Periconceptional Use of Opioids and the Risk of Neural Tube Defects

Abstract

OBJECTIVE Opioid medications are among the most effective analgesics. However, the consequences of opioid exposure to the developing human offspring are not known. We assessed whether maternal opioid use in the periconceptional period was associated with the risk of neural tube defects in the offspring. METHODS We used data from 1998 to 2010 from the Slone Epidemiology Center Birth Defects Study, an ongoing case–control study. Mothers were interviewed by telephone within 6 months of delivery about sociodemographic factors and exposures during pregnancy including detailed questions on type and timing of medication use. Mothers of 305 offsprings with neural tube defect were compared with mothers of 7,125 offsprings in the nonmalformed control group and 13,405 offsprings in the malformed control group. Periconceptional opioid use was defined as any reported use in the 2 months after the last menstrual period. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for study center. RESULTS A higher percentage of mothers of offsprings with neural tube defects (3.9%) reported using an opioid medication than mothers of offsprings in the nonmalformed control group (1.6%) and offsprings in the malformed control group (2.0%) with adjusted ORs of 2.2 (95% CI 1.2 24.2) and 1.9 (95% CI 1.0 23.4), respectively. When offsprings were restricted to those with spina bifida, the adjusted ORs were 2.5 (95% CI 1.3–5.0) and 2.2 (95% CI 1.1–4.1), respectively. CONCLUSION A 2.2-fold increase in risk would translate to a neural tube defect prevalence of 5.9 per 10,000 live births among women who use opioids. Overall, opioid use in the periconceptional period appeared to be associated with a modest increased risk of neural tube defects.

Opioid use during pregnancy: a population-based cohort study

“…Considering that opioids have been associated with neural tube defects, cardiac septal defects and the rise in neonatal hospital admissions associated with neonatal abstinence syndrome, our findings raise some concern. [9][10][11][12][13][14] A previous analysis of the overall Canadian population, for the period 2005-2010, showed a similar increase in opioid use of 13.1%. 29 US database studies have also shown increases in opioid use during pregnancy (from the mid-1990s to 2009), but the magnitude of change was generally larger than what we found, with increases in exposure ranging from 0.23-fold to 4.73-fold.…”

“…5,6,8 Although the effects of opioid use on the developing fetus are poorly understood and findings are varied, associations with complications, including neural tube defects and cardiac septal defects, have been found. [9][10][11] Neonatal abstinence syndrome, a drug-withdrawal syndrome that most commonly occurs after in utero exposure to opioids, has become one of the fastest growing reasons for neonatal hospital admissions. 11,12 Recent studies of opioid exposure in pregnancy have reported incidences of 4.3 to 5.9 cases of neonatal abstinence syndrome per 1000 births.…”

Use of tramadol in early pregnancy and congenital malformation risk

“…The latter finding contrasts to a Norwegian study [7] based on prospectively ascertained exposure information. A study from the American National Birth Defects Prevention Study [13] found an association between opioid use and a number of specific malformations but the study was retrospective with a possibility of recall bias and also had a high rate of non-responders and has therefore little informative value.…”

Complex regional pain syndrome and pregnancy

“…Broussard et al [7] case-control study found that therapeutic maternal opioid treatment within 1 month before and 3 months after conception was significantly associated with some types of congenital heart defects and, at a lower risk, other birth defects. Another study led by Yazdy et al [8] reported an increased risk of neural tube defects. In the other hand, a large population-based cohort study in Norway comparing women who had used codeine during pregnancy with those who had not found no significant association between codeine use and survival, congenital malformation or respiratory depression [9].…”