Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?

Vitamin D, known for its essential role in calcium and bone homeostasis, has multiple effects beyond the skeleton, including regulation of immunity and modulation of autoimmune processes. Several reports have shown suboptimal serum 25 hydroxyvitamin D [25(OH)D] levels in people with different inflammatory and autoimmune rheumatic conditions, and an association between 25(OH)D levels, disease activity and outcomes. Although most available data pertain to adults, insights often are extended to children. Juvenile rheumatic diseases (JRDs) are a significant health problem during growth because of their complex pathogenesis, chronic nature, multisystemic involvement, and long-term consequences. So far, there is no definitive or clear evidence to confirm the preventive or therapeutic effect of vitamin D supplementation in JRDs, because results from randomized controlled trials (RCTs) have produced inconsistent outcomes. This review aims to explore and discuss the potential role of vitamin D in treating selected JRDs. Medline/PubMed, EMBASE, and Scopus were comprehensively searched in June 2023 for any study on vitamin D supplementary role in treating the most common JRDs. We used the following keywords: "vitamin D" combined with the terms "juvenile idiopathic arthritis", "juvenile systemic scleroderma", "juvenile systemic lupus erythematosus", "juvenile inflammatory myopathies", "Behcet disease", "periodic fever syndromes" and "juvenile rheumatic diseases". Observational studies have found that serum 25(OH)D concentrations are lower in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile systemic scleroderma, Behcet disease and proinflammatory cytokine concentrations are higher. This suggests that vitamin D supplementation might be beneficial, however, current data are insufficient to confirm definitively the complementary role of vitamin D in the treatment of JRDs. Considering the high prevalence of vitamin D deficiency worldwide, children and adolescents should be encouraged to supplement vitamin D according to current recommendations. More interventional studies, especially well-designed RCTs, assessing the dose-response effect and adjuvant effect in specific diseases, are needed to determine the potential significance of vitamin D in JRDs treatment.

Non-disease specific patient-reported outcome measures of health-related quality of life in juvenile idiopathic arthritis: a systematic review of current research and practice.

Juvenile idiopathic arthritis (JIA), as a chronic condition, is associated with symptoms negatively impacting health-related quality of life (HRQL). Regarding growing interest in the implementation of the patient-reported outcome measures (PROMs), we aimed to review the non-disease specific PROMs addressing HRQL assessment, potentially useful in the clinical care of JIA and daily practice. A systematic literature search was conducted using MEDLINE/PubMed, Google Scholar, Scopus and Embase databases (1990 to 2021), with a focus on the recent 5-years period. Entry keywords included the terms: "children", "adolescents", "JIA", "chronic diseases", "HRQL", "PROMs" and wordings for the specific tools. Several available PROMs intended to measure HRQL, non-specific to JIA, were identified. The presented outcomes differed in psychometric properties, yet all were feasible in assessing HRQL in healthy children and those with chronic diseases. Both EQ-5D-Y and PedsQL have already been tested in JIA, showing relevant reliability, validity, and similar efficiency as disease-specific measurements. For PROMIS® PGH-7 and PGH-7 + 2, such validation and cross-cultural adaptation need to be performed. Considering the future directions in pediatric rheumatology, the large-scale implementation of PROMIS® PGH-7 and PGH-7 + 2 in JIA offers a particularly valuable opportunity. The PROMs reflect the patient perception of the chronic disease and allow to understand child's opinions. The PROMs may provide an important element of the holistic medical care of patients with JIA and a standardized tool for clinical outcomes, monitoring disease severity and response to treatment.

Coincidence of juvenile idiopathic arthritis and type 1 diabetes: a case-based review.

The study was aimed to review a rare coexistence of type 1 diabetes (T1D) and juvenile idiopathic arthritis (JIA) regarding different clinical approaches to the management and treatment options. Medical complications of the two autoimmune disorders in children and adolescents have been evaluated, particularly in those treated with glucocorticosteroids (GCS) and insulin. A review of the literature regarding reports on concomitant T1D and JIA was conducted using resources available in Medline, Google Scholar, and Web of Science databases, with a specific focus on the combination of T1D and JIA in a pediatric population. The review was extended by our analysis of two patients treated in a single center for this comorbidity. Eligible reports of four cases were found, and including our two original records, a total of six pediatric patients (5 females) were analyzed, of which three had also other autoimmune diseases (thyroiditis, coeliac disease, autoimmune hepatitis), whereas four had been treated with a long-term GCS, and two were receiving biological therapy (etanercept or adalimumab). Only one of them had good metabolic control of diabetes. Diabetes in childhood may coexist with other autoimmune diseases, including rheumatologic conditions. Hyperglycemia can worsen JIA therapy by induction and maintaining inflammation. Using modern diabetes technologies (like personal insulin pumps and continuous glucose monitoring) helps to minimize the deteriorating effect of JIA exacerbations and the rheumatoid treatment on metabolic control of diabetes.

