781 Impact of perinatal factors on biomarkers of cardiovascular disease risk in preadolescent children

Abstract

<h3>Background</h3> Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality in adults. Arterial structure and function changes that increase arterial stiffness occur gradually over years but may be influenced by the perinatal environment. <h3>Objectives</h3> To systematically review the literature to determine how the perinatal environment impacts arterial structure and function in preadolescent children, following PRISMA guidelines. <h3>Methods</h3> PubMed was searched using the terms: ‘pulse wave velocity’ (PWV), ‘carotid intima-media thickness’ (cIMT), ‘arterial stiffness index’ (SIx), ‘flow-mediated dilation’ (FMD), ‘flow imaging’, ‘laser flow Doppler’, ‘venous plethysmography’, ‘cardi* magnetic resonance imaging’, ‘aortic intima-media thickness’ (aIMT), ‘vascular ultrasound’ and ‘neonat*’, ‘paediatric’, ‘infant*’, ‘child*’. Case reports, case series, reviews, commentaries, conference proceedings, animal studies, articles not in English and articles with children &gt;12 years old were excluded. Articles exploring the impact of perinatal factors on arterial structure and function were included. <h3>Results</h3> 28/1084 studies identified were included. PWV, a measure of arterial stiffness, was performed in 20 studies, including brachio-femoral (bfPWV), carotid-femoral (cfPWV), brachio-radial (brPWV) and aortic PWV (aPWV). Two studies measured the augmentation index (AIx), and two measured stiffness index (SIx), both indicators of vessel stiffness. Five studies measured cIMT and aIMT, since wall thickness can influence arterial stiffness. 17/28 studies explored perinatal maternal factors. Maternal age, serum ferritin, ethnicity, and psychosocial stress did not significantly impact neonatal PWV. Oily fish consumption in late pregnancy was associated with lower childhood aortic PWV (0.084m/s/portion/week; 95% CI: −0.137 to −0.031;<i> p</i>=0.002); maternal alcohol consumption in the second trimester was associated with increased cfPWV at 9 years (0.2m/s higher; 95% CI: 0.06 – 0.4, <i>p</i>=0.02). Maternal diabetes was associated with higher neonatal and infant PWV (two studies). The reported impact of maternal blood pressure (BP) varied: no association was found with infant bfPWV, but an inverse relationship was found between neonatal aPWV and maternal BP (r=-0.57m/s; 95% CI -0.67 to -0.45). cIMT in five-year-olds was 0.61μm greater per 1mmHg increased maternal BP. Eight studies explored the impact of fetal growth restriction (FGR) or small for gestational age (SGA), and three explored prematurity. FGR infants had a greater rise in brPWV between 1 week and 6 months old compared to appropriately grown infants (1.5 vs 0.9cm/s increase, <i>p</i>=0.03); however, aPWV and SIx did not differ between groups. One-week-old SGA infants had higher weight-adjusted aIMT (383±163 vs 256±43μm/kg, <i>p</i>≤0.001) and SIx (2.0±1.7 vs 1.1±0.4β/kg, <i>p</i>=0.005) than appropriately grown infants. Prematurity was associated with increased aortic stiffness in 2/3 studies: for example, AIx values were 5% higher (95% CI: 2%-8%) in 11-year-olds born ≤25 weeks. However, in six-year-olds, SIx and cIMT were similar in term and preterm (&lt;27 weeks) cohorts. <h3>Conclusions</h3> Studies included used diverse methods and different ages of participants, and inconsistent definitions for SGA/FGR were applied. Nevertheless, the perinatal environment appears to influence offspring arterial structure and function in preadolescent children. Future research should aim to establish reference values for arterial stiffness-related measures in preadolescent children using consistent methodologies, in order to allow earlier, targeted clinical and public health interventions focused on those at the highest long-term cardiovascular risk.