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OBJECTIVES: Pregnancy alters hematologic state as measured by complete blood counts (CBC), but the longitudinal changes in CBC indices that define healthy pregnancies are not well established. Our objectives were (1) to define gestational age-specific reference intervals for CBCs and their longitudinal changes in a large United States-based cohort and (2) to use these reference intervals to examine associations between extreme CBC values and changes and risk of obstetric complications.DESIGN: Retrospective cohort study including electronic health record-based discovery and validation cohorts.SETTING: Academic medical center and affiliated health system in the United States between 1998 and 2022.PARTICIPANTS: Individuals with singleton pregnancies delivering after 30 weeks' gestation who presented for prenatal care prior to 20 weeks'. There were 45,992 pregnancies in the discovery cohort, 18% of whom had complications, and 50,603 in the validation cohort, 22% with complications.MAIN OUTCOME MEASURES: Composite outcome (hypertensive disorder of pregnancy, small for gestational age birthweight or preterm birth) and its individual components. We analyzed associations between CBC results and outcomes using generalized estimating equations for logistic regression with Bonferroni correction for multiple hypothesis testing.RESULTS: Hematocrit, hemoglobin, and red cell count values above their reference intervals were associated with increased risk of the composite obstetric complication: OR [95% CI] of 1.4 [1.2, 1.6] p=1.810 for hematocrit; 1.7[1.4, 1.9] p=1.410 for hemoglobin; and 1.6[1.4, 1.9] p=3.9×10 for red cell count. Extreme increase in hemoglobin (>0.67 g/dL) or red cell count (>0.07 10/mm) between 7-14 weeks' and 26-29 weeks' gestation was associated with increased risk for preterm birth (OR [95% CI] for hemoglobin 2.0[1.6, 2.6] p=210 and red cell count: 2.1[1.7, 2.6] p=910). Reference intervals in this cohort were often wider than those previously published for mean red cell volume, mean red cell hemoglobin, red cell count, and mean red cell hemoglobin concentration.CONCLUSIONS: Elevated measures of red blood cell count and large intra-pregnancy increases in those measures are associated with subsequent obstetric complications.