of FHR (count) from each routine care non-stress test (NST) in the third trimesters.
Measure: Fetal heart rate monitoring from NST Time: 27- 41 weeks gestationDescription: The biophysical profile uses electronic fetal heart rate monitoring to examine the fetus. There are five components measured during the biophysical examination (fetal breathing movements, gross body movement, fetal tone, amninotic fluid volume and whether the NST is reactive or nonreactive. A score of 2 points is given for each component The points are then added for a possible maximum score of 10. The test is continued until all criteria are met or 30 minutes have elapsed. HIgher scores are more favorable.
Measure: Biophysical profile score calculated from NST Time: 27 - 41 weeks gestationDescription: Hair cortisol levels will be obtained from maternal hair samples obtained at birth and 4 weeks after delivery, and compared between the naltrexone and buprenorphine groups. Higher hair cortisol levels in the mother may indicate exposure to higher levels of stress over the preceding 3 months period.
Measure: Maternal hair cortisol levels Time: Birth and 4 weeks post-deliveryDescription: Hair cortisol levels will be obtained from infant hair samples obtained at birth and 4 weeks after delivery, and compared between the naltrexone and buprenorphine groups. Higher hair cortisol levels in the infant may indicate exposure to higher levels of stress over the preceding 3 months period.
Measure: Infant hair cortisol levels Time: Birth and 4 weeks post-deliveryDescription: Fetal growth will be assessed at the time of routine growth scans at 18-20, and then q4 weeks until delivery. Fetal size will be compared to Intergrowth standards to produce z-scores and SGA (<10%ile) for averaged 2nd and 3rd trimester measurements.
Measure: Fetal growth based on ultrasound measurements Time: 18 - 41 weeks gestationDescription: Fetal, placental, or amniotic fluid anomalies identified during routine ultrasounds in the second and third trimesters will be documented.
Measure: Congenital fetal anomalies by ultrasound Time: 18 - 41 weeks gestationDescription: Infants will be routinely assessed at birth during the physical examination for any external anomalies.
Measure: Congenital anomalies by physical examination Time: BirthDescription: NAS diagnosis will be based on opioid withdrawal signs and symptoms in the infant after delivery as assessed by NAS withdrawal scores (either the Finnegan score or the via the ESC (Eat, Sleep, Console) assessment tool. The Finnegan scale assesses 21 of the most common signs of neonatal drug withdrawal syndrome and is scored on the basis of pathological significance and severity of the adverse symptoms, which sometimes requires pharmacological treatment. Measurements are performed every 4 hours, typically with 2-3 consecutive scores that are equal to or greater than 8, or 1-2 scores of 12 or greater, pharmacologic treatment for withdrawal is started. For the ESC assessment, clinicians assess whether or not the infant has poor feeding, is unable to sleep for at least 1 hour after feeding, and is consolable (rating of 1-3) due to symptoms of opioid withdrawal. Poor feeding, sleeping, or consolability triggers a huddle and possible start of pharmacologic treatment.
Measure: Diagnosis of Neonatal Abstinence Syndrome (NAS) Time: From birth to 30 daysDescription: The need for pharmacologic treatment will be recorded as Y/N as will the need for adjunctive agents.
Measure: Infant need for pharmacologic treatment Time: From birth to 30 daysDescription: The need for adjunctive agents will be recorded as Y/N
Measure: Infant need for adjunctive agent Time: From birth to 30 daysDescription: The total mgs of morphine/methadone needed for pharmacologic treatment and the total number of total opioid treatment days will be obtained from the birth hospitalization medical records.
Measure: Infant opioid replacement pharmacologic treatment Time: From birth to 30 daysDescription: Number of continuous days infant hospitalized after birth.
Measure: Infant birth hospitalization length of stay Time: From birth to 30 daysDescription: Growth parameters of infant weight in grams will be obtained by the clinician at birth, 4 weeks, and 12 months at each study visit. Percentiles will be calculated.
