Neonatal Abstinence Syndrome, Neonatal Opioid Withdrawal
Conditions
Keywords
Neonatal Abstinence Syndrome, Opioids
Brief summary
1: SPECIFIC Aim I: To compare treatment options for neonatal abstinence syndrome (NAS) due to in-utero narcotic exposure. One hundred eighty four full-term infants with a diagnosis of NAS requiring medications will be studied. Infants will be randomized to receive either morphine or methadone. It is hypothesized that morphine treated infants will do better and require fewer days in the hospital compared to methadone treated infants. 2\. SPECIFIC Aim II: To evaluate the effects of NAS treatment on long-term neurodevelopmental outcome. Infants will be evaluated with development testing at 18 months of age. It is hypothesized that morphine treated infants will have better neurodevelopmental outcomes. It is also hypothesized that neurobehavioral abnormalities identified at two weeks of age will correlate with neurodevelopmental impairment at 18 months. 3: SPECIFIC Aim III: To determine if common genetic variations in the genes involving narcotic action contribute to the severity of NAS. A DNA sample will be obtained from all infants and analyzed for differences in 3 key genes. This will then be correlated with short-term and long-term outcomes.
Detailed description
1: SPECIFIC Aim I: To compare the short term efficacy of morphine and methadone for the treatment of NAS. One hundred eighty four term infants with a diagnosis of NAS requiring pharmacotherapy will be studied. Infants born to mothers receiving adequate prenatal care and maintained on opioid agonist medication during pregnancy will be eligible. Infants will be randomized to receive either neonatal morphine solution or methadone in a double blind, double dummy design. It is hypothesized that morphine treated infants will require significantly fewer days in the hospital compared to methadone treated infants. While the primary outcome is the total length of initial hospital stay (LOS), total LOS related to NAS, total duration of medical treatment for NAS, the need for a second drug to control symptoms, and infant growth will also be evaluated as important secondary outcomes by medication group assignment. 2\. SPECIFIC Aim II: To evaluate the effects of NAS treatment on long-term neurodevelopmental outcome. Infants in both treatment groups will be evaluated at 18 months of age using the Bayley III Scales of Infant Development. It is hypothesized that morphine treated infants will have better neurodevelopmental outcomes at 18 months compared to methadone treated infants. It is also hypothesized that neurobehavioral abnormalities (from either treatment group) identified at two weeks of age using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) will correlate with neurodevelopmental impairment detected with the Bayley III. Early identification of infants at highest risk for impaired development will facilitate therapeutic interventions to improve outcome and decrease resource utilization. 3: SPECIFIC Aim III: To determine if single nucleotide polymorphisms (SNPs) in genes controlling opioid pharmacodynamics contribute to the severity of NAS. SNP genotyping from cord blood or buccal swabs will be obtained from all infants and correlated with short term outcomes (Aim 1) and neurodevelopment assessments (Aim 2) to confirm that genetic variation plays a major role in the severity and outcome of infants with NAS.
Interventions
DRUGNeonatal Morphine Solution
Infants randomized to this arm will receive neonatal morphine solution (0.2mg/mL) for first line therapy. Infants will be scored using the standardized Finnegan scoring system and will be initiated on treatment if they have 2 consecutive scores greater than or equal to 8 or 1 score greater than 12. Dosing will be weight and symptom based. A double dummy design will be used - each infant will be ordered for both a methadone/placebo study drug at 0.4 mg/mL and a morphine/placebo study drug at 0.2 mg/mL. Starting doses will range from 0.3mg/kg/day to 0.9mg/kg/day divided every 4 hours depending on the severity of the Finnegan scores. Doses will be increased to a maximum of 0.9mg/kg/day for continued scores generally \>8 caused primarily by worsening NAS. Infants will be weaned by 10% of the maximum dose once every 24 - 48 hours and the medication will be discontinued once at 25% of the maximum dose.
