Periconceptional use of opioids and the risk of neural tube defects

Obstet Gynecol. 2013 Oct;122(4):838-844. doi: 10.1097/AOG.0b013e3182a6643c.


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 -4.2) and 1.9 (95% CI 1.0 -3.4), 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.

Level of evidence: : II.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analgesics, Opioid / adverse effects*
  • Case-Control Studies
  • Female
  • Fertilization
  • Fetal Development
  • Humans
  • Logistic Models
  • Neural Tube Defects / chemically induced*
  • Pregnancy
  • Young Adult


  • Analgesics, Opioid