Objective: The prevalence of maternal overweight and fetal macrosomia is increasing. Fetal macrosomia is associated with increased risk of maternal and neonatal complications. The objective of the present study was to investigate if maternal metabolic parameters associated with maternal overweight were independent determinants of macrosomia (birth weight .4500 g or above the 95 percentile of the z-score for standardized birth weight). Design: Prospective population based cohort study of 2050 pregnancies and nested case control study. Methods: Outcome measures were adjusted risks for macrosomia in relation to early second trimester maternal serum lipids, glucose and insulin (cohort study) and leptin and insulin-like growth factor (73 cases and 146 matched controls). Results: Gestational diabetes was not independently associated with fetal macrosomia. First trimester body mass index (BMI), gestational weight gain and placental weight were associated with macrosomia. High serum insulin and non-high density lipoprotein (HDL)-cholesterol and low serum HDL-cholesterol were associated with increased risk of macrosomia independent of BMI, weight gain, placental weight and gestational diabetes. Slim women with macrosomic infants had higher insulin compared with those with normal weight infants. This relation was not found among obese women. Leptin was not associated with macrosomia after adjusting for maternal BMI. Conclusions: Blood parameters known to be associated with the metabolic syndrome were risk factors for macrosomia independent of maternal BMI.European Journal of Endocrinology 153 887-894