Breastfeeding on Injectable Opioid Agonist Therapy: A Case Report

Background

Injectable opioid agonist therapy (iOAT) is the highest-intensity treatment currently available in Canada for individuals with severe opioid use disorder. However, there is limited data on iOAT administration in the perinatal period, with no research, practice guidelines, or known reports of breastfeeding on iOAT. This article presents the first known case of an individual breastfeeding on iOAT.

Case summary

We present a case of a pregnant 32-year-old woman from Canada with severe opioid use disorder, who stabilized with iOAT and chose to breastfeed her infant. She presented to hospital at 38 + 6 gestation in labor, unstable in her substance use disorder despite multiple interventions and was initiated on iOAT (intravenous hydromorphone) shortly after delivery. Before initiation of breastfeeding the infant was admitted to the neonatal intensive care unit for monitoring. On day 9 of life the infant received breastmilk for the first time, and was discharged from neonatal intensive care unit on day 12 of life with no clinical evidence of sedation or respiratory depression. The infant maintained mixed feeding and at 58 days of life was discharged in the mother and father’s care, a healthy infant with stable vitals.

Discussion

This case suggests positive infant and maternal health and social outcomes for breastfeeding on iOAT. Further research on perinatal iOAT use and the pharmacokinetics of high-dose hydromorphone in breastmilk is required to inform clinical practice guidelines to safely support individuals and their infants who are impacted by substance use.

Injectable opioid agonist therapy (iOAT) is the highest-intensity treatment for individuals with severe opioid use disorder (OUD).^1,2 Despite growth in iOAT administration, there remains a gap in the literature regarding iOAT in the peripartum. Three cases on iOAT in pregnancy have been published, each demonstrating positive pregnancy outcomes.^3–5 Currently, there are no known published reports of breastfeeding while on iOAT. The extensive benefits of breastfeeding for mothers and infants are well established, including enhancing maternal-infant bonding, maternal confidence, and decreasing symptoms and need for pharmacological therapy in infants with neonatal abstinence syndrome (NAS).^6,7 A clinical protocol was implemented in 2019 for perinatal iOAT administration at the Families in Recovery (FIR) unit at BC Women’s Hospital, an in-patient unit that practices rooming in.^8,9 Outcomes of breastfeeding while on iOAT remain unknown.

We present the first known case of an individual breastfeeding on iOAT. The participant consented to an observational research study on perinatal iOAT, approved by the University of British Columbia’s Children’s and Women’s research ethics board, and funded by the Women's Health Research Institute. Additional written informed consent was obtained to publish this report.

CASE PRESENTATION

A 32-year-old G5T2A2L2 Indigenous woman presented to BC Women's Hospital in Vancouver, Canada, at 38 + 6 gestation in active labor. She presented with opioid withdrawal, anemia, malnourishment, hypertension, severe edema, and sepsis. History included 5 years of opioid intravenous drug use (IVDU), up to 2 g/d of fentanyl, 0.5 g/d methamphetamine, and 10 cigarettes daily. The individual was unable to stabilize her OUD on three prior hospital admissions in the antepartum. Previous admissions trialed methadone, slow-release oral morphine, and oral hydromorphone. In addition, iOAT was offered on one prior admission at 29 weeks gestation where the individual was being treated for sepsis and IVDU. She left hospital against medical advice before completing antibiotic treatment for endocarditis. The individual had previous history trialing sublingual buprenorphine several times in the community, with precipitated withdrawal and adverse reactions. Buprenorphine, including subcutaneous extended release was not offered due to this previous history. In addition, buprenorphine subcutaneous extended release is not recommended during pregnancy due to associations of teratogenicity in animal models and only became publicly funded within British Columbia in April 2020.

Despite instability in the antepartum, she received good community prenatal care with extensive patient outreach. At delivery, she was in stable housing and on income assistance. Her partner, who identifies as Indigenous, was the biological father of her pregnancy. The individual reported using intravenous (IV) fentanyl immediately before labor.

