RESUMO
OBJECTIVES: To determine the effects of in-utero exposure to maternal SARS-CoV-2 infection on offspring's neurodevelopment during the first year of life. METHODS: We performed a prospective cohort of babies exposed to SARS-CoV-2 during pregnancy, and a control group (CG) of unexposed babies in a low-income area in Brazil. Children's neurodevelopment was assessed using the guide for Monitoring Child Development in the Integrated Management of Childhood Illness context for both groups (at 1,2,3,4,5,6, 9, and 12 months), and the Ages & Stages Questionnaire (ASQ-3) for the exposed group (EG) (at 4, 6 and 12 months). RESULTS: We followed 137 children for 1 year, 69 in the COVID-19-EG, and 68 in the CG. All mothers were unvaccinated at the time of cohort inclusion, and maternal demographics were similar in the two groups. 20.3% of EG children and 5.9% of the CG received a diagnosis of neurodevelopmental delay within 12 months of life (P = 0.013, relative risk = 3.44; 95% confidence interval, 1.19- 9.95). For the EG, the prevalence of neurodevelopment impairment using Ages & Stages Questionnaire was 35.7% at 4 months, 7% at 6 months, and 32.1% at 12 months. CONCLUSION: SARS-CoV-2 exposure was associated with neurodevelopmental impairment, and specific guidelines are needed for the follow-up of these high-risk children to mitigate the long-term effects on children's health.
Assuntos
COVID-19 , Efeitos Tardios da Exposição Pré-Natal , Lactente , Gravidez , Criança , Feminino , Humanos , Estudos de Coortes , Brasil/epidemiologia , RNA Viral , Estudos Prospectivos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , COVID-19/epidemiologia , SARS-CoV-2 , MãesRESUMO
OBJECTIVE: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia. METHODS: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy. RESULTS: Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59. CONCLUSIONS: In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI.
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Asfixia Neonatal , Lesões Encefálicas , Doenças do Recém-Nascido , Recém-Nascido , Gravidez , Feminino , Lactente , Humanos , Estudos Retrospectivos , Asfixia/complicações , Imageamento por Ressonância Magnética/métodos , Asfixia Neonatal/complicações , Asfixia Neonatal/diagnóstico por imagem , Lesões Encefálicas/patologia , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
OBJECTIVE: To evaluate the impact of a parenteral lipid emulsion containing fish oil compared with a soybean oil based-lipid emulsion on the cognitive outcome and behavior of preschool children with extremely low birth weight. STUDY DESIGN: This was a retrospective secondary outcome analysis of a randomized controlled trial performed between June 2012 and June 2015. Infants with extremely low birth weight received either a mixed (soybean oil, medium chain triglycerides, olive oil, fish oil) or a soybean oil-based lipid emulsion for parenteral nutrition. Data from the Kaufman Assessment Battery for Children II, the Child Behavior Checklist 1.5-5, and anthropometry were collected from medical charts at 5.6 years of age. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 5 years 6 months of age, data of 153 of 206 infants (74%) were available for analysis. There were no significant differences in Kaufman Assessment Battery for Children II scores for Sequential/Gsm, Simultaneous/Gv, Learning/Glr, and Mental Processing Index (mixed lipid: median, 97.5 [IQR, 23.5]; soybean oil: median, 96 [IQR, 19.5]; P = .43) or Child Behavior Checklist 1.5-5 scores for internalizing problems, externalizing problems, or total problems (mixed lipid: median, 37 [IQR, 12.3]; soybean oil: median, 37 [IQR, 13.5]; P = .54). CONCLUSIONS: A RandomForest machine learning regression analysis did not show an effect of type of lipid emulsion on cognitive and behavioral outcome. Parenteral nutrition using a mixed lipid emulsion containing fish oil did not affect neurodevelopment and had no impact on child behavior of infants with extremely low birth weights at preschool age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.
