Association between stillbirth and illicit drug use and smoking during pregnancy

Abstract

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.

Figure 1

Cotinine and toxicology analyses comparing results from stillbirth and live birth pregnancies. The Stillbirth Collaborative Research Network stillbirth case status (SCRN case status) is defined as follows. A pregnancy is categorized as a stillbirth pregnancy if there are any stillbirths delivered and as a live birth pregnancy if all live births are delivered. A fetal death is defined by Apgar scores of 0 at 1–5 minutes and no signs of life by direct observation. Fetal deaths are classified as stillbirths if the best clinical estimate of gestational age at death is 20 or more weeks. Fetal deaths at 18–19 weeks without good dating are also included as stillbirths.