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A Prospective Controlled Study

Sohail Khattak, MD, FRCPC ; Guiti K-Moghtader, BSc; Kristen McMartin, MSc; Maru Barrera, PhD; Debbie Kennedy, MD; Gideon Koren, MD, FRCPC

JAMA. 1999;281:1106-1109.

Context  Numerous women of childbearing age are exposed occupationally to organic solvents. Previous retrospective studies have reported conflicting results regarding teratogenic risk.

Objective  To evaluate pregnancy and fetal outcome following maternal occupational exposure to organic solvents.

Design  A prospective, observational, controlled study.

Setting  An antenatal counseling service in Toronto, Ontario.

Patients  One hundred twenty-five pregnant women who were exposed occupationally to organic solvents and seen during the first trimester between 1987 and 1996. Each pregnant woman who was exposed to organic solvents was matched to a pregnant woman who was exposed to a nonteratogenic agent on age (±4 years), gravidity (±1), and smoking and drinking status.

Main Outcome Measure  Occurrence of major congenital malformations.

Results  Significantly more major malformations occurred among fetuses of women exposed to organic solvents than controls (13 vs 1; relative risk, 13.0; 95% confidence interval, 1.8-99.5). Twelve malformations occurred among the 75 women who had symptoms temporally associated with their exposure, while none occurred among 43 asymptomatic exposed women (P<.001). (One malformation occurred in a woman for whom such information was missing.) More of these exposed women had previous miscarriage while working with organic solvents than controls (54/117 [46.2%] vs 24/125 [19.2%]; P<.001). However, exposed women who had a previous miscarriage had rates of major malformation that were similar to exposed women who had no previous miscarriage.

Conclusions  Occupational exposure to organic solvents during pregnancy is associated with an increased risk of major fetal malformations. This risk appears to be increased among women who report symptoms associated with organic solvent exposure. Women's exposure to organic solvents should be minimized during pregnancy. Symptomatic exposure appears to predict higher fetal risk for malformations.

Author Affiliations: The Motherisk Program, Division of Clinical Pharmacology and Toxicology (Drs Khattak, Kennedy, and Koren, Mr Moghtader, and Ms McMartin), and the Department of Psychology (Dr Barrera), The Hospital for Sick Children, and the University of Toronto, Toronto, Ontario.

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