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Placenta · 2025

Midpregnancy maternal circulating angiogenic biomarkers: Associations with placental dysfunction-related pregnancy complications and fetal sex.

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Sundet Birgitte Kordt, Lødrup Carlsen Karin C, Haugen Guttorm, Hedlin Gunilla, Hilde Katarina, Jonassen Christine M, Nordlund Björn, Rehbinder Eva Maria, Rueegg Corina Silvia, Sjøborg Katrine, Skjerven Håvard O, Söderhäll Cilla, Vettukattil Riyas, Værnesbranden Magdalena R, Wiik Johanna, Staff Anne Cathrine, Sugulle Meryam

Аннотация

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.

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