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Hematologic dynamics during pregnancy and their association with obstetric complications: a retrospective cohort
Veronica Tozzo1,2,3, Rachel Petherbridge1,2, Kaitlyn James4
1Department of Pathology and Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.
Insights
Elevated red blood cell counts during pregnancy, particularly significant increases, are linked to a higher risk of obstetric complications. These findings help establish new reference intervals for complete blood counts in pregnant individuals.
Area of Science:
- Obstetrics and Gynecology
- Hematology
- Reproductive Medicine
Background:
- Pregnancy significantly alters hematologic parameters, necessitating updated reference intervals for complete blood counts (CBCs).
- Existing reference intervals for CBCs in pregnancy may not accurately reflect longitudinal changes in diverse populations.
Purpose of the Study:
- To establish gestational age-specific reference intervals for CBCs and their longitudinal changes in a large US cohort.
- To investigate the association between extreme CBC values and changes with obstetric complications.
Main Methods:
- Retrospective cohort study utilizing electronic health records from 1998-2022.
- Inclusion of discovery and validation cohorts comprising over 96,000 singleton pregnancies.
- Analysis of CBC indices and composite obstetric outcomes using generalized estimating equations.
Main Results:
- Elevated hematocrit, hemoglobin, and red cell count values were associated with increased risk of composite obstetric complications.
- Significant increases in hemoglobin and red cell count during pregnancy correlated with a higher risk of preterm birth.
- Established reference intervals were often wider than previously published values for several CBC indices.
Conclusions:
- Higher red blood cell counts and substantial intra-pregnancy increases in these measures are associated with adverse obstetric outcomes.
- The study provides crucial data for refining diagnostic criteria and monitoring pregnant individuals.
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=1.8×10-5 for hematocrit; 1.7[1.4, 1.9] p=1.4×10-10 for hemoglobin; and 1.6[1.4, 1.9] p=3.9×10-9 for 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=2×10-8 and red cell count: 2.1[1.7, 2.6] p=9×10-14). 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.
Conclusions:
Elevated measures of red blood cell count and large intra-pregnancy increases in those measures are associated with subsequent obstetric complications.
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