Early Life Determinants of Vascular Structure in Fetuses, Infants, Children, and Adolescents: A Systematic Review and Meta-Analysis

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To investigate the association between early life exposures during the first 1000days (conception to age 24months) and aortic intima-media thickness (aIMT), an early indicator of cardiovascular disease (CVD) risk, in youths. The MEDLINE, Embase, Scopus, CINAHL, and Allied and Complementary Medicine databases were searched from inception to July 2021. Eligibility criteria included observational controlled studies in youths aged <20years with risk factors/exposures during the first 1000days and aIMT measurements (unadjusted mean±SD). Outcome data were pooled using a random-effects meta-analysis. Meta-regression was used to investigate confounders. A total of 8657 articles were identified, of which 34 were included in our meta-analysis. The age of participants ranged from 22.9weeks gestation in utero to 10.9years. In the meta-analysis (n=1220 cases, n=1997 controls), the following factors were associated with greater aIMT: small for gestational age (SGA) status (14 studies, mean difference, 0.082mm; 95% CI, 0.051-0.112; P<.001; I2=97%), intrauterine growth restriction (6 studies; mean difference, 0.198mm, 95% CI, 0.088-0.309; P<.001; I2=97%), preeclampsia (2 studies; mean difference, 0.038mm; 95% CI, 0.024-0.051; P<.001; I2=38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089mm; 95% CI, 0.043-0.0136; P<.001; I2=93%). In meta-regression, older age (P<.001), higher prevalence of maternal smoking (P=.04), and SGA (P<.001) were associated with greater difference in aIMT in preterm participants compared with controls. Limitations included the high heterogeneity present in most meta-analyses and the scope of our meta-regression. Adverse early life exposures are associated with greater aIMT in youths, consistent with an increased risk for CVD later in life. Further research is needed to determine whether intervention and preventive strategies deliver clinical benefits to improve future cardiovascular health.