Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort study
Abstract Background Pregnancy is a complex biological process and serious complications can arise when the delicate balance between the maternal and semi-allogeneic fetal immune systems is disrupted or challenged. Gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth, and low birth weigh...
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2024-12-01
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| Online Access: | https://doi.org/10.1186/s12916-024-03797-y |
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| author | David Westergaard Agnete Troen Lundgaard Kilian Vomstein Line Fich Kathrine Vauvert Römmelmayer Hviid Pia Egerup Ann-Marie Hellerung Christiansen Josefine Reinhardt Nielsen Johanna Lindman Peter Christoffer Holm Tanja Schlaikjær Hartwig Finn Stener Jørgensen Anne Zedeler Astrid Marie Kolte Henrik Westh Henrik Løvendahl Jørgensen Nina la Cour Freiesleben Karina Banasik Søren Brunak Henriette Svarre Nielsen |
| author_facet | David Westergaard Agnete Troen Lundgaard Kilian Vomstein Line Fich Kathrine Vauvert Römmelmayer Hviid Pia Egerup Ann-Marie Hellerung Christiansen Josefine Reinhardt Nielsen Johanna Lindman Peter Christoffer Holm Tanja Schlaikjær Hartwig Finn Stener Jørgensen Anne Zedeler Astrid Marie Kolte Henrik Westh Henrik Løvendahl Jørgensen Nina la Cour Freiesleben Karina Banasik Søren Brunak Henriette Svarre Nielsen |
| author_sort | David Westergaard |
| collection | DOAJ |
| description | Abstract Background Pregnancy is a complex biological process and serious complications can arise when the delicate balance between the maternal and semi-allogeneic fetal immune systems is disrupted or challenged. Gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth, and low birth weight pose serious threats to maternal and fetal health. Identification of early biomarkers through an in-depth understanding of molecular mechanisms is critical for early intervention. Methods We analyzed the associations between 47 proteins involved in inflammation, chemotaxis, angiogenesis, and immune system regulation, maternal and neonatal health outcomes, and the baseline characteristics and pre-existing conditions of the mother in a prospective cohort of 1049 pregnant women around the 20th gestational week. We used Bayesian linear regression models to examine the impact of risk factors on biomarker levels and Bayesian cause-specific parametric proportional hazards models to analyze the effect of biomarkers on maternal and neonatal outcomes. We evaluated the predictive value of baseline characteristics and 47 proteins using machine-learning models and identified the most predictive biomarkers using Shapley additive explanation scores. Results Associations were identified between specific inflammatory markers and several conditions, including maternal age and pre-pregnancy body mass index, chronic diseases, complications from prior pregnancies, and COVID-19 exposure. Smoking during pregnancy affected GM-CSF and 9 other biomarkers. Distinct biomarker patterns were observed for different ethnicities. Within obstetric complications, IL-6 inversely correlated with pre-eclampsia risk, while birth weight to gestational age ratio was linked to markers including VEGF and PlGF. GDM was associated with IL-1RA, IL-17D, and eotaxin-3. Severe postpartum hemorrhage correlated with CRP, IL-13, and proteins of the IL-17 family. Predictive modeling yielded area under the receiver operating characteristic curve values of 0.708 and 0.672 for GDM and pre-eclampsia, respectively. Significant predictive biomarkers for GDM included IL-1RA and eotaxin-3, while pre-eclampsia prediction yielded the highest predictions when including MIP-1β, IL-1RA, and IL-12p70. Conclusions Our study provides novel insights into the interplay between preexisting conditions and immune dysregulation in pregnancy. These findings contribute to our understanding of the pathophysiology of obstetric complications and the identification of novel biomarkers for early intervention(s) to improve maternal and fetal health. |
| format | Article |
| id | doaj-art-57bc03c0d9224f6cb786832dae703c78 |
| institution | OA Journals |