Assuntos
Óleos de Peixe , Óleo de Soja , Humanos , Peso ao Nascer , Emulsões , Estudos Retrospectivos , Triglicerídeos , Cognição , Emulsões Gordurosas IntravenosasRESUMO
OBJECTIVE: To determine the incidence of hypoglycemia among infants with hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia, and to assess whether infants with hypoglycemia had more brain injury on magnetic resonance imaging (MRI) or differences in neurodevelopmental outcome. STUDY DESIGN: Single-center, retrospective cohort study including infants cooled for HIE. Hypoglycemia (blood glucose <36.0 mg/dL <2 hours and <46.8 mg/dL ≥2 hours after birth) was analyzed in the period before brain MRI. Brain injury was graded using a validated score. Motor and neurocognitive outcomes were assessed at 2 years for all survivors, and 5.5 years for a subset who had reached this age. RESULTS: Of 223 infants analyzed, 79 (35.4%) had hypoglycemia. MRI was performed in 187 infants. Infants with hypoglycemia (n = 65) had higher brain injury scores (P = .018). After adjustment for HIE severity, hypoglycemia remained associated with higher injury scores (3.6 points higher; 95% CI, 0.8-6.4). Hyperglycemia did not affect MRI scores. In survivors at 2 years (n = 154) and 5.5 years (n = 102), a univariable analysis showed lower 2-year motor scores and lower motor and cognitive scores at preschool age in infants with hypoglycemia. After adjustment for HIE severity, infants with hypoglycemia had 9 points lower IQs (P = .023) and higher odds of adverse outcomes at preschool age (3.6; 95% CI, 1.4-9.0). CONCLUSIONS: More than one-third of infants cooled for HIE had hypoglycemia. These infants had a higher degree of brain injury on MRI and lower cognitive function at preschool age. Strategies to avoid hypoglycemia should be optimized in this setting.
Assuntos
Lesões Encefálicas , Hipoglicemia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Lesões Encefálicas/complicações , Lesões Encefálicas/terapia , Pré-Escolar , Humanos , Hipoglicemia/complicações , Hipoglicemia/epidemiologia , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/terapia , Lactente , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine the optimal quantitative magnetic resonance (MR) biomarker in neonatal encephalopathy following therapeutic hypothermia based on scan timing. STUDY DESIGN: This retrospective study included 98 neonates (35-41 weeks of gestation) with neonatal encephalopathy, who underwent therapeutic hypothermia; diffusion-weighted imaging and proton MR spectroscopy were performed at 24-96 hours (n = 56) and 7-14 days (n = 92) after birth, respectively, to estimate apparent diffusion coefficient (ADC) values, N-acetylaspartate and N-acetylaspartylglutamate (tNAA), lactate, and choline concentrations, and lactate/tNAA, tNAA/choline ratios in the deep gray matter. Adverse outcomes included death or neurodevelopmental impairment at 18-22 months of age. We used receiver operating characteristic curves to examine the prognostic accuracy of each MR biomarker. RESULTS: Deep gray matter tNAA concentrations showed the best prognostic value, with an area under the curve (AUC) of 0.97 and 1.00 at 24-96 hours and 7-14 days after birth, respectively. At 24-96 hours of age, ADC values, lactate concentrations, and lactate/tNAA ratios showed prognostic value with AUCs of 0.90, 0.95, and 0.97, respectively. At 7-14 days of age, the AUCs of ADC values, lactate, and lactate/tNAA ratios were 0.61, 0.67, and 0.80, respectively; these were lower than those at 24-96 hours of age. CONCLUSIONS: During the first 2 weeks of life, the deep gray matter tNAA concentration was the most accurate quantitative MR biomarker. Although ADC values, lactate levels, and lactate/tNAA ratios also showed high prognostic value during 24-96 hours of life, only tNAA retained high prognostic value in the second week of life.
