PP-019 Comparing neonatal outcomes of pregnant women treated for opioid use disorder (OUD) with mono-buprenorphine to neonatal outcomes of pregnant women treated for oud with combination Buprenorphine + Naloxone

Over 20,000 U.S babies each year are diagnosed with Neonatal Abstinence Syndrome (NAS). These neonates require Neonatal Intensive Care Unit attention and are at risk for long term developmental issues.  Buprenorphine and methadone are standard treatments for opioid use disorder (OUD) during pregnancy, with buprenorphine being preferred due to its lower overdose risk and milder NAS symptoms. There has been insufficient investigation, however, into the comparative effectiveness of buprenorphine + naloxone (combination therapy), versus buprenorphine alone (mono therapy). Combination therapy has lower potential for misuse and diversion. The goal of this retrospective study was to determine if combination buprenorphine + naloxone therapy is an improved alternative for OUD in pregnancy by evaluating differences in neonatal outcomes in patients on combination therapy and also patients on mono therapy.

Four categories of mothers and infants were reviewed: 1- Mothers treated with mono-buprenorphine in our University Medication Assisted Therapy clinic, 2- Mothers treated with combination buprenorphine + naloxone in our clinic, 3- Mothers receiving prenatal care from our clinic but receiving mono-buprenorphine from an outside MAT clinic, and 4-Mothers receiving prenatal care from our clinic but receiving combination buprenorphine + naloxone from an outside MAT clinic. A total of 458 mother baby pairs underwent chart review assessment. We compared the following neonatal outcomes of the infants from each group: sex, weight, gestational age (GA) at delivery, APGAR scores at 1 and 5 minutes, infant ICD10 codes at delivery, highest Finnegan score, admission to and length of stay in the NICU, necessity of morphine replacement therapy, infant urine drug screen (UDS) results, and breastfeeding difficulties. We also compared mother's data between the groups: dosages, therapy changes, GA at delivery, pregnancy complications and maternal risk factors, gravida and parity, clinic and delivery UDS results, and maternal BMI throughout pregnancy.

Conclusions were determined with a proportion test, chi squared tests, and if needed, a Fisher’s exact test. P-values were adjusted using Benjamini Hochberg procedure. The combination therapy groups have a statistically significant lower proportion of NICU admissions than the mono therapy groups (p-value = 0.02789). No evidence that buprenorphine/naloxone administration provides any risk to maternal health was uncovered. Additional analysis indicates that the mean final buprenorphine dose for the women treated in the ETSU MAT clinic is lower than the mean final buprenorphine dose for the women who were treated in community clinics.
 
The participants were also analyzed based on buprenorphine dose and placed into three sub-categories: Subcategory A: 0-2 mg, Subcategory B: 3-7 mg, and Subcategory C: >8 mg. Analysis demonstrates that the mean final buprenorphine dose for women who received mono therapy is statistically greater than the mean final dose for women who were treated with combination therapy (p-value < 0.0001 and t = 5.6298). Proportional and Fisher’s analyses also indicates that the proportion of infant drug screens that result as “clean” are significantly less for Subcategory A compared to Subcategory B, meaning it is more likely that the infant has a negative UDS at delivery when their mother is on a lower buprenorphine dose of 0-2 mg rather than a higher dose of 3-7 mg.
 
The proportion of NICU admissions is significantly less for infants whose mothers are on a buprenorphine dose of 0-2 mg than those whose mothers are on a dose of 8 mg (p-value = 0.005607). The proportion of NICU admission is also significantly less for infants whose mothers are on 3-7 mg as compared to infants whose mothers are on a dose of more than 8 mg (p-value = 0.046515). However, NICU admission for dosage subcategory A and subcategory B (proportion): (p-value = 0.389) indicated that there is no statistical difference in the proportion of NICU admission between these two lowest dosage groups (< 8 mg).

We conclude that women who were treated with combination therapy for OUD in pregnancy were associated with a significantly lower proportion of NICU admissions for their infants than those treated with mono therapy.  Moreover, a lower final buprenorphine dose was associated with both a higher proportion of clean infant UDS’s and a lower proportion of NICU admissions.  These results indicate that combination therapy and tapered doses of buprenorphine could be associated with better neonatal outcomes.