Neonatal outcomes associated with in utero exposure to oxycodone, overall and by trimester of exposure: A retrospective cohort study

Running heading: Oxycodone in pregnancy
Published:November 21, 2022DOI:


      • Prenatal oxycodone exposure was not associated with an increased risk of congenital anomalies.
      • Prenatal oxycodone exposure was associated with an increased risk of pre-term birth.
      • Prenatal oxycodone exposure was associated with an increased risk of neonatal abstinence syndrome.


      Oxycodone is commonly used by pregnant women for the treatment of pain. However, the potential risk associated with its use in pregnancy have not been robustly evaluated. The objective of this study was to examine neonatal outcomes associated with prenatal oxycodone exposure. State dispensing records were matched with midwives records to identify women who had been dispensed oxycodone during pregnancy (n=302). A matched comparison group of women who had been prescribed oxycodone prior to pregnancy was also identified (n=604). Hospital, mortality and congenital abnormality data were obtained for each mother-child dyad. Neonatal outcomes were examined for association with any exposure during pregnancy and trimester specific exposure, using generalized linear models. First trimester exposure was not associated with a significant increased risk of congenital anomalies (OR: 1.74 95%CI: 0.78, 3.87). Second trimester exposure to oxycodone was associated with reduction in average length of gestation (aCoef:-0.83, 95%CI: -1.26, -0.41) and birth weight (aCoef:-188, 95%CI: -299, -76). Second trimester exposure was also associated with an increased risk of very pre-term birth (<32 weeks) (OR: 5.03, 95%CI: 1.95, 12.98) and admission to the special care nursery (aOR:1.99, 95%CI: 1.30, 3.03). Third trimester exposure to oxycodone was associated with a reduction in average length of gestation (aCoef:-0.33, 95%CI: -0.63, -0.02) compared with the comparison group. The use of oxycodone in pregnancy was not associated with an increased risk of congenital anomalies. However, oxycodone exposure was associated with a short period of gestation, pre-term birth, and NAS, which likely contributed to a longer period of hospitalization following birth.
      Perspective: This article assesses the neonatal risks associated with prenatal exposure to oxycodone, providing clinicians and patients with important information on the safety of oxycodone in the treatment of pain in pregnancy.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • ABS
        Socio-Economic indexes for areas, ABS cat. No. 4906.0.
        Australian Bureau of Statistics, Canberra2013 (Ed)
        • AIHW
        National core maternity indicators.
        Australian Institute of Health and Welfare, 2020
        • Anda EE
        • Nieboer E
        • Wilsgaard T
        • Kovalenko AA
        • Odland JØ.
        Perinatal mortality in relation to birthweight and gestational age: a registry-based comparison of Northern Norway and Murmansk County.
        Russia. Paediatric and Perinatal Epidemiology. 2011; 25: 218-227
        • Aziz K
        • Chadwick M
        • Baker M
        • Andrews W
        Ante- and intra-partum factors that predict increased need for neonatal resuscitation.
        Resuscitation. 2008; 79: 444-452
        • Bateman BT
        • Hernandez-Diaz S
        • Rathmell JP
        • Seeger JD
        • Doherty M
        • Fischer MA
        • Huybrechts KF.
        Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States.
        Anesthesiology. 2014; 120: 1216-1224
        • Bateman BT
        • Hernandez-Diaz S
        • Straub L
        • Zhu Y
        • Gray KJ
        • Desai RJ
        • Mogun H
        • Gautam N
        • Huybrechts KF.
        Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study.
        BMJ. 2021; 372 (n): 102
        • Berazategui JP
        • Aguilar A
        • Escobedo M
        • Dannaway D
        • Guinsburg R
        • de Almeida MFB
        • Saker F
        • Fernández A
        • Albornoz G
        • Valera M
        • Amado D
        • Puig G
        • Althabe F
        • Szyld E
        Risk factors for advanced resuscitation in term and near-term infants: a case–control study.