Assuntos
Encefalopatias/diagnóstico por imagem , Substância Cinzenta/metabolismo , Imageamento por Ressonância Magnética/métodos , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Dipeptídeos/metabolismo , Substância Cinzenta/diagnóstico por imagem , Humanos , Hipotermia Induzida , Recém-Nascido , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To evaluate the association of therapeutic hypothermia with magnetic resonance imaging (MRI) findings and 30-month neurodevelopment in term neonatal encephalopathy. STUDY DESIGN: Cross-sectional analysis of 30-month neurodevelopment (IQR 19.0-31.4) in a prospective cohort of mild-to-severe neonatal encephalopathy imaged on day 4 (1993-2017 with institutional implementation of therapeutic hypothermia in 2007). MRI injury was classified as normal, watershed, or basal ganglia/thalamus. Abnormal motor outcome was defined as Bayley-II psychomotor developmental index <70, Bayley-III motor score <85 or functional motor deficit. Abnormal cognitive outcome was defined as Bayley-II mental developmental index <70 or Bayley-III cognitive score <85. Abnormal composite outcome was defined as abnormal motor and/or cognitive outcome, or death. The association of therapeutic hypothermia with MRI and outcomes was evaluated with multivariable logistic regression adjusted for propensity to receive therapeutic hypothermia. RESULTS: Follow-up was available in 317 (78%) surviving children, of whom 155 (49%) received therapeutic hypothermia. Adjusting for propensity, therapeutic hypothermia was independently associated with decreased odds of abnormal motor (OR 0.15, 95% CI 0.06-0.40, P < .001) and cognitive (OR 0.11, 95% CI 0.04-0.33, P < .001) outcomes. This association remained statistically significant after adjustment for injury pattern. The predictive accuracy of MRI pattern for abnormal composite outcome was unchanged between therapeutic hypothermia-treated (area under the receiver operating curve 0.76; 95% CI 0.61-0.91) and untreated (area under the receiver operating curve 0.74; 95% CI 0.67-0.81) infants. The negative predictive value of normal MRI was high in therapeutic hypothermia-treated and untreated infants (motor 96% vs 90%; cognitive 99% vs 95%). CONCLUSIONS: Therapeutic hypothermia is associated with lower rates of brain injury and adverse 30-month outcomes after neonatal encephalopathy. The predictive accuracy of MRI in the first week of life is unchanged by therapeutic hypothermia. Normal MRI remains reassuring for normal 30-month outcome after therapeutic hypothermia.
Assuntos
Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/prevenção & controle , Adulto , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hipóxia-Isquemia Encefálica/terapia , Lactente , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico por imagem , Doenças do Recém-Nascido/terapia , Imageamento por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. METHODS: We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants' homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. RESULTS: Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P = .01) and low-birthweight infants (<2500 g) (P = .006) had lower composite ECL scores. CONCLUSIONS: In this prospective cohort of children without CZS, children with in utero ZIKV exposure had lower neurocognitive scores at 24 months.
Assuntos
Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Nicarágua/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Prospectivos , Infecção por Zika virus/epidemiologiaRESUMO
OBJECTIVE: To evaluate umbilical cord messenger RNA (mRNA) expression as biomarkers for the grade of hypoxic-ischemic encephalopathy (HIE) and long-term neurodevelopment outcome. STUDY DESIGN: Infants were recruited from the BiHiVE1 study, Ireland (2009-2011), and the BiHiVE2 study, Ireland, and Sweden (2013-2015). Infants with HIE were assigned modified Sarnat scores at 24 hours and followed at 18-36 months. mRNA expression from cord blood was measured using quantitative real-time polymerase chain reaction. RESULTS: We studied 124 infants (controls, n = 37; perinatal asphyxia, n = 43; and HIE, n = 44). Fzd4 mRNA increased in severe HIE (median relative quantification, 2.98; IQR, 2.23-3.68) vs mild HIE (0.88; IQR, 0.46-1.37; P = .004), and in severe HIE vs moderate HIE (1.06; IQR, 0.81-1.20; P = .003). Fzd4 mRNA also increased in infants eligible for therapeutic hypothermia (1.20; IQR, 0.92-2.37) vs those who were ineligible for therapeutic hypothermia group (0.81; IQR, 0.46-1.53; P = .017). Neurodevelopmental outcome was analyzed for 56 infants. Nfat5 mRNA increased in infants with severely abnormal (1.26; IQR, 1.17-1.39) vs normal outcomes (0.97; IQR, 0.83-1.24; P = .036), and also in infants with severely abnormal vs mildly abnormal outcomes (0.96; IQR, 0.80-1.06; P = .013). Fzd4 mRNA increased in infants with severely abnormal (2.51; IQR, 1.60-3.56) vs normal outcomes (0.74; IQR, 0.48-1.49; P = .004) and in infants with severely abnormal vs mildly abnormal outcomes (0.97; IQR, 0.75-1.34; P = .026). CONCLUSIONS: Increased Fzd4 mRNA expression was observed in cord blood of infants with severe HIE; Nfat5 mRNA and Fzd4 mRNA expression were increased in infants with severely abnormal long-term outcomes. These mRNA may augment current measures as early objective markers of HIE severity at delivery.
