Abstract Objectives To examine trends over time in diet and size of very preterm infants, and associations of diet with size at hospital discharge/transfer. Methods The authors studied 4062 surviving very preterm infants born < 32 weeks’ gestational age and < 1500 g between January 2012 and December 2020 from 12 Brazilian Neonatal Intensive Care Units. Diet type at discharge/transfer was classified as exclusive human milk, exclusive formula, or mixed. Outcomes were weight and head circumference at hospital discharge and the change in each from birth to discharge. The authors used linear regression to estimate adjusted associations of diet type with infant size, overall, and stratified by fetal growth category (small vs. appropriate for gestational age). The authors also examined trends in diet and infant size at discharge over the years. Results Infants’ mean gestational age at birth was 29.3 weeks, and the mean birth weight was 1136 g. Diet at discharge/transfer was exclusive human milk for 22 %, mixed for 62 %, and exclusive formula for 16 %. Infant size in weight and head circumference were substantially below the growth chart reference for all diets. Infants fed human milk and mixed diets were lighter and had smaller heads at discharge/transfer than infants fed formula only (weight z: −2.0, −1.8, and −1.5; head z: −1.3, −1.2 and −1.1 for exclusive human milk, mixed and exclusive formula respectively). Conclusion Results suggest high human milk use but gaps in nutrient delivery among hospitalized Brazilian very preterm infants, with little evidence of improvement over time. dischargetransfer transfer 406 3 weeks 150 201 202 1 Units overall small vs age. . age) years 293 29 29. 113 2 % 6 z 20 0 −2.0 18 8 −1.8 −1.5 15 5 13 −1.3 −1. 11 respectively. respectively respectively) 40 −2. −1 4 −2 −

Abstract Objectives To evaluate neonatal autopsy rates at a tertiary hospital in southern Brazil ascertain the level of agreement between premortem and postmortem diagnosis. Methods The authors reviewed all neonatal autopsies performed over a 10-year period and described the percentage of neonates who died and underwent autopsy. The authors tested for agreement between autopsy findings and the cause of death as defined by the neonatologist. Agreement between clinical diagnosis and autopsy findings was classified using the modified Goldman criteria. Additional findings at autopsy were grouped by organ system. Linear regression and multiple comparisons were used for statistical analyses. Results During the study period, 382 neonates died at the Neonatal Intensive Care Unit (NICU). Consent to perform an autopsy was obtained for 73 (19.1%). The complete agreement between autopsy findings and the neonatologist's premortem diagnosis was found in 48 patients (65.8%). Additional findings were obtained at autopsy in 25 cases (34.2%). In 5 cases (6.9%), the autopsy findings contributed to subsequent genetic counseling. Seven autopsies (9.6%) revealed a diagnosis that would have changed patient management if established premortem. The autopsy rate increased by an average of 1.87% each year. Conclusion Despite a high level of agreement between clinical diagnosis and pathological findings, autopsies provided relevant data regarding the cause of death, providing additional clinical information to neonatologists and allowing genetic counseling of family members.

Abstract Introduction Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/hyperactivity disorder (ADHD). Objective To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW. Methods 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children – Present and Lifetime Version (K-SADS-PL). IC was measured with Conners’ Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P).Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times. Conclusions ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children’s EFs are already so impaired that there is not much room for additional impairments imposed by ADHD.

