BACKGROUND: Weight-control interventions in pregnant women with overweight or obesity have limited effectiveness for fetal growth and birth outcomes. Interventions or prevention programs aiming at the pre-pregnancy period should be considered. However, how the woman's weight change before pregnancy affects fetal growth is not known. We investigated the association between weight change over the year before pregnancy and birth weight. METHODS AND FINDINGS: We used the inclusion data of 16,395 women from the ELFE French national birth cohort, a nationally representative cohort in which infants were enrolled at birth with their families in 2011. Maternal weight change was self-reported and classified into 3 groups: moderate weight variation or stable weight, weight loss > 5 kg, and weight gain > 5 kg or both weight loss and gain > 5 kg. Multiple linear regression models were used to investigate the association between pre-pregnancy weight change and a birth weight z-score calculated according to the French Audipog reference, adjusted for a large set of maternal characteristics. The analyses were stratified by maternal body mass index (BMI) at conception (<25 versus ≥25 kg/m2) and adjusted for BMI within these categories. We used the MacKinnon method to test the mediating effect of gestational weight gain (GWG) on these associations. Mother's mean age was 30.5 years, 87% were born in France, and 26% had overweight or obesity. For women in either BMI category at conception, GWG was more than 2 kg higher, on average, for women with weight loss before pregnancy than for women with stable weight or moderate weight variation. For women with BMI < 25 kg/m2 at conception, birth weight was significantly higher with weight loss than stable weight before pregnancy (β = 0.08 [95% CI 0.02; 0.14], p = 0.01), and this total effect was explained by a significant mediating effect through GWG. For women with BMI ≥ 25 kg/m2 at conception, birth weight was not associated with pre-pregnancy weight loss during the year before pregnancy. Mediation analysis revealed that in these women, the direct effect of pre-pregnancy weight loss that would have resulted in a smaller birth weight z-score (β = -0.11 [95% CI -0.19; -0.03], p = 0.01) was cancelled out by the GWG. The mediating effect of GWG was even higher when weight loss resulted from a restrictive diet in the year before pregnancy. Weight gain before pregnancy was not associated with birth weight. Although we included a large number of women and had extensive data, the only potential cause of pre-pregnancy weight loss that was investigated was dieting for intentional weight loss. We have no information on other potential causes but did however exclude women with a history of pre-pregnancy chronic disease. Another limitation is declaration bias due to self-reported data. CONCLUSIONS: Health professionals should be aware that GWG may offset the expected effect of weight loss before conception on fetal growth in overweight and obese women. Further studies are required to understand the underlying mechanisms in order to develop weight-control interventions and improve maternal periconceptional health and developmental conditions for the fetus.