Paraoxonase 1 (PON1) protects against oxidative modification of low density lipoproteins. The PON1 gene has 3 polymorphisms considered strong determinants of PON1 levels: Q192R and L55M in the coding region and C-108T in the promoter region. PON1 levels are also influenced by smoking. The authors hypothesized that PON1 variants could increase the risk of vascular thrombosis, leading in turn to placental insufficiency and small-for-gestational-age (SGA) birth. The author compared PON1 variants and haplotypes between 448 newborn SGA cases and 431 newborn controls from Montréal, Québec, Canada (1998-2000) and studied the effects of interaction with maternal smoking. Transmission of the variants in case-parent trios was used as validation of the case-control results; the authors combined case-control and family data to analyze the associations of variants with SGA birth. In the case-control analysis, the T allele from C-108T increased the risk of SGA birth (additive odds ratio = 1.30, 95% confidence interval (CI): 1.06, 1.59), and the TRL haplotype (T from C-108T, R from Q192R, and L from L55M) was associated with an odds ratio of 1.51 (95% CI: 1.07, 2.15). Among smokers, the CRL haplotype was protective (odds ratio = 0.48, 95% CI: 0.28, 0.82). Case-parent trio results were compatible with case-control results.