Assuntos
Asfixia Neonatal/genética , Receptores Frizzled/genética , Hipóxia-Isquemia Encefálica/genética , RNA Mensageiro/genética , Fatores de Transcrição/genética , Regulação para Cima , Asfixia Neonatal/sangue , Asfixia Neonatal/diagnóstico , Biomarcadores/sangue , Eletroencefalografia , Feminino , Seguimentos , Receptores Frizzled/metabolismo , Humanos , Hipóxia-Isquemia Encefálica/sangue , Recém-Nascido , Masculino , Prognóstico , RNA Mensageiro/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Transcrição/sangueRESUMO
OBJECTIVE: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability. STUDY DESIGN: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age. RESULTS: Outcomes were assessed in 113 of 126 infants. The composite adverse outcome was seen in 20 of 58 infants (35%) in the low threshold group and 28 of 55 (51%) in the high threshold (P = .07). The low threshold intervention was associated with a decreased risk of an adverse outcome after correcting for gestational age, severity of intraventricular hemorrhage, and cerebellar hemorrhage (aOR, 0.24; 95% CI, 0.07-0.87; P = .03). Infants with a favorable outcome had a smaller fronto-occipital horn ratio (crude mean difference, -0.06; 95% CI, -0.09 to -0.03; P < .001) at term-equivalent age. Infants in the low threshold group with a ventriculoperitoneal shunt, had cognitive and motor scores similar to those without (P = .3 for both), whereas in the high threshold group those with a ventriculoperitoneal shunt had significantly lower scores than those without a ventriculoperitoneal shunt (P = .01 and P = .004, respectively). CONCLUSIONS: In a post hoc analysis, earlier intervention was associated with a lower odds of death or severe neurodevelopmental disability in preterm infants with progressive posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.
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Hemorragia Cerebral/complicações , Hemorragia Cerebral/cirurgia , Ventrículos Cerebrais/patologia , Doenças do Prematuro/cirurgia , Transtornos do Neurodesenvolvimento/epidemiologia , Tempo para o Tratamento , Hemorragia Cerebral/psicologia , Pré-Escolar , Estudos de Coortes , Dilatação Patológica , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/psicologia , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/prevenção & controle , Punção Espinal , Derivação VentriculoperitonealRESUMO
OBJECTIVE: To develop an index to determine which opioid-exposed neonates have the most severe neonatal abstinence syndrome (NAS). STUDY DESIGN: Full-term neonates with NAS (n = 116) from mothers maintained on methadone or buprenorphine were enrolled from 8 sites into a randomized clinical trial of morphine vs methadone. Ninety-nine (85%) were evaluated at hospital discharge using the NICU Network Neurobehavioral Scale (NNNS). At 18 months, 83 of 99 (83.8%) were evaluated with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and 77 of 99 (77.7%) were evaluated with the Child Behavior Checklist (CBCL). RESULTS: Cluster analysis was used to define high (n = 21) and low (n = 77) NAS severity. Compared with infants in the low NAS severity cluster, infants in the high NAS severity cluster had a longer length of stay (P < .001), longer length of stay due to NAS (P < .001), longer duration of treatment due to NAS (P < .001), and higher total dose of the study drug (P < .001) and were more likely to have received phenobarbital (P < .001), to have been treated with morphine (P = .020), and to have an atypical NNNS profile (P = .005). The 2 groups did not differ in terms of maximum Finnegan score. At 18 months, in unadjusted analyses, compared with the high-severity cluster, the low-severity cluster had higher scores on the Bayley-III Cognitive (P = .013), Language (P < .001), and Motor (P = .041) composites and less total behavior problems on the CBCL (P = .028). In adjusted analyses, the difference in the Bayley-III Language composite remained (P = .013). CONCLUSIONS: Presumptive measures of NAS severity can be aggregated to develop an index that predicts developmental outcomes at age 18 months.