Measure: Infant weight Time: Birth, 4 weeks, and 12 monthsDescription: Growth parameters of infant length measured by the clinician in cm will be obtained at birth, 4 weeks, and 12 months at each study visit. Percentiles will be calculated.
Measure: Infant length Time: Birth, 4 weeks, and 12 monthsDescription: Growth parameters of infant head circumference in cm will be obtained by the clinician at birth, 4 weeks, and 12 months at each study visit. Percentiles will be calculated.
Measure: Infant head circumference Time: Birth, 4 weeks, and 12 monthsDescription: The NICU Network Neurobehavioral Scale (NNNS) is a comprehensive assessment of both neurologic integrity and behavioral functioning, including signs of stress. It assesses the full range of infant neurobehavioral performance (orientation to auditory and visual stimuli); infant stress (color changes, tremors, startles), neurologic functioning (reflexes, tone); some features of gestational age; self-soothing capacities; states and their organization. The 13 summary scores (i.e., orientation, habituation, hypertonicity, hypotonicity, excitability, arousal, lethargy, non-optimal reflexes, asymmetric reflexes, stress, self-regulation, quality of movement, handling) are typically used to summarize a clinical examination .
Measure: Infant neurobehavior-function assessed by the NNNS Time: 4 weeks of ageDescription: The Bayley III is a standard series of measurements used to assess the development of infants and toddlers, ages 1-42 months. It has 5 scales, 3 administered with child interaction - cognitive, motor, language, and 2 with parent questionnaires- social-emotional, adaptive behavior. A developmental quotient (DQ) is derived from the results.
Measure: Infant neurodevelopment assessed by Bayley III Time: 12 months of ageDescription: Naltrexone levels from maternal blood and plasma will be obtained at regular intervals for pharmacokinetic analysis.
Measure: Pharmacokinetic analysis of maternal naltrexone levels Time: 2nd trimester, 3rd trimester, delivery, 2-4 days after delivery, 4 weeks post-deliveryDescription: Naltrexone levels from infant blood and plasma will be obtained at regular intervals for pharmacokinetic analysis.
Measure: Pharmacokinetic analysis of infant naltrexone levels Time: Delivery, 2-4 days after delivery, 4 weeks post-deliveryDescription: Mothers will have a genome wide methylation profile at 36 weeks gestation from a blood sample.
Measure: Maternal DNA methylation profile Time: 36 weeks gestationDescription: Mothers will be genotyped for the ORPM1 A118G SNP at 36 weeks gestation from a blood sample to see if genotype is associated with treatment response and risk for relapse.
Measure: Mu opioid receptor (OPRM1) gene single nucleotide (SNP) genotype Time: 36 weeks gestationDescription: Mothers will have their OPRM1 methylation status examined via saliva samples to see if OPRM1 methylation is altered by maternal treatment.
Measure: Maternal saliva OPRM1 methylation status Time: Birth, 4 weeks postpartumDescription: Infants will have their OPRM1 methylation status examined via saliva samples at to see if OPRM1 methylation is altered by maternal treatment.
Measure: Infant saliva OPRM1 methylation status Time: Birth, 4 weeks postpartumDescription: Naltrexone levels will be measured from the breast milk of breastfeeding mothers who are on naltrexone.
Measure: Breast milk naltrexone level Time: 4 weeks postpartumDescription: Length of time mother continues medication assisted treatment (MAT) from provider or participant report
Measure: Retention in addiction treatment Time: up to 12 months post-deliveryDescription: Data on maternal healthcare utilization, including emergency room visits, primary care visits, and re-hospitalizations will be collected.
Measure: Maternal healthcare utilization Time: up to 12 months post-deliveryDescription: Data on infant healthcare utilization, including emergency room visits, primary care visits, and re-hospitalizations will be collected.
Measure: Infant healthcare utilization Time: up to 12 months post-deliveryCohort
There is one SNP
Mothers will be genotyped for the ORPM1 A118G SNP at 36 weeks gestation from a blood sample to see if genotype is associated with treatment response and risk for relapse.. Maternal saliva OPRM1 methylation status. --- A118G ---