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.

Early life determinants of arterial stiffness in neonates, infants, children and adolescents: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Certain exposures and risk factors during the first 1,000 days of life are known to influence future cardiovascular disease (CVD) risk. Pulse wave velocity (PWV) is a measure of arterial stiffness and a recognised surrogate marker of CVD. We performed a systematic review and meta-analyses to investigate whether early life exposures were associated with increased PWV compared with controls in youth. METHODS: Databases AMED, MEDLINE, EMBASE, CINAHL and Scopus were searched from inception until February 2022. ELIGIBILITY CRITERIA: observational controlled studies in youth aged <20 years with risk factors/exposure during the first 1,000 days and PWV measurement. This review is registered with PROSPERO (CRD42019137559). Outcome data were pooled using random-effects meta-analysis. Meta-regression was used to investigate potential confounders. RESULTS: We identified 24 eligible studies. Age of participants ranged from 1-day to 19-years at time of PWV assessment. Exposures included pre-term birth, small for gestational age (SGA), maternal diabetes and assisted reproductive technologies, none of which were significantly associated with PWV in meta-analysis. Sub-group analysis by age demonstrated increased PWV in childhood and adolescence in those exposed to maternal diabetes or born SGA. In meta-regression of pre-term studies, higher prevalence of SGA was associated with increased PWV compared with controls (p = 0.034, R2 = 1). CONCLUSIONS: We found limited evidence that youth exposed to maternal diabetes or born SGA have increased PWV, consistent with increased future CVD risk. These changes in PWV appear to manifest in later childhood and adolescence. Further research is required to better understand the observed relationships.

Biomarkers of dietary patterns: a systematic review of randomized controlled trials.

CONTEXT: Most methods for assessing dietary intake have considerable measurement error. Dietary biomarkers are objective tools for dietary assessment. Dietary biomarkers of dietary patterns have not been well described, despite modern dietary guidelines endorsing dietary patterns. OBJECTIVE: This systematic review sought to describe the dietary biomarkers commonly used to assess dietary patterns, and the novel biomarkers of dietary patterns identified by exploratory studies. DATA SOURCES: MEDLINE, Embase, Cochrane Central, PreMEDLINE, and CINAHL databases were searched. DATA EXTRACTION: Data extraction and bias assessment were undertaken in duplicate. DATA ANALYSIS: A qualitative approach was applied, without statistical analysis. CONCLUSION: In controlled settings, dietary biomarkers of single nutrients or of individual foods or food groups are commonly used to assess compliance with dietary patterns. However, currently, there are no dietary biomarkers or biomarker profiles that are able to identify the specific dietary pattern that has been consumed by an individual. Future work should seek to validate novel dietary biomarkers and biomarker profiles that are indicative of specific dietary patterns and their characteristics. A dietary biomarker panel consisting of multiple biomarkers is almost certainly necessary to capture the complexity of dietary patterns. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019129839.

Aortic intima media thickness in children and adolescents with type 1 diabetes: A systematic review.

AIMS: Greater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta-analysis compared aIMT in youth with type 1 diabetes and healthy controls. METHODS: A systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta-analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection. RESULTS: Meta-analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure. CONCLUSIONS: Type 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559).

Rab13 and Desmosome Redistribution in Uterine Epithelial Cells During Early Pregnancy.

The luminal uterine epithelial cells are the first point of contact with the implanting blastocyst. Dramatic changes occur in the structure and function of these cells at the time of receptivity including changes in the lateral junctional complex. While these morphological changes are important for uterine receptivity, currently there is no known mechanism of regulation of the lateral junctional complexes. Rab13, a member of the Rab (Ras-related in the brain) family of GTPases has a critical role in endosomal trafficking to the lateral plasma membrane and is involved in modulation of the tight junction in several cell types. The aim of this study is to investigate the role of Rab13 in changes to the lateral junctional complex at the time of receptivity. Immunofluorescence microscopy demonstrated no association between Rab13 and ZO-1 (a tight junction protein) or Rab13 and E-cadherin (an integral component of adherens junctions). Co-localisation was demonstrated between Rab 13 and desmoglein-2 at the time of fertilization and also at receptivity suggesting involvement of Rab13 in relocalisation of desmoglein-2 and formation of giant desmosomes in the apical part of the lateral plasma membrane at the time of uterine receptivity. We suggest that despite the loss of the adherens junction at the time of receptivity, the presently reported redistribution of desmosomes regulated by Rab13 allows the uterine epithelium to maintain structural integrity.