Prenatal Opioid Analgesics and the Risk of Adverse Birth Outcomes

Abstract

Background: It is unclear whether confounding accounts for the increased risk of preterm birth and small for gestational age (SGA) birth in opioid analgesic exposed pregnancies. Methods: Using universal coverage health data for Ontario, we assembled a cohort of mother-infant pairs without opioid use disorder (627,172 pregnancies and 509,522 women). We estimated risk ratios (RRs) between opioid analgesics and preterm birth, SGA birth, and stillbirth; neonatal abstinence syndrome was a secondary outcome. We used high-dimensional propensity scores and sensitivity analyses for confounding adjustment. Results: 4% of pairs were exposed, mainly to codeine (2%), morphine (1%), and oxycodone (1%). Compared with unexposed, the adjusted risk of preterm birth was higher with any (1.3, 95% confidence interval [CI] = 1.2, 1.3), first-(RR: 1.2, 95% CI = 1.2, 1.3), and second-trimester (RR: 1.3, 95% CI = 1.2, 1.4) opioid analgesic exposure. Preterm birth risk was higher for first-and second-trimester codeine, morphine, and oxycodone exposure, and for third-trimester morphine. There was a small increase in SGA with first-trimester exposure to any opioid analgesic or to codeine. Exposed pregnancies had an elevated stillbirth risk with any (RR: 1.6, 95% CI = 1.4, 1.8), first-and second-trimester exposure. Few infants had neonatal abstinence syndrome (N = 143); the risk was higher in exposed (RR: 3.6, 95% CI = 2.1, 6.0). In sensitivity analyses of unmeasured confounding, an elevated risk in exposed pregnancies persisted for preterm birth but not SGA. Conclusions: Opioid analgesic-exposed pregnancies had a small increased risk of preterm birth and possibly stillbirth after accounting for confounding by indication and sociodemographic factors.

Reviewing the Evidence on Prenatal Opioid Exposure to Inform Child Development Policy and Practice

“…Many have a history of severe mental illness and non-opioid substance use. Women using opioids for pain are less likely to have the same degree of socio-economic disadvantages than those on OAT, but are still at a higher risk than the general population (Camden et al 2021). Using data from both Ontario and England, UK, we have shown that 1 in 20 mothers of infants with NAS die within 10 years of delivery, which represents greater than a 10-fold increased risk compared with other mothers (Guttmann et al 2019).…”

“…Opioid use in pregnancy -including therapeutic use for pain management, treatment of opioid use disorder (OUD) and non-medical use of illegally obtained opioidshas increased dramatically over the past two decades in North America (Brogly et al 2017;Haight et al 2018). Approximately 1 in 20 (5.3%) infants born in Ontario have prenatal opioid exposure (POE), with higher rates in those whose mothers are younger and from low-income neighbourhoods or rural areas (Camden et al 2021). High rates (30%) have been documented in First Nations communities in Northwest Ontario (Dooley et al 2018).…”

“…After two decades of steady increases, POE has decreased from 6.1% in 2014 to 4.5% in 2019 in Ontario, representing approximately 5,100 births in 2019 (Figure 1) (Camden et al 2021). Declining rates were largely due to decreases in the use of opioids for pain, while rates of opioid agonist therapy (OAT) for treatment of OUD and opioid-related harm during pregnancy remained stable during this period (Camden et al 2021). The Sioux Lookout Meno Ya Win Health Centre provides a specialized integrated pregnancy program including opioid addiction treatment for a number of First Nations communities in northwestern Ontario.…”

“…Many of these socio-demographic and mental health characteristics of mothers who use opioids in pregnancy drive mother-child separation at birth through infant apprehension by social services. In Ontario, infant discharge to social services at birth ranges from 1% among women with prenatal opioid analgesic use to 17% among women using illegally obtained opioids in pregnancy (Camden et al 2021). Understanding the different contexts of opioid use has important implications for strategies to address both maternal well-being and child health and development.…”

“…Previous research has shown that compared with unexposed infants, infants with POE and NAS have an increased risk of low birth weight (Lisonkova et al 2019;Nørgaard et al 2015), preterm birth (birth before 37 weeks) (Alemu et al 2020;Brogly et al 2021;Corsi et al 2020;Maeda et al 2014) and stillbirth (Alemu et al 2020;Maeda et al 2014); and have poor fetal growth (Alemu et al 2020;Maeda et al 2014). The teratogenic effects of POE are still not well understood.…”