Resumo Objetivo: Avaliar a prevalência de síndrome metabólica "like" em população de crianças prematuras com muito baixo peso de nascimento (< 1500 gramas) aos dois anos de idade corrigida e identificar a ocorrência de fatores de risco associados. Métodos: Estudo transversal que incluiu prematuros nascidos durante um período de cinco anos com muito baixo peso de nascimento, avaliados aos dois anos de idade corrigida. A síndrome metabólica "like" foi definida pela presença de três ou mais desses critérios: circunferência abdominal ≥ percentil 90, glicemia de jejum ≥ 100 mg/dL, triglicerídeos ≥ 110 mg/dL, colesterol HDL ≤ 40 mg/dL e pressão arterial ≥ percentil 90. Resultados: Foram avaliados 214 prematuros abaixo de 1.500 gramas. A prevalência de síndrome metabólica "like" aos dois anos de idade corrigida foi 15,1%. Hipertensão arterial esteve presente em 57,5%, HDL ≤ 40 mg/dL em 29,2%, hipertrigliceridemia em 22,6% e aumento da circunferência abdominal acima do percentil 90 em 18,8%. Apenas 3,7% apresentaram hiperglicemia. A presença de leucomalácia periventricular foi um fator de risco independente para hipertensão arterial nessa idade (OR 2,34; IC 95% 0,079-0,69; p = 0,008); sobrepeso e obesidade aos dois anos de idade corrigida foram independentemente associados com síndrome metabólica "like" (OR 2,75, IC 95% CI 1,19-6,36; p = 0,018). Conclusão: Síndrome metabólica "like" ocorre em prematuros de muito baixo peso tão precocemente quanto dois anos de idade corrigida. Sobrepeso e obesidade de início precoce são fatores de risco significativos para síndrome metabólica "like", merecem intervenção apropriada para essa população de alto risco.

Abstract Objective: To assess the prevalence of metabolic syndrome-like symptoms in a population of preterm infants with very low birth weight (<1500 g) at 2 years of corrected age and identify the occurrence of associated risk factors. Methods: Cross-sectional study during a five-year period, including preterm infants born with very low birth weight evaluated at 2 years of corrected age. Metabolic syndrome-like symptoms was defined by the presence of three or more of these criteria: abdominal circumference ≥ 90th percentile, fasting blood glucose ≥ 100 mg/dL, triglycerides ≥ 110 mg/dL, HDL cholesterol ≤ 40 mg/dL, and blood pressure ≥ 90th percentile. Results: A total of 214 preterm infants with birth weight < 1500 g were evaluated. The prevalence of metabolic syndrome-like symptoms at 2 years of corrected age was 15.1%. Arterial hypertension was present in 57.5%, HDL ≤ 40 mg/dL in 29.2%, hypertriglyceridemia in 22.6%, and abdominal circumference above the 90th percentile in 18.8%. Only 3.7% had hyperglycemia. The presence of periventricular leukomalacia was an independent risk factor for arterial hypertension at this age (OR 2.34, 95% CI: 0.079–0.69, p = 0.008). Overweight and obesity at 2 years of corrected age were independently associated with metabolic syndrome-like symptoms (OR 2.75, 95% CI: 1.19–6.36, p = 0.018). Conclusion: Metabolic syndrome-like symptoms can be observed in very low birth weight preterm infants as early as 2 years of corrected age. Overweight and early-onset obesity are significant risk factors for metabolic syndrome-like symptoms, which deserves appropriate intervention for this high-risk population.

Resumo Objetivo: Recém-nascidos prematuros são considerados de risco para déficits no desenvolvimento motor, o que ocasiona a necessidade de acompanhamento nos primeiros anos de vida. O objetivo do presente estudo é revisar de forma sistemática as publicações que abordam o desenvolvimento motor amplo de crianças nascidas prematuras, avaliadas por meio da Alberta Infant Motor Scale (AIMS), de modo a apontar os principais desfechos motores. Fontes dos dados: Revisão sistemática das publicações de 2006 a 2015, indexadas nas bases de dados Pubmed, Scielo, Lilacs e Medline, nos idiomas inglês e português. A estratégia de busca incluiu palavras-chaves: prematuro, pré-termo, prematuridade, desenvolvimento motor, controle postural, seguimento, Alberta Infant Motor Scale, prematurity, pre-term, motor development, postural control e follow-up. Síntese dos dados: Foram identificados 101 artigos e selecionados 23, conforme critérios de inclusão. As idades das crianças avaliadas nos estudos incluíram os primeiros seis meses até os 15 ou 18 meses de idade corrigida. Variado percentual de atraso motor foi identificado na descrição dos desfechos motores de 10 estudos, de 4 a 53%, dependeu da idade em que o bebê foi avaliado. Os estudos apontam diferenças significativas no desenvolvimento motor de prematuros e crianças nascidas a termo, com descrição de escores brutos mais baixos nos resultados da AIMS de crianças prematuras. Conclusões: É fundamental que os serviços de seguimento de bebês de risco apresentem estratégias de avaliação e acompanhamento do desenvolvimento motor amplo de prematuros, a AIMS é uma ferramenta de avaliação indicada para identificar comportamentos motores atípicos nessa população.

