Birgitte Kordt Sundet , Karin C. Lødrup Carlsen , Guttorm Haugen , Gunilla Hedlin , Katarina Hilde , Christine M. Jonassen , Björn Nordlund , Eva Maria Rehbinder , Corina Silvia Rueegg , Katrine Sjøborg , Håvard O. Skjerven , Cilla Söderhäll , Riyas Vettukattil , Magdalena R. Værnesbranden , Johanna Wiik , Anne Cathrine Staff , Meryam Sugulle
{"title":"妊娠中期母体循环血管生成生物标志物:与胎盘功能障碍相关妊娠并发症和胎儿性别的关联","authors":"Birgitte Kordt Sundet , Karin C. Lødrup Carlsen , Guttorm Haugen , Gunilla Hedlin , Katarina Hilde , Christine M. Jonassen , Björn Nordlund , Eva Maria Rehbinder , Corina Silvia Rueegg , Katrine Sjøborg , Håvard O. Skjerven , Cilla Söderhäll , Riyas Vettukattil , Magdalena R. Værnesbranden , Johanna Wiik , Anne Cathrine Staff , Meryam Sugulle","doi":"10.1016/j.placenta.2025.09.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Placental function differs by fetal sex, and placental dysfunction is associated with adverse pregnancy outcomes. We aimed to investigate the role of midpregnancy maternal circulating placenta-associated angiogenic biomarkers and fetal sex in relation to placental dysfunction-related pregnancy complications.</div></div><div><h3>Methods</h3><div>The Preventing Atopic Dermatitis and Allergies in children birth cohort study provided maternal serum from 2511 pregnancies at gestational weeks 16–22. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed by immunoassays. Pregnancy complications (n = 385) included gestational hypertension, preeclampsia, preterm delivery, and/or newborn weight <10th percentile; categorized as ‘uncomplicated’, ‘complicated’ and ‘severely complicated’ pregnancies by zero, one or two or more complications. The risk of ‘any number of pregnancy complications’ by biomarkers tertiles were assessed in multivariable logistic regression models with interaction analyses of fetal sex.</div></div><div><h3>Results</h3><div>Midpregnancy median PlGF was lower and sFlt-1 higher in pregnancies with a female versus a male fetus, with median (interquartile range) sFlt-1/PlGF-ratio being 7.2 (4.9–10.2) versus 6.4 (4.3–9.0) in ‘uncomplicated’, 7.3 (4.7–10.7) versus 6.4 (4.5–9.0) in ‘complicated’, and 11.2 (5.4–22.7) versus 5.9 (4.8–13.4) in ‘severely complicated’ pregnancies. The risks of ‘any number of pregnancy complications’ were highest in the lowest tertile of PlGF (adjusted odds ratio (aOR) 1.6, 95 % confidence interval (CI): 1.2–2.2) and sFlt-1 (aOR 1.4, 95 % CI: 1.0–1.9) without influence of fetal sex (all, p<sub>interactions</sub> >0.05).</div></div><div><h3>Conclusion</h3><div>Circulating midpregnancy placenta-associated angiogenic biomarkers differed by fetal sex and pregnancy complications. The higher risk of pregnancy complications with low midpregnancy PlGF and/or sFlt-1 levels was not influenced by fetal sex.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 52-61"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Midpregnancy maternal circulating angiogenic biomarkers: Associations with placental dysfunction-related pregnancy complications and fetal sex\",\"authors\":\"Birgitte Kordt Sundet , Karin C. Lødrup Carlsen , Guttorm Haugen , Gunilla Hedlin , Katarina Hilde , Christine M. Jonassen , Björn Nordlund , Eva Maria Rehbinder , Corina Silvia Rueegg , Katrine Sjøborg , Håvard O. Skjerven , Cilla Söderhäll , Riyas Vettukattil , Magdalena R. Værnesbranden , Johanna Wiik , Anne Cathrine Staff , Meryam Sugulle\",\"doi\":\"10.1016/j.placenta.2025.09.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>Placental function differs by fetal sex, and placental dysfunction is associated with adverse pregnancy outcomes. We aimed to investigate the role of midpregnancy maternal circulating placenta-associated angiogenic biomarkers and fetal sex in relation to placental dysfunction-related pregnancy complications.</div></div><div><h3>Methods</h3><div>The Preventing Atopic Dermatitis and Allergies in children birth cohort study provided maternal serum from 2511 pregnancies at gestational weeks 16–22. