Whole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn's genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10-5). The IL12RB2 gene (p-value: 2.18x10-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.

Gastroschisis in the neonatal period: A prospective case-series in a Brazilian referral center.

BACKGROUND/PURPOSE: Gastroschisis is increasing in incidence and has low mortality and high morbidity. We describe the clinical and surgical characteristics of gastroschisis patients in a Brazilian referral center. METHODS: Single-center prospective case series of gastroschisis patients. The following two groups were formed depending on the intestinal characteristics: simple and complex patients. RESULTS: In total, 79 patients were enrolled, 89% of whom were classified as simple and 11% as complex. The baseline characteristics were similar between the groups, with the exception of the illness severity score. The complex group had a significantly smaller defect size, more reoperations and worse clinical outcomes than the simple group, with the initiation of feeding taking 1.5 times longer, the duration of total parenteral nutrition taking twice as long, and the length of hospitalization being 2.5 times longer; the complex group also included all the deaths that occurred. Overall, the survival rate was 96%. Patients who underwent the sutureless technique had significantly fewer wound infections and a decreased duration of mechanical ventilation than sutured patients. CONCLUSIONS: This study provides a comprehensive picture of gastroschisis during the neonatal period in a Brazilian referral center, emphasizing the significantly higher risk for morbidity and mortality among complex patients than among simple patients and the few advantages of the sutureless technique over the sutured technique in terms of closing the defect. TYPE OF STUDY: Prognostic. LEVEL OF EVIDENCE: IV.

Influence of gestational and perinatal factors on body composition of full-term newborns.

OBJECTIVE: To evaluate the influence of gestational and perinatal factors on body composition and birth weight of full-term newborns. METHOD: This was a cross-sectional study, within a prospective cohort, consisting of 124 postpartum women and their newborns. Data included the following: maternal age; ethnicity; pre-gestational body mass index; gestational weight gain; parity; gestational morbidities (hypertension and gestational diabetes mellitus); gestational age at birth; birth weight; and newborn's gender. Anthropometric and body composition data of the newborns were collected using air-displacement plethysmography (PeaPod® Infant Body Composition System-LMI; Concord, CA, USA). The stepwise technique was applied to a multiple linear regression model. RESULTS: The significant variables in the model that explained 84% of the variation in neonatal fat-free mass were: birth weight; maternal age; newborn's gender and gestational age. For body fat mass: birth weight; newborn's gender; gestational arterial hypertension; gestational diabetes; and gestational weight gain. These variables explained 60% and 46% of fat mass, in grams and as a percentage, respectively. Regarding birth weight, the significant factors were gestational age, pre-gestational BMI, and gestational weight gain. Female newborns showed higher body fat mass and male newborns had higher fat-free mass. CONCLUSION: Gestational and perinatal factors influence neonatal body composition. Early identification of these gestational factors, which may be modifiable, is necessary to prevent obesity and chronic noncommunicable diseases in the future.

Zika virus vertical transmission in children with confirmed antenatal exposure.

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.

Differences in energy expenditure in human donor milk versus formula milk in preterm newborns: A crossover study.

OBJECTIVE: The aim of this study was to compare the ratio between energy expenditure and caloric density in human donor milk versus formula milk in preterm newborn infants. METHODS: This was a crossover, randomized clinical trial with 29 preterm newborn infants receiving full diet. The infants were randomly assigned to receive either human milk or formula milk alternating, after a 24-h period. Energy expenditure was evaluated by indirect calorimetry. Total calorie and macronutrient values in the human milk were calculated individually with infrared technique; energy expenditure/caloric density ratio was calculated. RESULTS: Human donor milk energy expenditure/caloric density ratio was significantly greater than in formula milk at all time points. The total mean was 1.04 ± 0.27 for the human milk and 0.81 ± 0.11 for the formula. However, when we analyzed a subgroup of newborns that received human donor milk with >60 kcal/100 mL, there was no statistical difference (P = 0.36). The mean calorie values were 58.9 kcal/100 mL (human donor milk) and 81.4 kcal/100 mL (formula milk). CONCLUSION: Formula milk produced a better metabolic response than human donor milk. Human donor milk with higher caloric content showed no difference from formula, so the use of human donor milk with more caloric density should be reinforced.

