RESUMEN
AIM: Transcatheter closure of the patent ductus arteriosus (TCPDA) is increasingly used in preterm infants as an alternative to surgical ligation. However, clinically ill preterm infants are at risk of contrast nephropathy due to the angiography contrast agents used during the procedure. METHODS: We performed a single-centre before-and-after comparative study in VLBW infants to compare the kinetics of serum creatinine during the first 4 days after TCPDA with or without angiography. RESULTS: 69 patients were included and divided into two groups: TCPDA with (contrast+; n = 37) and without (contrast-, n = 32) use of contrast agent. The median dose [range] of contrast agent was 1.0 mL/kg [0.6-2.4 mL/kg]. The change in serum creatinine level between day 2 to 4 after TCPCA and baseline decreased in the contrast- group (-17% [-46%; 18%]), while it increased in the contrast+ group (7% [-24%; 202%] p = 0.002). Comparison of blood urea levels between groups showed similar significant differences. The change in serum creatinine between day 2 to 4 and baseline was significantly correlated with the dose of contrast agent (r2 = 0.682; p < 0.001). CONCLUSION: The use of contrast agents during TCPDA can potentially harm the renal function of very preterm infants. Therefore, we advise minimising or avoiding the use of contrast agents.
Asunto(s)
Conducto Arterioso Permeable , Conducto Arterial , Enfermedades del Prematuro , Lactante , Recién Nacido , Humanos , Recien Nacido Prematuro , Medios de Contraste/efectos adversos , Creatinina , Conducto Arterioso Permeable/diagnóstico por imagen , Riñón/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes.
Asunto(s)
Proteínas Portadoras/genética , Haploinsuficiencia/genética , Discapacidad Intelectual/genética , Trastornos del Neurodesarrollo/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética , Transcripción Genética , Animales , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , Corteza Cerebral/metabolismo , Ensamble y Desensamble de Cromatina/genética , Codón sin Sentido/genética , Trastornos del Conocimiento/genética , Mutación del Sistema de Lectura/genética , Hipocampo/metabolismo , Humanos , Discapacidad Intelectual/patología , Discapacidad Intelectual/psicología , Masculino , Ratones , Microcefalia/genética , Mutación Missense/genética , Trastornos del Neurodesarrollo/patología , Trastornos del Neurodesarrollo/fisiopatología , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Fenotipo , Proteínas Represoras , Conducta Social , Síndrome , Factores de Transcripción/química , Factores de Transcripción/metabolismo , TranscriptomaRESUMEN
OBJECTIVE: To describe the growth trajectory of children with congenital diaphragmatic hernia (CDH) during the first year, to assess the risk factors for growth failure (GF) at 1 year and to determine nutritional intakes at discharge required for early optimal growth. DESIGN: Single-centre retrospective cohort study based on data from a structured follow-up programme. SETTING AND PATIENTS: All neonates with CDH (2013-2019) alive at discharge and followed up to age 1. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Weight-for-age z-score (WAZ) at birth, 3, 6 and 12 months of age; risk factors for GF at age 1; energy and protein intake of infants achieving early optimal growth. RESULTS: Sixty-three of 65 neonates who were alive at discharge were included. Seven (11%) had GF at 1 year and 3 (4.8%) had a gastrostomy tube. The mean WAZ decreased in the first 3 months before catching up at 1 year (-0.6±0.78). Children with a severe form or born preterm experienced a deeper loss (from -1.5 to -2 z-scores) with late and limited catch-up. The median energy intake required to achieve positive or null weight growth velocity differed significantly according to CDH severity, ranging from 100 kcal/kg/day (postnatal forms) to 139 kcal/kg/day (severe prenatal forms) (p=0.009). CONCLUSIONS: Growth patterns of CDH infants suggest that nutritional risk stratification and feeding practices may influence growth outcomes. Our results support individualised and active nutritional management based on CDH severity, with energy requirements as high as 140% of recommended intakes for healthy term infants.