The developmental origins of adult disease theory support the concept that undernourished fetuses are at risk of developing metabolic syndrome due to the energy-saving ‘Thrifty Phenotype’. This metabolic plasticity represents an evolutionary adaptation that allows individuals to resist the intense pressure caused by cyclically recurring periods of nutritional deprivation. A comprehensive review was conducted following an extensive literature search in the PubMed/Medline and EMBASE databases concerning reports on fetal/intrauterine growth restriction and its metabolic-related long-term outcomes. We only included articles written in English that were published before 1 July 2024. There are several underlying mechanisms and metabolic and endocrine adjustments shaped by the perinatal environment, and they all contribute to progression towards adult disease. From in utero malnutrition or other insults during the fetal period to fetal programing and postnatal catch-up growth, it is difficult to identify the exact moment when this adaptative phenomenon meant to assure fetal survival and to set children on their own physiological growth curves lose its beneficial effect, establishing the trajectory to obesity, insulin resistance, and other hallmarks of metabolic syndrome. With clinical correspondence to an altered body mass, composition, and eating behaviors, it is evident that the metabolic complications linked to FGR are intricate and arise from disturbances in several pathways and organs, but the underlying processes responsible for the long-term consequences are just starting to be understood. The lack of continuity in perinatal-to-pediatric FGR research sets the challenge of exploring new directions in future scientific opportunities. These will hopefully represent a cornerstone in the management of FGR-related metabolic disorders in children, preventing these disorders from evolving into adult disease.

Background/Objectives: Fetal growth restriction (FGR) describes the situation of a fetus that fails to reach its genetic growth potential. Postnatal catch-up growth represents a central adaptive process, yet its timing and magnitude vary widely and may influence one individual’s state of health and later metabolic risk. This study aimed to characterize longitudinal growth trajectories from birth to 10 years in children born at term, affected antenatally by growth restriction, with a particular focus on the influence of sex and FGR severity on catch-up growth. Methods: We conducted a retrospective observational study including 170 term-born children with documented FGR, admitted to a tertiary pediatric center between 2019 and 2023. Anthropometric data (weight, length/height, BMI) at birth, 1, 2, 5, and 10 years were converted to World Health Organization (WHO) age- and sex-adjusted z-scores. Catch-up growth was defined as an increase of >0.67 SD. Participants were stratified by sex and FGR severity (moderate: 10th–3rd percentile; severe: <3rd percentile). Results: Severe FGR infants exhibited significantly lower birth anthropometrics but demonstrated more pronounced early catch-up in weight and length at 1 and 2 years (p < 0.01). By 5 and 10 years, growth trajectories converged between severity groups, with no differences in BMI at any age. Sex influenced absolute anthropometric values but not the probability of achieving catch-up growth. Conclusions: Among term-born FGR infants, severity—but not sex—shapes early postnatal growth. Despite early deficits, most children achieved substantial catch-up, underscoring the need for careful monitoring to support healthy, proportionate growth and mitigate subsequent metabolic risk.

Background/Objectives: Fetal growth restriction (FGR) represents a model of adverse intrauterine programming associated with an increased risk of cardiometabolic disorders later in life. We examined the relationships between birth weight, catch-up growth, adipokine signaling, and early cardiometabolic risk in adolescents. Methods: This cross-sectional study included 80 term-born adolescents (40 FGR, 40 controls) matched for age and sex. Anthropometry, blood pressure, lipid profile, fasting glucose, adipokines (leptin, adiponectin), and ghrelin levels were assessed. Associations between birth weight, growth rate, adipokines, and cardiometabolic outcomes were analyzed. Results: Birth weight was not associated with adiposity, lipid profile, blood pressure, or glycemic status (p > 0.05). In contrast, catch-up growth in the FGR group was correlated with increased BMI (ρ = 0.680, p < 0.001), central adiposity (ρ = 0.714, p < 0.001), systolic blood pressure (ρ = 0.448, p = 0.0037) and diastolic blood pressure (ρ = 0.325, p = 0.0409). Mediation analyses showed that the current BMI largely explains the associations between catch-up growth and cardiometabolic risk, systolic blood pressure, and waist circumference (β = 2.832 kg/m² per 1-unit increase in ΔZ; p < 0.001). The hypertensive effect of catch-up growth was amplified in overweight/obese adolescents (β = 8.13 mmHg; p = 0.006). Catch-up growth was independently associated with higher leptin (β = 220 ng/L; p = 0.022) and a higher leptin/ghrelin ratio (β = 2.330; p = 0.034). Conclusions: Postnatal growth acceleration, rather than fetal size alone, drives early cardiometabolic susceptibility following FGR through adiposity-mediated and endocrine pathways.

