Pregnancy‐Specific Reference Intervals for Maternal Biochemical Parameters and Associations With Adverse Pregnancy Outcomes in a Japanese Cohort

Aim To establish pregnancy‐specific reference intervals for key biochemical parameters and to assess their associations with adverse pregnancy outcomes in a large Japanese cohort. Methods This retrospective cohort study analyzed outpatient biochemical test data from 33 085 women with singleton pregnancies who delivered at a perinatal center in Japan between 2013 and 2023. Plasma glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid (UA), total cholesterol (TC), and triglycerides (TG) were measured during early (< 20 weeks), mid (20–29 weeks), and late (≥ 30 weeks) gestation. Reference intervals were established nonparametrically, and multivariable logistic regression was performed to assess associations with gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP). Results Glucose, AST, and ALT showed minimal changes across gestation, whereas TG, TC, and UA increased progressively. Across BMI categories, glucose, TG, and UA rose with higher BMI, whereas AST and TC tended to be higher in lower‐BMI groups after mid‐pregnancy. Higher TG levels at 20–29 weeks were independently associated with HDP, while higher AST and lower TC at 20–29 weeks also showed modest associations. In contrast, glucose and ALT showed no significant relationships with HDP. Elevated glucose levels in both early and mid‐pregnancy were the strongest correlates of GDM, followed by ALT, whereas AST demonstrated inverse associations. Conclusions This study established gestational age‐specific reference intervals for major biochemical parameters in Japanese pregnant women. TG, AST, and TC were associated with HDP, whereas glucose and ALT were associated with GDM, providing clinically relevant insights into metabolic adaptation and pregnancy risk assessment.