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1.
N Engl J Med ; 390(1): 44-54, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38169489

RESUMEN

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are presented in the current report - stunting (defined as a length-for-age z score that was more than two standard deviations below the median of a growth standard) at 12 months of age - was one of four primary outcomes of the trial. Intention-to-treat analyses were performed to estimate the relative risk of stunting. RESULTS: Adherence to the intervention was high, and the intervention resulted in lower prenatal and postnatal 24-hour personal exposures to fine particulate matter than the control (mean prenatal exposure, 35.0 µg per cubic meter vs. 103.3 µg per cubic meter; mean postnatal exposure, 37.9 µg per cubic meter vs. 109.2 µg per cubic meter). Among 3061 live births, 1171 (76.2%) of the 1536 infants born to women in the intervention group and 1186 (77.8%) of the 1525 infants born to women in the control group had a valid length measurement at 12 months of age. Stunting occurred in 321 of the 1171 infants included in the analysis (27.4%) of the infants born to women in the intervention group and in 299 of the 1186 infants included in the analysis (25.2%) of those born to women in the control group (relative risk, 1.10; 98.75% confidence interval, 0.94 to 1.29; P = 0.12). CONCLUSIONS: An intervention strategy starting in pregnancy and aimed at mitigating household air pollution by replacing biomass fuel with LPG for cooking did not reduce the risk of stunting in infants. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).


Asunto(s)
Contaminación del Aire Interior , Petróleo , Lactante , Femenino , Humanos , Embarazo , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Biomasa , Material Particulado/efectos adversos , Material Particulado/análisis , Culinaria , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/prevención & control
2.
Mol Cell ; 70(4): 707-721.e7, 2018 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-29754823

RESUMEN

DNA polymerase ε (POLE) is a four-subunit complex and the major leading strand polymerase in eukaryotes. Budding yeast orthologs of POLE3 and POLE4 promote Polε processivity in vitro but are dispensable for viability in vivo. Here, we report that POLE4 deficiency in mice destabilizes the entire Polε complex, leading to embryonic lethality in inbred strains and extensive developmental abnormalities, leukopenia, and tumor predisposition in outbred strains. Comparable phenotypes of growth retardation and immunodeficiency are also observed in human patients harboring destabilizing mutations in POLE1. In both Pole4-/- mouse and POLE1 mutant human cells, Polε hypomorphy is associated with replication stress and p53 activation, which we attribute to inefficient replication origin firing. Strikingly, removing p53 is sufficient to rescue embryonic lethality and all developmental abnormalities in Pole4 null mice. However, Pole4-/-p53+/- mice exhibit accelerated tumorigenesis, revealing an important role for controlled CMG and origin activation in normal development and tumor prevention.


Asunto(s)
Carcinogénesis/patología , ADN Polimerasa II/química , ADN Polimerasa II/fisiología , Replicación del ADN , Discapacidades del Desarrollo/etiología , Trastornos del Crecimiento/etiología , Leucopenia/etiología , Animales , Carcinogénesis/genética , Células Cultivadas , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/patología , Femenino , Humanos , Recién Nacido , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación , Proteína p53 Supresora de Tumor/fisiología
3.
Proc Natl Acad Sci U S A ; 119(41): e2209589119, 2022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-36197997

RESUMEN

Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.


Asunto(s)
Microbioma Gastrointestinal , Trastornos del Crecimiento , Intestino Delgado , Lípidos , Boca , Animales , Bacterias , Preescolar , Estudios Transversales , Trastornos del Crecimiento/etiología , Humanos , Complejo de Antígeno L1 de Leucocito , Metabolismo de los Lípidos , Síndromes de Malabsorción , Ratones , Modelos Teóricos , Boca/microbiología
4.
Hum Reprod ; 39(4): 724-732, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38384249

