Maternal Obesity Modulates Cord Blood Concentrations of Proprotein Convertase Subtilisin/Kexin-type 9 Levels

Abstract

Context In utero exposure to maternal obesity or diabetes is considered a pro-inflammatory state. Objective To evaluate whether cord blood Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9), that is regulated by inflammation and metabolic derangements, is elevated in neonates born to overweight, obese, or diabetic mothers. Methods A retrospective study in full-term neonates born between 2010 and 2023, at Brigham and Women’s Hospital. There were 116 neonates included in our study, of which 74 (64%) were born to overweight/obese mothers and 42 (36%) were born to non-overweight/non-obese mothers. Results Neonates born to overweight/obese mothers had significantly higher cord blood concentrations of PCSK9 compared to neonates born to non-overweight/non-obese group [323 (253-442) ng/ml compared to 270 (244-382) ng/ml, p=0.041]. We found no significant difference in cord blood concentrations of PCSK9 between neonates of diabetic mothers compared to neonates of non-diabetic mothers. In multivariate linear regression analysis, higher cord plasma PCSK9 concentration was significantly associated with maternal overweight/obesity status (b=50.12, 95%CI 4.02-96.22, p=0.033), after adjusting for gestational age, birth weight, male sex, and intrauterine growth restriction. Conclusion Neonates born to mothers with overweight/obesity have higher cord blood PCSK9 concentrations compared to non-overweight/non-obese group and higher cord blood PCSK9 concentrations were significantly associated with maternal overweight/obesity status, after adjusting for perinatal factors. Larger longitudinal studies are needed to examine the role of PCSK9 in the development of metabolic syndrome in high-risk neonates born to overweight, obese, or diabetic mothers.