OBJECTIVES: We aimed to investigate the potential associations between serum apolipoprotein levels in early pregnancy and the risk of gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. METHODS: This was an observational study of the population-based Odense Child Cohort. Pregnant women were followed from inclusion until childbirth. Apolipoprotein levels, including 12 apolipoproteins (ApoA-I, ApoA-II, ApoA-IV, ApoB, ApoC-I, ApoC-II, ApoC-III, ApoD, ApoE, ApoH, ApoJ, and ApoM) were measured by targeted proteomics using liquid chromatography mass spectrometry on late first trimester serum samples stored in a biobank. GDM was defined by WHO 2013 diagnostic criteria. RESULTS: A total of 991 pregnant women were included, of which 415 (41.9%) were diagnosed with GDM. GDM was associated with increasing ApoB (adjusted odds ratio [OR]: 1.26, P = .002) and ApoD levels (adjusted OR: 0.84, P = .021). ApoB levels in early pregnancy correlated significantly and positively with insulin resistance (r = 0.22, P <
.001) and beta-cell function in third trimester (r = 0.20, P <
.001), whereas early pregnancy ApoD levels were inversely correlated with insulin resistance (r = -0.14, P <
.001) and beta-cell function (r = -0.12, P <
.001). Finally, high levels of ApoD was significantly associated with lower risk of large-for-gestational-age infants (adjusted OR: 0.78, P = .041). CONCLUSIONS: High levels of ApoB and low levels of ApoD in early pregnancy were independently associated with an increased risk of GDM, insulin resistance, and large-for-gestational-age infants (low ApoD only), suggesting potential roles for future management of pregnancy outcomes.