Inflammatory markers in pregnancy – identifying drivers in four large cohorts
IntroductionAdaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. The design and interpretation of human biomarker stu...
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Frontiers Media S.A.
2025-06-01
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| author | Frederieke A. J. Gigase Frederieke A. J. Gigase Anna Suleri Anna Suleri Elena Isaevska Elena Isaevska Anna-Sophie Rommel Myrthe G. B. M. Boekhorst Olga Dmitrichenko Hanan El Marroun Hanan El Marroun Eric A. P. Steegers Manon H. J. Hillegers Ryan L. Muetzel Ryan L. Muetzel Whitney Lieb Charlotte A. M. Cecil Charlotte A. M. Cecil Charlotte A. M. Cecil Victor J. M. Pop Michael Breen Veerle Bergink Veerle Bergink Veerle Bergink Lot D. de Witte Lot D. de Witte Lot D. de Witte |
| author_facet | Frederieke A. J. Gigase Frederieke A. J. Gigase Anna Suleri Anna Suleri Elena Isaevska Elena Isaevska Anna-Sophie Rommel Myrthe G. B. M. Boekhorst Olga Dmitrichenko Hanan El Marroun Hanan El Marroun Eric A. P. Steegers Manon H. J. Hillegers Ryan L. Muetzel Ryan L. Muetzel Whitney Lieb Charlotte A. M. Cecil Charlotte A. M. Cecil Charlotte A. M. Cecil Victor J. M. Pop Michael Breen Veerle Bergink Veerle Bergink Veerle Bergink Lot D. de Witte Lot D. de Witte Lot D. de Witte |
| author_sort | Frederieke A. J. Gigase |
| collection | DOAJ |
| description | IntroductionAdaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. The design and interpretation of human biomarker studies require additional insights in the trajectories and drivers of peripheral immune markers. MethodsThe current study mapped maternal inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17A, IL-23, interferon-γ) during pregnancy and investigated the impact of demographic, environmental and genetic drivers on maternal inflammatory marker levels in four multi-ethnic and socio-economically diverse population-based cohorts with more than 12,000 pregnant participants. Additionally, pregnancy inflammatory markers were compared to pre-pregnancy levels. ResultsCytokines showed a high correlation with each other, but not with CRP. Inflammatory marker levels showed high variability between individuals, yet high concordance within an individual over time during and pre-pregnancy. Pre-pregnancy body mass index (BMI) explained ~ 9.6% of the variance in CRP, but less than 1% of the variance in cytokines. The polygenic score of CRP was the best predictor of variance in CRP (14.1%). Gestational age and previously identified inflammation drivers, including tobacco use and parity, explained less than 1% of variance in both cytokines and CRP.DiscussionOur findings corroborate differential underlying regulatory mechanisms of CRP and cytokines and are suggestive of an individual inflammatory marker baseline which is, in part, genetically driven. |
| format | Article |
| id | doaj-art-5a4ed73d280a48388e0d0d889bedae4a |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-5a4ed73d280a48388e0d0d889bedae4a2025-08-20T03:25:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15617981561798Inflammatory markers in pregnancy – identifying drivers in four large cohortsFrederieke A. J. Gigase0Frederieke A. J. Gigase1Anna Suleri2Anna Suleri3Elena Isaevska4Elena Isaevska5Anna-Sophie Rommel6Myrthe G. B. M. Boekhorst7Olga Dmitrichenko8Hanan El Marroun9Hanan El Marroun10Eric A. P. Steegers11Manon H. J. Hillegers12Ryan L. Muetzel13Ryan L. Muetzel14Whitney Lieb15Charlotte A. M. Cecil16Charlotte A. M. Cecil17Charlotte A. M. Cecil18Victor J. M. Pop19Michael Breen20Veerle Bergink21Veerle Bergink22Veerle Bergink23Lot D. de Witte24Lot D. de Witte25Lot D. de Witte26Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsThe Generation R Study Group, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsThe Generation R Study Group, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsThe Generation R Study Group, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Medical and Clinical Psychology, Tilburg University, Tilburg, NetherlandsDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Psychology, Education and Child Studies, Erasmus School of Social and Behavioral Sciences, Erasmus University, Rotterdam, NetherlandsDepartment of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands0Department of Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Medical and Clinical Psychology, Tilburg University, Tilburg, NetherlandsDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, United States1Department of Psychiatry, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States2Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands3Department of Psychiatry, Radboud University Medical Center, Nijmegen, NetherlandsIntroductionAdaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. The design and interpretation of human biomarker studies require additional insights in the trajectories and drivers of peripheral immune markers. MethodsThe current study mapped maternal inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17A, IL-23, interferon-γ) during pregnancy and investigated the impact of demographic, environmental and genetic drivers on maternal inflammatory marker levels in four multi-ethnic and socio-economically diverse population-based cohorts with more than 12,000 pregnant participants. Additionally, pregnancy inflammatory markers were compared to pre-pregnancy levels. ResultsCytokines showed a high correlation with each other, but not with CRP. Inflammatory marker levels showed high variability between individuals, yet high concordance within an individual over time during and pre-pregnancy. Pre-pregnancy body mass index (BMI) explained ~ 9.6% of the variance in CRP, but less than 1% of the variance in cytokines. The polygenic score of CRP was the best predictor of variance in CRP (14.1%). Gestational age and previously identified inflammation drivers, including tobacco use and parity, explained less than 1% of variance in both cytokines and CRP.DiscussionOur findings corroborate differential underlying regulatory mechanisms of CRP and cytokines and are suggestive of an individual inflammatory marker baseline which is, in part, genetically driven.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1561798/fullpregnancyimmunologymaternal immune activationinflammatory marker dynamicscohort studyintra-individual correlation |
| spellingShingle | Frederieke A. J. Gigase Frederieke A. J. Gigase Anna Suleri Anna Suleri Elena Isaevska Elena Isaevska Anna-Sophie Rommel Myrthe G. B. M. Boekhorst Olga Dmitrichenko Hanan El Marroun Hanan El Marroun Eric A. P. Steegers Manon H. J. Hillegers Ryan L. Muetzel Ryan L. Muetzel Whitney Lieb Charlotte A. M. Cecil Charlotte A. M. Cecil Charlotte A. M. Cecil Victor J. M. Pop Michael Breen Veerle Bergink Veerle Bergink Veerle Bergink Lot D. de Witte Lot D. de Witte Lot D. de Witte Inflammatory markers in pregnancy – identifying drivers in four large cohorts Frontiers in Immunology pregnancy immunology maternal immune activation inflammatory marker dynamics cohort study intra-individual correlation |
| title | Inflammatory markers in pregnancy – identifying drivers in four large cohorts |
| title_full | Inflammatory markers in pregnancy – identifying drivers in four large cohorts |
| title_fullStr | Inflammatory markers in pregnancy – identifying drivers in four large cohorts |
| title_full_unstemmed | Inflammatory markers in pregnancy – identifying drivers in four large cohorts |
| title_short | Inflammatory markers in pregnancy – identifying drivers in four large cohorts |
| title_sort | inflammatory markers in pregnancy identifying drivers in four large cohorts |
| topic | pregnancy immunology maternal immune activation inflammatory marker dynamics cohort study intra-individual correlation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1561798/full |
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