Hematologic dynamics during pregnancy and their association with obstetric complications: a retrospective cohort study
Authors: Tozzo Veronica , Petherbridge Rachel , James Kaitlyn , Hsu Sarah , Michalopoulos Chloe , Foy Brody H. , Thaweethai Tanayott , Mow Christopher , Maya Jacqueline , Camero Carolina Batlle , Shook Lydia , Gray Kathryn J. , Mauney Logan , Higgins John M. , Powe Camille E. 
Published: February 2025

AbstractObjectivesPregnancy 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.DesignRetrospective cohort study including electronic health record-based discovery and validation cohorts.SettingAcademic medical center and affiliated health system in the United States between 1998 and 2022.ParticipantsIndividuals 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 measuresComposite 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.ResultsHematocrit, 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=1.8x10−5for hematocrit; 1.7[1.4, 1.9] p=1.4x10−10for hemoglobin; and 1.6[1.4, 1.9] p=3.9×10−9for red cell count. Extreme increase in hemoglobin (>0.67 g/dL) or red cell count (>0.07 106/mm3) 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=2x10−8and red cell count: 2.1[1.7, 2.6] p=9x10−14). 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.ConclusionsElevated measures of red blood cell count and large intra-pregnancy increases in those measures are associated with subsequent obstetric complications.Summary boxWhat is already known on this topicPregnancy causes significant changes in hematologic state as measured by routine complete blood counts (CBCs).What this study addsWe studied more than 95,000 pregnancies and found that elevations (both absolute and relative to baseline 1sttrimester values) in hematocrit, hemoglobin, and red cell count are associated with adverse pregnancy outcomes including hypertensive disorder of pregnancy, small for gestational age birthweight, and preterm birth.MeaningRoutinely collected prenatal CBCs may provide an opportunity to identify those at risk for obstetric complications.