Drug used to arrest preterm labor sensitizes the brain to neurotoxicants.

Rhodes MC, Seidler FJ, Qiao D, Tate CA, Cousins MM, Slotkin TA. 2004. Does pharmacotherapy for preterm labor sensitize the developing brain to environmental neurotoxicants? Cellular and synaptic effects of sequential exposure to terbutaline and chlorpyrifos in neonatal rats. Toxicol Appl Pharmacol 195:203-217.

A growing body of evidence suggests that exposure to environmental toxicants in utero or very early after birth can have life-long effects. This phenomenon is referred to as the fetal basis of adult disease. Hypertension, diabetes mellitus, asthma, and cardiovascular diseases are but a few of the illnesses that have been suggested as possible effects from early-life exposures, Recently, NIEHS grantee Theodore A. Slotkin of Duke University Medical Center and his colleagues investigated how separate and combined exposures to terbutaline, a drug used to arrest preterm labor, and to the organophosphate pesticide chlorpyrifos affect several indices of brain cell growth and function.

Premature labor occurs in approximately 20% of all U.S, pregnancies, with preterm delivery--a leading cause of neonatal morbidity and mortality--occurring in nearly half these cases. Drugs to arrest preterm labor, particularly terbutaline, are used in as many as 1 million pregnancies annually. Chlorpyrifos, a known developmental neurotoxicant, is used worldwide.

Rat pups were given terbutaline on days 2-5 after birth, followed by chlorpyrifos on days 11-14. Neither treatment affected the growth or viability of the young rats; however, both elicited alterations in brain cell differentiation and cholinergic innervation at day 15, persisting into adulthood at day 60. Biomarkers of brain cell number, cell size, and neuritic projections were affected by both agents alone. However, the combined exposure produced more severe effects by both additive and synergistic mechanisms.

These findings suggest that terbutaline, like chlorpyrifos, is a developmental neurotoxicant. The authors conclude that the use of terbutaline to prevent preterm labor may be creating a subpopulation that is more sensitive to the adverse neural effects of organophosphate pesticides. Further studies are needed to repeat these findings, but if the results are confirmed, use of these compounds may warrant additional scrutiny.