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Infants of smokers have much higher rates of respiratory infection, asthma and airway disease. The current study assessed the effects of maternal smoking in pregnancy on neonatal toll-like-receptor (TLR)-mediated immune responses as a possible contributing factor to the elevated rates of respiratory illness. In a prospective birth cohort, the cord blood immune responses of neonates of smoking and nonsmoking mothers were compared. Maternal and cord serum cotinine were measured to confirm the level of cigarette smoke exposure. Neonatal cytokine responses were assessed to optimal doses of TLR2, TLR3, TLR4 and TLR9 ligands. Cotinine levels confirmed maternal reporting of cigarette smoking in pregnancy, with significantly higher cotinine levels in maternal and cord blood compared with the nonsmoking group. Infants of smoking mothers showed significantly attenuated innate TLR-mediated responses compared with infants of nonsmokers. The current findings indicate that in addition to effects on developing airways, maternal smoking also has significant immunological effects in pregnancy, which could contribute to the well recognised, subsequent increased risk of respiratory infections and asthma. These effects appear to be mediated through effects on toll-like receptor-mediated innate response pathways, which also promote regulatory pathways in the inhibition of allergic immune responses in the postnatal period, suggesting that other environmental interactions are highly relevant to the "hygiene hypothesis".

Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses