Nurturing Infants to Prevent Atopic Dermatitis and Food Allergies: A Longitudinal Study.

BACKGROUND: Atopic dermatitis (AD) at a young age often precedes the development of food allergies. Although AD affects millions of infants worldwide, prenatal and postnatal risk factors, and their association with the development of food allergies later on, are not fully elucidated. This study seeks to investigate AD epidemiology in infancy and its risk factors, examining early-life factors (both prenatal and postnatal) that could contribute to the later development of food allergies. METHODS: Between January 2019 and December 2019, 501 infants were included in this prospective cohort study. Longitudinal data collection was performed through maternal interviews, the first one conducted within three days after the delivery and the second within 24 to 36 months after the delivery, encompassing variables such as demographics, family history of atopy, maternal smoking, antibiotic use during pregnancy, the mode of delivery, breastfeeding history, food practices, and greenness exposure within 3 days from delivery, while they were still in the hospital. RESULTS: Maternal smoking during pregnancy (p = 0.001) and an older sibling atopy history (p = 0.03) was significantly linked to AD incidence. Cesarean section delivery (p = 0.04) was associated with a higher risk of food allergies in infants with AD. Having a garden at home correlated with a higher likelihood of AD (p = 0.01), and food elimination without medical guidance (p = 0.02) due to AD correlated with an elevated risk of food allergies. CONCLUSIONS: Encouraging timely allergenic food introduction while promoting dietary diversity, rich in plant-based foods, maternal smoking cessation, and professional dietary guidance may help minimize AD and food allergy risk. Future studies should address the role of greenness in the development of AD and food allergies.

Hypogonadism in adolescent girls: treatment and long-term effects.

BACKGROUND AND AIM: Hypogonadism in adolescent females presents as delayed puberty or primary amenorrhea. Constitutional delay of growth and puberty, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism represent the principal differential diagnosis of delayed puberty. Girls with hypogonadism require hormone replacement therapy to initiate and sustain puberty. We aimed to provide a brief review concerning treatment for female adolescents with hypogonadism and further to focus on current data regarding long-term effects of therapy. METHODS: The published studies and articles of the international literature were used regarding the approach to adolescent girls with hypogonadism. RESULTS: The aim of therapy is the development of secondary sexual characteristics and achievement of target height, body composition and bone mass, to promote psychosexual health and, finally, to maximize the potential for fertility. Hypogonadal females need long-term HRT, so it is of great importance to fully define risks and benefits of therapy. CONCLUSIONS: The optimal pubertal induction in women contains both estrogens and progesterone regimens.  Different therapeutic options have been described over the years in the literature, but larger randomized trials are required in order to define the ideal approach. The latest acquisitions in the field seem to propose that transdermal 17ß-estradiol and micronized progesterone present the most physiological formulations available for this purpose. Further studies and follow up are needed concerning the long-term effects of HRT in adolescents.

Risk factors for meningococcal disease in children and adolescents: a systematic review and META-analysis.

Invasive meningococcal disease (IMD) remains a major cause of mortality and morbidity in children worldwide. A systemic review in PubMed and Cochrane Controlled Trials Register was performed for articles on risk factors for IMD in children and adolescents published during a 20-year period (19/09/1998 to 19/09/2018). Inclusion and exclusion criteria were established and applied. The data were meta-analyzed using random-effect model and the results were presented on forest plots separately for each risk factor. We identified 12,559 studies (duplicates removed). Titles, abstracts, and full texts were screened and finally, six studies (five case-control and one cohort study) were included in qualitative synthesis, five in meta-analysis. The median age of meningococcal disease (MD) cases was 72.2 months (0-19 years). Household crowding, smoking exposure, close relationships, and recent respiratory tract infections conferred a more than twofold risk for IMD in exposed individuals compared to controls [overcrowded living OR 2.52 (95% CI 1.75-3.63), exposure to smoke OR 2.10 (95% CI 1.00-4.39), kissing OR 2.00 (95% CI: 1.13-3.51), and recent respiratory tract infection OR 3.13 (95% CI 2.02-4.86)]. Attendance of religious events was associated with a decreased risk [0.47 (95% CI, 0.28-0.79)].Conclusion: Our review highlights the importance of individual characteristics as risk factors for IMD in childhood and adolescence. Preventive policies may consider individual as well as social-environmental factors to target individuals at risk.What is Known:• Close relationships, household crowding, and recent respiratory tract infections are major risk factors for IMD.• Passive smoking is a major risk factor for IMD.What is New:• Intimate kissing, household crowding, and passive smoking were found to double the risk of IMD.• Recent respiratory tract infections almost tripled the risk for IMD.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis.

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor-negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely.

Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab.

