An Alternative Approach to Low-Dose Buprenorphine Induction in Pregnancy and Postpartum

Low-dose buprenorphine induction offers an alternative approach to standard buprenorphine initiation for pregnant and newly postpartum people with opioid use disorder.

Abstract

Low-dose buprenorphine induction, unlike traditional methods, does not require that individuals experience at least moderate withdrawal before initiation. This technique has been widely used and studied in the general population; however, research in pregnancy is limited. We aimed to evaluate obstetric and neonatal outcomes after low-dose buprenorphine induction. In this retrospective case series, we reviewed all cases of low-dose induction during pregnancy or within 6 weeks postpartum at an urban academic medical center over a 3-year period. Nine patients started buprenorphine using this method, and all but one completed induction. There was a high rate of treatment retention and no apparent associated adverse neonatal events. Four individuals are in sustained remission and currently parenting. Though further research is needed, low-dose buprenorphine induction appears effective in the obstetric population.

Buprenorphine and methadone are first-line treatments for opioid use disorder (OUD) in pregnancy due to demonstrated maternal and neonatal benefit.¹ Unlike methadone, traditional buprenorphine induction requires that individuals experience at least moderate withdrawal before administration to minimize the risk of precipitated withdrawal. Low-dose buprenorphine induction with opioid continuation (previously described in the literature as “microinduction”) avoids withdrawal before initiation.² With fentanyl dominating the drug supply, the risk of precipitated withdrawal has increased, making low-dose buprenorphine induction with opioid continuation a favorable option for many patients.³ Although this method has been widely used and researched among the general population with OUD, literature in pregnancy is limited to two case reports and two small case series, none of which report obstetric or neonatal outcomes.^4–7 We sought to evaluate perinatal outcomes after utilization of this technique.

METHODS

We conducted a retrospective case series of all pregnant and postpartum people treated with low-dose buprenorphine induction with opioid continuation for OUD at Massachusetts General Hospital from January 2020 through October 2023. The maternal cohort was identified using an IRB-approved database of all opioid-exposed newborns Electronic medical records were reviewed to determine whether low-dose buprenorphine induction with opioid continuation was used during pregnancy or within 6 weeks postpartum. Maternal demographics, substance use history, psychiatric comorbidities, pregnancy complications, and neonatal outcomes were abstracted from the existing database. Records were reviewed for buprenorphine protocol used, induction location, gestational age at initiation, substances used immediately prior, induction length, successful completion, presence of precipitated withdrawal, and whether individuals remained connected to medical care. The Mass General Brigham IRB approved this study as exempt health/medical records research.

RESULTS

Nine patients underwent low-dose buprenorphine induction with opioid continuation while pregnant or newly postpartum (Table 1). All patients in our cohort were White, non-Hispanic, English-speaking, publicly insured, cis-gender, and diagnosed with moderate-to-severe OUD. Three had co-existing cocaine use disorder, one had stimulant and benzodiazepine use disorder, and all but one had nicotine dependence. Four used substances intravenously, four had experienced at least one overdose, and six had a history of substance-related complications including hepatitis C virus infection, endocarditis, and skin and soft tissue infections. All patients had a history of medication treatment for OUD, although only two were receiving outpatient methadone immediately before starting low-dose buprenorphine induction with opioid continuation. The majority (7/9) had other psychiatric diagnoses. Four had a history of homelessness, and three had documented justice system involvement.

Table 1.