DRUGMethadone
Infants randomized to this group will receive methadone oral solution (0.4mg/mL) for first line therapy. Infants will be scored using the standardized Finnegan scoring system and will be initiated on treatment if they have 2 consecutive scores greater than or equal to 8 or 1 score greater than or equal to 12. Dosing will be weight and symptom based. Starting doses will range from 0.3mg/kg/day to 0.9mg/kg/day divided every 8 hours depending on the severity of the Finnegan scores. To maintain blinding of the two study arms, a double dummy design will be used - each infant will receive both methadone/placebo study drug at 0.4 mg/mL and a morphine/placebo study drug at 0.2 mg/mL. Doses will be increased to a maximum of 0.9mg/kg/day for continued scores generally \>8 caused primarily by worsening NAS as needed. Infants will be weaned by 10% of the maximum dose once every 24-48 hours and the medication will be discontinued once at 25% of the maximum dose.
DRUGPhenobarbital
A second line medication will be added once the infant reaches maximum doses of the study drug (morphine or methadone) for continued scores generally \>8. Infants will be loaded with 20mg/kg of phenobarbital with the option to re-load with 10mg/kg q8-12 hours for 2 more doses if needed for continued high scores. Maintenance therapy of 5mg/kg/day will be initiated 12 - 24 hours after the last loading dose. Phenobarbital trough levels will be monitored with goal levels of 20 - 30 mcg/mL. Phenobarbital will be weaned only after the infant has been weaned off of the study drug. Weaning will begin 48 hours after the study drug has been stopped by 20% of the maximum total daily dose every 3 days for scores \<8. An infant may be discharged home 48 - 72 hours after the first wean. The remaining wean will be outlined in the discharge prescription, and followed up on by study staff with the goal of the phenobarbital discontinuation within a 2 week period.
Sponsors
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Mother receiving methadone or buprenorphine (BPH) from a licensed physician or drug treatment program, or an opioid prescribed by a licensed health care worker for treatment of chronic pain. 2. Need for treatment of NAS by Finnegan Scoring criteria 3. Gestational age \>37 weeks at birth defined by best obstetrical estimate 4. Medically stable in the opinion of the Attending Physician 5. Mother receiving adequate or intermediate prenatal care from a qualified physician or midwife as defined by the Prenatal Care Adequacy Index 6. Singleton pregnancy 7. Mother able to provide informed consent 8. Infant able to take oral medications
Exclusion criteria
1. Gestation \<37 weeks at entry defined by best obstetrical estimate 2. Major congenital abnormalities including genetic syndromes 3. Serious medical illness such as sepsis, asphyxia, seizures, or respiratory failure 4. Mother abusing alcohol during pregnancy (average of 3 or more drinks per week in the last 30 days) 5. Multiple gestations 6. Mother received inadequate prenatal care as defined by the Prenatal Care Adequacy Index.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of Hospital Stay (LOS) | Participants will be monitored during their entire hospitalization, expected mean 22 days. | Participants were monitored for the duration of their hospitalization, an expected mean of 22 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Hospital Stay (LOS) Due to Neonatal Abstinence Syndrome (NAS) | Participants were monitored for the duration of their hospitalization, expected mean 22 days. | Participants were monitored for the duration of their hospitalization attributable to NAS only. |
| Length of Treatment (LOT) | Participants were monitored for the duration of their hospitalization. | Total number of days infant treated with replacement opioids while admitted to the hospital. |
| Maximum Daily Dose of Replacement Opioid | Participants were monitored for the duration of their hospitalization. | Maximum daily dose of neonatal morphine solution or methadone during the hospitalization |
| Mean Finnegan Score (FS) | Participants were monitored during their entire hospitalization | Mean Finnegan withdrawal score during the duration of hospitalization. |
| Growth Outcome: Weight Change From Birth to 18 Months | Birth to 18 month follow-up visit | Growth outcome weight (lbs) depicted as difference in averaged weights from birth to 18 month follow-up visit. Standard deviations were averaged between birth and 18 mo time points. |
| Growth Outcome: Head Circumference at 18 Months | 18 month follow-up visit | Average head circumference growth outcome at 18 month follow-up visit. |
| Maximum Finnegan Score | Participants monitored for the duration of their hospitalization. | Maximum Finnegan score during the hospitalization |
| Growth Outcome: Length at 18 Months | 18 month follow-up visit | Average length (cm) at 18 month follow-up visit. |
| Number of Infants Needing a Second NAS Medication | Participants were monitored for the duration of their hospitalization, an average of 22 days. | Number of infants treated with a second medication following protocol, phenobarbital. If the Finnegan Score remained elevated (still scored ≥8 two times consecutively, or still scored once ≥12) despite increasing to a predetermined maximal opioid dose (methadone or morphine), phenobarbital was administered (20-mg/kg loading dose followed by 4-5 mg/kg daily). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment | Assessment at 18 month follow-up visit | The Bayley Scales of Infant and Toddler Development (BSID-III) assesses the development of infants and children (1-42 months) through a series of developmental play tasks, identifying children with developmental delay. Raw scores of completed items are summarized within three distinct scale scores (Cognitive Scale, Language Scale, Motor Scale). Scale scores are each converted to composite scores to determine the child's performance compared with scores of age-matched children of typical development (percentile rank). A higher composite score indicates more ideal developmental outcome (range 40-160). At 18 month follow-up visit, participants were assessed using the BSID-III for cognitive, language and motor scale composite score outcomes. |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at Tufts Medical Center, Baystate Children's Hospital, Boston Medical Center, Maine Medical Center, Shands Jacksonville Medical Center, University of Pittsburgh Medical Center, Vanderbilt University Medical Center, and Women & Infants Hospital of Rhode Island.
