Abstract
Abstract Introduction/Background Although erythropoiesis is impaired and anemia frequent in neonates born preterm, hematopoiesis in adults born preterm has not been previously studied. We hypothesize that adverse neonatal events durably affect erythropoiesis regulation, leading to a difference in hemoglobin levels in young adults born preterm compared to those born term. Objectives We thus aimed to evaluate hemoglobin and erythropoietin levels in young adults born preterm, to identify neonatal events associated with erythropoiesis in adulthood and to examine the relationships of hemoglobin levels with respiratory function and blood pressure. Design/Methods This study included 101 young adults (ages 18-29 years) born preterm (≤29 weeks of gestation) and 105 full-term controls. We measured office blood pressure using automated oscillometric device, complete blood count, serum erythropoietin levels (ELISA) and pulmonary function test. Group comparisons were performed using Student’s t or Mann-Whitney U tests. Correlations were assessed using Pearson’s coefficient and test. We performed a mediation analysis to assess the relationship between blood pressure, hemoglobin levels and preterm birth. Results Tobacco use and sex adjusted hemoglobin levels were 5.3 (95% CI: 2.9, 7.7) g/L higher in preterm-born individuals compared to controls (Table). We did not observe a difference in erythropoietin levels (7.3±3.4 and 8.12±3.40 U/L in the term and the preterm groups, respectively, p=0.102). Duration of oxygen supplementation in the neonatal period was independently associated with higher hemoglobin levels in the preterm group. In adults born preterm with bronchopulmonary dysplasia, airflow limitation was associated with higher hemoglobin levels. Both systolic (SBP) and diastolic (DBP) blood pressure were increased in individuals born preterm (p=0.042 and p=0.0008, respectively). Higher hemoglobin levels were associated with higher SBP and DBP, independently of term or preterm status. Mediation analysis (Figure) suggests that hemoglobin increase contributes to 37% and 32% of the effect of preterm birth on SBP and DBP, respectively. Conclusion While erythropoietin levels are similar between groups, hemoglobin levels are higher in young adults born preterm, especially in cases of bronchopulmonary dysplasia and airflow limitation. Hemoglobin increase is associated with elevated blood pressure in this population. Understanding mechanisms of impaired erythropoiesis regulation in adults born preterm will be important in designing antihypertensive approaches specific to this population. Results shown as mean ± SD or medians (25%-75%) and comparisons were performed using Student’s t test or Mann-Whitney U test, when appropriate. Systolic blood pressure (SBP). B. Diastolic blood pressure (DBP). Hb: hemoglobin. ACME: Average Causal Mediation Effect. B: unstandardized regression coefficient. All estimations are adjusted for sex.
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