Endocrine Abstracts

Background: Cardiometabolic (CM) risk is linked to being small for gestational age (SGA, birthweight <-2SDS). Suboptimal fetal growth alone may be linked with greater CM risk without resulting in SGA. Therefore, we focused on CM risk in children born following pregnancies at higher risk for growth restriction, irrespective of birthweight.

Aims: 1. To identify associations between fetal and childhood weight trajectories and CM risk markers. 2. To define molecular pathways associated with CM risk.

Methods: We recruited 81 children aged 3-6 years, following term pregnancies at increased risk of growth restriction based on maternal antenatal serology (pregnancy associated plasma protein-A <0.415 multiples of the median (MoM), alpha fetoprotein >2.2 MoM or inhibin A >2 MoM). Body mass index (BMI) SDS, abdominal circumference (AC), mid-upper arm circumference (MUAC), %fat, systolic blood pressure (SBP) and brachial augmentation index (AI) were recorded. With consent, fasting blood samples were collected for CM markers and ‘omics analyses (n=31). Δfetal ([birthweight centile minus 23-week estimated fetal weight centile]/days) and Δchild ([weight centile minus birthweight centile]/years) were divided into quartiles and differences in CM markers compared between Q1 and Q4. Differentially expressed genes (DEGs) and metabolites (DEMs) were established using EdgeR and MetaboAnalyst. Gene set enrichment analysis (GSEA), a method used to identify over-represented genes within a set, enabled identification of pathways.

Results: 69% (56/81) had Δfetal <0, but only 12% (10/81) were born SGA. SBP was higher and HDL lower in Δfetal Q1 (lowest intrauterine weight gain) vs Q4 (highest intrauterine weight gain). SBP, BMI SDS, AC, MUAC, AI and %fat were higher in Δchild Q4 (highest childhood weight gain) vs Q1 (lowest childhood weight gain) (all p<0.05). GSEA based on DEGs between Δchild quartiles highlighted a pathway including ARG1. Ornithine was a DEM between Δfetal quartiles and also Δchild quartiles.

Conclusions: Low Δfetal and high Δchild were associated with CM risk, with a less favourable CM profile after pregnancies with suboptimal fetal growth. ‘Omics analyses uncovered the arginine-nitric-oxide pathway, which has previously been associated with hypertension. Ornithine and ARG1 could represent early-life indicators for hypertension in later-life.