A population‐based study of concurrent prescriptions of opioid analgesic and selective serotonin reuptake inhibitor medications during pregnancy and risk for adverse birth outcomes

Abstract

Background Pregnant women with painful conditions often have mental health problems, including depression and anxiety. Co‐morbid conditions may cause pregnant women to use multiple medications, although safety of such practice is poorly understood. Objectives We investigated the influence of combined prescriptions of opioid analgesics and selective serotonin reuptake inhibitors (SSRIs) during pregnancy on two adverse birth outcomes. Methods We analysed Swedish population‐based births (n = 688 914) between 2007 and 2013. Using national registers, we obtained data on filled medication prescriptions, birth outcomes, and a wide range of parental characteristics. We estimated preterm birth and small‐for‐gestational‐age risk following independent or combined prescriptions of the two medications compared with no filled prescriptions for either medication. We adjusted for confounders using inverse probability of treatment weights. Results After adjusting for confounders, preterm birth risk was higher among women with opioid analgesic prescriptions only (5.9%; risk ratio [RR] 1.27, 95% confidence interval [CI] 1.22, 1.33), SSRIs only (6.2%; RR 1.34, 95% CI 1.27, 1.42), and both medications (7.8%; RR 1.70, 95% CI 1.47, 1.96) compared with unexposed women (4.6%). The interaction between the medications on preterm birth was small (risk difference [RD] 0.4%, 95% CI −0.8%, 1.6%); relative excess risk due to interaction [RERI] 0.09, 95% CI −0.17, 0.34; RR 1.00, 95% CI 0.85, 1.17). For small for gestational age, risk was approximately 2% across all groups, and there was no interaction between the medications (RD 0.3%, 95% CI −0.4%, 1.1%); RERI 0.15, 95% CI −0.16, 0.47; RR 1.15, 95% CI 0.87, 1.52). Conclusions Compared with unexposed pregnancies, those with either medication alone had a small increased risk for preterm birth but no increased risk for small for gestational age. The magnitude of associations with combined exposure to both medications were not greater than the sum of the associations with each medication considered individually.

Patterns of Substance Use During Early Pregnancy and Associations With Behavioral Health Characteristics

“…These findings are consistent with and expand on previous research showing that mental health conditions are associated with increased risk of use of specific substances 4,13 and specific combinations of substances during pregnancy. 11,14 Our findings have important clinical implications. First, it is important for clinicians to recognize that the vast majority of women who used substances during early pregnancy fell into the clusters that included individuals who predominantly used only alcohol or only cannabis early in pregnancy.…”

“…12 Research with pregnant individuals has also shown that mental health symptoms predict increased risk of use of specific substances 4,13 and specific combinations of substances. 11,14 However, empirical data on what specific substances are used in combination among pregnant individuals are lacking. These data are needed to better tailor prenatal substance use interventions to meet the unique needs of pregnant individuals with distinct patterns of substance use.…”

“…Research with pregnant individuals has also shown that mental health symptoms predict increased risk of use of specific substances 4,13 and specific combinations of substances 11,14 . However, empirical data on what specific substances are used in combination among pregnant individuals are lacking.…”

Prescription opioid use in Australian women of reproductive age: Implications for unplanned pregnancies

“…The short‐ and long‐term consequences of in utero opioid exposure on maternal and foetal health and development remain ill‐defined due to the systematic exclusion of pregnant women from clinical trials 19 . While postmarket observational studies have linked opioid use during pregnancy with congenital malformations in infants 15,16,20–26 and adverse obstetric 17,23,27,28 and neonatal outcomes, 17,23,29–32 uncertainty remains as to whether these associations represent causal relationships.…”

“…Observational studies have reported associations between first trimester prescription opioid exposure and congenital malformations in infants such as oral clefts 15,16,20–26 . Adverse perinatal outcomes such as placenta‐mediated pregnancy complications and neonates born small for gestational age 15,17,23,27,29,32 have been observed following use of prescription opioids anytime during pregnancy. While the existing research has largely focused on assessing opioids as a class, there is some evidence to suggest that individual opioids, such as codeine (alone or in combination), oxycodone and tramadol, confer specific risks of harm 15,22,23,33,34 …”