Salivary Content Might be Associated With Skeletal Status in Postmenopausal Women: SilesiaOsteoActive Study Results.

AIM: The aim of the study was to investigate whether salivary mineral content may be associated with bone status in women after menopause. MATERIAL AND METHODS: The study group consisted of 125 postmenopausal women aged 64.3 ± 6.9 yr, derived from the epidemiological SilesiaOsteoActive Study. All participants underwent hip and spine bone densitometry using dual energy X-ray absorptiometry, dental examination, and saliva content analysis. Data for salivary pH, copper, calcium, phosphorus, and zinc concentrations were evaluated. RESULTS: Mean femoral neck bone mineral density (BMD) was 0.739 ± 0.118 g/cm2, total hip BMD 0.891 ± 0.14 g/cm2, and spine BMD 0.868 ± 0.14 g/cm2. Salivary pH was significantly lower in women with spinal osteoporosis defined as T-score below -2.5, compared to individuals with normal BMD (pH: 6.65 ± 0.67 vs 6.96 ± 0.58, p < 0.05). There was a significant though weak inverse correlation between Ca concentration in saliva and femoral neck BMD (r = -0.23, p < 0.05). CONCLUSIONS: High salivary calcium content and low salivary pH may be indicative of low hip and decreased spine BMD, respectively. These associations may reflect demineralization process (calcium redistribution) influencing bone, and a negative effect of acidity on mineral tissues, although causal pathway remains not clear.

Regular physical activity as a physiological factor contributing to extend partial remission time in children with new onset diabetes mellitus-Two years observation.

BACKGROUND: Beneficial effects of physical activity (PA) are confirmed in patients with all types of long-lasting diabetes. The possibility of PA to be a factor prolonging remission phase in children with new-onset type 1 diabetes (T1D) has not yet been thoroughly studied. OBJECTIVE: The aim of the study was to elucidate the influence of regular PA on prevalence of partial remission (PR), metabolic control, daily insulin requirement (DIR), and C-peptide secretion in children newly diagnosed with T1D. METHODS: A total of 125 children diagnosed with T1D were studied prospectively for 2 years. Patients were controlled every 3 months and advised with PA according to ISPAD recommendations. Anthropometric parameters, HbA1c, C-peptide level and DIR were analyzed. Patients' PA level was assessed using a self-designed questionnaire. RESULTS: We classified 43% of participants as physically-active. In this group, lower HbA1c after 2 years, lower DIR after 3, 6 months, and after 2 years (all P < .05) were found. At discharge from hospital, the prevalence of DIR < 0.5 U/kg/24 h with near normoglycemia was similar in both groups. Then, we observed higher PR prevalence in active group lasting over time and resulting in 44% vs 13% after 2 years (P < .001). C-peptide after 2 years was comparable in both groups, with higher prevalence of clinically significant levels (>0.2 nmoL/L) in active group: 79.6% vs 61.4% (P = .029). CONCLUSIONS: These data support the view that regular PA may essentially contribute to extending PR time in pediatric diabetes, and may therefore lead to a better long-term metabolic control of the disease.

Evidence of a significant vitamin D deficiency among 9-13-year-old Polish children: results of a multicentre study.