Pre-assignment details
If infant was diagnosed with NAS (Finnegan score ≥8 on two consecutive occasions, or ≥12 on single assessment) and research pharmacy staff were unavailable for preparation of trial drug, infant could receive one dose of morphine prior to randomization. Dosing was based on weight and Finnegan scores.
Participants by arm
| Arm | Count |
|---|---|
| Randomized: Methadone First line therapy: 0.4mg/mL oral solution, based on weight and symptoms.
Clinical monitoring: Infants scored using standardized Finnegan system;
Regimen: Initiated treatment w/ 2 consec. scores ≥8, or 1 score ≥12. Starting doses range 0.3mg/kg/day - 0.9mg/kg/day, divided every 8hrs depending on the severity of Finnegan scores. Doses were increased to max of 0.9mg/kg/day for contd. scores generally \>8 caused primarily by worsening NAS, as needed. Weaned by 10% of max dose every 24-48 hours; Medication discontinued once at 25% of max dose.
Second Line Therapy: Phenobarbital (20mg/kg) was added once infant reached max methadone doses for contd. scores generally \>8. Option to re-load w/ 10mg/kg q8-12 hours for 2 more doses if needed for contd. high scores. Maintenance therapy of 5mg/kg/day was initiated 12 - 24hrs after last loading dose. Phenobarbital trough levels monitored, w/ goal levels 20 - 30 mcg/mL. Weaning procedure outlined in protocol. | 58 |
| Randomized: Neonatal Morphine Solution First line therapy: 0.2mg/mL solution, based on weight and symptoms.
Clinical monitoring: Infants scored using standardized Finnegan system;
Regimen: Initiated treatment w/ 2 consec. scores ≥8, or 1 score ≥12. Starting doses range 0.3mg/kg/day - 0.9mg/kg/day, divided every 4hrs depending on the severity of Finnegan scores. Doses were increased to max of 0.9mg/kg/day for contd. scores generally \>8 caused primarily by worsening NAS, as needed. Weaned by 10% of max dose every 24 - 48 hours; Medication discontinued once at 25% of max dose.
