Buprenorphine versus Methadone for Opioid Use Disorder in Pregnancy

Suarez, Elizabeth A.; Huybrechts, Krista F.; Straub, Loreen; Hernández–Dı́az, Sonia; Jones, Hendrée E.; Connery, Hilary S.; Davis, Jonathan M.; Gray, Kathryn J.; Lester, Barry M.; Terplan, Mishka; Mogun, Helen; Bateman, Brian T.

doi:10.1056/nejmoa2203318

Cited by 48 publications

(32 citation statements)

References 31 publications

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“…It is uncertain if pyloric stenosis is congenital or acquired, and suggested risk factors include preterm birth, cesarean delivery, male sex, maternal smoking, bottle feeding, and macrolide antibiotic exposure in the neonatal period. [22][23][24][25] These risk factors are not likely explanations for the association we observed; the risk of preterm birth is increased with methadone exposure, 3 and between-group differences in other risk factors are not expected. While the majority of pyloric stenosis cases were in male infants, the increase in risk with buprenorphine compared with methadone was sustained in both male and female infants.…”

Section: Discussionmentioning

confidence: 88%

“…We also explored the possibility that there may be increased monitoring in the neonatal period in patients treated with methadone due to increased risk of neonatal abstinence syndrome compared with buprenorphine. [3][4][5]19 However, the median days from delivery to diagnosis did not differ meaningfully between buprenorphine-and methadone-exposed infants, suggesting that detection bias does not explain these results. Such detection bias also would not apply to malformations immediately apparent at birth, including oral clefts, clubfoot, and limb malformations.…”

Section: Discussionmentioning

confidence: 88%

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First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations

Suarez,

Bateman,

Straub

et al. 2024

JAMA Intern Med

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ImportanceUse of buprenorphine or methadone to treat opioid use disorder is recommended in pregnancy; however, their teratogenic potential is largely unknown.ObjectiveTo compare the risk of congenital malformations following in utero exposure to buprenorphine vs methadone.Design, Setting, and ParticipantsThis population-based cohort study used health care utilization data from publicly insured Medicaid beneficiaries in the US from 2000 to 2018. A total of 13 360 pregnancies with enrollment from 90 days prior to pregnancy start through 1 month after delivery and first trimester use of buprenorphine or methadone were included and linked to infants. Data were analyzed from July to December 2022.ExposureA pharmacy dispensing of buprenorphine or a code for administration of methadone in the first trimester.Main Outcomes and MeasuresPrimary outcomes included major malformations overall and malformations previously associated with opioids (any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, clubfoot, and oral clefts). Secondary outcomes included other organ system–specific malformations. Risk differences and risk ratios (RRs) were estimated comparing buprenorphine with methadone, adjusting for confounders with propensity score overlap weights.ResultsThe cohort included 9514 pregnancies with first-trimester buprenorphine exposure (mean [SD] maternal age, 28.4 [4.6] years) and 3846 with methadone exposure (mean [SD] maternal age, 28.8 [4.7] years). The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone. After confounding adjustment, buprenorphine was associated with a lower risk of malformations compared with methadone (RR, 0.82; 95% CI, 0.69-0.97). Risk was lower with buprenorphine for cardiac malformations (RR, 0.63; 95% CI, 0.47-0.85), including both ventricular septal defect (RR, 0.62; 95% CI, 0.39-0.98) and secundum atrial septal defect/nonprematurity-related patent foramen ovale (RR, 0.54; 95% CI, 0.30-0.97), oral clefts (RR, 0.65; 95% CI, 0.35-1.19), and clubfoot (RR, 0.55; 95% CI, 0.32-0.94). Results for neural tube defects were uncertain given low event counts. In secondary analyses, buprenorphine was associated with a decreased risk of central nervous system, urinary, and limb malformations but a greater risk of gastrointestinal malformations compared with methadone. These findings were consistent in sensitivity and bias analyses.Conclusions and RelevanceIn this cohort study, the risk of most malformations previously associated with opioid exposure was lower in buprenorphine-exposed infants compared with methadone-exposed infants, independent of measured confounders. Malformation risk is one factor that informs the individualized patient decision regarding medications for opioid use disorder in pregnancy.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 88%

