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Periconceptional Use of Opioids and the Risk of Neural Tube Defects

Yazdy, Mahsa M. PhD; Mitchell, Allen A. MD; Tinker, Sarah C. PhD; Parker, Samantha E. MSPH; Werler, Martha M. ScD

doi: 10.1097/AOG.0b013e3182a6643c
Original Research

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.


Opioids used in the periconceptional period may increase the risk of neural tube defects.

Slone Epidemiology Center at Boston University, Boston, Massachusetts; and the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.

Corresponding author: Mahsa M. Yazdy, PhD, Slone Epidemiology Center, 1010 Commonwealth Avenue, Boston, MA 02215; e-mail:

Supported by the Centers for Disease Control and Prevention (DD000697).

The authors thank Dawn Jacobs, RN, MPH, Fiona Rice, MPH, Rita Krolak, RN, Kathleen Sheehan, RN, Moira Quinn, RN, Clare Coughlin, RN, Laurie Cincotta, RN, Mary Thibeault, RN, Nancy Rodriquez-Sheridan, Ileana Gatica, Laine Catlin Fletcher, Carolina Meyers, Joan Shander, Julia Venanzi, Mark Abcede, and Judy Jean, RN, for their assistance in data collection; Katherine Kelley, RPh, for assistance in classifying of medications; and Nastia Dynkin for computer programming.

Presented as a poster at the 7th International Conference on Neural Tube Defects, November 6–9, 2011, Austin, Texas.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Financial Disclosure Dr. Werler is on advisory boards of manufacturer-sponsored studies that evaluate pregnancy outcomes among women treated with medications for rheumatoid arthritis. Dr. Mitchell owned stock (until August 2012) in Johnson & Johnson, which markets various analgesics; he also serves on the advisory committee of the Biogen-Idec, Tysabri Pregnancy Registry. The other authors did not report any potential conflicts of interest.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.