ISEE-0741 Background and Objective: Maternal exposure to environmental tobacco smoke (ETS) has been reported to be associated with children’s neurobehavioral development but there have been few studies investigating the genetic susceptibilities to maternal ETS exposure during pregnancy on children’s neurodevelopment. The potential health effects are still unclear. The aim of this study was to explore the modification effect of metabolic gene polymorphisms and cord blood cotinine levels on children’s neurodevelopment at three days of age. Methods: The study population was 117 mother-infant pairs who gave birth in Taiwan between August 2004 and January 2005 from Taiwan Birth Panel Study. We interviewed them using a structured questionnaire before delivery, collected umbilical cord blood at birth, and performed the Neonatal Neurobehavioral Examination–Chinese Version (NNE-C) after birth within three days. The NNE-C scale consisted of three parts: behavioral responses, tone and motor patterns, primitive reflexes, and each part contains nine items to test by trained physical therapists. The higher the score is, the poorer the child’s performance. The cotinine in cord blood was used as an indicator of environmental tobacco smoke and was analyzed by using HPLC-MS/MS. The detection limited of this method was 0.05 ng/mL. CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were identified from infant’s DNA. Multiple linear regression models were used to explore the effect of ETS exposure and gene interaction on early child neurodevelopment. Results: High cord blood cotinine exposure combined with a GSTM1 polymorphism was associated with a negative NNE-C score (b ± SE =−1.14 ± 0.47, P-value = 0.016) and a negative primitive reflexes score (b ± SE = −1.97 ± 0.87, P-value = 0.025). Conclusion: It can be concluded that the GSTM1 metabolic gene can modify the effect of maternal exposure to ETS on early child neurodevelopment.