Joint association of preconception fasting plasma glucose and body mass index with adverse pregnancy outcomes: a retrospective cohort study in China

Maternal preconception body mass index (BMI) and fasting plasma glucose (FPG) are independently associated with adverse pregnancy outcomes. However, previous studies have rarely evaluated both additive and multiplicative interactions between preconception FPG and BMI across multiple pregnancy outcomes. This study aimed to evaluate their joint associations with adverse pregnancy outcomes. This was a retrospective cohort study of the National Free Preconception Checkup Project database in China, comprising 8,057,713 childbearing-aged women (median age, 26 years) between 2013 and 2020. Maternal preconception FPG was classified as hypoglycemia (< 3.9 mmol/L without a history of diabetes), normal (3.9- < 5.6 mmol/L without a history of diabetes), impaired fasting glucose (IFG, 5.6- < 7.0 mmol/L without a history of diabetes), and diabetes mellitus (DM, ≥ 7.0 mmol/L or with history of diabetes); BMI was categorized as underweight (< 18.5 kg/m 2 ), normal (18.5- < 24.0 kg/m 2 ), overweight (24.0- < 28.0 kg/m 2 ), and obesity (≥ 28.0 kg/m 2 ). Robust Poisson regression and interaction analyses were used to assess the associations with adverse pregnancy outcomes, including medically indicated termination, spontaneous abortion, preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA), birth defects, and perinatal death. Restricted cubic splines were used to assess the dose–response relationship. Of 8,057,713 included participants, 40.69% had preconception abnormalities in either FPG or BMI. Compared with women with normal FPG and BMI, women with both obesity and DM had the highest risk of medically indicated termination (adjusted risk ratio 1.49, 95% confidence interval 1.29–1.72), spontaneous abortion (1.38, 1.24–1.55), PTB (1.39, 1.26–1.53), LGA (1.87, 1.76–1.99), and perinatal death (2.31, 1.76–3.05). Conversely, the highest risks for SGA (1.41, 1.32–1.50) and birth defects (2.19, 1.34–3.58) were observed in underweight women with DM. In absolute terms, women with both obesity and DM had 2.38% and 9.08% higher risks of PTB and LGA, respectively, than women with normal FPG and BMI. Positive additive interactions between hyperglycemia and elevated BMI were outcome-specific and were not observed for SGA, birth defects, or perinatal death. Moreover, the dose–response relationships of elevated FPG and adverse pregnancy outcomes were steeper in women with higher BMI, while relationships of elevated BMI with adverse pregnancy outcomes were similarly more pronounced among women with higher FPG. In contrast, SGA risk was predominantly associated with preconception underweight, with less variation across FPG levels. Preconception FPG and BMI were jointly associated with adverse pregnancy outcomes, with outcome-specific additive interactions between hyperglycemia and elevated BMI. These findings suggested that dual assessment of BMI and FPG in preconception care may improve risk stratification, and prospective interventional studies are needed to determine whether modifying these factors improves pregnancy outcomes among singleton pregnancies.