Assuntos
Síndrome de Abstinência Neonatal/diagnóstico , Índice de Gravidade de Doença , Analgésicos Opioides/administração & dosagem , Análise por Conglomerados , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Metadona/administração & dosagem , Morfina/administração & dosagem , Síndrome de Abstinência Neonatal/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/complicações , Gravidez , Complicações na GravidezRESUMO
OBJECTIVE: To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants. STUDY DESIGN: The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24 months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 12 and 24 months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12 months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P = .71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P = .48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P = .69). At 24 months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P = .17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P = .54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P = .53). CONCLUSIONS: Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.
Assuntos
Emulsões Gordurosas Intravenosas/uso terapêutico , Óleos de Peixe/uso terapêutico , Transtornos do Neurodesenvolvimento/prevenção & controle , Nutrição Parenteral , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Azeite de Oliva/uso terapêutico , Óleo de Soja/uso terapêutico , Triglicerídeos/uso terapêuticoRESUMO
OBJECTIVES: To examine the association between mortality or neurodevelopmental impairment at 18-24 months of corrected age and the Transport Risk Index of Physiologic Stability (TRIPS) score on admission to the neonatal intensive care unit (NICU) in extremely premature infants. STUDY DESIGN: Retrospective cohort study of extremely premature infants (inborn and outborn) born at 22-28 weeks of gestational age and admitted to NICUs in the Canadian Neonatal Network between April 2009 and September 2011. TRIPS scores and clinical data were collected from the Canadian Neonatal Network database. Follow-up data at 18-24 months of corrected age were retrieved from the Canadian Neonatal Follow-Up Network database. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, Edition III. The primary outcome was death or significant neurodevelopmental impairment at 18-24 months of corrected age. The secondary outcomes were individual components of the Bayley Scales of Infant and Toddler Development, Edition III assessment. RESULTS: A total of 1686 eligible infants were included. A TRIPS score of ≥20 on admission to the NICU was significantly associated with mortality (aOR 2.71 [95% CI, 2.02-3.62]) and mortality or significant neurodevelopmental impairment (aOR 1.91 [95% CI, 1.52-2.41]) at 18-24 months of corrected age across all gestational age groups of extremely premature infants. CONCLUSION: The TRIPS score on admission to the NICU can be used as an adjunctive, objective tool for counselling the parents of extremely premature infants early after their admission to the NICU.
Assuntos
Deficiências do Desenvolvimento/etiologia , Doenças do Prematuro/mortalidade , Medição de Risco , Bases de Dados Factuais , Deficiências do Desenvolvimento/mortalidade , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/etiologia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To evaluate the effects of pharmacologic treatment of neonatal abstinence syndrome on neurodevelopmental outcome from a randomized, controlled trial. STUDY DESIGN: Eight sites enrolled 116 full-term newborn infants with neonatal abstinence syndrome born to mothers maintained on methadone or buprenorphine into a randomized trial of morphine vs methadone. Ninety-nine infants (85%) were evaluated at hospital discharge using the NICU Network Neurobehavioral Scale. At 18 months, 83 of 99 infants (83.8%) were evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition and 77 of 99 (77.7%) with the Child Behavior Checklist (CBCL). RESULTS: Primary analyses showed no significant differences between treatment groups on the NICU Network Neurobehavioral Scale, Bayley Scales of Infant and Toddler Development-Third Edition, or CBCL. However in post hoc analyses, we found differences by atypical NICU Network Neurobehavioral Scale profile on the CBCL. Infants receiving adjunctive phenobarbital had lower Bayley Scales of Infant and Toddler Development-Third Edition scores and more behavior problems on the CBCL. In adjusted analyses, internalizing and total behavior problems were associated with use of phenobarbital (P = .03; P = .04), maternal psychological distress (measured by the Brief Symptom Inventory) (both P < .01), and infant medical problems (both P = .02). Externalizing problems were associated with maternal psychological distress (P < .01) and continued maternal substance use (P < .01). CONCLUSIONS: Infants treated with either morphine or methadone had similar short-term and longer term neurobehavioral outcomes. Neurodevelopmental outcome may be related to the need for phenobarbital, overall health of the infant, and postnatal caregiving environment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958476.