Abstract Objective: Premature newborns are considered at risk for motor development deficits, leading to the need for monitoring in early life. The aim of this study was to systematically review the literature about gross motor development of preterm infants, assessed by the Alberta Infant Motor Scale (AIMS) to identify the main outcomes in development. Data source: Systematic review of studies published from 2006 to 2015, indexed in Pubmed, Scielo, Lilacs, and Medline databases in English and Portuguese. The search strategy included the keywords: Alberta Infant Motor Scale, prematurity, preterm, motor development, postural control, and follow-up. Data summary: A total of 101 articles were identified and 23 were selected, according to the inclusion criteria. The ages of the children assessed in the studies varied, including the first 6 months up to 15 or 18 months of corrected age. The percentage variation in motor delay was identified in the motor outcome descriptions of ten studies, ranging from 4% to 53%, depending on the age when the infant was assessed. The studies show significant differences in the motor development of preterm and full-term infants, with a description of lower gross scores in the AIMS results of preterm infants. Conclusions: It is essential that the follow-up services of at-risk infants have assessment strategies and monitoring of gross motor development of preterm infants; AIMS is an assessment tool indicated to identify atypical motor development in this population.

Resumo Objetivo: A hipotermia terapêutica reduz a lesão cerebral e melhora o desfecho neurológico de recém-nascidos após insulto hipóxico isquêmico. Indicada para recém-nascidos a termo ou próximo do termo com evidência de asfixia perinatal e encefalopatia hipóxico isquêmica (EHI). Fontes dos dados: Foi feita uma procura no PubMed por publicações sobre hipotermia terapêutica em recém-nascidos com asfixia perinatal e selecionadas aquelas julgadas mais relevantes pelos autores. Síntese dos dados: Há duas técnicas de resfriamento corpóreo: hipotermia seletiva da cabeça e hipotermia corpórea total. A temperatura de resfriamento deve ser 34,5 ºC para seletiva de cabeça e 33,5 ºC para corpórea total; temperaturas inferiores a 32 ºC são menos neuroprotetoras e abaixo de 30 ºC há efeitos adversos sistêmicos graves. Indica-se o início da hipotermia terapêutica até seis horas após o nascimento, pois estudos evidenciaram que essa é a janela terapêutica da agressão hipóxico e isquêmica. A hipotermia deve ser mantida por 72 horas com rigorosa monitoração da temperatura corporal do recém-nascido. A hipotermia tem sido efetiva em reduzir sequelas neurológicas, principalmente em recém-nascidos de termo ou próximo do termo com encefalopatia hipóxico isquêmica moderada e em melhorar o prognóstico em longo prazo dos recém-nascidos com EHI. Conclusão: A hipotermia terapêutica é uma técnica neuroprotetora indicada para recém-nascidos com asfixia perinatal.

Abstract Objective: Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). Sources: A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. Summary of the findings: There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 ºC for selective head cooling and 33.5 ºC for total body cooling. Temperatures lower than 32 ºC are less neuroprotective, and temperatures below 30 ºC are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6 hours after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 hours, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate HIE. Conclusion: Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and HIE.

