RESUMEN
Importance: Although birth defects in children with congenital Zika syndrome (CZS) are expected to result in significant intellectual disabilities, the extent of delay and profiles of development have yet to be fully described. Objectives: To describe the neurodevelopmental profiles of children with CZS and to test whether prenatal and postpartum characteristics were associated with the severity of developmental delays. Design, Setting, and Participants: This is a case series of the trajectories of developmental, behavioral, and medical needs of 121 young children with CZS who were assessed at a specialized rehabilitation center in Recife, Brazil, beginning in January 2018 as part of 5-year longitudinal study. Children were included if they had serologic confirmation of Zika virus and met clinical criteria accompanied by parental report of suspected exposure to Zika virus during pregnancy. Exposures: Prenatal Zika virus exposure. Main Outcomes and Measures: The Brazilian version of the Bayley Scales of Infant and Toddler Development, Third Edition, was administered by trained assessors as part of an initial comprehensive assessment battery. Caregiver interviews and medical record reviews were conducted to gather basic demographic information and medical comorbidities. Linear regression was used to identify potential factors for development. Results: The sample included 121 young children (mean [SD] age, 31.2 [1.9] months; 61 [50.4%] girls). At age approximately 2.5 years, nearly all children in this sample demonstrated profound developmental delays across all domains of functioning, with a mean (SD) developmental age equivalent to approximately 2 to 4 months (eg, cognitive domain, 2.24 [3.09] months; fine motor subscale, 2.15 [2.93] months; expressive language subscale, 2.30 [2.52] months). A relative strength was found in receptive language, with scores on this scale significantly higher than most other domains (eg, cognition: t = 3.73; P < .001; fine motor: t = 6.99; P < .001). Head circumference at birth was the single strongest factor associated with outcomes across all developmental domains (eg, cognitive: ß = 1.41; SE, 0.67; P = .04; fine motor: ß = 1.36; SE, 0.49; P = .007). Conclusions and Relevance: The findings of this study provide important information regarding the severity of disability that these children and their families will experience. The findings also establish an initial point from which to monitor developmental trajectories, medical comorbidities (eg, seizures), effectiveness of interventions, and cumulative consequences on families.
Asunto(s)
Discapacidades del Desarrollo/epidemiología , Microcefalia/complicaciones , Infección por el Virus Zika/complicaciones , Brasil/epidemiología , Preescolar , Discapacidades del Desarrollo/complicaciones , Femenino , Humanos , Estudios Longitudinales , Masculino , Embarazo , Infección por el Virus Zika/congénitoRESUMEN
OBJECTIVE: To evaluate the performance of a 2-tiered newborn screening method for mucopolysaccharidosis type I (MPS I) in North Carolina. STUDY DESIGN: The screening algorithm included a flow injection analysis-tandem mass spectrometry assay as a first-tier screening method to measure α-L-iduronidase (IDUA) enzyme activity and Sanger sequencing of the IDUA gene on dried blood spots as a second-tier assay. The screening algorithm was revised to incorporate the Collaborative Laboratory Integrated Reports, an analytical interpretive tool, to reduce the false-positive rate. A medical history, physical examination, IDUA activity, and urinary glycosaminoglycan (GAG) analysis were obtained on all screen-positive infants. RESULTS: A total of 62 734 specimens were screened with 54 screen-positive samples using a cut-off of 15% of daily mean IDUA activity. The implementation of Collaborative Laboratory Integrated Reports reduced the number of specimens that screened positive to 19 infants. Of the infants identified as screen-positive, 1 had elevated urinary GAGs and a homozygous pathogenic variant associated with the severe form of MPS I. All other screen-positive infants had normal urinary GAG analysis; 13 newborns had pseudodeficiency alleles, 3 newborns had variants of unknown significance, and 2 had heterozygous pathogenic variants. CONCLUSIONS: An infant with severe MPS I was identified and referred for a hematopoietic stem cell transplant. Newborn IDUA enzyme deficiency is common in North Carolina, but most are due to pseudodeficiency alleles in infants with normal urinary GAG analysis and no evidence of disease. The pilot study confirmed the need for second-tier testing to reduce the follow-up burden.
Asunto(s)
Mucopolisacaridosis I/diagnóstico , Tamizaje Neonatal , Algoritmos , Dermatán Sulfato/orina , Pruebas Genéticas , Variación Genética , Glicosaminoglicanos/orina , Heparitina Sulfato/orina , Humanos , Iduronidasa/sangre , Iduronidasa/genética , Recién Nacido , Mucopolisacaridosis I/genética , North Carolina , Derivación y Consulta/estadística & datos numéricos , Análisis de Secuencia , Espectrometría de Masas en TándemRESUMEN
The recent Zika outbreak and its link to microcephaly and other birth defects in infants exposed in utero have garnered widespread international attention. Based on the severity of birth defects the extent of impairment in these infants is expected to be profound; however, virtually nothing is known regarding the developmental and behavioral sequela of congenital Zika syndrome. This pilot study collected parent-reported patterns of development and sleep in 47 infants with confirmed congenital Zika syndrome who are being followed for clinical services at the Altino Ventura Foundation (FAV) in Recife, Brazil. With assistance from clinicians at FAV, caregivers completed Brazilian Portuguese versions of the Ages and Stages Questionnaire, 3rd edition (ASQ-3) and the Brief Infant Sleep Questionnaire (BISQ). All infants were between 13-22 months of age at the time of the assessment. At 16 months of age, none of the children displayed age appropriate developmental skills. Most (~ 75%) mastered some communication and gross motor skills at around a 6-8-month level. Communication and gross motor skills were relative strengths for the sample, while problem-solving and fine motor skills were relative weaknesses. Sleep was noted to be a problem for around 18% of the sample. In utero exposure to the Zika virus will have lifelong consequences for affected children and their families. Understanding the developmental and behavioral trajectories of affected infants will help identify appropriate family supports to improve quality of life.