MOM NEST Study: Maternal Opioid Medication: Naltrexone Efficacy Study

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

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

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.

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.

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.

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.

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.

Fetal, placental, or amniotic fluid anomalies identified during routine ultrasounds in the second and third trimesters will be documented.

Infants will be routinely assessed at birth during the physical examination for any external anomalies.

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.

The need for pharmacologic treatment will be recorded as Y/N as will the need for adjunctive agents.

The need for adjunctive agents will be recorded as Y/N

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.

Number of continuous days infant hospitalized after birth.

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.

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.

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.

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 .

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.

Naltrexone levels from maternal blood and plasma will be obtained at regular intervals for pharmacokinetic analysis.

Naltrexone levels from infant blood and plasma will be obtained at regular intervals for pharmacokinetic analysis.

Mothers will have a genome wide methylation profile at 36 weeks gestation from a blood sample.

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.

Mothers will have their OPRM1 methylation status examined via saliva samples to see if OPRM1 methylation is altered by maternal treatment.

Infants will have their OPRM1 methylation status examined via saliva samples at to see if OPRM1 methylation is altered by maternal treatment.

Naltrexone levels will be measured from the breast milk of breastfeeding mothers who are on naltrexone.

Length of time mother continues medication assisted treatment (MAT) from provider or participant report

Data on maternal healthcare utilization, including emergency room visits, primary care visits, and re-hospitalizations will be collected.

Data on infant healthcare utilization, including emergency room visits, primary care visits, and re-hospitalizations will be collected.