Low-Dose Buprenorphine Induction Details and Sample Protocol^*

	Maternal Age (y)	Parity	Setting	GA at Induction (Wk)	Opioids Before Induction	Induction Length (d)	Supportive Medications Patient Used	Protocol	Maintenance Dose	Follow-Up Care as of March 2024
1	35	Multiparous	Inpatient	17 3/7	Illicit fentanyls, methadone (used for inpatient stabilization)	3	Lorazepam, ondansetron, clonidine, loperamide	Belbuca 225 micrograms every 3 h, 450 micrograms every 3 h, Suboxone 12 mg daily	Suboxone 12 mg daily	20 prenatal visits, sustained remission postpartum with more than 6 mo of follow-up, parenting, remains on buprenorphine
2	37	Multiparous	Inpatient	20 5/7	Prescribed oral morphine and IV hydromorphone	10	Hydroxyzine, clonazepam	Subutex 1 mg daily, 1 mg twice/d, 2 mg twice/d, 4 mg twice/d	Subutex 24 mg daily (discharged on 4 mg twice/d)	23 prenatal visits, no postpartum visits, remained on buprenorphine and connected with general medical care
3	32	Multiparous	Outpatient	21 5/7	Illicit fentanyls, nonprescribed opioids	15	Lorazepam	Suboxone 0.25 mg daily, 0.25 mg twice/d, 0.5 mg twice/d, 1 mg twice/d, 2 mg twice/d, 2 mg 3 times/d, 4 mg twice/d, 8 mg every morning + 4 mg every evening, 8 mg 3 times/d	Suboxone 24 mg daily	10 prenatal visits, sporadic postpartum care over less than 3 mo, transitioned to buprenorphine XR
4	32	Primiparous	Outpatient, transitioned to inpatient	22 5/7	Methadone (maintenance treatment), illicit fentanyls	9	Clonazepam, clonidine	Belbuca 750 micrograms daily, 900 micrograms twice/d, suboxone 4 mg twice/d, 6 mg twice/d	Suboxone 6 mg twice/d	19 prenatal visits, more than 1 y of follow-up postpartum, on buprenorphine extended release, receiving psychiatric care, does not have custody
5	33	Multiparous	Outpatient	22 6/7	Methadone (maintenance treatment), illicit fentanyls	10	None	Suboxone 0.5 mg daily, 0.5 mg twice/d, 1 mg twice/d, 2 mg twice/d, 3 mg twice/d, 4 mg twice/d, 8 mg twice/d	Suboxone 8 mg twice/d (evening dose split)	14 prenatal visits, more than 6 mo postpartum follow-up, initially in remission and parenting on buprenorphine, recently lost to follow-up
6	40	Multiparous	Outpatient	27 1/7	Illicit fentanyls	Did not complete	Hydroxyzine, quetiapine	Subutex 0.5 mg every 3 h, 1 mg every 3 h	NA	23 prenatal visits, more than 2 y follow-up postpartum, sustained remission on methadone, parenting
7	39	Multiparous	Inpatient	33 3/7	Illicit fentanyls, methadone (used for inpatient stabilization)	7, experienced precipitated withdrawal	Hydroxyzine, clonazepam, clonidine, quetiapine	Belbuca 225 micrograms twice/d, 450 micrograms twice/d, 900 micrograms twice/d, subutex 4 mg twice/d, 8 mg twice/d	Subutex 8 mg twice/d	Lost to follow-up
8	24	Multiparous	Inpatient	Postpartum	Methadone (maintenance treatment), prescribed oxycodone	7	Ondansetron	Belbuca 75 micrograms twice/d, 150 micrograms twice/d, 300 micrograms twice/d, 450 micrograms twice/d, suboxone 2 mg twice/d, 4 mg twice/d, 8 mg twice/d	Suboxone 8 mg twice/d	More than 1 y postpartum follow-up, parenting, initially transitioned to buprenorphine XR, most recently off MOUD
9	37	Primiparous	Inpatient	Postpartum	Illicit fentanyls, methadone (used for inpatient stabilization)	4	Clonidine, quetiapine	Belbuca 225 micrograms every 3 h, 450 micrograms every 3 h, suboxone 12 mg daily	Suboxone 12 mg daily	Sustained remission postpartum with more than 2 y of follow-up, still parenting, remains on buprenorphine

GA, gestational age; IV, intravenous; XR, extended release; NA, not applicable; MOUD, medications for opioid use disorder.

^*Sample Inpatient Protocol Based on Clinical Experience (Must be tailored to individual patient needs and available buprenorphine formulations. Comfort medication recommendations beyond the scope of this study.)

Day 1: Belbuca (buprenorphine buccal film) 225 micrograms ×1 dose. Continue methadone or other opioids being used to control withdrawal or pain.

Day 2: Belbuca 225 micrograms every 12 hours ×2 doses.

Day 3: Belbuca 450 micrograms every 12 hours ×2 doses.

Day 4: Belbuca 900 micrograms every 12 hours ×2 doses.

Day 5: Suboxone (buprenorphine/naloxone) 4-1 mg every 12 hours ×2 doses. Last dose of methadone or other opioids being used to control withdrawal.

Day 6: Suboxone 8-2 mg every 12 hours. Stop methadone or other opioids being used to control withdrawal. Continue opioids for acute or chronic pain as needed. Continue uptitration of Suboxone as needed.

Five patients underwent inpatient low-dose buprenorphine induction with opioid continuation, two immediately after delivery, two admitted antepartum exclusively for OUD stabilization, and one during an antepartum admission for osteomyelitis. Four patients opted for outpatient induction, including one who did not finish the induction and another who transitioned to the inpatient setting to complete induction. One patient experienced precipitated withdrawal but completed the induction and had no adverse obstetric or neonatal outcomes.

