Background/Aims: Since the introduction of Assisted Reproduction Technologies (ART), including classic In Vitro Fertilization (IVF) and Intacytoplasmic Sperm Injection (ICSI), in clinical practice, several studies have addressed concerns regarding the long-term health of the offspring, revealing indications of an adverse cardiometabolic outcome. Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulating level is significantly associated with an increased risk of cardiovascular events and may be used as a reliable biomarker. In this study, we aimed at investigating the PCSK9 levels and lipidemic profile of children born ART compared with naturally conceived (NC) controls.
Methods: In this cross-sectional, case-control study, 73 sex- and age-matched children (mean age 98±35 months) of ART (ICSI: n=33, classic IVF: n=40) and 73 NC children were assessed. Blood was drawn for assessment of lipid biomarkers, including PCSK9 and Lp(a) levels, as well as glycemic and inflammatory biomarkers. The role of age in levels of PCSK9 was also evaluated, when age was considered as a categorical variable. For the purpose of this analysis, subjects were classified according to their age in 3 groups (group 1: <8 years, group 2: 810 years and group 3: ≥10 years).
Results: In the univariate model of the overall population, circulating PCSK9 levels were related to total cholesterol (r=0.186, P=0.025), LDL (r=0.180, P=0.029) and systolic blood pressure (SBP) (ρ=0.199, P=0.021). Also, in the univariate model of the overall population, circulating Lp(a) levels were related to age (r=0.269, P=0.001), apoB (r=0.214, P=0.01), birth weight (r=−0.183, P=0.037), height (r=0.263, P=0.001), waist to hip ratio (r=−0.350, P<0.001), Homeostasis Model Assessment of insulin resistance (r=0.319, P<0.001), insulin (r=0.316, P<0.001), and high-sensitivity C-reactive protein (ρ=0.241, P=0.018). No significant differences were observed regarding lipid parameters between ART and NC children. However, after adjusting for gender and LDL, a significant interaction was found between age groups and conception method (P for interaction<0.001, Figure), indicating that ART children increase their PCSK9 levels with age in contrary to NC children where levels of PCSK9 decrease with age. Moreover, after adjusting for age, gender and LDL, ART children conceived with IVF showed significantly higher levels of Lp(a) compared to ART children conceived with ICSI (6.5 mg/dl vs. 12.0 mg/dl, P=0.022)
Conclusion: This study demonstrates for the first time that PCSK9 levels increase with age in ART children indicating a gradual deterioration of lipidemic profile that could lead to increased cardiovascular risk in the future.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology