Background: Probiotic supplementation to women during pregnancy and lactation can modulate breast milk composition, with immune benefits being transferred to their infants. Aim: The aim of the study was to evaluate the effect of high-dose probiotic supplementation to women during late pregnancy and lactation on cytokine profile and secretory IgA (sIgA) in breast milk and thus to study if differences in breast milk composition can affect lactoferrin and sIgA levels in stool samples of newborns. The safety of maternal probiotic administration on neonatal growth pattern and gastrointestinal symptoms were also evaluated. Methods: In a double-blind, placebo-controlled, randomized trial, 66 women took either the probiotic (n = 33) or a placebo (n = 33) daily. Levels of interleukins (IL-6, IL-10 and IL-1β), transforming growth factor-β1 (TGF-β1), and sIgA in breast milk; and the level of sIgA and lactoferrin in newborn stool samples were analyzed at birth and then again at one month of life. Antropometrical evaluation and analysis of gastrointestinal events in newborns was also performed. Results: Probiotic maternal consumption had a significant impact on IL6 mean values in colostrum and on IL10 and TGF-β1 mean values in mature breast milk. Fecal sIgA mean values were higher in newborns whose mothers took the probiotic product than in the control group. Probiotic maternal supplementation seems to decrease incidence of infantile colic and regurgitation in infants. Conclusion: High-dose multi-strain probiotic administration to women during pregnancy influences breast milk cytokines pattern and sIgA production in newborns, and seems to improve gastrointestinal functional symptoms in infants.

The pubertal development onset is controlled by a network of genes that regulate the gonadotropin releasing hormone (GnRH) pulsatile release and the subsequent increase of the circulating levels of pituitary gonadotropins that activate the gonadal function. Although the transition from pre-pubertal condition to puberty occurs physiologically in a delimited age-range, the inception of pubertal development can be anticipated or delayed due to genetic and epigenetic changes or environmental conditions. Most of the genetic and epigenetic alterations concern genes which encode for kisspeptin, GnRH, LH, FSH and their receptor, which represent crucial factors of the hypothalamic-pituitary-gonadal (HPG) axis. Recent data indicate a central role of the epigenome in the regulation of genes in the hypothalamus and pituitary that could mediate the flexibility of pubertal timing. Identification of epigenetically regulated genes, such as Makorin ring finger 3 (MKRN3) and Delta-like 1 homologue (DLK1), respectively responsible for the repression and the activation of pubertal development, provides additional evidence of how epigenetic variations affect pubertal timing. This review aims to investigate genetic, epigenetic, and environmental factors responsible for the regulation of precocious and delayed puberty.

The purpose of this narrative review was to investigate the key determinants of musculoskeletal health in childhood and adolescence, with particular attention to the role of physical activity. First, we examined the importance of bone modeling and remodeling in maintaining the bone health and the integrity and mechanical characteristic of the skeleton. In addition, we reported the evidence on an appropriate calcium and vitamin D intake, as well as local load variation in achieving proper peak bone mass. Proteomic and transcriptomic studies identified the skeletal muscle “secretoma”, consisting of several myokines involved in endocrine and paracrine functions. Among these, we explored the role of irisin, a myokine involved in the muscle-bone crosstalk, and in the regulation of metabolic pathways. It is known that physical activity during growing positively impacts on skeleton and can protect by bone loss in adulthood. However, there are still concerns about the optimal interval duration and exercise intensity, particularly at the pubertal growth spurt which represents a window of opportunity to increase skeletal strength. We reported data from clinical trials performed in the last 5 years analyzing the impact of the type and timing of physical activity during childhood on skeletal development. Finally, we reported recent data on the significance of physical activity in some rare diseases.

Sickle bone disease (SBD) is a chronic and invalidating complication of Sickle cell disease (SCD), a multisystem autosomal recessive genetic disorder affecting millions of people worldwide. Mechanisms involved in SBD are not completely known, especially in pediatric age. Among the hypothesized pathogenetic mechanisms underlying SBD are bone marrow compensatory hyperplasia and bone ischemic damage, both secondary to vaso-occlusive crisis (VOC), which leads to cell sickling, thus worsening local hypoxia with a negative impact on osteoblast recruitment. Furthermore, the hypoxia is a strong activator of erythropoietin, which in turn stimulates osteoclast precursors and induces bone loss. Hemolysis and iron overload due to a chronic transfusion regimen could also contribute to the onset of bone complications. Vitamin D deficiency, which is frequently seen in SCD subjects, may worsen SBD by increasing the resorptive state that is responsible for low bone mineral density, acute/chronic bone pain, and high fracture risk. An imbalance between osteoblasts and osteoclasts, with a relative decrease of osteoblast recruitment and activity, is a further possible mechanism responsible for the impairment of bone health in SCD. Moreover, delayed pubertal growth spurt and low peak bone mass may explain the high incidence of fracture in SCD adolescents. The aim of this review was to focus on the pathogenesis of SBD, updating the studies on biochemical, instrumental, and biological markers of bone metabolism. We also evaluated the growth development and endocrine complications in subjects affected with SCD.

Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to long-term metabolic and cardiovascular diseases. The “Developmental Origins of Health and Disease” (DOHaD) paradigm provides a framework for understanding how early life environmental exposures, particularly during the periconceptional, fetal, and neonatal periods, can program future health outcomes through epigenetic mechanisms. Epigenetic modifications alter gene expression without changing the DNA sequence and are increasingly recognized as key mediators in the development of obesity. This narrative review summarizes current findings on the early determinants of childhood obesity, emphasizing the molecular and epigenetic pathways involved. A comprehensive literature search was conducted across multiple databases and international sources, focusing on recent studies from the past decade. Both human and animal research were included to provide a broad perspective. This review aims to consolidate recent insights into early life influences on obesity, underscoring the need for preventive strategies starting as early as the preconception period.