Assuntos
Metadona/farmacologia , Metadona/uso terapêutico , Morfina/farmacologia , Morfina/uso terapêutico , Entorpecentes/farmacologia , Entorpecentes/uso terapêutico , Síndrome de Abstinência Neonatal/tratamento farmacológico , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/crescimento & desenvolvimento , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fenobarbital/uso terapêuticoRESUMO
OBJECTIVE: To identify factors associated with neurodevelopmental impairment (NDI) in patients with bronchopulmonary dysplasia (BPD). STUDY DESIGN: We identified 151 patients with moderate to severe BPD from 2010 to 2014 with complete Bayley Scales of Infant Development (BSID) scores at 24 months corrected age. We defined NDI as any diagnosis of cerebral palsy or ≥1 BSID composite scores of <80. RESULTS: The mean corrected age at BSID was 23 ± 1 months; 18% had a cognitive score of <80, 37% had a communication score of <80, and 26% had a motor score of <80. Cerebral palsy was diagnosed in 22 patients (15%); 84 (56%) patients did not have NDI. Patients with NDI had lower birth weight, but there was no difference in gestational age at birth, severe intraventricular hemorrhage (IVH), necrotizing enterocolitis, or patent ductus arteriosus ligation compared with patients with no NDI. Ventilator days were greater in patients with NDI than in patients without NDI. More patients with NDI received furosemide and systemic corticosteroids and the hospital length of stay was longer than in patients with no NDI. Logistic regression modeling demonstrated that for every additional 100 g of birth weight the odds of NDI decreased by 35% and for every additional hospital day the odds of NDI increased by 1.3%. CONCLUSIONS: In our cohort of patients with moderate to severe BPD, the majority had no NDI, and low birth weight and length of hospital stay were associated with increased risk of developing NDI. This finding suggests that there are potentially modifiable factors associated with better neurodevelopmental outcomes in patients with BPD that deserve further study.
Assuntos
Displasia Broncopulmonar/complicações , Recém-Nascido Prematuro , Transtornos do Neurodesenvolvimento/etiologia , Medição de Risco/métodos , Pré-Escolar , Feminino , Seguimentos , Idade Gestacional , Humanos , Incidência , Lactente , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Ohio/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To assess the outcomes in actively managed extremely preterm infants after admission to a neonatal intensive care unit. STUDY DESIGN: Retrospective cohort of 255 infants born at 22-25 weeks of gestation between 2006 and 2015 at a single study institution. Infants were excluded for congenital anomaly, death in delivery room, or parental request for palliation (n = 7). Neurodevelopmental outcomes were analyzed for 169 of 214 survivors (78.9%) at 18-22 months of corrected age. Outcomes were evaluated using the Mann-Whitney U, χ2, or Fisher exact test, where appropriate. In addition, cognitive scores of the Bayley Scales of Infant-Toddler Development (3rd edition) were assessed using generalized estimating equations. RESULTS: Seventy infants born at 22-23 weeks of gestation (22 weeks, n = 20; 23 weeks, n = 50) and 178 infants born at 24-25 weeks of gestation (24 weeks, n = 79; 25 weeks, n = 99 infants) were included. Survival to hospital discharge of those surviving to NICU admission was 78% (55/70; 95% CI, 69%-88%) at 22-23 weeks and 89% (159/178; 95% CI, 84%-93% at 24-25 weeks; P = .02). No or mild neurodevelopmental impairment in surviving infants was 64% (29/45; 95% CI, 50%-77%) at 22-23 weeks and 76% (94/124; 95% CI, 68%-83%; P = .16) at 24-25 weeks. CONCLUSIONS: Although survival was lower in infants born at 22-23 weeks than at 24-25 weeks of gestation, the majority of survivors in both groups had positive outcomes with no or mild neurodevelopmental impairments. Further evaluation of school performance is warranted.