Second Line Therapy: Phenobarbital (20mg/kg) was added once infant reached max morphine doses for contd. scores generally \>8. Option to re-load w/ 10mg/kg q8-12 hours for 2 more doses if needed for contd. high scores. Maintenance therapy of 5mg/kg/day was initiated 12 - 24hrs after last loading dose. Phenobarbital trough levels monitored, w/ goal levels 20 - 30 mcg/mL. Weaning procedure outlined in protocol. | 58 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Parent requested exclusion from analysis | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized: Methadone | Randomized: Neonatal Morphine Solution | Total |
|---|---|---|---|
| Age, Customized | 3.2 days STANDARD_DEVIATION 1.3 | 3.5 days STANDARD_DEVIATION 1.6 | 3.4 days STANDARD_DEVIATION 1.6 |
| Infant APGAR score at 1 minute Score ≥7 | 54 Participants | 53 Participants | 107 Participants |
| Infant APGAR score at 1 minute Score <7/Data missing | 4 Participants | 5 Participants | 9 Participants |
| Infant APGAR Score at 5 minutes Score ≥7 | 57 Participants | 57 Participants | 114 Participants |
| Infant APGAR Score at 5 minutes Score <7/Data missing | 1 Participants | 1 Participants | 2 Participants |
| Infant birth weight | 3186 grams STANDARD_DEVIATION 488 | 3128 grams STANDARD_DEVIATION 487 | 3146 grams STANDARD_DEVIATION 486 |
| Infant mean gestational age | 39.2 weeks STANDARD_DEVIATION 1.2 | 39.1 weeks STANDARD_DEVIATION 1.1 | 39.2 weeks STANDARD_DEVIATION 1.2 |
| Infant mean head circumference | 33.9 cm STANDARD_DEVIATION 1.7 | 33.7 cm STANDARD_DEVIATION 1.8 | 33.8 cm STANDARD_DEVIATION 1.7 |
| Infant urine toxicology Missing | 3 Participants | 2 Participants | 5 Participants |
| Infant urine toxicology Negative | 14 Participants | 14 Participants | 28 Participants |
| Infant urine toxicology Positive | 41 Participants | 42 Participants | 83 Participants |
| Initial site of NAS care General Pediatric Unit | 16 Participants | 18 Participants | 34 Participants |
| Initial site of NAS care Newborn Unit | 16 Participants | 16 Participants | 32 Participants |
| Initial site of NAS care NICU | 17 Participants | 17 Participants | 34 Participants |
| Initial site of NAS care Special Care Nursery | 9 Participants | 7 Participants | 16 Participants |
| Maternal opioid use Buprenorphine | 20 Participants | 19 Participants | 39 Participants |
| Maternal opioid use Methadone | 38 Participants | 35 Participants | 73 Participants |
| Maternal opioid use Prescription opioids for pain | 0 Participants | 4 Participants | 4 Participants |
| Maternal psychiatric diagnoses No psychiatric diagnoses/Unknown | 16 Participants | 21 Participants | 37 Participants |
| Maternal psychiatric diagnoses Psychiatric diagnoses | 42 Participants | 37 Participants | 79 Participants |
| Maternal psychiatric medication during pregnancy No psychiatric medication during pregnancy/Unknown | 38 Participants | 42 Participants | 80 Participants |
| Maternal psychiatric medication during pregnancy Psychiatric medication during pregnancy | 20 Participants | 16 Participants | 36 Participants |
| Maternal Smoking Frequency during Pregnancy Smoked >5 cigarettes per day | 33 Participants | 15 Participants | 48 Participants |
| Maternal Smoking Frequency during Pregnancy Unknown/Data Missing | 25 Participants | 43 Participants | 68 Participants |
| Maternal Smoking Status during Pregnancy Did not smoke during pregancy/Data missing | 9 Participants | 14 Participants | 23 Participants |
| Maternal Smoking Status during Pregnancy Smoked during pregnancy | 49 Participants | 44 Participants | 93 Participants |
| Maternal urine toxicology Data Missing | 4 Participants | 9 Participants | 13 Participants |
| Maternal urine toxicology Negative urine toxicology | 41 Participants | 33 Participants | 74 Participants |
| Maternal urine toxicology Positive urine toxicology | 13 Participants | 16 Participants | 29 Participants |
| Maximum Finnegan score prior to starting treatment | 12.9 units on a scale STANDARD_DEVIATION 2.9 | 12.6 units on a scale STANDARD_DEVIATION 2.8 | NA units on a scale |
| Primary feeding during hospitalization Breast milk (exclusive or with formula supplement) | 36 Participants | 26 Participants | 62 Participants |
| Primary feeding during hospitalization Formula only | 22 Participants | 32 Participants | 54 Participants |
| Race/Ethnicity, Customized Infant Race/Ethnicity Hispanic | 6 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized Infant Race/Ethnicity Other | 6 Participants | 10 Participants | 16 Participants |
| Race/Ethnicity, Customized Infant Race/Ethnicity White | 46 Participants | 42 Participants | 88 Participants |
| Sex: Female, Male Female | 29 Participants | 29 Participants | 58 Participants |
| Sex: Female, Male Male | 29 Participants | 29 Participants | 58 Participants |
| Single dose of morphine prior to randomization No dose of morphine prior to randomization | 35 Participants | 41 Participants | 76 Participants |
| Single dose of morphine prior to randomization Single dose of morphine prior to randomization | 23 Participants | 17 Participants | 40 Participants |
| Site of initial care before treatment Newborn Nursery | 55 Participants | 48 Participants | 103 Participants |
| Site of initial care before treatment NICU | 3 Participants | 10 Participants | 13 Participants |
| Site of initial care before treatment Other | 0 Participants | 0 Participants | 0 Participants |
| Starting dose of study drug Level I: 0.3 mg/kg/day | 26 Participants | 32 Participants | 58 Participants |
| Starting dose of study drug Level I: 0.7 mg/kg/day | 7 Participants | 5 Participants | 12 Participants |
| Starting dose of study drug Level II: 0.5 mg/kg/day | 25 Participants | 21 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 58 |
| other Total, other adverse events | 8 / 58 | 6 / 58 |
| serious Total, serious adverse events | 5 / 58 | 3 / 58 |
Outcome results
Primary
Length of Hospital Stay (LOS)
Participants were monitored for the duration of their hospitalization, an expected mean of 22 days.