OBJETIVO: Analisar os efeitos da terapêutica adotada para o canal arterial (CA) em recém-nascidos (RN) < 1.000gadmitidos em unidades neonatais (UN) da Rede Brasileira de Pesquisas Neonatais (RBPN), sobre os desfechos: óbito, displasia broncopulmonar (DBP), hemorragia intraventricular grave (HIVIII/IV), retinopatia da prematuridade cirúrgica (ROPcir), enterocolite necrosante cirúrgica (ECNcir) e o desfecho combinado óbito e DBP. MÉTODOS: Estudo multicêntrico, de coorte, coleta de dados retrospectiva, incluindo RN de 16 UN da RBPN de 01/01/2010 a 31/12/2011, PN < 1.000 g, idade gestacional (IG) < 33 semanas e diagnóstico ecocardiográfico de PCA. Excluídos: óbitos ou transferências até o terceiro dia de vida, infecções congênitas ou malformações. Grupos:G1 - conservadora (sem intervenção medicamentosa ou cirúrgica), G2 - farmacológica (indometacina ou ibuprofeno) e G3 - cirúrgico (com ou sem tratamento farmacológico anterior). Analisou-se: uso de esteroide antenatal, parto cesárea, PN, IG, Apgar5' < 4, sexo masculino, SNAPPE II, síndrome do dDesconforto respiratório (SDR), sepse tardia, ventilação mecânica (VM), surfactante < 2 horas de vida, tempo de VM e os desfechos: óbito, dependência de oxigênio com 36 semanas (DBP36s), HIV III/IV, ROPcir, ECNcir e óbito/DBP36s. Estatística: Teste t-Student, Qui-Quadrado ou teste Exato de Fisher. Testes de Regressão Binária Logística e Regressão Múltipla Stepwise Backward. MedCalc (Medical Calculator) software, versão 12.1.4.0.p < 0,05. RESULTADOS: Foram selecionados 1.097 RN e 494 foram incluídos: G1-187 (37,8%), G2-205 (41,5%) e G3-102 (20,6%). Verificou-se: maior mortalidade (51,3%) no G1 e menor no G3(14,7%); maior frequência DBP36s (70,6%) e ROPcir (23,5%) no G3; maior frequência de óbito/DBP36s no G2 (58,0%). As abordagens farmacológica (OR-0,29; 95%, IC-0,14-0,62) e conservadora (OR-0,34; 95%, IC- 0,14-0,79) foram protetoras somente para o desfecho óbito/DBP36sem. CONCLUSÃO: Em RN com PCA, a abordagem conservadora relacionou-se à maior mortalidade, a cirúrgica à ocorrência de DBP36s e ROPcir., enquanto o tratamento farmacológico mostrou-se protetor para o desfecho óbito/DBP36sem.

OBJECTIVE: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. METHODS: This was a multicentric cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. Outcomes: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Statistics: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2 (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34; 95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks. CONCLUSION: The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks.

OBJECTIVE: Ophthalmologic examination for retinopathy of prematurity is a painful procedure. Pharmacological and non-pharmacological interventions have been proposed to reduce pain during eye examinations. This study aims to evaluate the analgesic effect of 25% glucose using a validated pain scale during the first eye examination for retinopathy of prematurity in preterm infants with birth weight <1,500 g and/or gestational age <32 weeks. METHODS: A masked, randomized clinical trial for one dose of 1 ml of oral 25% glucose solution 2 minutes before the first ophthalmologic examination for retinopathy of prematurity was conducted between March 2008 and April 2010. The results were compared to those of a control group that did not receive oral glucose solution. Pain was evaluated using a Neonatal Infant Pain Scale immediately before and immediately after the ophthalmologic examination in both groups. Clinicaltrials.gov: NCT00648687 RESULTS: One hundred and twenty-four patients who were examined for the first time for retinopathy of prematurity were included. Seventy were included in the intervention group and 54 in the control group. The number of patients with pain immediately before the procedure was similar in both groups. The number of patients with pain after ophthalmologic examination was 15.7% in the intervention group and 68.5% in the control group (p<0.001). CONCLUSIONS: One ml of oral 25% glucose solution given 2 minutes before an ophthalmologic examination for retinopathy of prematurity was an effective measure for pain relief.

