ObjectiveWe aimed to assess whether maternal first-trimester low body mass index (BMI) has a protective effect against macrosomia.MethodsThis was a cross-sectional study from January 1, 2011, to June 30, 2021, and 84,900 participants were included. The predictive performance of maternal first-trimester and parental pre-pregnancy BMI for macrosomia was assessed using the area under the receiver-operating characteristics curve (AUC). Multivariate logistic regression analyses were performed to evaluate the independent effect of maternal first-trimester low BMI on macrosomia. Interactions were investigated to evaluate the potential variation of the effect of first-trimester low BMI across different groups. Furthermore, interactions were also examined across groups determined by multiple factors jointly: a) gestational diabetes mellitus (GDM)/GDM history status, parity, and maternal age; and b) GDM/GDM history status, fetal sex, and season of delivery.ResultsThe proportion of macrosomia was 6.14% (5,215 of 84,900). Maternal first-trimester BMI showed the best discrimination of macrosomia (all Delong tests: P < 0.001). The protective effect of maternal first-trimester low BMI against macrosomia remained significant after adjusting for all confounders of this study [adjusted odds ratios (aOR) = 0.37, 95% CI: 0.32–0.43]. Maternal first-trimester low BMI was inversely associated with macrosomia, irrespective of parity, fetal sex, season of delivery, maternal age, and GDM/GDM history status. The protective effect was most pronounced among pregnant women without GDM/GDM history aged 25 to 29 years old, irrespective of parity (multipara: aOR = 0.32, 95% CI: 0.22–0.47; nullipara: aOR = 0.32, 95% CI: 0.24–0.43). In multipara with GDM/GDM history, the protective effect of low BMI was only observed in the 30- to 34-year-old group (aOR = 0.12, 95% CI: 0.02–0.86). For pregnant women without GDM/GDM history, the protective effect of maternal first-trimester low BMI against macrosomia was the weakest in infants born in winter, irrespective of fetal sex (female: aOR = 0.45, 95% CI: 0.29–0.69; male: aOR = 0.39, 95% CI: 0.28–0.55).ConclusionMaternal first-trimester low BMI was inversely associated with macrosomia, and the protective effect was most pronounced among 25- to 29-year-old pregnant women without GDM/GDM history and was only found among 30- to 34-year-old multipara with GDM/GDM history. The protective effect of maternal first-trimester low BMI against macrosomia was the weakest in winter among mothers without GDM/GDM history.