| issn | 1741-7015 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj-art-57bc03c0d9224f6cb786832dae703c782025-08-20T02:31:47ZengBMCBMC Medicine1741-70152024-12-0122111510.1186/s12916-024-03797-yImmune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort studyDavid Westergaard0Agnete Troen Lundgaard1Kilian Vomstein2Line Fich3Kathrine Vauvert Römmelmayer Hviid4Pia Egerup5Ann-Marie Hellerung Christiansen6Josefine Reinhardt Nielsen7Johanna Lindman8Peter Christoffer Holm9Tanja Schlaikjær Hartwig10Finn Stener Jørgensen11Anne Zedeler12Astrid Marie Kolte13Henrik Westh14Henrik Løvendahl Jørgensen15Nina la Cour Freiesleben16Karina Banasik17Søren Brunak18Henriette Svarre Nielsen19Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreDepartment of Clinical Microbiology, Copenhagen University Hospital HvidovreDepartment of Clinical Biochemistry, Copenhagen University Hospital HvidovreDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Obstetrics and Gynecology, Copenhagen University Hospital HvidovreAbstract Background Pregnancy is a complex biological process and serious complications can arise when the delicate balance between the maternal and semi-allogeneic fetal immune systems is disrupted or challenged. Gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth, and low birth weight pose serious threats to maternal and fetal health. Identification of early biomarkers through an in-depth understanding of molecular mechanisms is critical for early intervention. Methods We analyzed the associations between 47 proteins involved in inflammation, chemotaxis, angiogenesis, and immune system regulation, maternal and neonatal health outcomes, and the baseline characteristics and pre-existing conditions of the mother in a prospective cohort of 1049 pregnant women around the 20th gestational week. We used Bayesian linear regression models to examine the impact of risk factors on biomarker levels and Bayesian cause-specific parametric proportional hazards models to analyze the effect of biomarkers on maternal and neonatal outcomes. We evaluated the predictive value of baseline characteristics and 47 proteins using machine-learning models and identified the most predictive biomarkers using Shapley additive explanation scores. Results Associations were identified between specific inflammatory markers and several conditions, including maternal age and pre-pregnancy body mass index, chronic diseases, complications from prior pregnancies, and COVID-19 exposure. Smoking during pregnancy affected GM-CSF and 9 other biomarkers. Distinct biomarker patterns were observed for different ethnicities. Within obstetric complications, IL-6 inversely correlated with pre-eclampsia risk, while birth weight to gestational age ratio was linked to markers including VEGF and PlGF. GDM was associated with IL-1RA, IL-17D, and eotaxin-3. Severe postpartum hemorrhage correlated with CRP, IL-13, and proteins of the IL-17 family. Predictive modeling yielded area under the receiver operating characteristic curve values of 0.708 and 0.672 for GDM and pre-eclampsia, respectively. Significant predictive biomarkers for GDM included IL-1RA and eotaxin-3, while pre-eclampsia prediction yielded the highest predictions when including MIP-1β, IL-1RA, and IL-12p70. Conclusions Our study provides novel insights into the interplay between preexisting conditions and immune dysregulation in pregnancy. These findings contribute to our understanding of the pathophysiology of obstetric complications and the identification of novel biomarkers for early intervention(s) to improve maternal and fetal health.https://doi.org/10.1186/s12916-024-03797-yWomen’s healthCOVID-19ImmunologyPregnancyRisk predictionPre-eclampsia |
| spellingShingle | David Westergaard Agnete Troen Lundgaard Kilian Vomstein Line Fich Kathrine Vauvert Römmelmayer Hviid Pia Egerup Ann-Marie Hellerung Christiansen Josefine Reinhardt Nielsen Johanna Lindman Peter Christoffer Holm Tanja Schlaikjær Hartwig Finn Stener Jørgensen Anne Zedeler Astrid Marie Kolte Henrik Westh Henrik Løvendahl Jørgensen Nina la Cour Freiesleben Karina Banasik Søren Brunak Henriette Svarre Nielsen Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort study BMC Medicine Women’s health COVID-19 Immunology Pregnancy Risk prediction Pre-eclampsia |
| title | Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort study |
| title_full | Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort study |
| title_fullStr | Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort study |
| title_full_unstemmed | Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort study |
| title_short | Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week—a prospective cohort study |
| title_sort | immune changes in pregnancy associations with pre existing conditions and obstetrical complications at the 20th gestational week a prospective cohort study |
| topic | Women’s health COVID-19 Immunology Pregnancy Risk prediction Pre-eclampsia |
| url | https://doi.org/10.1186/s12916-024-03797-y |
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