Pregnancy outcome following opioid exposure: A cohort study

Abstract

Introduction Opioids constitute a cornerstone of pain relief treatment. However, opioid safety during pregnancy has not been well established. Recent studies reported an association between in utero opioid exposure and spina bifida. Methods In order to further evaluate the association of opioids exposure during pregnancy with adverse pregnancy outcomes, we conducted a large historical cohort by linking four databases: medications dispensations, births, pregnancy terminations for medical reasons and infant hospitalizations during the years of 1999–2009. Confounders that were controlled for included maternal age, ethnicity, maternal diabetes, smoking status, parity, obesity, year and folic acid intake. A secondary analysis for total major malformations and for spina bifida was performed using propensity score matching for first trimester exposure. Results Of the 101,586 women included in the study, 3003 were dispensed opioids during the first trimester. Intrauterine exposure to opioids was not associated with overall major malformations (adjusted odds ratio (aOR) 0.97, 95% CI 0.83–1.13), cardiovascular malformations (aOR = 0.89, 95% CI 0.70–1.13) other malformations by systems or spina bifida in particular. However, the risk for spina bifida among newborns and abortuses who were exposed to codeine was four times higher than that of the unexposed (aOR = 4.42, 95% CI 1.60–12.23). This association remained significant in a secondary analysis using propensity score matching. Third trimester exposure to opioids was not associated with low birth weight (aOR = 1.08, 95% CI 0.77–1.52), perinatal death (aOR = 1.38, 95% CI 0.64–2.99) and other adverse pregnancy outcomes. Conclusions These findings suggest that opioids exposure (as a homogenous group) is not a significant risk factor for overall major malformations. Exposure to codeine during the first trimester was found to be associated with increased risk of spina bifida. However, this finding was based on a small number of cases and need to be verified in future work.

Prescribed opioid analgesics in early pregnancy and the risk of congenital anomalies: a population-based cohort study

“…[10][11][12][13] Recent studies with Medi caid and private insurance health data from the United States suggested small increases in minor congenital anomalies and oral cleft anomalies with prenatal exposure to opioid analgesics. 10,14 Some studies have reported an increased risk of any anomaly, 15,16 heart anomalies, 7,[16][17][18] spina bifida, 7,19,20 oral cleft anomalies, 10,15,21 gastroschisis 7 and clubfoot 16,22,23 with exposure. Other studies, however, have found no association with any anomaly, 22,24 major 10,14,19,22,24,25 or minor 14 anomalies, neural tube anom alies, 10,19,22,26 clubfoot 10 or heart anomalies.…”

“…10,14 Some studies have reported an increased risk of any anomaly, 15,16 heart anomalies, 7,[16][17][18] spina bifida, 7,19,20 oral cleft anomalies, 10,15,21 gastroschisis 7 and clubfoot 16,22,23 with exposure. Other studies, however, have found no association with any anomaly, 22,24 major 10,14,19,22,24,25 or minor 14 anomalies, neural tube anom alies, 10,19,22,26 clubfoot 10 or heart anomalies. 8,15,19,22,27,28 Discrepant findings likely arise from different methodologies, including def initions of exposure and anomalies evaluated.…”

Prevalence of prescription opioid use during pregnancy in eight US health plans during 2001–2014

“…Opioids are commonly prescribed to treat pain but use is associated with increased risks of opioid use disorder and opioid overdose. [1][2][3][4] Further, use of opioids during pregnancy has been associated with the development of congenital malformations, [5][6][7] and prolonged use with neonatal opioid withdrawal syndrome. 8,9 It is therefore important to understand the prevalence of prescription opioid use during pregnancy and trends over time.…”

Opioid use in pregnancy: An emerging health crisis

“…17,[31][32][33][34] While some have identified an increased risk of cardiac, neural tube and abdominal wall defects, 32,33 others have not. 17,34,35 A recent ecological study using data from 20 US states identified an association between areas of high maternal opioid use and an increasing prevalence of gastroschisis (a congenital anomaly of the abdominal wall). 36 From 2006 to 2015, the prevalence of gastroschisis was 1.6 times higher in areas with high opioid prescription rates compared to areas with low prescription rates.…”