RESUMEN

STUDY QUESTION: Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol? SUMMARY ANSWER: Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst). WHAT IS KNOWN ALREADY: Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved. STUDY DESIGN, SIZE, DURATION: A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from 35 French ART centres, leading to the inclusion of a total of 72 789 fresh ET, 10 602 slow-freezing FET, and 39 062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect. MAIN RESULTS AND THE ROLE OF CHANCE: Transfers led to, respectively, 19 006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21 704) or artificial cycles (n = 34 237), leading to 5910 and 10 322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26 585 live-born singletons, 16 413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage. LIMITATIONS, REASONS FOR CAUTION: No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used. WIDER IMPLICATIONS OF THE FINDINGS: Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders. STUDY FUNDING/COMPETING INTEREST(S): This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Infertilidad , Nacimiento Prematuro , Embarazo , Masculino , Femenino , Recién Nacido , Humanos , Peso al Nacer , Congelación , Estudios Retrospectivos , Criopreservación/métodos , Edad Gestacional , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Transferencia de Embrión/efectos adversos , Transferencia de Embrión/métodos , Índice de Embarazo , Infertilidad/etiología , Trastornos del Crecimiento/etiología
5.
Am J Med Genet A ; 194(7): e63603, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38511620

RESUMEN

There is an emerging body of evidence showing that young patients, post haematopoietic stem cell transplantation (HSCT), can develop skeletal changes that mimic an osteochondrodysplasia process. The key discriminator is that these children have had otherwise normal growth and skeletal development before the therapeutic intervention (HSCT), typically for a haematological malignancy. Herein we present that case of a boy who underwent HSCT for Haemophagocytic Lymphohistiocytosis (HLH) aged 2 years. Following Intervention with HSCT this boy's growth has severely decelerated (stature less than 1st centile matched for age) and he has developed a spondyloepiphyseal dysplasia.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfohistiocitosis Hemofagocítica , Osteocondrodisplasias , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Preescolar , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/patología , Linfohistiocitosis Hemofagocítica/etiología , Trastornos del Crecimiento/patología , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/genética
6.
Trop Med Int Health ; 29(4): 292-302, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38327260

RESUMEN

BACKGROUND: Preterm infants often have poor short- and long-term growth. Kangaroo mother care supports short-term growth, but longer-term outcomes are unclear. METHODS: This study analysed longitudinally collected routine clinical data from a South African cohort of preterm infants (born <37 weeks gestation) attending the outpatient follow-up clinic of a tertiary-level hospital (Tshwane District, South Africa) for 1 year between 2012 and 2019. At 1 year, small-for-gestational age (SGA) and appropriate-for-gestational age (AGA) infants were compared with regard to age-corrected anthropometric z-scores (weight-for-age [WAZ], length-for-age [LAZ], weight-for-length [WLZ] and BMI-for-age [BMIZ]) and rates of underweight (WAZ < -2), stunting (LAZ < -2), wasting (WLZ < -2) and overweight (BMIZ> + 2). Multiple regression analysis was used to investigate associations between maternal/infant characteristics and rates of underweight, stunting, wasting and overweight. RESULTS: At 1 year, compared with AGA infants (n = 210), SGA infants (n = 111) had lower WAZ (-1.26 ± 1.32 vs. -0.22 ± 1.24, p < 0.001), LAZ (-1.50 ± 1.11 vs. -0.60 ± 1.06, p < 0.001), WLZ (-0.66 ± 1.31 vs. 0.11 ± 1.24, p < 0.001) and BMIZ (-0.55 ± 1.31 vs. 1.06 ± 1.23, p < 0.001), despite larger WAZ gains from birth (+0.70 ± 1.30 vs. +0.05 ± 1.30, p < 0.001). SGA infants had significantly more stunting (34.2% vs. 9.1%; p < 0.001), underweight (31.2% vs. 7.2%; p < 0.001) and wasting (12.6% vs. 4.3%, p = 0.012), with no difference in overweight (4.5% vs. 7.7%, p = 0.397). In multiple regression analysis, birth weight-for-GA z-score more consistently predicted 1-year malnutrition than SGA. CONCLUSION: Preterm-born SGA infants remain more underweight, stunted and wasted than their preterm-born AGA peers at 1 year, despite greater WAZ gains. Interventions for appropriate catch-up growth especially for SGA preterm infants are needed.