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed by immunoassays. Pregnancy complications (n = 385) included gestational hypertension, preeclampsia, preterm delivery, and/or newborn weight <10th percentile; categorized as ‘uncomplicated’, ‘complicated’ and ‘severely complicated’ pregnancies by zero, one or two or more complications. The risk of ‘any number of pregnancy complications’ by biomarkers tertiles were assessed in multivariable logistic regression models with interaction analyses of fetal sex.</div></div><div><h3>Results</h3><div>Midpregnancy median PlGF was lower and sFlt-1 higher in pregnancies with a female versus a male fetus, with median (interquartile range) sFlt-1/PlGF-ratio being 7.2 (4.9–10.2) versus 6.4 (4.3–9.0) in ‘uncomplicated’, 7.3 (4.7–10.7) versus 6.4 (4.5–9.0) in ‘complicated’, and 11.2 (5.4–22.7) versus 5.9 (4.8–13.4) in ‘severely complicated’ pregnancies. The risks of ‘any number of pregnancy complications’ were highest in the lowest tertile of PlGF (adjusted odds ratio (aOR) 1.6, 95 % confidence interval (CI): 1.2–2.2) and sFlt-1 (aOR 1.4, 95 % CI: 1.0–1.9) without influence of fetal sex (all, p<sub>interactions</sub> >0.05).</div></div><div><h3>Conclusion</h3><div>Circulating midpregnancy placenta-associated angiogenic biomarkers differed by fetal sex and pregnancy complications. The higher risk of pregnancy complications with low midpregnancy PlGF and/or sFlt-1 levels was not influenced by fetal sex.</div></div>\",\"PeriodicalId\":20203,\"journal\":{\"name\":\"Placenta\",\"volume\":\"171 \",\"pages\":\"Pages 52-61\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Placenta\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0143400425006903\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Placenta","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143400425006903","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
Midpregnancy maternal circulating angiogenic biomarkers: Associations with placental dysfunction-related pregnancy complications and fetal sex
Introduction
Placental function differs by fetal sex, and placental dysfunction is associated with adverse pregnancy outcomes. We aimed to investigate the role of midpregnancy maternal circulating placenta-associated angiogenic biomarkers and fetal sex in relation to placental dysfunction-related pregnancy complications.
Methods
The Preventing Atopic Dermatitis and Allergies in children birth cohort study provided maternal serum from 2511 pregnancies at gestational weeks 16–22. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed by immunoassays. Pregnancy complications (n = 385) included gestational hypertension, preeclampsia, preterm delivery, and/or newborn weight <10th percentile; categorized as ‘uncomplicated’, ‘complicated’ and ‘severely complicated’ pregnancies by zero, one or two or more complications. The risk of ‘any number of pregnancy complications’ by biomarkers tertiles were assessed in multivariable logistic regression models with interaction analyses of fetal sex.
Results
Midpregnancy median PlGF was lower and sFlt-1 higher in pregnancies with a female versus a male fetus, with median (interquartile range) sFlt-1/PlGF-ratio being 7.2 (4.9–10.2) versus 6.4 (4.3–9.0) in ‘uncomplicated’, 7.3 (4.7–10.7) versus 6.4 (4.5–9.0) in ‘complicated’, and 11.2 (5.4–22.7) versus 5.9 (4.8–13.4) in ‘severely complicated’ pregnancies. The risks of ‘any number of pregnancy complications’ were highest in the lowest tertile of PlGF (adjusted odds ratio (aOR) 1.6, 95 % confidence interval (CI): 1.2–2.2) and sFlt-1 (aOR 1.4, 95 % CI: 1.0–1.9) without influence of fetal sex (all, pinteractions >0.05).
Conclusion
Circulating midpregnancy placenta-associated angiogenic biomarkers differed by fetal sex and pregnancy complications. The higher risk of pregnancy complications with low midpregnancy PlGF and/or sFlt-1 levels was not influenced by fetal sex.
期刊介绍:
Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.