A Population-Based Study to Quantify the Risks of Opioid Analgesics in Pregnancy - PROJECT SUMMARY
Prescription opioid use in pregnancy has increased dramatically over the past two decades. Yet, few studies
have examined the impact of opioids used for pain on adverse pregnancy outcomes. Some data suggest that
prenatal opioid analgesics may be associated with a higher risk of certain birth defects. However, evidence is
limited by discrepant study results, poor maternal recall of medication use, and small sample sizes. In addition
to these concerns, there are little data on the risk of preterm and small for gestational age birth following opioid
analgesic exposure, and stillbirth has not been studied. Evidence of the safe use of prenatal opioid analgesics
is thus inconclusive.
The primary goal of this study is to determine the risks associated with exposure to opioids for pain in
pregnancy independent of biases that have affected prior studies. We will examine several important adverse
pregnancy outcomes possibly associated with such exposure including specific birth defects, preterm birth,
small for gestational age birth, and stillbirth. The outcomes of maternal and infant opioid dependence following
prenatal opioid analgesic exposure also will be evaluated. To achieve this goal we have assembled a
population-based cohort of all pregnancies in Ontario, Canada (N≈790,000) from 2012-2017, 30,262 of which
were exposed to opioid analgesics during pregnancy. Using modern methods such as high-dimensional
propensity score adjustment and sensitivity analyses of alternative referents (including infants unexposed to
opioid analgesics and infants unexposed to opioid analgesics but prenatally exposed to other analgesics), we
will determine the associations between particular opioid analgesic exposures during the etiologically relevant
windows of gestation and these maternal and infant outcomes. This will be the first study to examine the
duration and dose of prenatal analgesic opioids on the risk of these adverse outcomes. Our population-based
cohort study will provide estimates of the absolute risk of these outcomes, which cannot be estimated from
existing US case-control studies, and which are needed to inform maternal treatment choices.
Studies of the safety of prenatal medications in extant US data such as Medicaid exclude 80% of pregnancies
(i.e., women with restricted benefits, capitated care, private insurance, or incomplete enrollment during
pregnancy) to have complete pregnancy data, which may result in selection bias or results that cannot be
generalized. Concerns of generalizability also apply to US private insurance beneficiaries. To overcome these
limitations we propose a population-based cohort study using an extant database of universal healthcare
coverage and complete prescription data for Ontario, Canada’s most populous province of 13 million. Clinical
care and characteristics of pregnant women in the US and Canada are similar, thus the results of this study will
have direct relevance for US providers and pregnant women. Better understanding of the risks of prenatal
opioid analgesics will direct treatment of pain in pregnancy and management of exposed infants.