        Archives of Disease in Childhood - Fetal and Neonatal Edition. 2017; 102: F44-F50
        • Blair EM
        • Liu Y
        • de Klerk NH
        • Lawrence DM.
        Optimal fetal growth for the Caucasian singleton and assessment of appropriateness of fetal growth: an analysis of a total population perinatal database.
        BMC Pediatr. 2005; 5: 13
        • Bower C
        • Rudy E
        • Callaghan A
        • Quick J
        • Nassar N
        Age at diagnosis of birth defects.
        Birth Defects Res A Clin Mol Teratol. 2010; 88: 251-255
        • Bowie AC
        • Werler MM
        • Velez MP
        • Li W
        • Camden A
        • Guttmann A
        • Brogly SB.
        Prescribed opioid analgesics in early pregnancy and the risk of congenital anomalies: a population-based cohort study.
        Canadian Medical Association Journal. 2022; 194: E152-E162
        • Broussard CS
        • Rasmussen SA
        • Reefhuis J
        • Friedman JM
        • Jann MW
        • Riehle-Colarusso T
        • Honein MA.
        Maternal treatment with opioid analgesics and risk for birth defects.
        Am J Obstet Gynecol. 2011; 204 (.e311-314.e311): 314
        • Caissie N
        • Héroux J
        • Lefebvre M
        • Lamarche D
        • Dubois M-C
        • Rivard G
        • D'Aragon F
        Opioids for Cesarean delivery under general anesthesia and neonatal outcome: a historical cohort study.
        Canadian Journal of Anesthesia/Journal canadien d'anesthésie. 2022; 69: 1017-1024
        • Dave CV
        • Goodin A
        • Zhu Y
        • Winterstein A
        • Wang X
        • Alrwisan A
        • Hartzema A.
        Prevalence of maternal-risk factors related to neonatal abstinence syndrome in a commercial claims database: 2011-2015.
        Pharmacotherapy. 2019; 39: 1005-1011
        • Desai RJ
        • Hernandez-Diaz S
        • Bateman BT
        • Huybrechts KF.
        Increase in prescription opioid use during pregnancy among Medicaid-enrolled women.
        Obstet and Gynecol. 2014; 123: 997-1002
        • Elliott TE
        • Frail CK
        • Pawloski PA
        • Thomas AJ
        • Werner AM
        • Rossom RC.
        Opioid use during pregnancy, observations of opioid use, and secular trend from 2006 to 2014 at HealthPartners medical group.
        Clin J Pain. 2018; 34: 707-712
        • Holman CDAJ
        • Bass AJ
        • Rouse IL
        • Hobbs MST.
        Population-based linkage of health records in Western Australia: development of a health services research linked database.
        Australian and New Zealand Journal of Public Health. 1999; 23: 453-459
        • Kelly L
        • Dooley J
        • Cromarty H
        • Minty B
        • Morgan A
        • Madden S
        • Hopman W.
        Narcotic-exposed neonates in a First Nations population in northwestern Ontario: incidence and implications.
        Can Fam Physician. 2011; 57: e441-e447
        • Kelly L
        • Guilfoyle J
        • Dooley J
        • Antone I
        • Gerber-Finn L
        • Dooley R
        • Brunton N
        • Kakegamuck K
        • Muileboom J
        • Hopman W
        • Cromarty H
        • Linkewich B
        • Maki J
        Incidence of narcotic abuse during pregnancy in northwestern Ontario: three-year prospective cohort study.
        Can Fam Physician. 2014; 60: e493-e498
        • Kelty E
        • Hulse G.
        A retrospective cohort study of birth outcomes in neonates exposed to naltrexone in utero: a comparison with methadone-, buprenorphine- and non-opioid-exposed neonates.
        Drugs. 2017; 77: 1211-1219
        • Kelty EA
        • Cumming CN
        • Preen DB.
        Contribution of pharmaceutical drugs of dependence to the incidence of neonatal abstinence syndrome in Western Australia between 2003 and 2018.
        Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2022; 42: 405-410
        • Lynch MM
        • Squiers LB
        • Kosa KM
        • Dolina S
        • Read JG
        • Broussard CS
        • Frey MT
        • Polen KN
        • Lind JN
        • Gilboa SM
        • Biermann J.
        Making Decisions About Medication Use During Pregnancy: Implications for Communication Strategies.
        Matern Child Health J. 2018; 22: 92-100
        • Mogren IM
        • Pohjanen AI.
        Low back pain and pelvic pain during pregnancy: prevalence and risk factors.
        Spine. 2005; 30: 983-991
        • Nechuta S
        • Mukhopadhyay S
        • Golladay M
        • Rainey J
        • Krishnaswami S.
        Trends, patterns, and maternal characteristics of opioid prescribing during pregnancy in a large population-based cohort study.
        Drug and Alcohol Dependence. 2022; 233109331
        • Nezvalová-Henriksen K
        • Spigset O
        • Nordeng H.
        Effects of codeine on pregnancy outcome: results from a large population-based cohort study.
        European Journal of Clinical Pharmacology. 2011; 67: 1253-1261
        • NHMRC
        The National Statement on Ethical Conduct in Human Research.
        National Health and Medical Research Council, Canberra2007
        • Picchietti DL
        • Hensley JG
        • Bainbridge JL
        • Lee KA
        • Manconi M
        • McGregor JA
        • Silver RM
        • Trenkwalder C
        • Walters AS.
        Consensus clinical practice guidelines for the diagnosis and treatment of restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation.
        Sleep Med Rev. 2015; 22: 64-77
        • Rementería JL
        • Bhatt K.
        Withdrawal symptoms in neonates from intrauterine exposure to diazepam.
        J Pediatr. 1977; 90: 123-126
        • Sanz EJ
        • De-las-Cuevas C
        • Kiuru A
        • Bate A
        • Edwards R.
        Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis.
        The Lancet. 2005; 365: 482-487
        • Sujan AC
        • Quinn PD
        • Rickert ME
        • Wiggs KK
        • Larsson H
        • Lichtenstein P
        • Öberg AS
        • D'Onofrio BM
        A nation-wide Swedish study of opioid analgesic prescribing patterns during pregnancy and associated preexisting mental health conditions.
        The Journal of Maternal-Fetal & Neonatal Medicine. 2021; : 1-7
        • Wachman EM.
        How might maternal poverty impact the course of neonatal opioid withdrawal syndrome?.
        J Addict Med. 2020; 14: 93-94
        • Wang SM
        • Dezinno P
        • Maranets I
        • Berman MR
        • Caldwell-Andrews AA
        • Kain ZN.
        Low back pain during pregnancy: prevalence, risk factors, and outcomes.
        Obstet Gynecol. 2004; 104: 65-70
        • Wen X
        • Belviso N
        • Lebeau R
        • Bratberg J
        • Cotton B
        • Ward K
        • Erickson-Owens D
        • Kogut S.
        Prescription opioid use among pregnant women enrolled in Rhode Island medicaid.
        R I Med J. 2019; 102: 35-40
        • Wen X
        • Belviso N
        • Murray E
        • Lewkowitz AK
        • Ward KE
        • Meador KJ.
        Association of gestational opioid exposure and risk of major and minor congenital malformations.
        JAMA Network Open. 2021; 4 (-e215708)e215708
        • Wu WH
        • Meijer OG
        • Uegaki K
        • Mens JM
        • van Dieen JH
        • Wuisman PI
        • Ostgaard HC.
        Pregnancy-related pelvic girdle pain (PPP), I: Terminology, clinical presentation, and prevalence.
        Eur Spine J. 2004; 13: 575-589
        • Zhao J-P
        • Berthod C
        • Sheehy O
        • Kassaï B
        • Gorgui J
        • Bérard A.
        Prevalence and duration of prescribed opioid use during pregnancy: a cohort study from the Quebec Pregnancy Cohort.
        BMC Pregnancy and Childbirth. 2021; 21: 800