PURPOSE: To evaluate the extent to which the population of Polish preadolescents is vitamin D deficient and to assess seasonal variations in vitamin D status. PARTICIPANTS AND METHODS: A total of 720 healthy children aged 9-13 years (409 girls, 311 boys) residing in 6 representative geographical locations in Poland were studied. A parental-assisted questionnaire provided data on nutritional habits, vitamin D supplements and sun exposure. Serum concentration of 25-hydroxyvitamin was determined twice, after the winter in March and after the summer in October. RESULTS: In March, vitamin D deficiency (25-50 nmol/L) was found in 64%, and severe deficiency (< 25 nmol/L) in 20.2% of children. In October, the deficiency and severe deficiency were still noticed in 25.9 and 0.1% of children, respectively. The mean serum concentration of 25-OHD was 52% higher in October (55.4 ± 14.0 nmol/L) than in March (36.4 ± 13.5 nmol/L), (p < 0.01). In children with 25-OHD < 50 nmol/L in March, their 25-OHD concentration increased by 64% through March to October (32.5 ± 8.2 vs. 53.2 ± 7.9 nmol/L, p < 0.01). An association was found between 25-OHD concentration and regular consumption of vitamin D supplements, cod-liver oil and fish. CONCLUSIONS: The majority of preadolescent Polish boys and girls show vitamin D deficiency after the winter period, although a distinct amelioration over summertime is found in this age group. There is a need to implement effective prevention and intervention strategies in the management of vitamin D deficiency among schoolchildren in Poland, with the supplementation throughout the entire year.

Correction to: Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis.

In the Original Publication, the e-mail address of the author Milan Petronijevic is incorrect. The correct e-mail address is milanpetronijevic@yahoo.com.

Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis.

Osteoarthritis (OA) is characterized by deterioration of the joints and associated with considerable pain and disability. OA is a chronic disease that requires intervention with both non-pharmacological and pharmacological treatment modalities and, inevitably, disease progression may necessitate successive treatments throughout the course of the disease. There is increasing data on the shortfalls of current pharmacological treatment of OA, and safety concerns associated with analgesic therapy use in OA arising from increasing evidence of gastrointestinal, cardiovascular, hepatic and renal adverse events with paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). Consequently, symptomatic slow-acting drugs for OA (SYSADOAs) may now be considered as a first-line treatment for knee OA, with a particular emphasis placed on the outstanding benefit: risk ratio of pharmaceutical-grade glucosamine and chondroitin sulfate formulations. In this short communication we review recent publications concerned with the safety of paracetamol, NSAIDs and SYSADOAs. Greater understanding of the benefits and limitations of current medications will lead to better disease management in OA. Furthermore, adherence to guideline recommendations across Europe and internationally, such as those from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), will promote evidence-based medicine and patient-centric care, ultimately leading to greater physician and patient satisfaction.

A 23-year follow-up of a male with Hajdu-Cheney syndrome due to NOTCH2 mutation.

We present a natural history of a 32-year-old man with Hajdu-Cheney syndrome (HJCYS), because of the de novo truncating mutation in the exon 34 of NOTCH2 (c.6424-6427delTCTG, p.Ser2142ArgfsX4), who has been followed up for a period of 23 years (between 9 and 32 years). During follow-up, we observed abnormalities of vision, hearing, voice, and progression of craniofacial features in the form of skeletal dysplasia with affected skull, dentition, spine, limbs, fingers, and toes. Low bone mineral density and history of fragility fractures also suggested primary osteoporosis being a clinical manifestation. According to Stengel-Rutkowski, Schimanek, and Wernheimer (1984; Human Genetics, 6, 272-295), systematic data acquisition has been used for quantitative analysis of anthropological, radiographic, and clinical features at childhood, adolescence, and young adulthood separately. A detailed phenotype description together with the results of reanalysis of 14 reports so far published on patients with HJCYS and NOTCH2 mutation showed similar phenotype evolution with age. The spectrum of observed features may improve diagnostic tools for HJCYS at different periods of the lifespan.

Serum profile of transferrin isoforms in juvenile idiopathic arthritis: a preliminary study.

