Objectives: To evaluate periconceptional maternal biochemical and hematological parameters and vitamin profiles in relation to the risk of early pregnancy loss and birth weight. Design: Prospective longitudinal study. Setting: University Medical Centre Nijmegen, Academic Medical Centre, Amsterdam, Maria and Elisabeth Hospitals, Tilburg, and Catharina Hospital, Eindhoven, The Netherlands. Subjects: A cohort of 240 women recruited before pregnancy. Interventions: Blood samples were taken preconceptional and at 6 and 10 weeks amenorrhea in which the concentrations of hemoglobin, hematocrit, creatinin, uric acid, total protein, serum iron, total iron-binding capacity, ferritin, and the concentrations of retinol, tocopherol, thiamine, riboflavin, pyridoxal-5'-phosphate, cobalamin and folate were analyzed. Main outcome measures: Risk of early pregnancy loss and birth weight. Results: The risk of early pregnancy loss increased with increasing prepregnancy weight, and when the periconceptional decline in hematocrit, creatinin and uric acid was less profound (slope: P < 0.01). Maternal smoking was negatively associated with birth weight (mean reduction of 183 g, P < 0.05). Maternal age and prepregnancy weight were positively associated with birth weight (P < 0.01). No significant associations were found between vitamin concentrations and risk of early pregnancy loss or birth weight. Conclusions: Several periconceptional biochemical parameters are significantly associated with early pregnancy loss. The effects of maternal periconceptional health on embryonic development and subsequent pregnancy outcome should be further explored.