BACKGROUND: Chronic Myeloid Leukemia (CML) is a rare myeloproliferative disease in childhood. Treatment in CML includes Tyrosine Kinase Inhibitors (TKI\'s), which inhibit the cytoplasmic kinase BCR/ABL. Tyrosine kinases play a key role in the secretion of growth hormone and insulin-like growth factor1 (IGF-1).
OBJECTIVE: The aim of this systematic review was to study the effect of TKIs on the growth of children and adolescents with CML.
METHODS: English-language publications were searched in the PubMed/Cochrane library/Google Scholar databases (2002-2023), and retrieved studies were assessed according to PRISMA-Statement and Newcastle- Ottawa-scale.
RESULTS: The search strategy yielded 1066 articles. After applying the inclusion/exclusion criteria, 941 were excluded based on title screening and 111 on abstract review. The systematic review included 14 articles (11 retrospective observational studies/3 clinical trials). Twelve studies reported data on the prevalence of growth disorders after the administration of 1st generation TKIs (imatinib). Two studies reported a negative effect of 2nd generation TKIs (dasatinib/nilotinib) on physical growth. Four studies recorded a decrease in height z-score after treatment compared to baseline. Two 1st-generation TKIs studies reported data on children\'s final height; one reported restoration of final height to normal after the onset of puberty, despite initial slowing, and the final height was lower than mid-parental target height. Serum IGF-1 levels were reported in 2 studies to be within normal range, while in 3 studies, a significant decrease was documented. Considerable study heterogeneity was observed related to dosage/duration of treatment/disease phase/stage of puberty/ethnicity.
CONCLUSIONS: A negative effect of TKIs on the growth and final height of children was noted.

The care of infants at risk of poor growth and development is a global priority. To inform new WHO guidelines update on prevention and management of growth faltering among infants under six months, we examined the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants between 0 and 6 months. We searched nine electronic databases from January 2000 to August 2021, included interventional studies, evaluated the quality of evidence for seven outcome domains (anthropometric recovery, child development, anthropometric outcomes, mortality, readmission, relapse, and non-response) and followed the GRADE approach for certainty of evidence. We identified thirteen studies with preterm and/or low birth weight infants assessing effects of breastfeeding counselling or education (n = 8), maternal nutrition supplementation (n = 2), mental health (n = 1), relaxation therapy (n = 1), and cash transfer (n = 1) interventions. The evidence from these studies had serious indirectness and high risk of bias. Evidence suggests breastfeeding counselling or education compared to standard care may increase infant weight at one month, weight at two months and length at one month; however, the evidence is very uncertain (very low quality). Maternal nutrition supplementation compared to standard care may not increase infant weight at 36 weeks postmenstrual age and may not reduce infant mortality by 36 weeks post-menstrual age (low quality). Evidence on the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants under six months with growth faltering is limited and of \'low\' to \'very low\' quality. This emphasizes the urgent need for future research. The protocol was registered with PROSPERO (CRD42022309001).

Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects of inflammation and negative effects of glucocorticoids (used as therapeutic option) on the growth hormone axis and locally on the growth plate and bone metabolism. In the last decade, the introduction of biologics has changed the disease course regarding consequences and outcomes. Anyway in some cases, treatment with biologics has failed in restoring normal growth in patients with juvenile idiopathic arthritis; in contrast, several studies have reported improved height velocity and growth rate in patients with juvenile idiopathic arthritis treated with growth hormone. This study aimed to evaluate the impact of growth hormone treatment on the growth and pubertal development in juvenile idiopathic arthritis patients through a narrative review of the literature over the last four decades.

Growth failure is among the most prevalent and devastating consequences of prematurity. Up to half of all extremely preterm neonates struggle to grow despite modern nutrition practices. Although elegant preclinical models suggest causal roles for the gut microbiome, these insights have not yet translated into biomarkers that identify at-risk neonates or therapies that prevent or treat growth failure. This systematic review aims to identify features of the neonatal gut microbiota that are positively or negatively associated with early postnatal growth. We identified 860 articles, of which 14 were eligible for inclusion. No two studies used the same definitions of growth, ages at stool collection, and statistical methods linking microbiota to metadata. In all, 58 different taxa were associated with growth, with little consensus among studies. Two or more studies reported positive associations with Enterobacteriaceae, Bacteroides, Bifidobacterium, Enterococcus, and Veillonella, and negative associations with Citrobacter, Klebsiella, and Staphylococcus. Streptococcus was positively associated with growth in five studies and negatively associated with growth in three studies. To gain insight into how the various definitions of growth could impact results, we performed an exploratory secondary analysis of 245 longitudinally sampled preterm infant stools, linking microbiota composition to multiple clinically relevant definitions of neonatal growth. Within this cohort, every definition of growth was associated with a different combination of microbiota features. Together, these results suggest that the lack of consensus in defining neonatal growth may limit our capacity to detect consistent, meaningful clinical associations that could be leveraged into improved care for preterm neonates.