Asunto(s)
Método Madre-Canguro , Desnutrición , Lactante , Niño , Recién Nacido , Humanos , Recien Nacido Prematuro , Sudáfrica/epidemiología , Estudios de Seguimiento , Delgadez/epidemiología , Sobrepeso , Edad Gestacional , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Desnutrición/epidemiología
7.
Br J Nutr ; 131(7): 1189-1195, 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38012887

RESUMEN

Undernutrition is a major public health problem in developing countries. Around 40·2 % of children are stunted in Pakistan. This longitudinal study aimed to assess the effectiveness of locally produced ready-to-use supplementary foods in the prevention of stunting by detecting change in of children in intervention v. control arm against the 2006 WHO growth reference. A community-based non-randomised cluster-controlled trial was conducted from January 2018 to December 2020 in the district of Kurram, Khyber Pakhtunkhwa, Pakistan. A total of 80 clusters (each cluster comprising ≈ 250-300 households) were defined in the catchment population of twelve health facilities. Children aged 6-18 months were recruited n 1680. The intervention included a daily ration of 50 g - locally produced ready-to-use-supplementary food (Wawa-Mum). The main outcome of this study was a change in length for age z-score (LAZ) v. WHO growth standards. Comparison between the interventions was by t test and ANOVA. Cox proportional hazard models were used to assess the association between stunting occurrence and the utilisation of locally produced supplement. Out of the total 1680, fifty-one out of the total 1680, 51·1 out of the total 1680 and 51·1 % (n 859) were male. Mean age 13·9 months (sd + 859) were male. Mean age 13·9 months (sd + -4·4). At baseline, 36·9 % (n 618) were stunted. In the intervention group, mean LAZ score significantly increased from -1·13(2·2 sd) at baseline to -0·93(1·8 sd) at 6-month follow-up (P value 0·01) compared with the control group. The incidence rate of stunting in the intervention arm was 1·3 v. 3·4 per person year in the control arm. The control group had a significantly increased likelihood of stunting (Hazard Ratio (HR) 1·7, 95 % CI 1·46, 2·05, P value < 0·001) v. the intervention group. Locally produced ready-to-use supplementary food is an effective intervention for reducing stunting in children below 2 years of age. This can be provided as part of a malnutrition prevention package to overcome the alarming rates of stunting in Pakistan.


Asunto(s)
Desnutrición , Niño , Humanos , Masculino , Lactante , Preescolar , Femenino , Estudios Longitudinales , Pakistán/epidemiología , Desnutrición/epidemiología , Suplementos Dietéticos , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/prevención & control , Trastornos del Crecimiento/etiología
8.
Curr Opin Pediatr ; 36(4): 463-466, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38747200

RESUMEN

PURPOSE OF REVIEW: Congenital adrenal hyperplasia (CAH) is a relatively common disorder and one of the most challenging conditions seen by pediatric endocrinologists. Poor linear growth in CAH has been recognized for many years. There are new insights to explain this abnormality and shed light on strategies to promote normal growth. RECENT FINDINGS: Published data suggest that the dose of hydrocortisone during two critical periods of rapid growth, namely infancy and at puberty, has a fundamental effect on growth velocity, and by definition adult height. To prevent over-treatment, hydrocortisone dosage should remain within the range of 10-15 mg/m 2 body surface area per day. Precursor steroids such as 17-hydroxy progesterone (17OHP) should not be suppressed to undetectable levels. In fact, 17OHP should always be measurable, as complete suppression suggests over-treatment. SUMMARY: CAH is a challenging disorder. High-quality compliance within the consultation setting, with the patient seeing the same specialist at every visit, will be rewarded by improved long-term growth potential. Quality auxological monitoring can avoid phases of growth suppression. New therapy with CRH receptor antagonists may lead to a more nuanced approach by allowing fine tuning of hydrocortisone replacement without the need to suppress ACTH secretion.