It is reported that alterations in protein glycosylation are present in adult rheumatic diseases; however, the data related to pediatric rheumatic conditions are very scarce. The aim of this study was to assess the effect of juvenile idiopathic arthritis (JIA) on the serum glycosylation profile of transferrin isoforms. Twenty-five patients with different clinical forms of an active JIA and 22 healthy controls were studied. Serum samples were analyzed by capillary electrophoresis on MINICAP electrophoretic system (Sebia, France) to determine the levels of transferrin isoforms. In patients with JIA, tetrasialotransferrin (median 82.6%; range 68.8-99.5) concentration was lower (P = 0.032), and pentasialotransferrin (median 14%; range 0.5-31.2) was higher (P = 0.020) in comparison to controls (median 84.45; range 79.8-87.4; median 11.55; range 9.7-16.1, respectively). No significant correlations between concentration of transferrin isoforms and disease activity score (JADAS 27) or the degree of disability (VAS and CHAQ) were found. Erythrocyte sedimentation rate and CRP levels correlated positively with disialotransferrin (R = 0.493, P = 0.017; R = 0.850, P < 0.001, respectively) and pentasialotransferrin (R = 0.533, P = 0.006; R = 0.491, P = 0.045, respectively), and negatively with trisialotransferrin (R = - 0.546, P = 0.007; R = - 0.515, P = 0.049, respectively) and tetrasialotransferrin (R = - 0.436, P = 0.029; R = - 0.504, P = 0.039, respectively). This preliminary study shows the shifts in transferrin isoforms profile among patients with JIA. Our data indicate a potential clinical utility of the transferrin isoforms measurement, especially tetrasialotransferrin and pentasialotransferrin. Further prospective studies on larger groups of patients should be conducted to validate the results.

Vitamin D: Musculoskeletal health.

Perhaps the role of Vitamin D supplementation has been most exhaustively studied in calcium absorption, skeletal wellbeing, muscular potency, balance and risk of falling. Nonetheless, new data has emerged and the recent research on sarcopenia makes the topic increasingly interesting. Given the socioeconomic burden of the musculoskeletal consequences of hypovitaminosis D it is vital to keep abreast with the latest literature in the field. The recommended Vitamin D supplementation dose should suffice to increase the serum 25 hydroxyvitamin D level to 30 ng/mL (75 nmol/L) and this level should be optimally maintained with a maintenance dose, particularly for those diagnosed with osteoporosis.

What Do Children with Chronic Diseases and Their Parents Think About Pediatricians? A Qualitative Interview Study.

Objectives The aim of this study was to determine how pediatric patients and their parents perceive health care during hospital stays, what are their expectations of doctor behaviors, and which components of care do they consider to be the most important. Methods A qualitative descriptive study was carried out using the open interview technique. Twenty-six parents and 22 children undergoing hospital treatment participated. Results Our analysis identified two major themes: (1) doctor verbal and non-verbal behaviors, which included informing and explaining, conversations on topics other than the illness, tone of voice and other behaviors; and (2) perceived strategies used by doctors. This category included claims of doctors' intentional use of medical jargon to avoid addressing parental questions directly. Parents admitted that they did not understand medical vocabulary, but they also thought they might understand more of the medical issues if the doctor spoke using terms comprehensible to them. Conlcusions Our study shows the importance of interpersonal relationship affecting patient perception of quality of pediatric care. Parents of pediatric patients perceive that doctors behave in ways that deflect parents' questions and avoid providing them with medical information. Such behaviors include doctors excusing themselves by saying they are busy and using medical jargon. Medical students and doctors should be trained to communicate effectively with patients and their parents and develop skills to convey information in a simple and comprehensible way.

Serum matrix metalloproteinase-9 levels and severity of symptoms in boys with attention deficit hyperactivity disorder ADHD/hyperkinetic disorder HKD.

The serum levels of matrix metalloproteinase-9 (MMP-9) in neuropsychiatric disorders of adults have been widely investigated. So far, no studies have been conducted on the relationship of MMP-9 and cognitive domains in children with two phenotype models, attention deficit/hyperactivity disorder and hyperkinetic disorder (ADHD/HKD). The aim of this research was to evaluate and test the hypothesis that serum MMP-9 levels are associated with the severity of symptoms in children with ADHD/HKD and to compare the results in two models of this disorder. The study group comprised 37 Caucasian boys aged 7-12 years with HKD, being a subset of the combined ADHD subtype. Intellectual functions were measured using Wechsler Intelligence Scale for Children-Revised. The analysis of serum concentrations of MMP-9 was based on a quantitative sandwich ELISA. The statistical regression analysis revealed a correlation between increased serum MMP-9 levels and severity of symptoms in the ADHD (ß = 0.33; p = 0.043) and HKD (ß = 0.34, p = 0.037) model. According to the results, elevated levels of serum MMP-9 in boys with HKD may be associated with clinical impulsivity domain (ß = 0.38; p = 0.019).

Bone mineral density, thyroid function, and gonadal status in young adult survivors of childhood cancer.

