Association Between Stillbirth and Illicit Drug Use and Smoking During Pregnancy

Varner, Michael W. MD; Silver, Robert M. MD; Rowland Hogue, Carol J. PhD; Willinger, Marian PhD; Parker, Corette B. DrPH; Thorsten, Vanessa R. MPH; Goldenberg, Robert L. MD; Saade, George R. MD; Dudley, Donald J. MD; Coustan, Donald MD; Stoll, Barbara MD; Bukowski, Radek MD; Koch, Matthew A. MD, PhD; Conway, Deborah MD; Pinar, Halit MD; Reddy, Uma M. MD, MPH; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network

doi: 10.1097/AOG.0000000000000052
Contents: Original Research

OBJECTIVE: To compare illicit drug and smoking use in pregnancies with and without stillbirth.

METHODS: The Stillbirth Collaborative Research Network conducted a case–control study from March 2006 to September 2008, covering more than 90% of deliveries to residents of five a priori–defined geographically diverse regions. The study attempted to include all stillbirths and representative liveborn controls. Umbilical cord samples from cases and controls were collected and frozen for subsequent batch analysis. Maternal serum was collected at delivery and batch analyzed for cotinine.

RESULTS: For 663 stillbirth deliveries, 418 (63%) had cord homogenate and 579 (87%) had maternal cotinine assays performed. For 1,932 live birth deliveries, 1,050 (54%) had cord homogenate toxicology and 1,545 (80%) had maternal cotinine assays performed. A positive cord homogenate test for any illicit drug was associated with stillbirth (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.16–3.27). The most common individual drug was cannabis (OR 2.34 95% CI 1.13–4.81), although the effect was partially confounded by smoking. Both maternal self-reported smoking history and maternal serum cotinine levels were associated in a dose–response relationship with stillbirth. Positive serum cotinine less than 3 ng/mL and no reported history of smoking (proxy for passive smoke exposure) also were associated with stillbirth (OR 2.06, 95% CI 1.24–3.41).

CONCLUSION: Cannabis use, smoking, illicit drug use, and apparent exposure to second-hand smoke, separately or in combination, during pregnancy were associated with an increased risk of stillbirth. Because cannabis use may be increasing with increased legalization, the relevance of these findings may increase as well.

LEVEL OF EVIDENCE: II

Cannabis use, smoking, illicit drug use, and apparent exposure to second-hand smoke, separately or in combination, during pregnancy are associated with an increased risk of stillbirth.

*For a list of other members of the Stillbirth Collaborative Research Network, see the Appendix online at http://links.lww.com/AOG/A455.

University of Utah School of Medicine, Salt Lake City, Utah; Rollins School of Public Health, Emory University, and Emory University School of Medicine, Atlanta, Georgia; the Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; RTI International, Research Triangle Park, North Carolina; Columbia University, New York, New York; the University of Texas Medical Branch at Galveston, Galveston, and the University of Texas Health Science Center at San Antonio, San Antonio, Texas; and Brown University School of Medicine, Providence, Rhode Island.

Corresponding author: Michael W. Varner, MD, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, 30 North 1900 East, Room 2B200, Salt Lake City, UT 84132; e-mail: Michael.varner@hsc.utah.edu.

Supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health: U10-HD045953 (Brown University, Providence, Rhode Island); U10-HD045925 (Emory University, Atlanta, Georgia); U10-HD045952 (University of Texas Medical Branch at Galveston, Galveston, Texas); U10-HDO45955 (University of Texas Health Sciences Center at San Antonio, San Antonio, Texas); U10-HD045944 (University of Utah Health Sciences Center, Salt Lake City, Utah); and U01-HD045954 (RTI International, Research Triangle Park, North Carolina).

The authors thank the following members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Scientific Advisory and Safety Monitoring Board for their review of the study protocol, materials, and progress: Reverend Phillip Cato, PhD; James W. Collins, Jr, MD, MPH; Terry Dwyer, MD, MPH; William P. Fifer, PhD; John Ilekis, PhD; Marc Incerpi, MD; George Macones, MD, MSCE; Richard M. Pauli, MD, PhD; Raymond W. Redline, MD; Elizabeth Thom, PhD (chair) as well as all of the other physicians, study coordinators, research nurses, and patients who participated in the Stillbirth Collaborative Research Network.

Presented in part at the 2011 Society for Maternal-Fetal Medicine annual meeting, February 10–12, 2011, San Francisco, California.

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2014 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.