BACKGROUND: We report four pediatric subjects with Cushing\'s disease (CD) diagnosed in the Czech Republic. We focus on initial symptoms of Cushing\'s syndrome (CS) which can lead to early diagnosis, on typical symptoms of CS in children, their age and sex distribution, the mean length of symptoms prior to diagnosis, indication for examination, post-cure growth, sexual development and pituitary function in our four CD patients after transsphenoidal pituitary surgery (TSS). We describe the diagnostic process leading to confirmation of CD and we emphasize the biochemical and radiological diagnostic difficulties.
CONCLUSIONS: Pediatric CD has a number of features distinct from adult CD. Our retrospective analysis confirmed the presence of growth retardation and change in facial appearance with development of moon face as the first symptoms of CS. According to our observation, growth retardation is prior to development of moon face. The other typical symptoms frequently seen in pediatric patients are pseudo-precocious puberty in both sexes, hirsutism in pubertal girls due to excessive adrenal androgen secretion and pubertal delay. A corticotropin-releasing hormone (CRH) test and especially bilateral inferior petrosal sinus sampling for ACTH (BIPSS) contribute to confirming the diagnosis of CD and excluding ectopic ACTH syndrome in children with unvisible adenoma on pituitary magnetic resonance imaging (MRI).

BACKGROUND: Oral isotretinoin, a systemic retinoid and a vitamin A derivative, has been widely utilized to treat acne in both adult and pediatric populations. Additionally, systemic retinoids have also been utilized to treat neuroblastoma in pediatric patients. Common side effects associated with oral isotretinoin include dry eyes, dry mouth, elevated liver enzymes, depression, and arthralgia. Less common side effects of isotretinoin include hearing loss, pseudotumor cerebri, anaphylaxis, and skeletal abnormalities including growth arrest. The U.S. Food and Drug Administration (FDA) has received reports of premature epiphyseal closure in patients treated with isotretinoin retinoids, which are commonly prescribed by primary care providers as a treatment for acne. It is important to raise awareness of the potential side effects of isotretinoin to enable informed treatment decisions before beginning an isotretinoin regimen.
OBJECTIVE: This chapter aims to elucidate that isotretinoin, given at various doses and durations, has been associated with growth plate abnormalities, which can lead to premature epiphyseal closure.
METHODS: Two databases were utilized for the literature review and were conducted at different time periods. Our literature review was conducted between December 2020 and June 2021, utilizing PubMed with the following search terms: \"isotretinoin\" and \"isotretinoin and premature epiphyseal closure.\" In April 2021, we searched the FDA\'s \"Drug Data and Adverse Event Report System\" utilizing the terms \"isotretinoin\" and \"epiphysis premature fusion.\" We included in our query reports of patients worldwide under 18 years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin. Studies published in English between 1980 and 2020 were also included, as well as background sources relating to an isotretinoin profile with side effects and dosing. We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. Growth plate abnormalities associated with retinoid derivatives other than isotretinoin were also excluded.
RESULTS: A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin. The FDA received 41 reports worldwide of premature epiphyseal closure related to isotretinoin in patients under 18 years of age. Additionally, premature epiphyseal closure and growth plate abnormalities occurred in nine patients with various durations and doses of isotretinoin ranging from the lowest dose of 0.5 mg/kg/day for a few months to 3.5 mg/kg/day for years.
CONCLUSIONS: Isotretinoin-induced premature epiphyseal closure and growth plate deformities seem to be linked to higher doses of isotretinoin for the duration of months to years. There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment, which are much lower compared to the high doses utilized for neuroblastoma. Based on this study, isotretinoin appears to impact the growth plates of proximal tibia and distal femur. A cause-and-effect relationship between isotretinoin and premature epiphyseal closure cannot be concluded.