Assuntos
Doenças do Prematuro/terapia , Unidades de Terapia Intensiva Neonatal , Terapia Intensiva Neonatal/organização & administração , Hemorragia Cerebral Intraventricular/diagnóstico , Deficiências do Desenvolvimento/terapia , Enterocolite Necrosante/terapia , Feminino , Seguimentos , Idade Gestacional , Mortalidade Hospitalar , Humanos , Lactente , Lactente Extremamente Prematuro , Masculino , Transtornos do Neurodesenvolvimento/terapia , Sistema de Registros , Retinopatia da Prematuridade/terapia , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
OBJECTIVE: To compare pulmonary and neurodevelopmental outcomes in extremely preterm infants with evolving bronchopulmonary dysplasia treated with either a 42-day course of dexamethasone or 9-day course(s) of dexamethasone. STUDY DESIGN: This was a prospective, randomized study in 59 infants ≤27 weeks of gestation born between October 2006 and December 2010, who at day 10-21 of life had ventilatory support with mean airway pressure ≥8 cm H2O and FiO2 ≥60%. Infants received dexamethasone 0.5 mg/k/day × 3 days followed by a slow taper (42-day group, n = 30) or dexamethasone 0.5 mg/k/day followed by a rapid taper (9-day group, n = 29). Infants in the 9-day group received additional 9-day courses if they again required entry support. The primary outcome was intact survival (normal neurologic examination, IQ >70, and functioning in school without supplemental educational support) at 7 years of age. RESULTS: The 42-day and 9-day groups were similar for mean gestational age (25 weeks) and all baseline characteristics. Nineteen of 29 infants (66%) in the 9-day group received only 1 course of dexamethasone; therefore, the total steroid dose for the 42-day group (7.56 mg/kg) was significantly greater than that for the 9-day group (4.04 mg/kg), P < .001. Infants in the 42-day group had shorter duration of ventilation (25 vs 37 days), P < .005, received fewer transfusions (2 vs 3.5), P < .01, and reached full enteral feeds earlier (40 vs 46 days), P < .05. Intact survival at school age was significantly increased in the 42-day group (75%) compared with the 9-day group (34%), P < .005. CONCLUSION: A 42-day tapering course of dexamethasone in extremely preterm infants at high risk for bronchopulmonary dysplasia decreased hospital morbidities and increased rate of survival without handicap compared with a treatment protocol that attempted to minimize steroid exposure.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Dexametasona/administração & dosagem , Doenças do Prematuro/tratamento farmacológico , Esteroides/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Idade Gestacional , Glucocorticoides/uso terapêutico , Ventilação de Alta Frequência , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Resultado do TratamentoRESUMO
OBJECTIVE: To determine growth and its relationship to IQ in children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery within the first year of life. STUDY DESIGN: Prospective single-center cohort study on 143 children (91 males) with different types of CHD (29 univentricular). Children with recognized genetic disorders were excluded. Growth (weight, height, and head circumference [HC]) was assessed at birth, before surgery, and at 1, 4, and 6 years and compared with Swiss growth charts. IQ was assessed at 6 years using standardized tests. Univariate and multivariable linear regressions were performed to determine predictors of HC and IQ at 6 years. RESULTS: HC at birth was in the low average range (33rd percentile, P = .03), and weight (49th percentile, P = .23) and length (47th percentile, P = .06) were normal. All growth measures declined until the first surgery, with a catch-up growth until 6 years for height (44th percentile, P = .07) but not for weight (39th percentile, P = .003) or for HC (23rd percentile, P < .001). Children undergoing univentricular palliation showed poorer height growth than other types of CHD (P = .01). Median IQ at 6 years was 95 (range 50-135). Lower IQ at 6 years was independently predicted by lower HC at birth, lower socioeconomic status, older age at first bypass surgery, and longer length of intensive care unit stay. CONCLUSIONS: Smaller HC at birth and postnatal factors are predictive of impaired intellectual abilities at school age. Early identification should alert clinicians to provide early childhood interventions to optimize developmental potential.