First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations

Suarez,

Bateman,

Straub

et al. 2024

JAMA Intern Med

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“…This percent linkage is lower than percentages reported in other infant‐linked data, though methods used to calculate linkage percentages vary with respect to numerator and denominator inclusion as well as percentage calculation before versus after application of study‐specific inclusion and exclusion criteria (Table 5). 5,12–14 …”

Section: Discussionmentioning

confidence: 99%

Characteristics and outcomes of pregnancies in the Maternal Outcomes Masterset real‐world database

Gibbs,

Ali,

Albright

et al. 2023

Pharmacoepidemiology and Drug

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PurposeDescribe patient characteristics and pregnancy outcomes among all pregnant patients, and additionally describe infant outcomes among the subset with linked infants in the Maternal Outcomes Masterset (MOM).MethodsWe used closed claims within the MOM data to identify publicly and privately insured patients at the first record of pregnancy January 1, 2018–December 1, 2021, with ≥180 days baseline enrollment. We described characteristics during baseline and follow‐up (until an observed pregnancy endpoint, disenrollment, or 42‐week maximum). We described maternal and infant characteristics overall and by infant linkage and contextualized them within national statistics.ResultsAmong the 1 438 861 pregnant patients meeting the study criteria, the most common pregnancy endpoint recorded was live birth (42%) followed by spontaneous abortion (14%). Among 602 721 patients with a live birth, 99% had a week‐specific gestational age recorded and 35% had at least one linked infant. Patients with infant linkage and sufficient follow‐up (N = 155 621) had similar baseline comorbidities, pregnancy complications, and gestational age at delivery as those without any linkage. However, more patients with linkage had commercial coverage (70% vs. 31%), and were therefore older (50% vs. 31% aged ≥30 years) and more likely to have an unknown race (57% vs. 34%).ConclusionsIn this large sample of pregnant patients, maternal and infant characteristics generally align with national statistics, providing confidence in the use of this data source for pregnancy research. Further, confirmation that the subset of patients with infant linkage is similar to the overall pregnancy cohort provides assurance that this subset can be considered representative.

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“…A meta-analysis assessing 16 cohort studies and four randomized control trials demonstrated higher birth weight and body length, reduced prematurity, and lower risk of adverse events for birthing people in buprenorphine-exposed pregnancies relative to methadone, but also demonstrated higher dropout with buprenorphine [46]. A subsequent large cohort study of public insurance data demonstrated lower rates of NOWS, preterm birth, small for gestational age, and low birthweight in neonates exposed to buprenorphine, with no difference in cesarean deliveries or morbidity for the birthing person [47].…”

Section: First-line Agent Selectionmentioning

confidence: 95%

Pharmacotherapy for opioid use disorder in pregnancy

Trammel,

Whitley,

Kelly

2024

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of review Opioid use disorder (OUD) in pregnancy has significantly in the last decade, impacting 8.2 per 1000 deliveries. OUD carries significant risk of morbidity and mortality for both the birthing person and neonate, but outcomes for both are improved with opioid agonist treatment (OAT). Here, we describe the recommended forms of OAT in pregnancy, updates to the literature, and alternate OAT strategies, and share practical peripartum considerations for patients on OAT. Recent findings Recent studies comparing buprenorphine and methadone have reaffirmed previous findings that buprenorphine is associated with superior outcomes for the neonate, without clear differences in morbidity or mortality for the birthing person. Optimal initiation and dosing of OAT remains unclear, with several recent studies evaluating methods of initiation, as well as a potential role for higher and more rapid dosing in the fentanyl era. Alternative products such as buprenorphine-naloxone and extended-release buprenorphine are of significant research interest, though randomized prospective data are not yet available. Summary Buprenorphine and methadone are standard of care for treatment of OUD during pregnancy, and multiple patient factors impact the optimal choice. Insufficient data exist to recommend alternative agents as a primary strategy currently. All patients with OUD in pregnancy should be counseled regarding OAT. Video http://links.lww.com/COOG/A94

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Buprenorphine versus Methadone for Opioid Use Disorder in Pregnancy

Cited by 48 publications

References 31 publications

First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations

First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations

Characteristics and outcomes of pregnancies in the Maternal Outcomes Masterset real‐world database

Pharmacotherapy for opioid use disorder in pregnancy

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