Background: Congenital heart disease (CHD) co-occurring with fetal growth restriction (FGR) is clinically important but incompletely characterized. We assessed the proportion and subtype spectrum of CHD in term-born children with FGR, and factors associated with its presence and complexity. Methods: Retrospective analysis of 375 term singleton children with documented FGR at a tertiary pediatric center. CHD required echocardiographic confirmation; isolated patent foramen ovale was excluded. Patients with multiple lesions were hierarchically classified as simple or complex. Multivariable logistic regression was restricted to characteristics available at or before birth. Results: CHD was confirmed in 96/375 children (25.6%): 71 (74.0%) simple, 25 (26.0%) complex. Atrial septal defect and patent ductus arteriosus were most frequent (each 45.8%), followed by patent foramen ovale (44.8%) and ventricular septal defect (32.3%). Severe FGR (aOR 2.012, 95% CI 1.222–3.313; p = 0.006) and genetic syndrome (aOR 5.969, 95% CI 2.565–13.889; p < 0.001) were independently associated with CHD presence. Within the CHD subgroup, genetic syndrome was also associated with complex disease (aOR 5.156, 95% CI 1.651–16.104; p = 0.005). Diagnosis occurred before six months in 95.8%. Hospitalization outcomes and comorbidity burden did not differ by complexity. Conclusions: FGR severity and genetic syndrome were both independently associated with the presence of a cardiac defect, and genetic syndrome was further associated with its complexity. These findings support targeted rather than universal echocardiographic assessment. Directionality cannot be established from postnatal data.

Background/Objectives: Fetal growth restriction (FGR) and small for gestational age (SGA) status are related but distinct entities, both linked to increased long-term cardiometabolic risk, potentially mediated by the gut microbiome–metabolome axis during the first 1000 days of life. This review synthesizes current evidence on gut dysbiosis, host and microbial metabolites, catch-up growth, and probiotic interventions in these populations. Methods: A structured narrative review of human and animal studies published in English between January 2010 and August 2026 was conducted across PubMed/MEDLINE, Embase, Scopus, and Web of Science. Results: Reported alterations in gut microbial composition and function are heterogeneous, without a single, consistently replicated taxonomic signature, and much of the evidence derives from SGA or preterm cohorts rather than antenatally confirmed FGR. Metabolomic studies recurrently implicate host amino-acid, acylcarnitine, and phospholipid pathways, but small samples, heterogeneous platforms, and incomplete reporting of metabolite identification, normalization, and gestational age at sampling limit comparability. Mechanistic animal studies support selected pathways linking maternal dysbiosis to placental dysfunction, though the full sequence from early microbial alterations to catch-up growth and cardiometabolic risk remains unproven in humans. Gut microbial diversity has been associated with catch-up weight gain in one small SGA cohort, and delayed microbiota maturation with postnatal growth failure in some, but not all, preterm cohorts. Evidence from preterm populations supports benefits of selected probiotic preparations for some neonatal outcomes, while effects on short-term growth are modest and heterogeneous; probiotics have not been shown to modify catch-up-growth quality or long-term cardiometabolic outcomes after FGR, and safety and efficacy appear product-, strain-, and population-specific. Conclusions: Current evidence supports plausible, partially demonstrated mechanistic links between FGR/SGA, gut dysbiosis, and cardiometabolic programming, but not a fully validated causal pathway in humans. Future studies should distinguish FGR from SGA, assess body composition alongside growth, and evaluate product-specific probiotic efficacy and safety with long-term follow-up.

Background: Idiopathic nephrotic syndrome (NS) in children is characterized by urinary protein loss and potential disruptions in trace element homeostasis. The dynamic changes in zinc, copper, and magnesium levels in relation to disease activity remain incompletely defined. Objective: This study aimed to evaluate serum zinc, copper, and magnesium and urinary copper and magnesium alterations in homeostasis in pediatric nephrotic syndrome and to examine their associations with disease stage, proteinuria, disease duration, renal function, and corticosteroid response. Materials and Methods: This is a prospective cohort study involving 108 participants, including 74 pediatric patients with idiopathic nephrotic syndrome and 34 healthy controls, comprising 164 clinical and biological assessments. Serum and urinary concentrations of Zn, Cu, and Mg were analyzed, alongside clearance parameters and the fractional excretion of magnesium. Statistical analysis included non-parametric tests, Spearman correlations, ROC analysis, and multivariable logistic regression. Results: Serum zinc levels were significantly lower during active disease phases and normalized during remission (p < 0.001); however, these differences in serum zinc concentration with stages of the NS disappeared after adjustment for serum protein levels (p = 0.424), suggesting a transport deficit secondary to hypoproteinemia. Although serum zinc concentrations were also significantly reduced in patients with concomitant infection, adjustment for serum protein levels attenuated this association, and the zinc-to-protein ratio did not differ significantly according to infection status (p = 0.08). Urinary copper levels and clearance were elevated during active disease and positively correlated with proteinuria (rho = 0.35–0.38; p < 0.001); the Cu/Zn ratio varied significantly across disease stages (p < 0.001) and was associated with both disease activity and a tendency toward corticosteroid resistance. Magnesium demonstrated a pattern of tubular conservation during active phases, with elevated fractional excretion values during remission (p < 0.001) and inverse correlations with proteinuria. Disease duration, but not relapse burden, was positively correlated with serum zinc and fractional magnesium excretion and inversely correlated with serum magnesium. In the multivariable analysis, serum proteins emerged as the sole independent predictor of disease activity, while age and the Cu/Zn ratio were associated with corticosteroid resistance. Conclusions: Pediatric nephrotic syndrome induces significant alterations in zinc, copper, and magnesium homeostasis, dependent on glomerular permeability and plasma protein status. Zinc changes with stages of NS likely reflect a secondary transport defect. In contrast, zinc changes with infection likely occurred because of a shift of zinc to the intracellular compartment. Urinary copper serves as a marker of glomerular permeability and magnesium highlights tubular adaptation. The Cu/Zn ratio and magnesium handling parameters may prove clinically useful in monitoring disease activity and treatment response.