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

OBJECTIVE: To investigate the association between early life exposures during the first 1000 days (conception to age 24 months) and aortic intima-media thickness (aIMT), an early indicator of cardiovascular disease (CVD) risk, in youths. STUDY DESIGN: 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 <20 years with risk factors/exposures during the first 1000 days and aIMT measurements (unadjusted mean ± SD). Outcome data were pooled using a random-effects meta-analysis. Meta-regression was used to investigate confounders. RESULTS: A total of 8657 articles were identified, of which 34 were included in our meta-analysis. The age of participants ranged from 22.9 weeks gestation in utero to 10.9 years. 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, 0.082 mm; 95% CI, 0.051-0.112; P < .001; I2 = 97%), intrauterine growth restriction (6 studies; mean difference, 0.198 mm, 95% CI, 0.088-0.309; P < .001; I2 = 97%), preeclampsia (2 studies; mean difference, 0.038 mm; 95% CI, 0.024-0.051; P < .001; I2 = 38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089 mm; 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. CONCLUSIONS: 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.

Leptin partially mediates the association between early-life nutritional supplementation and long-term glycemic status among women in a Guatemalan longitudinal cohort.

BACKGROUND: Early-life exposure to improved nutrition is associated with decreased risk of diabetes but increased risk of obesity. Leptin positively correlates with adiposity and has glucose-lowering effects, thus it may mediate the association of early-life nutrition and long-term glycemic status. OBJECTIVES: We aimed to investigate the role of leptin in the differential association between early-life nutrition and the risks of obesity and diabetes. METHODS: We analyzed data from a Guatemalan cohort who were randomly assigned at the village level to receive nutritional supplements as children. We conducted mediation analysis to examine the role of leptin in the associations of early-life nutrition and adult cardiometabolic outcomes. RESULTS: Among 1112 study participants aged (mean ± SD) 44.1 ± 4.2 y, 60.6% were women. Cardiometabolic conditions were common: 40.2% of women and 19.4% of men were obese, and 53.1% of women and 41.0% of men were hyperglycemic or diabetic. Median (IQR) leptin concentration was 15.2 ng/mL (10.2-17.3 ng/mL) in women and 2.7 ng/mL (1.3-5.3 ng/mL) in men. Leptin was positively correlated with BMI (Spearman's ρ was 0.6 in women, 0.7 in men). Women exposed to improved nutrition in early life had 2.8-ng/mL (95% CI: 0.3, 5.3 ng/mL) higher leptin and tended to have lower fasting glucose (-0.8 mmol/L; -1.8, 0.2 mmol/L, nonsignificant) than unexposed women. There were no significant differences in leptin (-0.7 ng/mL; -2.1, 0.8 ng/mL) or fasting glucose (0.2 mmol/L; -0.5, 0.9 mmol/L) in men exposed to improved nutrition in early life compared with unexposed men. Leptin mediated 34.9% of the pathway between early-life nutrition and fasting glucose in women. The mediation in women was driven by improved pancreatic ß-cell function. We did not observe the mediation effect in men. CONCLUSIONS: Leptin mediated the glucose-lowering effect of early-life nutrition in women but not in men.