INTRODUCTION: During the last years, changes in the diagnosis and treatment have caused a significant increase of the number of young adults who experienced cancer in childhood. This enlarging population is affected by many health problems, including multiple hormone deficiencies and bone mineral deficits. This is the first polish study assessing bone mineral density and endocrine status in young adult cancer survivors. MATERIAL AND METHODS: A total of 76 long-term survivors treated for pediatric cancer were identified. The mean age at the time of study was 24.1 ±3.5 years. Bone mineral density and TSH, fT3, fT4, FSH, LH, estradiol and testosterone level were assessed for each patient. RESULTS: Nine subjects were diagnosed with subclinical hypothyroidism. We found higher level of TSH in the study group, in comparison with control group (p = 0.015). Eighteen patients had increased level of FSH. In the study group higher number of patients with high FSH level was found in comparison with the control group (p = 0.049). A low BMD was observed in 7 patients whereas mild BMD deficits were found in 19 participants. CONCLUSIONS: In conclusion, our data show that young adult cancer survivors might experienced various hormonal problems including low bone mass, thyroid impairment and gonadal dysfunction. Some of the patients required treatment, but they were not diagnosed before this study. There is the lack of proper clinical assessment among adult childhood cancer survivors in Poland. Therefore, we demonstrated the need for a comprehensive plan for longitudinal follow-up for late effects in these population.

Urinary citrate excretion in healthy children depends on age and gender.

BACKGROUND: Hypocitraturia is considered a major risk factor for calcium stone formation. However, there is no widely accepted reference database of urinary citrate excretion in children. The aim of our study was to determine the amount of citrate eliminated in the urine over a 24-h period in a pediatric cohort and to determine an optimal unit reflecting excretion. METHODS: The study cohort comprised 2,334 healthy boys and girls aged 2-18 years. The levels of urinary citrate were assessed by an enzymatic method in 24-hour urine and expressed in absolute values, as urinary concentration, citrate/creatinine ratio, per kilogram of body weight, in relation to 1.73 m2, and as the calcium/citrate index. RESULTS: Similar incremental age-related citraturia rates were observed in both male and female subjects until puberty during which time citrate excretion became significantly higher in girls. Urinary citrate adjusted for creatinine and for body weight showed a significantly decreasing trend with increasing age in both sexes. Urinary citrate corrected for body surface was weakly correlated with age. Thus, the assumption of 180 mg/1.73 m2/24 h for males and 250 mg/1.73 m2/24 h for females as lower cut-off values appeared to be reliable from a practical perspective. CONCLUSIONS: We found distinct sex-dependent differences in citraturia at the start of puberty, with significantly higher values of urinary citrate in girls than in boys. Further prospective studies are warranted to elucidate whether this difference represents a differentiated risk of urolithiasis.

Limited utility of salivary mineral content in prediction of fragility fractures among postmenopausal women.

BACKGROUND: Osteoporosis is a metabolic disease characterized by increased bone fragility. As it is characterized as a general skeletal disease, changes can also be seen in the stomatognathic system (edentulism, wrong fitting of dentures, etc.). The question is whether early changes in the salivary mineral content and acid-base balance may reflect skeletal status and risk of bone fracture. OBJECTIVES: The objective of the study was to evaluate whether minerals in the saliva were associated with skeletal fractures in a population of postmenopausal women. MATERIAL AND METHODS: In this observational study, dental examinations along with the collection of saliva were conducted in 117 randomly recruited women (mean age 64.6 ±5.9 years). The study group included 23 study participants with fractures, of which 10 had a history of osteoporotic fractures. Saliva samples for mineral content including copper (Cu), zinc (Zn), calcium (Ca), and phosphorus (P), as well as salivary pH were collected and analyzed to determine associations between salivary mineral content and fracture risk. RESULTS: As a result, the median pH value was 6.8, and the median levels for Cu (0.35 µmol/L), Zn (0.61 µmol/L), Ca (0.7 mmol/L), and P (6.64 mmol/L) were observed. No differences were noted in salivary mineral content and acid-basic balance between the fractured and non-fractured participants. CONCLUSIONS: The results of our study suggest that salivary mineral content has limited usability in predicting skeletal fragility in postmenopausal women when used alone.

Correspondence between Ca²âº and calciuria, citrate level and pH of urine in pediatric urolithiasis.