Of the seven patients who underwent low-dose buprenorphine induction with opioid continuation during pregnancy, only one delivered a newborn with 5-minute Apgar score less than 7 (Table 2). That newborn was delivered 3 months after low-dose buprenorphine induction with opioid continuation at 35 weeks of gestation by emergent cesarean under general anesthesia. Five newborns received pharmacologic therapy for neonatal opioid withdrawal syndrome. All nine newborns were reported to the child protection system as was standard practice at that time for any substance-exposed newborn. There was a high rate of treatment retention, with seven patients remaining on buprenorphine in either sublingual or injection form at their 6-week postpartum visits. Only one patient was lost to follow-up care. At the time of this study, four individuals had at least 1 year of sustained remission and parenting.

Table 2.

Neonatal Outcomes Among Individuals Who Received Low-Dose Buprenorphine Induction in Pregnancy or Postpartum

	GA at Delivery (Wk)	Mode of Delivery, Analgesia	Delivery Complications	Birth Weight (g) (Percentile)	1-Min Apgar Score, 5-Min Apgar Score	Location(s) of Neonatal Care	Reason for NICU Admission	Maternal Psychiatric Medications at Delivery	Neonatal Urine Toxicology Test Result (Nonprescribed)	Pharmacologic Treatment for NOWS	Day of Life at Discharge	Length of Opioid Treatment (d)
1	39 5/7	Vaginal, epidural		3,590 (69)	8, 9	Nursery		None	Negative	No	5	NA
2	37 1/7	Vaginal, epidural		2,195 (3)	9, 9	Nursery and special care nursery		Gabapentin, clonazepam, Adderall	Negative	Yes	14	12
3	35 3/7	Emergent cesarean, general	PPROM, PTL, footling breech	2,480 (52)	2, 4	Special care nursery and NICU	Respiratory distress, prematurity	None	Cocaine	Yes	13	7
4	37 5/7	Cesarean, combined spinal epidural		3,170 (45)	8, 8	NICU	Respiratory distress in the setting of VACTERL with tetralogy of Fallot	None	Fentanyl	Yes	47	36
5	37 1/7	Vaginal, epidural		2,350 (7)	8, 9	Nursery		None	Negative	No	4	NA
6	39 5/7	Vaginal, combined spinal epidural		3,385 (39)	7, 9	Nursery		Trazodone, clonazepam, sertraline	Negative	No	5	NA
7	39 0/7	Vaginal, epidural		3,060 (35)	8, 9	Nursery and special care nursery		Fluoxetine, alprazolam, Adderall	Fentanyl, cocaine	Yes	5 (transferred)	Unknown
8	33 0/7	Emergent cesarean, general	PPROM, cord prolapse, chorioamnionitis	1,840 (32)	3, 8	Special care nursery and NICU	Respiratory distress, prematurity	Clonidine, aripiprazole	Negative	No	16 (transferred)	NA
9	35 5/7	Emergent cesarean, spinal	Severe preeclampsia, intracranial hemorrhage	2,715 (55)	8, 9	Nursery and NICU	Respiratory distress, prematurity	Lorazepam	Fentanyl	Yes	16	14

GA, gestational age; NICU, neonatal intensive care unit; NOWS, neonatal opioid withdrawal syndrome; NA, not available; PPROM, premature prelabor rupture of membranes; PTL, preterm labor; VACTERL, vertebral anomalies, anal atresia, cardiac malformations, tracheoesophageal fistula with esophageal atresia, renal anomalies, and limb anomalies.

DISCUSSION

Challenges with traditional buprenorphine induction require new approaches to meet the needs of pregnant and newly postpartum people with OUD. Previous small studies have demonstrated the feasibility of low-dose buprenorphine induction with opioid continuation in this population, and our findings detailing both maternal and neonatal outcomes provide further support.^4–7 Despite a high degree of medical and psychosocial complexity, the majority of patients completed the protocol, remained on buprenorphine, and stayed connected to care. This method seemed especially useful in cases of high ongoing opioid requirements after cesarean delivery, allowing seamless buprenorphine stabilization without triggering severe withdrawal symptoms at a time when maternal stability is critical for early parenting success.

Protocols for low-dose buprenorphine induction with opioid continuation vary across institutions, and further research is needed to determine the optimal approach in pregnancy and postpartum. As seen in our case series, even within one institution, initial buprenorphine dose and time to dose stabilization is highly individualized and affected by differential access to various buprenorphine products. However, we hope to equip obstetricians and substance use disorder care professionals with a framework for low-dose buprenorphine induction with opioid continuation (see Table 1 for sample protocol).

Further research with larger, more diverse patient populations is needed to better characterize the optimal regimen and who might benefit most, along with qualitative research to understand the patient experience. Although that research is underway, we encourage treatment teams supporting pregnant and postpartum patients through buprenorphine induction to consider using low-dose buprenorphine induction with opioid continuation.