She delivered by caesarean section at 38 + 6 gestation with APGARS of 6, 8, and 9 at 1, 5, and 10 minutes. Delivery complications included postpartum hemorrhage requiring intrauterine balloon tamponade, blood transfusion, and anesthesia support for intravenous access.

The individual met the criteria for perinatal iOAT, including significant duration of opioid IVDU, unsuccessful trials of oral agonist therapy, capacity to consent, and adverse events.⁸ Informed consent was reviewed and she requested a trial of iOAT. Injectable opioid agonist therapy dosage was titrated based on the individual’s tolerance and clinical effect with the utilization of The Pasero Opioid-induced Sedation Scale.¹⁰ Starting dose was 20 mg IV hydromorphone and titration to 120 mg three times a day (TID), 32 mg every hour (q1h) pro re nata (as needed) (PRN) oral hydromorphone and 70 mg oral methadone daily (Table 1). Highest dose of iOAT occurred on day 5 at 120 mg IV hydromorphone TID, 60 mg q1h PRN oral hydromorphone, and 100 mg oral methadone. Postpartum pain management may have impacted iOAT dosage; however, the rapid iOAT titration allowed this individual to remain in hospital to effectively treat her OUD.

TABLE 1.

Timeline of Admission, Infant Day of Life, Infant Feeding, Infant Eat Sleep and Console Assessment, Infant Huddle Decisions, Daily Infant Morphine, Infant Respiratory Monitoring, Maternal Analgesics, and Maternal Postpartum Interventions

Admitted	Infant Day of Life	Weight (g)	Breastmilk, EBM, Enfamil 68 k/cal	ESC*	Huddle Decisions	Total Daily Infant Morphine (mg)	Lowest Infant Respiratory Rate (BPM)	Corresponding SaO2	Total Daily Maternal Analgesics (mg)	Maternal Interventions
NICU	0	3015	—	E = y C = 1 P/C = 5 H = n	Infant admitted to NICU for respiratory distress and meconium aspirations	0	40	100	Hydromorphone = 228 Methadone = 80	Delivery complications of postpartum hemorrhage requiring intrauterine balloon tamponade
	1	Unknown	Enf = 20 mL	E = y C = 2 P/C = 5 H = n		0	28	100	iOAT = 100 Hydromorphone PRN = 228 Methadone = 100	iOAT initiated
	2	3017	Enf = 110 mL	E = y C = 2 P/C = 5, 4, 2 H = n	Poor feeding infant NG feeding tube inserted Infant morphine initiated	0.24	31	100	iOAT = 210 Hydromorphone PRN = 400 Methadone = 100	Blood transfusion
	3	3017	Enf = 257 mL	E = n C = 2 P/C = 5, 3 H = n		0.72	23	100	iOAT = 290 Hydromorphone PRN = 128 Methadone = 100
	4	2935	Enf = 197 mL	E = n C = 2 P/C = 5, 1, 2 H = n	Feeding improved NG feeding tube removed	0.78	32	100	iOAT = 250 Hydromorphone PRN = 64 Methadone = 100
	5	2910	Enf = 421 mL	E = n C = 2 P/C = 5, 3 H = n		0.78	40	100	iOAT = 360 Hydromorphone PRN = 60 Methadone = 100	Highest iOAT titration
FIR	6	2840	Enf = 431 mL	E = n C = 1, 2 P/C = 1 H = n	Lowest infant weight loss: 5.8% of birth weight	0.78	48	Not recorded	iOAT = 360 Hydromorphone PRN = 0 Methadone = 120
	7	2880	Enf = unknown	E = n C = 1, 2 P/C = 1 H = n		0.6	48	Not recorded	iOAT = 360 Hydromorphone PRN = 48 Methadone = 130
	8	2900	Enf = unknown	E = n C = 1, 2 P/C = 1 H = n	Regular infant morphine discontinued and morphine PRN ordered	0.66	48	Not recorded	iOAT = 220 Hydromorphone PRN = 0 Methadone = 120	Beginning of iOAT gradual titration down
NICU	9	2880	EBM: 72 mL Enf: 100 mL	E = n C = 2 P/C = 1 H = n		0.6	43	99	iOAT = 220 Hydromorphone PRN = 60 Methadone = 140	Maternal negative HIV PCR test result
	10	2925	BM: 30 and 10 minutes EBM: 327 mL Enf: 170 mL	E = n C = 1, 2 P/C = 1 H = n	Infant required no further morphine after breastfeeding and morphine was discontinued	0.2	30	97	iOAT = 220 Hydromorphone PRN = 60 Methadone = 140
	11	2990	EBM: 337 mL Enf: 385 mL	E = n C = 1, 2 P/C = 1 H = n		0	28	100	iOAT = 220 Hydromorphone PRN = 0 Methadone = 140
	12	2997	BM: 30 minutes EBM: 340 mL Enf: 440 mL	E = n C = 1, 2 P/C = 1 H = n		0	38	100	iOAT = 220 Hydromorphone PRN = 60 Methadone = 145
FIR	13	3130	Stable mixed feeding- 50% BM	E = n C = 1, 2 P/C = 1, 2 H = n		0	48	Not recorded	iOAT = 110 Hydromorphone PRN = 0 Methadone = 155
	14	3140		E = n C = 1, 2 P/C = 1, 2 H = n		0	48	Not recorded	iOAT = 220 Hydromorphone PRN = 0 Methadone = 155
	15–57	N/A				0			Maternal iOAT dose discontinued after day 47 of titration	Addition of slow release oral morphine at day 42 of iOAT administration with patient informed consent
Discharged	58	5005							Slow release oral morphine = 1200 Methadone = 190