BACKGROUND: Hypercalciuria and hypocitraturia are considered the most important risk factors for urolithiasis. Citrate binds to urinary calcium to form a soluble complex which decreases the availability of ionized calcium (Ca(2+)) necessary for calcium oxalate formation and phosphate crystallization. The aims of this study were to assess the Ca(2+) fraction in relation to total calciuria, citraturia and urinary pH and to determine whether urinary Ca(2+) concentration is a helpful biomarker in metabolic evaluation of children with urolithiasis. METHODS: We collected 24-h urine samples from 123 stone-forming children and adolescents with hypocitraturia and from 424 healthy controls. Total calciuria (total calcium, Catotal), Ca(2+), pH, citrate, oxalate and Bonn Risk Index (BRI) were assessed and compared between the two groups. RESULTS: Total calciuria and Ca(2+) content were higher in stone-formers than in the healthy children. In both stone-formers and controls, Ca(2+) content was inversely related to citraturia and urinary pH, whereas the Ca(2+)/Catotal ratio differed slightly between the groups. A large variability in Ca(2+) level was found across individuals in both groups. The BRI increased with increasing calciuria and urine acidity. CONCLUSIONS: Compared to controls, stone-formers with hypocitraturia demonstrated a higher urinary Ca(2+) concentration, but this was proportional to calciuria. The large individual variability in urinary Ca(2+) content limits its practical use in metabolic evaluation of children with urolithiasis. However, the Ca/Citrate ratio may be a useful clinical tool in evaluating children with urolithiasis.

Subclinical cardiovascular system changes in obese patients with juvenile idiopathic arthritis.

OBJECTIVE: We aimed to determine the prevalence of excess body mass in juvenile idiopathic arthritis (JIA) children and to investigate the influence of obesity into the early, subclinical changes in cardiovascular system in these patients. METHODS: Fifty-eight JIA patients, aged median 13 years, were compared to 36 healthy controls. Traditional cardiovascular risk factors and inflammatory markers (hsCRP, IL-6, TNF α, adiponectin) were studied together with IMT (intima-media thickness), FMD (flow mediated dilation), and LVMi (left ventricle mass index) as surrogate markers of subclinical atherosclerosis. RESULTS: Thirteen JIA children (22%) were obese and had increased systolic blood pressure, cholesterol, triglycerides, insulin, HOMA, hsCRP, and IL-6 compared to nonobese JIA and controls. FMD was decreased compared to nonobese JIA and controls, whereas IMT and LVMi were increased. In multivariate regression analysis, TNF α, SDS-BMI, and systolic blood pressure were independent predictors of early CV changes in JIA. CONCLUSIONS: Coincident obesity is common in JIA children and is associated with insulin resistance, dyslipidemia, and increased levels of inflammatory markers leading to early changes in cardiovascular system. Thus, medical care of children with JIA should include strategies preventing cardiovascular disease by maintenance of adequate body weight.

Insights into Prevention of Health Complications in Small for Gestational Age (SGA) Births in Relation to Maternal Characteristics: A Narrative Review.

Small for gestational age (SGA) births are a significant clinical and public health issue. The objective of this review was to summarize maternal biological and socio-demographic factors and preventive strategies used to reduce the risk of SGA births. A literature search encompassing data from the last 15 years was conducted using electronic databases MEDLINE/PubMed, Google Scholar and Scopus to review risk factors and preventive strategies for SGA. Current evidence shows that primiparity, previous stillbirths, maternal age ≤24 and ≥35 years, single motherhood, low socio-economic status, smoking and cannabis use during pregnancy confer a significant risk of SGA births. Studies on alcohol consumption during pregnancy and SGA birth weight are inconclusive. Beneficial and preventive factors include the "Mediterranean diet" and dietary intake of vegetables. Periconceptional folic acid supplementation, maternal 25-hydroxyvitamin D, zinc and iron levels are partly associated with birth weight. No significant associations between COVID-19 vaccinations and birthweight are reported. A midwifery-led model based on early and extensive prenatal care reduces the risk of SGA births in women with low socio-economic status. Major preventive measures relate to the awareness of modifiable and non-modifiable risk factors of SGA, leading to changes in parents' lifestyles. These data support that education, monitoring during pregnancy, and implementing preventive strategies are as important as biological determinants in risk reduction of SGA births.