RESUMO
OBJECTIVE: To test feasibility and safety of administering sildenafil in neonates with neonatal encephalopathy (NE), developing brain injury despite therapeutic hypothermia (TH). STUDY DESIGN: We performed a randomized, double-blind, placebo-controlled phase Ib clinical trial between 2016 and 2019 in neonates with moderate or severe NE, displaying brain injury on day-2 magnetic resonance imaging (MRI) despite TH. Neonates were randomized (2:1) to 7-day sildenafil or placebo (2 mg/kg/dose enterally every 12 hours, 14 doses). Outcomes included feasibility and safety (primary outcomes), pharmacokinetics (secondary), and day-30 neuroimaging and 18-month neurodevelopment assessments (exploratory). RESULTS: Of the 24 enrolled neonates, 8 were randomized to sildenafil and 3 to placebo. A mild decrease in blood pressure was reported in 2 of the 8 neonates after initial dose, but not with subsequent doses. Sildenafil plasma steady-state concentration was rapidly reached, but decreased after TH discontinuation. Twelve percent of neonates (1/8) neonates died in the sildenafil group and 0% (0/3) in the placebo group. Among surviving neonates, partial recovery of injury, fewer cystic lesions, and less brain volume loss on day-30 magnetic resonance imaging were noted in 71% (5/7) of the sildenafil group and in 0% (0/3) of the placebo group. The rate of death or survival to 18 months with severe neurodevelopmental impairment was 57% (4/7) in the sildenafil group and 100% (3/3) in the placebo group. CONCLUSIONS: Sildenafil was safe and well-absorbed in neonates with NE treated with TH. Optimal dosing needs to be established. Evaluation of a larger number of neonates through subsequent phases II and III trials is required to establish efficacy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT02812433.
Assuntos
Asfixia Neonatal , Lesões Encefálicas , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Recém-Nascido , Humanos , Citrato de Sildenafila/efeitos adversos , Asfixia/complicações , Estudos de Viabilidade , Asfixia Neonatal/terapia , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Doenças do Recém-Nascido/terapia , Hipóxia-Isquemia Encefálica/terapia , Hipotermia Induzida/métodos , Método Duplo-CegoRESUMO
OBJECTIVE: To create reference charts for sitting height to standing height ratio (SitHt/Ht) for children in the US, and to describe the trajectory of SitHt/Ht during puberty. STUDY DESIGN: This was a cross-sectional study using data from the 1988-1994 National Health and Nutrition Examination Survey III, a strategic random sample of the US population. Comparison between non-Hispanic White (NHW), non-Hispanic Black (NHB) and Mexican American groups was performed by ANOVA to determine if a single population reference chart could be used. ANOVA was used to compare SitHt/Ht in pre-, early, and late puberty. RESULTS: NHANES III recorded sitting height and standing height measurements in 9569 children aged 2-18 years of NHW (n = 2715), NHB (n = 3336), and Mexican American (n = 3518) ancestry. NHB children had lower SitHt/Ht than NHW and Mexican American children throughout childhood (P < .001). In both sexes, the SitHt/Ht decreased from prepuberty to early puberty and increased in late puberty. Sex-specific percentile charts of SitHt/Ht vs age were generated for NHB and for NHW and Mexican American youth combined. CONCLUSIONS: SitHt/Ht assessment can detect disproportionate short stature in children with skeletal dysplasia, but age-, sex-, and population-specific reference charts are required to interpret this measurement. NHB children in the US have significantly lower SitHt/Ht than other children, which adds complexity to interpretation. We recommend the use of standardized ancestry-specific reference charts in screening for skeletal dysplasias and have developed such charts in this study.
Assuntos
Estatura/etnologia , Gráficos de Crescimento , Valores de Referência , Postura Sentada , Adolescente , Negro ou Afro-Americano , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Americanos Mexicanos , Inquéritos Nutricionais , Estados Unidos , População BrancaRESUMO
OBJECTIVES: To evaluate the timing of a delayed rise in thyroid-stimulating hormone (TSH) levels in preterm infants with congenital hypothyroidism, and to determine whether cases of congenital hypothyroidism would be missed by using current consensus guidelines of repeat screening at approximately 2 weeks of age or 2 weeks after the first screening. STUDY DESIGN: The study was performed over a 13-year period (January 2004-December 2016). Whole-blood TSH samples were collected between 72 and 120 hours after birth. Repeat samples were collected weekly in preterm infants until the infant was term-corrected (37 weeks' gestation). Patients were followed up to determine whether congenital hypothyroidism was permanent or transient. RESULTS: Twenty-seven (50.9%) preterm infants born at <33 weeks of gestation who were diagnosed with congenital hypothyroidism had delayed TSH elevation and would not have been detected on first newborn screen. Twelve of these infants (40.7%) with delayed TSH elevation had decompensated hypothyroidism at diagnosis (free thyroxine [FT4] <10 pmol/L), and 4 had severe congenital hypothyroidism (FT4 <5.5 pmol/L) at diagnosis. If screening had been repeated only at 2 weeks of life, 13 infants (48%) with delayed TSH elevation would not have been identified. Of the 27 infants with delayed TSH elevation, 6 (22%) have permanent congenital hypothyroidism, and another 12 will be reevaluated at age 3 years. CONCLUSION: Repeat screening for congenital hypothyroidism in preterm infants is necessary to avoid missing cases of congenital hypothyroidism with delayed TSH elevation. Repeat screening once at 2 weeks of life will miss infants with delayed TSH elevation and decompensated permanent congenital hypothyroidism.
Assuntos
Hipotireoidismo Congênito/diagnóstico , Triagem Neonatal/métodos , Tireotropina/sangue , Hipotireoidismo Congênito/sangue , Diagnóstico Tardio/prevenção & controle , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Irlanda , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Acute diarrhea is an important cause of morbidity and mortality in children. Oral rehydration salts (ORS) have lowered mortality without having an effect on the duration or severity of diarrhea. Some studies have reported that heat-killed Lactobacillus bacteria have a beneficial effect in the treatment of acute diarrhea. In this placebo-controlled study the duration of diarrhea was compared for 2 types of treatment: Lactobacillus LB (Lacteol) in association with oral rehydration and oral rehydration alone. PATIENTS AND METHODS: A total of 80 nondehydrated children between the ages of 3 months and 4 years with acute watery diarrhea were randomly assigned to be treated with Lactobacillus LB or placebo plus ORS. The primary endpoint was the duration of diarrhea; intake of ORS and change in body weight between the time of randomization and the last assessment were also measured. RESULTS: In 71 of the 80 patients, diarrhea was resolved: 36 in the Lactobacillus LB group and 35 in the placebo group. Several clinical characteristics of the 2 treatment groups were comparable at baseline. Median duration of diarrhea was 16.6 hours in the placebo group compared with 10.0 hours in the Lactobacillus LB group (P = 0.275). In the subgroup with a duration of diarrhea of more than 24 hours at inclusion, duration of diarrhea measured from that point was shorter for the Lactobacillus LB group (30.4 h vs 8.2 h; P = 0.044). ORS intake was similar for both groups. Lactobacillus LB was well tolerated, with only one patient experiencing an adverse effect. CONCLUSIONS: Lactobacillus LB is an effective and safe treatment for children with well-established diarrhea (>24 h).