*The ESC assessment tool documents items key to the functioning of the infant. The following questions are coded in the table above.

E, Poor Eating (y, yes or n, no).

C, Support needed to console (1, able to self-console; 2, able to console [and stay consoled] with caregiver support within 10 minutes; 3, unable to console [or cannot stay consoled] with caregiver support within 10 minutes).

P/C, parent/caregiver present for (1, more than 3 hours; 2, 2 to 3 hours; 3, 1 to 2 hours; 4, less than 1 hour; 5, no parent/caregiver present).

H, Recommend bedside RN and parent/caregiver huddle (y, yes or n, no).

ESC indicates Eat Sleep Console; HIV, human immunodeficiency virus; iOAT, injectable opioid agonist therapy.

At delivery, the infant was transferred to the on-site neonatal intensive care unit (NICU) for respiratory distress, which resolved within 24 hours. The infant was cared for with the Eat Sleep Console (ESC) model,¹¹ and on day 2 of life started on 0.04 mg/kg q4h PRN oral morphine due to need for nasogastric feeds. The infant received 0.12 mg q4h and 0.06 mg q4h PRN oral morphine on day 6 with maximum weight loss 5.8%. On day 6, infant was transferred from NICU to FIR.

The individual expressed a strong desire to breastfeed, and had an informed consent discussion before onset of breastfeeding on iOAT. This informed consent supported individual choice in infant feeding. Discussion points included the maternal and infant benefits of breastfeeding, lack of published outcomes, expected risk of infant sedation, respiratory depression, and necessity of close observation. The iOAT breastfeeding draft protocol at BC Women's Hospital included a negative maternal HIV PCR test at birth, 96 hours substance-free (due to concerns of contaminants in street drug supply),¹² and transfer to the mother-infant rooming-in unit in NICU for a 48-hour minimum observation period.

On day 9 of life, the infant’s morphine was discontinued and morphine PRN was ordered. Infant received 72 mL expressed breast milk (EBM) for the first time on day 9, when maternal iOAT dose was 110 mg IV hydromorphone BID. On day 10, infant received 155 mL of formula and 0.10 mg q4h PRN of morphine (a weaned dose) at 4:00 am and 8:00 am. The individual received 110 mg IV hydromorphone at 8:00 am, and by 11:00 am infant latched to breast for 30 minutes. Infant was monitored for NAS symptoms and was alert and active, feeding and sleeping well, and morphine was discontinued. There were no clinically relevant apneas, bradycardias, desaturations, signs of respiratory depression, or excessive sedation.