(1) Introduction: Current evidence on managing infants under six months with growth failure or other nutrition-related risk is sparse and low quality. This review aims to inform research priorities to fill this evidence gap, focusing on breastfeeding practices. (2) Methods: We searched PubMed, CINAHL Plus, and Cochrane Library for studies on feeding interventions that aim to restore or improve the volume or quality of breastmilk and breastfeeding when breastfeeding practices are sub-optimal or prematurely stopped. We included studies from both low- and middle-income countries and high-income countries. (3) Results: Forty-seven studies met the inclusion criteria. Most were from high-income countries (n = 35, 74.5%) and included infants who were at risk of growth failure at birth (preterm infants/small for gestational age) and newborns with early growth faltering. Interventions included formula fortification or supplementation (n = 31, 66%), enteral feeds (n = 8, 17%), cup feeding (n = 2, 4.2%), and other (n = 6, 12.8%). Outcomes included anthropometric change (n = 40, 85.1%), reported feeding practices (n = 16, 34%), morbidity (n = 11, 23.4%), and mortality (n = 5, 10.6%). Of 31 studies that assessed formula fortification or supplementation, 30 reported anthropometric changes (n = 17 no effect, n = 9 positive, n = 4 mixed), seven morbidity (n = 3 no effect, n = 2 positive, n = 2 negative), five feeding (n = 2 positive, n = 2 no effect, n = 1 negative), and four mortality (n = 3 no effect, n = 1 negative). Of eight studies that assessed enteral feed interventions, seven reported anthropometric changes (n = 4 positive, n = 3 no effect), five feeding practices (n = 2 positive, n = 2 no effect, n = 1 negative), four morbidity (n = 4 no effect), and one reported mortality (n = 1 no effect). Overall, interventions with positive effects on feeding practices were cup feeding compared to bottle-feeding among preterm; nasogastric tube feed compared to bottle-feeding among low birth weight preterm; and early progressive feeding compared to delayed feeding among extremely low birth weight preterm. Bovine/cow milk feeding and high volume feeding interventions had an unfavourable effect, while electric breast pump and Galactagogue had a mixed effect. Regarding anthropometric outcomes, overall, macronutrient fortified formula, cream supplementation, and fortified human milk formula had a positive effect (weight gain) on preterm infants. Interventions comparing human breastmilk/donor milk with formula had mixed effects. Overall, only human milk compared to formula intervention had a positive effect on morbidity among preterm infants, while none of the interventions had any positive effect on mortality. Bovine/cow milk supplementation had unfavourable effects on both morbidity and mortality. (4) Conclusion: Future research should prioritise low- and middle-income countries, include infants presenting with growth failure in the post-neonatal period and record effects on morbidity and mortality outcomes.

To date, 13 patients with interstitial microduplications involving Xq25q26.2 have been reported. Here, we report 6 additional patients from 2 families with duplications involving Xq25q26.2. Family I carries a 5.3-Mb duplication involving 26 genes. This duplication was identified in 3 patients and was associated with microcephaly, growth failure, developmental delay, and dysmorphic features. Family II carries an overlapping 791-kb duplication that involves 3 genes. This duplication was identified in 3 patients and was associated with learning disability and speech delay. The size and gene content of published overlapping Xq25q26.2 duplications vary, making it difficult to define a critical region or establish a genotype-phenotype correlation. However, patients with overlapping duplications have been found to share common clinical features including microcephaly, growth failure, intellectual disability, learning difficulties, and dysmorphic features. The 2 families presented here provide additional insight into the phenotypic spectrum and clinical significance of duplications in this region.

Chronic malnutrition, including stunting, is an important example of a global challenge that spans multiple sectors, specifically health, agriculture, and the environment. The objective of this paper is to review current knowledge on the causes and consequences of chronic malnutrition and their relationship with multiple sectors. Understanding the causes includes approaching chronic malnutrition from the basic, underlying, and immediate levels. The causes reach from macro-level environmental influences to specific micronutrient intake. In order to effectively address stunting, it is important to understand the timing of stunting and the ability of individuals to catch up in terms of linear growth, cognitive ability, and immune function. The consequences of chronic malnutrition are transgenerational and they have an impact at the individual, community, and national level in the short- and long-term. There are still many gaps in knowledge regarding both the causes and consequences of chronic malnutrition, particularly when it comes to the interaction with agriculture and the environment, and understanding these gaps is important to addressing the burden of chronic malnutrition through evidence-based interventions.