Time frame: Participants will be monitored during their entire hospitalization, expected mean 22 days.
Population: Includes infants requiring treatment for NAS who were randomized to either methadone or morphine study intervention. Analysis does not include Standard Clinical Care cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone | Length of Hospital Stay (LOS) | 21.8 days | Standard Deviation 15 |
| Neonatal Morphine Solution | Length of Hospital Stay (LOS) | 23.2 days | Standard Deviation 8.8 |
Secondary
Growth Outcome: Head Circumference at 18 Months
Average head circumference growth outcome at 18 month follow-up visit.
Time frame: 18 month follow-up visit
Population: Participants who were continuously enrolled and attended the 18 month follow-up visit for developmental and growth measures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone | Growth Outcome: Head Circumference at 18 Months | 47.8 cm | Standard Deviation 2.4 |
| Neonatal Morphine Solution | Growth Outcome: Head Circumference at 18 Months | 48.2 cm | Standard Deviation 2.3 |
Secondary
Growth Outcome: Length at 18 Months
Average length (cm) at 18 month follow-up visit.
Time frame: 18 month follow-up visit
Population: Participants who were continuously enrolled and attended the 18 month follow-up visit for developmental and growth measures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone | Growth Outcome: Length at 18 Months | 82.1 cm | Standard Deviation 4.6 |
| Neonatal Morphine Solution | Growth Outcome: Length at 18 Months | 81.7 cm | Standard Deviation 5.2 |
Secondary
Growth Outcome: Weight Change From Birth to 18 Months
Growth outcome weight (lbs) depicted as difference in averaged weights from birth to 18 month follow-up visit. Standard deviations were averaged between birth and 18 mo time points.
Time frame: Birth to 18 month follow-up visit
Population: Participants who were continuously enrolled and attended the 18 month follow-up visit for developmental and growth measures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone | Growth Outcome: Weight Change From Birth to 18 Months | 19.1 lbs | Standard Deviation 2.5 |
| Neonatal Morphine Solution | Growth Outcome: Weight Change From Birth to 18 Months | 18.7 lbs | Standard Deviation 2.8 |
Secondary
Length of Hospital Stay (LOS) Due to Neonatal Abstinence Syndrome (NAS)
Participants were monitored for the duration of their hospitalization attributable to NAS only.
Time frame: Participants were monitored for the duration of their hospitalization, expected mean 22 days.
Population: Includes infants requiring treatment for NAS who were randomized to either methadone or morphine study intervention. Analysis does not include Standard Clinical Care cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone | Length of Hospital Stay (LOS) Due to Neonatal Abstinence Syndrome (NAS) | 18.9 days | Standard Deviation 7.9 |
| Neonatal Morphine Solution | Length of Hospital Stay (LOS) Due to Neonatal Abstinence Syndrome (NAS) | 21.1 days | Standard Deviation 6.9 |
Secondary
Length of Treatment (LOT)
Total number of days infant treated with replacement opioids while admitted to the hospital.
Time frame: Participants were monitored for the duration of their hospitalization.
