RESUMEN
BACKGROUND: Intraventricular hemorrhage (IVH) is a serious problem in preterm infants. Brazilian national data are unknown. OBJECTIVE: To evaluate the incidence and temporal trend of IVH in very low birth weight (VLBW) preterm infants of 18 centers of the Brazilian Network on Neonatal Research. STUDY DESIGN: National prospective multicenter cohort study including inborn VLBW preterm infants aged 230/7- 336/7 weeks' gestation, admitted between 2013 and 2018. The center with the mean incidence rate was used as reference. We applied two adjustments models using perinatal variables, and perinatal + neonatal diseases. RESULTS: Of 6,420 infants, 1951/30.4% (range 27.1-33.8%) had IVH and the disease showed a significant trend towards an overall increase in incidence over time (p = 0.003), especially in three centers. Severe IVH (grade III or IV) occurred in 32.2% (range 29.2-34.5%) of those affected by IVH, with a stable incidence. After adjustments for perinatal variables, the differences persisted among centers: for global IVH, 7 centers had significantly lower rates (OR ranging from 0.31 to 0.62), and 2 presented rates higher than the reference center (OR ranging from 2.00 to 12.46) for severe HIV. Considering perinatal and neonatal variables, 6 centers had significantly lower rates (OR ranging from 0.36 to 0.60) for global IVH than the reference center and 3 had statistically higher rates (OR 1.72, 1.86 and 11.78) for severe forms. CONCLUSION: The incidence rate of IVH in this Brazilian cohort was high and it revealed an increasing trend towards over time. The severe IVH rate was also worrisome.
Asunto(s)
Enfermedades del Prematuro , Recien Nacido Prematuro , Brasil/epidemiología , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/etiología , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Enfermedades del Prematuro/epidemiología , Embarazo , Estudios ProspectivosRESUMEN
Holoprosencephaly (HPE) is the failure of the embryonic forebrain to develop into 2 hemispheres promoting midline cerebral and facial defects. The wide phenotypic variability and causal heterogeneity make genetic counseling difficult. Heterozygous variants with incomplete penetrance and variable expressivity in the SHH, SIX3, ZIC2, and TGIF1 genes explain â¼25% of the known causes of nonchromosomal HPE. We studied these 4 genes and clinically described 27 Latin American families presenting with nonchromosomal HPE. Three new SHH variants and a third known SIX3 likely pathogenic variant found by Sanger sequencing explained 15% of our cases. Genotype-phenotype correlation in these 4 families and published families with identical or similar driver gene, mutated domain, conservation of residue in other species, and the type of variant explain the pathogenicity but not the phenotypic variability. Nine patients, including 2 with SHH pathogenic variants, presented benign variants of the SHH, SIX3, ZIC2, and TGIF1 genes with potential alteration of splicing, a causal proposition in need of further studies. Finding more families with the same SIX3 variant may allow further identification of genetic or environmental modifiers explaining its variable phenotypic expression.