Association of fetal sex with angiogenic factors in normotensive and hypertensive pregnancy states.

Abstract

With the incorporation of angiogenic biomarkers into clinical practice, identification of potential modifiers of the angiogenic profile, including fetal sex, is essential. In this retrospective cohort analysis, patients with hypertensive disorders of pregnancy (HDP) and normotensive pregnancies were enrolled upon admission to Labor and Delivery. Blood samples for angiogenic factors were assessed using an automated platform. Clinical and demographic information was abstracted from each patient's medical records. Soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) levels and their ratio in relation to fetal sex in patients with normotensive pregnancies compared to those with HDP were evaluated. A total of 617 patients were analyzed (299 normotensive, 113 gestational hypertensive, 71 chronic hypertensive, and 134 preeclamptic patients). There was no difference between the number of patients who had a male fetus among preeclampsia and normotensive parturients (56.0% vs 50.2%, p=0.26). Normotensive patients carrying a male fetus had significantly higher sFlt1 (pg/ml) (3168 [IQR: 2160-4945] vs 2678 [IQR: 1752-4271]; p=0.01) and sFlt1/PlGF ratios (18 [IQR: 7-44] vs 12 [IQR: 5-30]; p=0.01) in comparison to pregnant patients carrying a female fetus. This difference between fetal sexes was not observed in the angiogenic profile of patients with HDP. Our study of primarily Black, obese patients demonstrates that normotensive patients carrying a male fetus have a significantly higher sFlt1 and sFlt1/PlGF ratio as compared to those carrying a female fetus at term gestation. Fetal sex should be considered as a covariate when studying angiogenic factors in normotensive pregnant patients.