Intrauterine growth retardation after long-term maternal salicylate administration in the rabbit

The effects of chronic maternal salicylism on fetal growth were studied in chronically catheterized pregnant rabbits. Graded intravenous infusions of sodium salicylate were given continuously between days 22 and 29 of gestation. Maternal plasma salicylate concentrations (mean +/- SD) of 12.0 +/- 1.6 mg/dl (low-dose group) or 24.1 +/- 5.3 mg/dl (high-dose group) were achieved. Control rabbits were infused with saline solution. Pups were delivered by hysterotomy on day 29. Fetal/maternal salicylate concentration ratios were near unity for both infusion groups. There were significant dose-related reductions (mean +/- SD) in fetal weight (control, 39.7 +/- 6.7 gm; low-dose group, 34.4 +/- 6.4 gm; high-dose group, 22.2 +/- 7.1 gm; p less than 0.001) and in crown-rump length (control, 9.7 +/- 0.45 cm; low-dose group, 9.1 +/- 0.68 cm; high-dose group, 7.7 +/- 0.86 cm; p less than 0.001). There was a significant reduction in fetal brain weight only in the high-dose group, and brain weight/fetal weight ratios were increased, suggesting relative sparing of brain growth. Liver weight was significantly reduced in both low- and high-dose groups. In contrast to results in previous animal studies, standardized intravenous maternal salicylate administration in rabbits induced a reproducible and dose-dependent asymmetrical fetal growth retardation.