Influence of gestational and perinatal factors on body composition of full-term newborns / Influência de fatores gestacionais e perinatais na composição corporal de recém-nascidos a termo

Abstract Objective: To evaluate the influence of gestational and perinatal factors on body composition and birth weight of full-term newborns. Method: This was a cross-sectional study, within a prospective cohort, consisting of 124 postpartum women and their newborns. Data included the following: maternal age; ethnicity; pre-gestational body mass index; gestational weight gain; parity; gestational morbidities (hypertension and gestational diabetes mellitus); gestational age at birth; birth weight; and newborn's gender. Anthropometric and body composition data of the newborns were collected using air-displacement plethysmography (PeaPod® Infant Body Composition System-LMI; Concord, CA, USA). The stepwise technique was applied to a multiple linear regression model. Results: The significant variables in the model that explained 84% of the variation in neonatal fat-free mass were: birth weight; maternal age; newborn's gender and gestational age. For body fat mass: birth weight; newborn's gender; gestational arterial hypertension; gestational diabetes; and gestational weight gain. These variables explained 60% and 46% of fat mass, in grams and as a percentage, respectively. Regarding birth weight, the significant factors were gestational age, pre-gestational BMI, and gestational weight gain. Female newborns showed higher body fat mass and male newborns had higher fat-free mass. Conclusion: Gestational and perinatal factors influence neonatal body composition. Early identification of these gestational factors, which may be modifiable, is necessary to prevent obesity and chronic noncommunicable diseases in the future.

Resumo Objetivo: Avaliar a influência de fatores gestacionais e perinatais na composição corporal e no peso de nascimento de recém-nascidos a termo. Método: Estudo transversal, dentro de uma coorte prospectiva, composto por 124 puérperas e seus recém-nascidos. Os dados incluíram: idade materna; etnia; índice de massa corpórea pré-gestacional; ganho de peso gestacional; paridade; morbidades gestacionais, (hipertensão arterial e diabetes mellitus gestacional); idade gestacional do nascimento; peso de nascimento; e sexo do recém-nascido. Os dados antropométricos e de composição corporal dos recém-nascidos foram coletados com a pletismografia por deslocamento de ar (PeaPod®). Foi aplicada a técnica de stepwise no modelo de regressão linear múltipla. Resultados: As variáveis significativas do modelo que explicou 84% da variação da massa livre de gordura neonatal foram: peso de nascimento; idade materna; sexo do recém-nascido; e idade gestacional. Para a massa de gordura corporal: peso de nascimento; sexo do recém-nascido; hipertensão arterial gestacional; diabetes gestacional; e ganho de peso gestacional. Essas variáveis explicaram 60% e 46% da massa de gordura, em gramas e percentual, respectivamente. Em relação ao peso de nascimento os fatores significativos foram: idade gestacional; IMC pré-gestacional; e ganho de peso gestacional. Os recém-nascidos do sexo feminino apresentaram maior massa de gordura corporal e os do sexo masculino maior massa livre de gordura. Conclusão: Fatores gestacionais e perinatais influenciam a composição corporal neonatal. A identificação precoce desses fatores gestacionais, que podem ser modificáveis, é necessária para prevenção de obesidade e de doenças crônicas não transmissíveis no futuro.

Freezing and thawing effects on fat, protein, and lactose levels of human natural milk administered by gavage and continuous infusion.