Asunto(s)
Hiperplasia Suprarrenal Congénita , Hidrocortisona , Humanos , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Hiperplasia Suprarrenal Congénita/diagnóstico , Niño , Adolescente , Hidrocortisona/uso terapéutico , Estatura/efectos de los fármacos , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/etiología , Lactante , Preescolar
9.
Pediatr Blood Cancer ; 71(7): e30995, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38616355

RESUMEN

Hemochromatosis (HC) is characterized by the progressive accumulation of iron in the body, resulting in organ damage. Endocrine complications are particularly common, especially when the condition manifests in childhood or adolescence, when HC can adversely affect linear growth or pubertal development, with significant repercussions on quality of life even into adulthood. Therefore, a timely and accurate diagnosis of these disorders is mandatory, but sometimes complex for hematologists without endocrinological support. This is a narrative review focused on puberty and growth disorders during infancy and adolescence aiming to offer guidance for diagnosis, treatment, and proper follow-up. Additionally, it aims to highlight gaps in the existing literature and emphasizes the importance of collaboration among specialists, which is essential in the era of precision medicine.


Asunto(s)
Trastornos del Crecimiento , Sobrecarga de Hierro , Humanos , Adolescente , Niño , Sobrecarga de Hierro/etiología , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/fisiopatología , Masculino , Hemocromatosis/diagnóstico , Hemocromatosis/terapia , Femenino , Trastornos Gonadales/etiología , Pubertad/fisiología , Preescolar
10.
Pediatr Blood Cancer ; 71(8): e31117, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38804882

RESUMEN

BACKGROUND: Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. METHODS: Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. RESULTS: Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7 ± 1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p < .01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (ß = 0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (ß = -0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (ß = -0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (ß = -0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. CONCLUSIONS: Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.


Asunto(s)
Inhibidores de la Aromatasa , Estatura , Supervivientes de Cáncer , Hormona de Crecimiento Humana , Neoplasias , Humanos , Masculino , Inhibidores de la Aromatasa/uso terapéutico , Estudios Retrospectivos , Estatura/efectos de los fármacos , Adolescente , Hormona de Crecimiento Humana/deficiencia , Niño , Neoplasias/tratamiento farmacológico , Estudios de Seguimiento , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/patología , Adulto , Pronóstico , Quimioterapia Adyuvante
11.
Pediatr Transplant ; 28(5): e14803, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38899494

RESUMEN

BACKGROUND: Growth retardation and short final height is a common complication of chronic kidney disease (CKD) beginning in childhood, with profound deleterious effects on quality of life, mental health, and social achievement. Despite optimal treatments of causative factors for growth retardation in children with CKD, more than 50% of patients reach end-stage renal failure with a height >2 SD below the mean, and most do not demonstrate "catch-up" growth after receiving a kidney transplant. Four decades ago, recombinant human growth hormone (rhGH) treatment was introduced after studies showed increased growth velocity and improved height SDS in uremic subjects. Since then, an abundance of published data showed significant improvements in health-related quality of life, and most studies revealed no significant adverse effects. Clinical practice guidelines recommended rhGH treatment in CKD Stages 3-5D and after transplantation. Despite these guidelines, this therapy remained underutilized. Most commonly cited barriers to the implementation of rhGH treatment were the need for daily injections, financial challenges, physicians' unfamiliarity with guidelines, and fear of adverse events. CONCLUSIONS: rhGH has been shown to improve growth and final height in short children with CKD, with minimal adverse effects. Despite data of its successful use generated over 3 decades, this treatment is underutilized. More judicious utilization of the treatment should emphasize educating patients, their care givers, and members of the multidisciplinary treating team. Additional studies are needed to assess the longer-term rhGH treatment in larger cohorts of patients, leading to additional supportive data and clearer recommendations.


Asunto(s)
Trastornos del Crecimiento , Hormona de Crecimiento Humana , Trasplante de Riñón , Calidad de Vida , Humanos , Niño , Hormona de Crecimiento Humana/uso terapéutico , Trastornos del Crecimiento/etiología , Estatura/efectos de los fármacos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Insuficiencia Renal Crónica/complicaciones , Resultado del Tratamiento , Proteínas Recombinantes/uso terapéutico , Guías de Práctica Clínica como Asunto , Adolescente
12.
BMC Endocr Disord ; 24(1): 62, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724932

RESUMEN

BACKGROUND: This study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control. PATIENTS AND METHODS: Two hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay. RESULTS: We found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05). CONCLUSION: Children with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature.