Infant monitoring was continuous with cardiopulmonary monitoring, oxygen saturation, and q1h vitals for 24 hours, and subsequent q3h vitals until transfer out of NICU. On FIR vitals were assessed 2 times daily until discharge. On day 11, infant received 337 mL EBM and 385 mL of formula with no breastfeeding. On this day, the infant had one low respiratory rate of 28 bpm, this was not clinically significant as the saturation was 100%, with ESC reassuring. On day 12, infant latched to breast for 30 minutes and received 340 mL EBM and 440 mL formula. Day 12 the infant was off morphine, gaining weight, exhibiting no symptoms of sedation, respiratory depression or NAS and was transferred back to FIR.

The infant maintained mixed feeds including formula, EBM, and breastfeeding. Maternal iOAT was slowly titrated down until discontinuation on day 47 of infant life, with methadone titrated up and addition of slow-release oral morphine. The individual was discharged on 190 mg methadone and 1200 mg slow-release oral morphine. There was no evidence of maternal substance use clinically or in the voluntary urine drug screens since birth. At day 58 the infant was discharged in the mother and father’s care with community supports, and collaboration with child services.

Four months postdischarge, the individual was administered the Ages & Stages Questionnaire.¹³ The infant scored above the cutoff score in all developmental domains including communication, gross motor, fine motor, problem solving, and personal-social. Notably, the individual had regained custody of her two other children.

DISCUSSION

Injectable opioid agonist therapy is an evidence-based treatment for severe OUD.^3–5 Published case studies of iOAT during pregnancy are promising. There is no published literature on the use of iOAT during breastfeeding, and there is limited literature on hydromorphone in general during breastfeeding. A pharmacokinetic study that collected breastmilk samples after a single 2-mg intranasal dose of hydromorphone reported a milk/plasma (M/P) ratio of 2.56, peak milk levels occurred 2 hours after the dose, and half-life of elimination from milk was 10.5 hours. Calculated infant dose was 0.67%.¹⁴ Despite what appears to be low levels of hydromorphone transfer into breastmilk, a published report of a newborn being breastfed by a mother on 4 mg oral hydromorphone q4 required resuscitation and naloxone administration for drowsiness, apnea and bradycardia.¹⁵

There is a gap in data on the safety and pharmacokinetics of high-dose hydromorphone during breastfeeding and long-term neurodevelopmental outcomes. The current case presented high doses of iOAT up to 120 mg IV TID, approximately equal to 1000 to 1800 mg oral hydromorphone.¹⁶ Infants exposed to high-dose opioids in utero are likely to have much different tolerance for breastmilk containing maternal prescribed opioids than an opioid naive infant. The 48-hour minimum time period for observation of the infant was based on the 10.5 hours half-life of hydromorphone reported in milk and the unknown pharmacokinetics of hydromorphone in neonates.¹⁷ Interesting in this case was the infant’s rapid ability to titrate off oral morphine upon breastfeeding. Further research is required to understand the pharmacokinetics of hydromorphone in breastmilk and in infants.

Informed choice of infant feeding is supported at FIR, with monitoring of infants exposed to high-dose maternal hydromorphone. It should be noted that this infant required a short amount of time in the NICU (71 hours). Neonatal intensive care unit bed capacity for infants may be a limitation. The feasibility of infant monitoring in the NICU or cardiac monitoring outside of the NICU should be further investigated.

This is the first known case of an individual breastfeeding on iOAT, reporting positive infant and maternal health and social outcomes. This case illustrates the ability to support individuals to effectively stabilize from severe IVDU, while also safely meeting the individual’s goals to bond with and breastfeed their infant. Person-centered care can be expanded to meet the goals of individuals and their families. Future research on breastfeeding while on iOAT is required to support clinical decision making and inform clinical practice guidelines.