OBJECTIVES: to analyze the changes in human milk macronutrients: fat, protein, and lactose in natural human milk (raw), frozen and thawed, after administration simulation by gavage and continuous infusion. METHOD: an experimental study was performed with 34 human milk samples. The infrared spectrophotometry using the infrared analysis equipment MilkoScan Minor® (Foss, Denmark) equipment was used to analyze the macronutrients in human milk during the study phases. The analyses were performed in natural (raw) samples and after freezing and fast thawing following two steps: gavage and continuous infusion. The non-parametric Wilcoxon test for paired samples was used for the statistical analysis. RESULTS: the fat content was significantly reduced after administration by continuous infusion (p<0.001) during administration of both raw and thawed samples. No changes in protein and lactose content were observed between the two forms of infusion. However, the thawing process significantly increased the levels of lactose and milk protein. CONCLUSION: the route of administration by continuous infusion showed the greatest influence on fat loss among all the processes required for human milk administration.

Freezing and thawing effects on fat, protein, and lactose levels of human natural milk administered by gavage and continuous infusion / Efeito do congelamento e descongelamento nos níveis de gordura, proteína e lactose do leite humano natural administrados por gavagem e infusão contínua

OBJECTIVES: to analyze the changes in human milk macronutrients: fat, protein, and lactose in natural human milk (raw), frozen and thawed, after administration simulation by gavage and continuous infusion. METHOD: an experimental study was performed with 34 human milk samples. The infrared spectrophotometry using the infrared analysis equipment MilkoScan Minor(r) (Foss, Denmark) equipment was used to analyze the macronutrients in human milk during the study phases. The analyses were performed in natural (raw) samples and after freezing and fast thawing following two steps: gavage and continuous infusion. The non-parametric Wilcoxon test for paired samples was used for the statistical analysis. RESULTS: the fat content was significantly reduced after administration by continuous infusion (p < 0.001) during administration of both raw and thawed samples. No changes in protein and lactose content were observed between the two forms of infusion. However, the thawing process significantly increased the levels of lactose and milk protein. CONCLUSION: the route of administration by continuous infusion showed the greatest influence on fat loss among all the processes required for human milk administration. .

OBJETIVO: analisar as alterações dos macronutrientes gordura, proteína e lactose no leite humano natural, congelado e descongelado, após a simulação da administração da dieta por gavagem e infusão contínua. MÉTODO: foi conduzido um estudo experimental com 34 amostras de leite humano. Foi utilizada a técnica da espectofotometria infravermelha (Milko Scan Minor(r)) para analisar os macronutrientes do leite humano nas etapas do estudo. As amostras foram analisadas na forma natural (crua) e após congelamento e descongelamento rápido nas duas formas de infusão: gavagem e infusão contínua. Foi usado o teste não paramétrico de Wilcoxon para amostras pareadas na análise estatística. RESULTADO: a gordura apresentou redução significativa após administração por infusão contínua (p < 0,001), tanto durante administração na forma natural quanto na forma descongelada. Não houve alteração da proteína e lactose segundo forma de infusão no leite descongelado e no leite in natura. O processo de descongelamento aumentou significativamente os níveis de lactose e de proteína do leite. CONCLUSÃO: a via de administração por infusão contínua foi o procedimento que mais influenciou na perda de gordura, dentre todos os processos necessários para administração do leite humano. .

Eventos adversos associados à exsanguíneotransfusão na doença hemolítica perinatal: experiência de dez anos / Adverse events related to exchange transfusion in newborn infants with hemolytic disease: ten years of experience