Asunto(s)
Diabetes Mellitus Tipo 1 , Factor I del Crecimiento Similar a la Insulina , Pubertad , Humanos , Niño , Adolescente , Femenino , Masculino , Egipto/epidemiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Pubertad/fisiología , Hormonas Esteroides Gonadales/sangre , Antropometría , Biomarcadores/sangre , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/diagnóstico , Estatura , Pubertad Tardía/etiología , Pubertad Tardía/diagnóstico , Pubertad Tardía/sangre , Pronóstico , Estudios Transversales , Estudios de Seguimiento , Péptidos Similares a la Insulina
13.
Pediatr Nephrol ; 39(9): 2667-2677, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38637343

RESUMEN

BACKGROUND: Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. METHODS: We evaluated obesity and longitudinal growth among children (1-18 years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. RESULTS: We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. CONCLUSIONS: Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.


Asunto(s)
Síndrome Nefrótico , Obesidad Infantil , Humanos , Síndrome Nefrótico/epidemiología , Síndrome Nefrótico/complicaciones , Niño , Masculino , Femenino , Preescolar , Estudios Prospectivos , Obesidad Infantil/epidemiología , Obesidad Infantil/complicaciones , Adolescente , Lactante , Incidencia , Factores de Riesgo , Prevalencia , Estatura , Índice de Masa Corporal , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Ontario/epidemiología
14.
Pediatr Nephrol ; 39(9): 2691-2701, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38671228

RESUMEN

BACKGROUND: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. METHODS: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. RESULTS: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (ß - 7.5 × 10-6, CI - 1.2 × 10-5, - 3 × 10-6, p = 0.001) and incident cases of NS (vs. prevalent) (ß - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (ß 0.16, CI 0.04, 0.29, p = 0.01) over time. CONCLUSION: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.


Asunto(s)
Estatura , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Masculino , Femenino , Niño , Preescolar , Estatura/efectos de los fármacos , Adolescente , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/diagnóstico , Estudios Longitudinales , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Rituximab/administración & dosificación , Rituximab/efectos adversos
15.
Eur J Pediatr ; 183(5): 2173-2182, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38376595

RESUMEN

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.


Asunto(s)
Enfermedad Celíaca , Humanos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/fisiopatología , Enfermedad Celíaca/dietoterapia , Femenino , Masculino , Niño , Estudios Retrospectivos , Preescolar , Estudios de Seguimiento , Adolescente , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/diagnóstico , Índice de Masa Corporal , Estatura , Antropometría/métodos , Aumento de Peso/fisiología , Peso Corporal
16.
Am J Hum Biol ; 36(6): e24039, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38189589

RESUMEN

OBJECTIVES: Infant growth is recognized to vary over the short term, with periods of greater and lesser linear growth velocity. Our objectives were to (1) examine the potential differences in overall growth profiles between children who experienced cumulative growth faltering in the first year of life consistent with that seen by many children living in poverty in low- and middle-income countries, versus children without growth faltering and (2) test whether biological factors were associated with the timing of magnitude of growth saltations. METHODS: Thrice-weekly measurements of length were recorded for n = 61 Peruvian infants (28 boys and 33 girls) enrolled from birth to 1 year. A total of 6040 measurements were analyzed. We tested for the evidence of saltatory growth and used hurdle models to test whether the timing and magnitude of saltations varied between children with greater or lesser growth faltering. RESULTS: There were no differences in the duration of stasis periods or magnitude of growth saltations between children who were stunted at 1 year old (N = 18) versus those who were not stunted (N = 43). Children who experienced greater declines in LAZ in the first year of life trended toward longer periods between saltations than those with less of a decline (14.5 days vs. 13.4 days, p = .0512). A 1-unit increase in mid upper arm circumference for age Z-score in the 21 days prior was associated with 35% greater odds of a saltation occurring (p < .001), and a 0.128 cm greater saltation (p < .001). CONCLUSIONS: After characterizing infant growth into periods of saltation and stasis, our results suggest that increases in weight preceded increases in length.