Assuntos
Ponte Cardiopulmonar/métodos , Desenvolvimento Infantil , Deficiências do Desenvolvimento/epidemiologia , Cardiopatias Congênitas/complicações , Deficiência Intelectual/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/etiologia , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Deficiência Intelectual/etiologia , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To determine the neurodevelopment outcomes after therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE) and identify the neonatal magnetic resonance imaging (MRI) findings associated with neurological outcome in a middle-income country. STUDY DESIGN: All infants born after 35 completed weeks' gestation with signs of moderate to severe encephalopathy and evidence of perinatal asphyxia before 6 hours of life were submitted to whole-body hypothermia and were imaged at 18 ± 8.4 days of life (range 7-33 days) after birth. Surviving infants had the neurodevelopment outcome assessed at 12 to 18 months of age by trained professional masked to MRI findings. RESULTS: Forty-eight infants included, MRI scans were obtained from 34 infants; 14 (29.1%) patients died during hospitalization before MRI was performed. Nine (64.3%) of 14 patients were classified as severe encephalopathy presented Posterior Limb Internal Capsule (PLIC) sign at the MRI, 10 (71.4%) thalamus and basal ganglia (TBG) lesion, 9 (64.3%) white matter (WM) lesion, and 7 (50.0%) cortical lesion. Severe encephalopathy was associated with the motor delay at 12-18 months by Bayley III, Alberta Infant Motor Scale (AIMS), and Gross Motor Function Classification System (GMFCS) scores (p = .020, p = .048, p = .033, respectively), but not for the cognitive (p = .167) or language skills (p = .309). Lower BSID-III motor, cognitive, and language composite scores were associated with PLIC sign (p = .047; p = .006 and p = .003, respectively). TBG lesion (p = .051) and cortical lesion (p = .030) were associated with lower language composite score. Motor delay by AIMS and the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI were observed (p < .001; p = .002; p = .001 and p = .027, respectively); as well as higher GMFCS score were associated with the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI (p < .001; p = .001; p = .001, and p = .011, respectively). CONCLUSIONS: Brain MRI in neonates with HIE after therapeutic hypothermia is a valuable tool for diagnosis of encephalopathy cerebral abnormalities and is an early predictor of outcome in infants treated with whole body hypothermia for HIE in the Brazilian experience.
Assuntos
Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Imageamento por Ressonância Magnética/métodos , Adulto , Asfixia Neonatal/complicações , Brasil/epidemiologia , Estudos de Casos e Controles , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Hipotermia Induzida/mortalidade , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/mortalidade , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Estudos Longitudinais , Masculino , Gravidez , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: To evaluate whether the presence of patent ductus arteriosus (PDA) in preterm infants worsens long-term neurodevelopmental outcomes. STUDY DESIGN: This was a secondary observational analysis of data from 1090 preterm low-birthweight infants in the Infant Health and Development Program (IHDP), a multicenter longitudinal cohort study of outcomes assessed from 3 to 18 years of age. Multivariable analysis was adjusted for IHDP treatment group (intervention or follow-up), birth weight, maternal race, maternal education, infant sex, maternal preconception weight, Home Observation Measurement of the Environment (HOME) total score at 12 months, neonatal health index, and gestational age. RESULTS: Of the 1090 patients (49% male) included in the analysis, 135 had a PDA. Mean birth weight (1322 g vs 1871 g; P < .0001) and gestational age (30.2 weeks vs 33.4 weeks, P < .0001) were lower and mean ventilator days (11.8 vs 1.3; P < .0001), vasopressor use (12.6% vs 1.2%; P < .0001), and congestive heart failure (8.9% vs 0.1%; P < .0001) were higher in the PDA group. There were no differences between the PDA and no-PDA groups in maternal education level and HOME total score at age 12 months. Multivariable analysis demonstrated no between-group differences in cognitive development or behavioral competence at age 3, 8, and 18 years. CONCLUSIONS: The presence of a PDA in moderately preterm, low-birthweight infants does not impact long-term neurodevelopmental outcomes.