Background Adequate maternal thyroxine (T4) concentrations during the first half of pregnancy are fundamental to the embryo’s or fetus’ neural development. Organophosphate pesticides (OP) can act as thyroid disruptors and genetic polymorphisms for paraoxonase 1 (PON1), an enzyme that detoxifies OP, could be involved in individual’s susceptibility to them. We assessed the association between para-occupational exposure to pesticides, including OP, during pregnancy and maternal hypothyroxinemia, as well as the potential genetic susceptibility conferred by PON1 polymorphisms. Methods We analyzed information from 381 healthy pregnant women (< 17 gestational weeks), who lived in a floricultural region of Mexico where pesticides, including OP, are routinely used. Women who were para-occupationally exposed to pesticides were those whose partner had an occupation involving contact with these products. Thyroid-Stimulating Hormone (TSH) and free T4 concentrations were determined using ELISA, and hypothyroxinemia was defined as free T4 concentrations <0.76 ng/dL. PON1192QR , PON155LM and PON1–108CT polymorphisms were determined through Polymerase Chain Reaction (PCR). The association between para-occupational exposure and genetic polymorphisms and hypothyroxinemia was estimated using logistic regression models. Results One hundred and sixty two women (42.52%) were classified as para-occupationally exposed to pesticides. Hypothyroxinemia prevalence was 54%, and it was not significantly associated with pesticide para-occupational exposure (OR: 1.21 95% CI 0.75–1.94). Independently of para-occupational exposure, the likelihood of hypothyroxinemia was higher among women who were carriers of PON155MM than in those with PON155LL genotype (OR MM vs LL : 3.03; 95%CI 1.62, 5.70). PON1192 RR (OR RR vs QQ : 1.72; 95%CI 0.93, 3.17) and PON1–108TT (OR TT vs CC : 1.60; 95%CI 0.90, 2.70) genotypes were marginally associated with hypothyroxinemia. No significant interaction was observed between pesticides para-occupational exposure and PON1 polymorphisms. Conclusions These results suggest that PON1 polymorphisms could affect thyroid function during pregnancy in women living in areas where pesticides, including OP, are routinely used. Low exposure variability in this population, could be a possible explanation for the lack of association between para-occupational exposure and thyroid function.

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