Asunto(s)
Trastornos del Crecimiento , Humanos , Perú , Lactante , Masculino , Femenino , Recién Nacido , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Estatura , Desarrollo Infantil
17.
Public Health Nutr ; 27(1): e76, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38384260

RESUMEN

OBJECTIVE: The objective of this study was to explore the relationship between various forms of child nutritional disorders and early childhood development in Bangladesh. DESIGN: We analysed data from the nationally representative cross-sectional 2019 Multiple Indicator Cluster Survey. Early childhood development was evaluated using the Early Childhood Development Index (ECDI), which comprised 10 yes-or-no questions across four domains: literacy-numeracy, physical well-being, socio-emotional development, and learning abilities. Nutritional disorders (e.g. stunting, wasting, and underweight) were measured based on the World Health Organization's height and weight guidelines. To investigate the relationships between child development and nutritional disorders, we used multilevel logistic regression models. SETTING: Bangladesh. PARTICIPANTS: Data of 9,455 children aged 3 and 4 years. RESULTS: Approximately 38 % of the children analysed experienced a nutritional disorder, with stunting being the most prevalent at 28·15 %. Overall, 25·27 % did not meet expected developmental progress measured by the ECDI. Stunted children were more likely to be off track developmentally, while those without any nutritional disorder were more likely to be on track. Socio-demographic factors, including age, sex, attendance in early childhood education programme, maternal education, maternal functional difficulties, region, and income, were identified as determinants of ECDI. CONCLUSIONS: Childhood nutrition and socio-demographic factors significantly affect multiple developmental domains and overall ECDI among children aged 3-4 years. Prioritising policies and programmes that improve nutrition and address these determinants are crucial for fostering optimal development in children.


Asunto(s)
Desarrollo Infantil , Trastornos Nutricionales , Niño , Preescolar , Humanos , Lactante , Bangladesh/epidemiología , Estudios Transversales , Estado Nutricional , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología
18.
Public Health Nutr ; 27(1): e58, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38311339

RESUMEN

OBJECTIVE: The current study aims to determine household-, maternal- and child-related factors influencing nutritional status among children under five in Mali. DESIGN: Quantitative cross-sectional study using secondary data extracted from Mali DHS-VI 2018. SETTING: Urban and rural areas of Mali. PARTICIPANTS: A total of 8908 children participated, with 3999 in the younger age group (0-24 months) and 4909 in the older age group (25-59 months). RESULTS: In the younger age group, the prevalence of stunting, wasting and underweight was 18·8 % (95 % CI%: 17·5, 20·0), 24·6 % (95 % CI: 23·2, 26·0) and 13·2 % (95 % CI: 12·1, 14·3), respectively, while in the older age group, it was 24·9 % (95 % CI: 23·7, 26·2), 22·7 % (95 % CI: 21·5, 24·0) and 5·7 % (95 % CI: 5·0, 6·5), respectively. Being average or large size at birth, having piped source of water, receiving Zn, deworming, high maternal BMI, receiving Fe during pregnancy, higher maternal education and being rich were associated with lower odds of one or more form of undernutrition in both groups. On the other hand, children who were anaemic, drank from a bottle, maternal anaemia, current pregnancy of mothers and living in rural areas were associated with higher odds of stunting, wasting or underweight. Interestingly, children who received Fe supplementation had a higher odds of wasting in the younger group but lower odds of all forms of undernutrition in the older group. CONCLUSIONS: This study emphasised the potential risk factors associated with undernutrition in children. Children who consume non-potable water, have mothers with lower levels of education and BMI and reside in rural areas are more likely to experience undernutrition.


