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.