Rituximab (RTX) is a monoclonal antibody against CD20, commonly used in the treatment of hematological malignancies and autoimmune diseases. The use of RTX is related to the development of hypogammaglobulinemia and infections. Aim of this review is to summarize the evidence supporting the association of specific risk factors with the development of hypogammaglobulinemia and infections post-RTX. Immunological complications are more common in patients with malignant diseases as compared to non-malignant diseases. Moreover, the use of more than one dose of RTX, maintenance regimens, low pre-treatment basal immunoglobulin levels and the association with Mycophenolate and purine analogues represent risk factors for the development of hypogammaglobulinemia. The number of RTX courses, the evidence of low IgG levels for more than 6 months, the use of G-CSF, the occurrence of chronic lung disease, cardiac insufficiency, extra-articular involvement in patients with rheumatoid arthritis, low levels of IgG and older age have been correlated with a higher risk of infections. Even though the heterogeneity of the studies in terms of study population age and underlying disease, RTX schedules as well as differences in pre-treatment or concomitant therapy doesn't allow drawing definitive conclusions, the study of the literature highlight the association of specific risk factors with the occurrence of hypogammaglobulinemia and/or infections. A long term randomized controlled clinical trial could be useful to define a personalized evidence-based risk management plan for patients treated with RTX.

Incidence and morbidity of urinary tract infection in a prospective cohort of children.

AIM: Information on the epidemiology of childhood urinary tract infections (UTIs) is scarce and mostly based on retrospective data. This study investigated incidence rates, morbidity and risk factors for UTIs in a prospective cohort of children. METHODS: We explored UTIs in a representative cohort of 1049 neonates from birth to 6 years of age, using maternal interviews that were verified by hospital records. The majority (88.2%) completed the first-year, and more than half (56.2%) completed the 6-year follow-up. RESULTS: By 6 years of age, more than 10% of our sample had been affected by UTIs. The cumulative incidence for the first year of life was 3.77%, without significant differences between genders, and for one to 6 years, it was 6.81% and 5.7 times higher in girls than boys. Clinical information was available for 63 children: 25 were hospitalised, 16 suffered recurrences, 10 received prophylaxis, eight had urinary tract malformations, three required surgery, and two had impaired renal function. CONCLUSION: UTIs affected approximately 4% and 10% of children by the ages of one and 6 years, respectively, and their incidence was related to gender and age. Morbidity was considerable, recurrences were common, and despite advances in management, long-term consequences may still be encountered.

Protective effect of exclusive breastfeeding against infections during infancy: a prospective study.

OBJECTIVE: To prospectively investigate the effects of breastfeeding on the frequency and severity of infections in a well-defined infant population with adequate vaccination coverage and healthcare standards. STUDY DESIGN: In a representative sample of 926 infants, successfully followed up for 12 months, feeding mode and all infectious episodes, including acute otitis media (AOM), acute respiratory infection (ARI), gastroenteritis, urinary tract infection, conjunctivitis and thrush, were recorded at 1, 3, 6, 9 and 12 months of life. RESULTS: Infants exclusively breastfed for 6 months, as per WHO recommendations, presented with fewer infectious episodes than their partially breastfed or non-breastfed peers and this protective effect persisted after adjustment for potential confounders for ARI (OR 0.58, 95% CI 0.36 to 0.92), AOM (OR 0.37, 95% CI 0.13 to 1.05) and thrush (OR 0.14, 95% CI 0.02 to 1.02). Prolonged exclusive breastfeeding was associated with fewer infectious episodes (r(s)=-0.07, p=0.019) and fewer admissions to hospital for infection (r(s)=-0.06, p=0.037) in the first year of life. Partial breastfeeding was not related to protective effect. Several confounding factors, including parental age and education, ethnicity, presence of other siblings, environmental tobacco smoke exposure and season of birth were demonstrated to have an effect on frequency of infections during infancy. CONCLUSIONS: Findings from this large-scale prospective study in a well-defined infant population with adequate healthcare standards suggest that exclusive breastfeeding contributes to protection against common infections during infancy regarding and lessens the frequency and severity of infectious episodes. Partial breastfeeding did not seem to provide this protective effect.

Risk factors related to intention to breastfeed, early weaning and suboptimal duration of breastfeeding.

AIM: To identify maternal and infantile factors affecting intention to breastfeed, early weaning and duration of breastfeeding. DESIGN/SUBJECTS: In a prospective cohort study, 1049 mothers were interviewed after delivery and at 1, 3, 6, 9 and 12 months post-partum. RESULTS: Of 1049 mothers, 942 (89.7%) intended to breastfeed. Negative attitude was associated with lack of breastfeeding previous offspring, multiparity, admission to neonatal ward, tobacco use, prematurity and male gender (OR: 10.1, 2.67, 3.02, 2.63, 2.40 and 1.54, respectively). Six hundred and twenty-three mothers (60.7%) were breastfeeding at month 1. Early weaning was associated with lack of breastfeeding previous offspring, tobacco use, prematurity, admission to neonatal ward, caesarean section (OR: 12.3, 3.39, 2.33, 2.22, 1.34), low education (p < 0.0001) and young age (p = 0.034). Factors negatively affecting total duration of breastfeeding included lack of breastfeeding previous offspring (3.91 vs. 16.2 weeks, p < 0.001), tobacco use (6.78 vs. 15.9 weeks, p < 0.001), low education (p < 0.001), early re-employment (12.5 vs. 15.1 weeks, p < 0.01) and prematurity (p < 0.005). CONCLUSION: Maternal negative attitude, tobacco use and early re-employment are factors negatively affecting breastfeeding that can be liable to intervention. All health professionals involved in perinatal medicine share a part of responsibility in sustaining breastfeeding, particularly in high-risk groups of mothers.