Asunto(s)
Desnutrición , Estado Nutricional , Recién Nacido , Femenino , Embarazo , Humanos , Lactante , Anciano , Preescolar , Delgadez/epidemiología , Delgadez/etiología , Estudios Transversales , Malí/epidemiología , Desnutrición/etiología , Trastornos del Crecimiento/etiología , Prevalencia , Agua
19.
Public Health Nutr ; 27(1): e29, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38253537

RESUMEN

OBJECTIVE: This study investigated the trend of effect estimates of the key risk factors of childhood stunting and anaemia between 2003 and 2017. DESIGN: A secondary analysis of the Demographic Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) data for the Ghanaian population between 2003 and 2017. Associations of selected socio-demographic (child age and gender; maternal age and education), economic (household wealth), environmental, dietary (minimum dietary diversity and iodine use) and health system (place of delivery and vaccination) factors were explored using the Poisson regression model. Trend analysis was explored using a fitted linear regression line on a time series plot. SETTING: Ghana. PARTICIPANTS: Children under 5 years. RESULTS: The results showed a reduction in the prevalence of stunting and anaemia over the 15-year duration. These health outcomes were found to be negatively associated with a wide array of socio-demographic (child age and gender, maternal age and education, residency), economic (household wealth), dietary (iodised salt use) and health service (place of delivery and vaccination) factors; however, the most consistent statistically significant association was observed between child's age and belonging to the poor wealth quintile. CONCLUSION: In order to prevent these indicators of child malnutrition, key consideration must be given to the early developmental stages of life. Child health policies must focus on addressing the key contextual factors of child malnutrition.


Asunto(s)
Anemia , Trastornos de la Nutrición del Niño , Niño , Humanos , Preescolar , Ghana/epidemiología , Encuestas Epidemiológicas , Factores de Riesgo , Anemia/epidemiología , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Demografía
20.
BMC Public Health ; 24(1): 488, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365615

RESUMEN

BACKGROUND: Stunting in children is the term for reduced linear growth and development, which is frequently brought on by a persistently inadequate diet, recurrent infections and chronic diseases or poor health conditions. Apart from the classic covariates of stunting, which include diet and illness, the relative contribution of household air pollution to chronic nutrition conditions is least studied. Hence, this study is conducted to investigate the impact of household air pollution on the linear growth of under-five children in Jimma town, Ethiopia. METHODS: A prospective cohort study was employed to collect data from 280 under-five children who lived in households using solid fuel (exposed group, n = 140) and clean fuel (unexposed group, n = 140). Height-for-age Z scores were compared in both groups over a 12-month follow-up period. The difference in differences estimators were used for comparison of changes in the height-for-age Z scores from baseline to end line in exposed and non-exposed groups. The independent effect of the use of solid fuels on height-for-age Z scores was analyzed through a multivariable linear regression model. Statistical Significances were declared at P < 0.05 and 95% CI level. RESULTS: In an unadjusted model (Model 1), compared with the clean fuel type, the mean difference in the height-for-age Z score of children in households using solid fuel was lower by 0.54 (-0.54, 95% CI -0.97, -0.12, P = 0.011). The beta coefficient remained negative after adjusting for age and sex (Model 2 -0.543, 95% CI -1.373, -0.563) and sociodemographic variables (Model 3: -0.543, 95% CI -1.362, -0.575). In the final model (Model 4), which adjusted for wealth quantile, dietary practice, water, sanitation and hygiene status and household food insecurity access scale, the beta coefficient held the same and significant (beta: -0.543, 95% CI -1.357, -0.579, P < 0.001). Higher HAZ scores were observed among female child (ß: = 0.48, 95%CI: 0.28, 0.69), Child with father attended higher education (ß: = 0.304 95%CI: 0.304, 95% CI 0.19, 0.41) as compared to male gender and those who did not attend a formal education, respectively. In contrast, child living in households with poor hygiene practices had lower HAZ score (ß: -0.226, 95% CI: -0.449, -0.003), P < 0.001. CONCLUSIONS: Exposure to indoor air pollution was inversely related to linear growth. Furthermore, sex, educational status and hygiene were found relevant predictors of linear growth. In such a setting, there is a need to step up efforts to design and implement public education campaigns regarding the health risks associated with exposure to household air pollution. Promoting improvements to kitchen ventilation and the use of improved cooking stoves, which will help to mitigate the detrimental effects of indoor air pollution on child growth impairment and its long-term effects.


Asunto(s)
Contaminación del Aire Interior , Contaminación del Aire , Niño , Humanos , Masculino , Femenino , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Etiopía/epidemiología , Estudios Prospectivos , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Culinaria
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