Early life determinants of vascular structure in foetuses, infants, children and adolescents: A systematic review and meta-analysis

Background and Aims : The first 1,000 days of life shape lifelong health, including cardiovascular disease (CVD) risk. Aortic intima-media thickness (aIMT), a measure of subclinical atherosclerosis, is an early indicator of CVD, amenable to change from as early as in-utero. We investigated the association between early life risk factors/exposures during the first 1,000 days and aIMT in youth.Methods: MEDLINE, EMBASE, Scopus, CINAHL and AMED were searched from inception to July 2021. Eligible criteria: observational controlled studies in youth aged <20 years with risk factors/exposures during the first 1,000 days and aIMT measurement. Outcome data were pooled using random-effects meta-analysis. Meta-regression and moderator analysis were used to investigate potential confounders.Results: 8,657 articles were identified and 34 included. Age ranged 22.9 weeks gestation in-utero to 10.9 years. In meta-analysis (n= 1,220 cases, n=1,977 controls), greater aIMT was associated with small for gestational age (SGA): 14 studies, mean difference (MD) 0.082mm, [95% CI 0.051, 0.112], p<.001, I2=97%; intrauterine growth restriction (IUGR), 6 studies, 0.198mm [0.088, 0.309], p<.001, I2=97.3%; preeclampsia: 2 studies, 0.038mm [0.024, 0.051], p<.001, I2=38%, and large for gestational age (LGA): 3 studies, 0.089mm [0.043, 0.0136], p<.001, I2=93%. In meta regression, older age (p<.001), maternal smoking (p=.040) and SGA (p<.001) were associated with greater difference in aIMT in pre-term participants vs controls.Conclusions: Greater aIMT in youth with SGA, IUGR, preeclampsia or LGA is putatively consistent with increased risk for CVD later in life. Further research is required to determine whether intervention and preventative strategies reduce future CVD risk in this population. Background and Aims : The first 1,000 days of life shape lifelong health, including cardiovascular disease (CVD) risk. Aortic intima-media thickness (aIMT), a measure of subclinical atherosclerosis, is an early indicator of CVD, amenable to change from as early as in-utero. We investigated the association between early life risk factors/exposures during the first 1,000 days and aIMT in youth. Methods: MEDLINE, EMBASE, Scopus, CINAHL and AMED were searched from inception to July 2021. Eligible criteria: observational controlled studies in youth aged <20 years with risk factors/exposures during the first 1,000 days and aIMT measurement. Outcome data were pooled using random-effects meta-analysis. Meta-regression and moderator analysis were used to investigate potential confounders. Results: 8,657 articles were identified and 34 included. Age ranged 22.9 weeks gestation in-utero to 10.9 years. In meta-analysis (n= 1,220 cases, n=1,977 controls), greater aIMT was associated with small for gestational age (SGA): 14 studies, mean difference (MD) 0.082mm, [95% CI 0.051, 0.112], p<.001, I2=97%; intrauterine growth restriction (IUGR), 6 studies, 0.198mm [0.088, 0.309], p<.001, I2=97.3%; preeclampsia: 2 studies, 0.038mm [0.024, 0.051], p<.001, I2=38%, and large for gestational age (LGA): 3 studies, 0.089mm [0.043, 0.0136], p<.001, I2=93%. In meta regression, older age (p<.001), maternal smoking (p=.040) and SGA (p<.001) were associated with greater difference in aIMT in pre-term participants vs controls. Conclusions: Greater aIMT in youth with SGA, IUGR, preeclampsia or LGA is putatively consistent with increased risk for CVD later in life. Further research is required to determine whether intervention and preventative strategies reduce future CVD risk in this population.