Improving Outcomes in Neonatal Abstinence Syndrome

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 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.

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.