OBJETIVO: Avaliar a frequência da prescrição de medicamentos de uso não licenciado (UL) e off-label (OL) em recém-nascidos internados em unidade de tratamento intensivo neonatal de hospital de nível terciário e verificar a associação do seu uso com a gravidade dos pacientes. MÉTODOS: Estudo observacional de coorte dos medicamentos prescritos no período de 6 semanas da internação de neonatos, entre julho e agosto de 2011. Os medicamentos foram classificados em UL e OL para dose, frequência, apresentação, faixa etária e indicação, de acordo com bulário eletrônico aprovado pela Food and Drug Administration. Os pacientes foram acompanhados até alta hospitalar ou 31 dias de internação, com registro diário do Neonatal Therapeutic Intervention Scoring System. RESULTADOS: Foram identificados 318 itens de prescrição para 61 pacientes (média de cinco itens/paciente) e apenas 13 pacientes com uso de medicamentos adequados (21%). Identificaram-se prevalências de 7,5% para prescrições UL e de 27,7% para OL. O uso OL mais prevalente foi para medicamentos não padronizados para faixa etária - 19,5%. Computaram-se 57 medicações - um paciente recebeu 10 fármacos UL/OL na internação. A prevalência de usos OL foi maior em prematuros < 35 semanas e nos com escores de gravidade mais elevados (p = 0,00). CONCLUSÕES: A prevalência de neonatos expostos a medicamentos UL/OL durante a internação hospitalar foi elevada, especialmente naqueles com maior escore de gravidade no Neonatal Therapeutic Intervention Scoring System. Embora haja apreciação geral de que neonatos, especialmente pré-termo, tenham alta taxa de uso de medicamentos, uma avaliação incluindo diferentes culturas e países é necessária para priorizar áreas de pesquisa futura na farmacoterapêutica dessa população vulnerável.

OBJECTIVE: To analyze the frequency of unlicensed (UL) and off-label (OL) prescriptions in neonates admitted to the neonatal intensive care unit of a tertiary care hospital and to determine their association with patients' severity. METHODS: Observational cohort study including drugs prescribed during hospitalization of neonates over a 6-week period between July and August 2011. The drugs were classified as UL and OL for dose, frequency, presentation, age group, or indication, according to an electronic list of drugs approved by the Food and Drug Administration. Patients were followed until hospital discharge or 31 days of hospitalization, with daily records of the Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS: We identified 318 prescription items for 61 patients (average of five items/patient); there were only 13 patients with appropriate use of medications (21%). A prevalence of 7.5% was identified for UL prescriptions and 27.7% for OL, and the most prevalent OL use was that related to age group - 19.5%. Fifty-seven medications were computed - one patient received 10 UL/OL drugs during hospitalization. The prevalence of OL uses was higher in preterm infants < 35 weeks and in those with higher severity scores (p = 0.00). CONCLUSIONS: The prevalence of neonates exposed to UL/OL drugs during hospitalization was high, especially for those with higher NTISS scores. Although there is general appreciation that neonates, especially preterm infants, have a high rate of drug use, an assessment including different cultures and countries is still needed to prioritize areas for future research in the pharmacotherapy of this vulnerable population.

OBJECTIVE: To evaluate intraocular pressure in very low birth weight preterm infants and correlate it with postconceptional age. METHODS: The intraocular pressure in a prospective cohort of very low birth weight premature infants (defined as a birth weight <1,500 g and gestational age <32 weeks) admitted to Hospital de Clínicas de Porto Alegre , Brazil was evaluated weekly. The evaluated outcome was the variation in the intraocular pressure following changes in the postconceptional age (defined as the gestational age at birth plus the age in weeks at the time of examination) in the weeks following preterm birth. Mixed-effects models were used for the statistical analysis to determine the intraocular pressure variation according to postconceptional age, and means and 10th and 90th percentiles were calculated for the intraocular pressure values. RESULTS: Fifty preterm infants with a mean gestational age of 29.7 ± 1.6 weeks and a mean birth weight of 1,127.7 ± 222.7 g were evaluated. The mean intraocular pressure for the entire cohort considering both eyes was 14.9 ± 4.5 mmHg, and 13.5% of all recorded intraocular pressure values were greater than 20 mmHg. The analysis revealed a mean reduction in the intraocular pressure of 0.29 mmHg for each increase in postconceptional age (p = 0.047; 95% CI: -0.58 to -0.0035). The mean intraocular pressure (P10-P90) decreased from 16.3 mmHg (10.5222.16) at 26.3 weeks to 13.1 mmHg (7.28-18.92) at 37.6 weeks of postconceptional age. CONCLUSIONS: The mean intraocular pressure in very low birth weight preterm infants was 14.9 ± 4.5 mmHg. This value decreased 0.29 mmHg per week as the postconceptional age increased.