OBJETIVO:Determinar a incidência dos eventos adversos atribuíveis à exsanguíneotransfusão ocorridos em uma Unidade de Terapia Intensiva Neonatal (UTIN) e sua associação com a gravidade clínica do paciente. MÉTODOS: Foram incluídos no estudo todos os recém-nascidos internados com diagnóstico de doença hemolítica perinatal por aloimunização Rh em uma unidade neonatal no período de dez anos. Os pacientes foram separados em dois grupos de acordo com o quadro clínico anterior à exsanguíneotransfusão e calculou-se o risco relativo para cada evento adverso entre os grupos. RESULTADOS: 300 recém-nascidos foram internados com diagnóstico de anemia hemolítica por aloimunização Rh durante o período do estudo. Desses, 143 foram submetidos a 207 exsanguíneotransfusões, sendo que 93 (65 por cento) realizaram apenas um procedimento. A principal indicação da exsanguíneotransfusão foi a velocidade de hemólise (57 por cento). A incidência de eventos adversos foi 22,7 por cento e a mortalidade associada ao procedimento ocorreu em 0,7 por cento dos pacientes. Os eventos adversos, em sua maioria, foram assintomáticos e o mais comum foi a plaquetopenia. Os pacientes do Grupo 2, que apresentarem icterícia associada a outros agravos clínicos antes do procedimento, tiveram um risco 2,1 vezes maior de apresentar eventos adversos graves (RR: 2,1; IC 95 por cento: 1,3-3,4). Houve apenas um óbito relacionado ao procedimento no período. CONCLUSÕES: Apesar de a exsanguíneotransfusão ser um procedimento frequentemente utilizado em casos de hiperbilirrubinemia grave, é alta a incidência de eventos adversos a ela relacionada, principalmente se a condição clínica do paciente for instável antes do procedimento.

OBJECTIVE:To determine the incidence of adverse events associated with exchange-transfusions performed during the past ten years and to evaluate if there is association between the severity of patient's clinical condition before the procedure and the incidence of adverse events. METHODS: All infants admitted to treat hemolytic disease secondary to Rhesus Alloimunoization in the Neonatal Intensive Care Unit were enrolled in the study. Patients were divided into two groups: Group 1, neonates admitted solely for asymptomatic hyperbilirubinemia before the exchange transfusion; Group 2, neonates with other medical conditions besides the hemolytic jaundice. Incidence of adverse events was determined, as well as the relative risk of each adverse event. RESULTS: 300 newborn infants with Rh hemolytic jaundice were studied. A total of 143 patients underwent 207 exchange transfusions. The rate of increase in the serum bilirubin levels (>0,5mg/dL/hour) was the main indication for exchange transfusion. Adverse events occurred in 22.7 percent of the cases and the mortality rate was 0.7 percent. The majority of adverse events were asymptomatic, and low platelet count was the most frequent one. The incidence of serious adverse events (bradycardia or heart arrhythmias and thrombocytopenia) was 2.1 times higher in Group 2 than in Group 1 (RR: 2.1; CI: 95 percent 1.3-3.4). There was one death during the study period associated to the procedure. CONCLUSIONS: Although exchange transfusion is a frequent procedure for treating severe neonatal hyperbilirubinemia, the incidence of adverse events is high, especially if patients' clinical condition is unstable before the procedure.

Desafios para a humanizacão do cuidado em uma unidade de terapia intensiva neonatal cirúrgica / Challenges for humanization of care in a surgical neonatal intensive care unit

Este estudo analisa cuidados ambientais e relacões de atendimento em Unidade de Terapia Intensiva Neonatal Cirúrgica, refletindo sobre potencialidades e obstáculos para promocão de cuidado humanizado. A pesquisa, realizada em uma instituicão de nível terciário, utilizou o método da observacão participante enfocando, por cinco meses, relacões profissional-bebê, profissional-responsável e mãe-bebê. Foram observadas rotinas contemplando condicões ambientais e necessidades de bebês e famílias, e estratégias para reducão de ruído e luminosidade, com diferentes níveis de efetividade. O consolo e bem-estar dos bebês eram proporcionados por suporte do corpo e uso da succão não-nutritiva. Tais condutas não eram sistematizadas e revelaram contradicões e ambigüidades. O acesso dos pais era incentivado, porém sinais de dificuldades como medo, inseguranca e estresse na relacão pais-bebês, indicaram necessidade de ampliacão dos cuidados dirigidos à família. Posturas e práticas em UTIs Neonatais são permeadas por conflitos, negociacões e adaptacões ao trabalho, constituindo um desafio à construcão de um modelo assistencial humanizado, que alie diferentes tecnologias, respeito e acolhimento às necessidades intersubjetivas de pacientes e profissionais e reconhecimento das lógicas culturais das famílias.