Population: Includes infants requiring treatment for NAS who were randomized to either methadone or morphine study intervention. Analysis does not include Standard Clinical Care cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methadone | Length of Treatment (LOT) | 14.7 days | Standard Deviation 8 |
| Neonatal Morphine Solution | Length of Treatment (LOT) | 16.6 days | Standard Deviation 6.9 |
Secondary
Maximum Daily Dose of Replacement Opioid
Maximum daily dose of neonatal morphine solution or methadone during the hospitalization
Time frame: Participants were monitored for the duration of their hospitalization.
Population: Data were not collected due to insufficient funding to carry out data collection.
Secondary
Maximum Finnegan Score
Maximum Finnegan score during the hospitalization
Time frame: Participants monitored for the duration of their hospitalization.
Population: Data were not collected due to insufficient funding to carry out data collection.
Secondary
Mean Finnegan Score (FS)
Mean Finnegan withdrawal score during the duration of hospitalization.
Time frame: Participants were monitored during their entire hospitalization
Population: Data were not collected due to insufficient funding to carry out data collection.
Secondary
Number of Infants Needing a Second NAS Medication
Number of infants treated with a second medication following protocol, phenobarbital. If the Finnegan Score remained elevated (still scored ≥8 two times consecutively, or still scored once ≥12) despite increasing to a predetermined maximal opioid dose (methadone or morphine), phenobarbital was administered (20-mg/kg loading dose followed by 4-5 mg/kg daily).
Time frame: Participants were monitored for the duration of their hospitalization, an average of 22 days.
Population: Includes infants requiring treatment for NAS who were randomized to either methadone or morphine study intervention. Analysis does not include Standard Clinical Care cohort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methadone | Number of Infants Needing a Second NAS Medication | 10 Participants |
| Neonatal Morphine Solution | Number of Infants Needing a Second NAS Medication | 17 Participants |
Other Pre-specified
Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment
The Bayley Scales of Infant and Toddler Development (BSID-III) assesses the development of infants and children (1-42 months) through a series of developmental play tasks, identifying children with developmental delay. Raw scores of completed items are summarized within three distinct scale scores (Cognitive Scale, Language Scale, Motor Scale). Scale scores are each converted to composite scores to determine the child's performance compared with scores of age-matched children of typical development (percentile rank). A higher composite score indicates more ideal developmental outcome (range 40-160). At 18 month follow-up visit, participants were assessed using the BSID-III for cognitive, language and motor scale composite score outcomes.
Time frame: Assessment at 18 month follow-up visit
Population: Includes subjects who were randomized and remained enrolled at 18 month follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone | Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment | Cognitive Composite | 100.1 scores on a scale (Composite) | Standard Deviation 21.6 |
| Methadone | Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment | Language Composite | 96.0 scores on a scale (Composite) | Standard Deviation 17.1 |
| Methadone | Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment | Motor Composite | 103.6 scores on a scale (Composite) | Standard Deviation 17.3 |
| Neonatal Morphine Solution | Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment | Language Composite | 94.2 scores on a scale (Composite) | Standard Deviation 18.2 |
| Neonatal Morphine Solution | Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment | Cognitive Composite | 98.1 scores on a scale (Composite) | Standard Deviation 17.2 |
| Neonatal Morphine Solution | Cognitive, Language, and Motor Development From 18 Month Bayley III Neurodevelopmental Assessment | Motor Composite | 99.1 scores on a scale (Composite) | Standard Deviation 17.2 |
Post Hoc
Number of Infants Needing a Dose Increase
One Finnegan score ≥12, or two consecutive scores ≥8 affirms the requirement for pharmacological treatment or increasing treatment dosage. If the infant continued to have two consecutive Finnegan Scores ≥8 two times consecutively, or one ≥12, the dose was increased to the next level. (Level I: 0.3 mg/kg/day) (Level II: 0.5 mg/kg/day) (Level III: 0.7 mg/kg/day) A higher Finnegan score indicates greater severity of NAS (min 0, max 50).
Time frame: Participants were monitored for the duration of their hospitalization, an average of 22 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methadone | Number of Infants Needing a Dose Increase | 22 Participants |
| Neonatal Morphine Solution | Number of Infants Needing a Dose Increase | 28 Participants |