The Influence of Early Nutrition on Neurodevelopmental Outcomes in Preterm Infants.

Premature infants, given their limited reserves, heightened energy requirements, and susceptibility to nutritional deficits, require specialized care. AIM: To examine the complex interplay between nutrition and neurodevelopment in premature infants, underscoring the critical need for tailored nutritional approaches to support optimal brain growth and function. DATA SOURCES: PubMed and MeSH and keywords: preterm, early nutrition, macronutrients, micronutrients, human milk, human milk oligosaccharides, probiotics AND neurodevelopment or neurodevelopment outcomes. Recent articles were selected according to the authors' judgment of their relevance. Specific nutrients, including macro (amino acids, glucose, and lipids) and micronutrients, play an important role in promoting neurodevelopment. Early and aggressive nutrition has shown promise, as has recognizing glucose as the primary energy source for the developing brain. Long-chain polyunsaturated fatty acids, such as DHA, contribute to brain maturation, while the benefits of human milk, human milk oligosaccharides, and probiotics on neurodevelopment via the gut-brain axis are explored. This intricate interplay between the gut microbiota and the central nervous system highlights human milk oligosaccharides' role in early brain maturation. CONCLUSIONS: Individualized nutritional approaches and comprehensive nutrient strategies are paramount to enhancing neurodevelopment in premature infants, underscoring human milk's potential as the gold standard of nutrition for preterm infants.

Autopsy in a Neonatal Intensive Care Unit: pathological and clinical agreement

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.

Autopsy in a Neonatal Intensive Care Unit: pathological and clinical agreement.

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.

Meconium microbiota predicts clinical early-onset neonatal sepsis in preterm neonates.

BACKGROUND: Early-onset neonatal sepsis (EONS) remains one of the leading causes of morbidity and mortality related to premature birth, and its diagnosis remains difficult. Our goal was to evaluate the intestinal microbiota of the first meconium of preterm newborns and ascertain whether it is associated with clinical EONS. METHODS: In a controlled, prospective cohort study, samples of the first meconium of premature infants with a gestational age (GA) ≤32 weeks was obtained at Hospital de Clínicas de Porto Alegre and DNA was isolated from the samples. 16S rDNA based microbiota composition of preterm infants with a clinical diagnosis of EONS was compared to that of a control group. RESULTS: 40 (48%) premature infants with clinical diagnosis of EONS and 44 (52%) without EONS were included in the analysis. The most abundant phylum detected in both groups, Proteobacteria, was more prevalent in the sepsis group (p = .034). 14% of variance among bacterial communities (p = .001) correlated with EONS. The genera most strongly associated with EONS were Paenibacillus, Caulobacter, Dialister, Akkermansia, Phenylobacterium, Propionibacterium, Ruminococcus, Bradyrhizobium, and Alloprevotella. A single genus, Flavobacterium, was most strongly associated with the control group. CONCLUSION: These findings suggest that the first-meconium microbiota is different in preterm neonates with and without clinical EONS.

Use of Azithromycin for the Prevention of Lung Injury in Mechanically Ventilated Preterm Neonates: A Randomized Controlled Trial.

INTRODUCTION: Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. METHODS: This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for Ureaplasma. Patients were followed up throughout the hospital stay for the outcomes of death and broncho-pulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). RESULTS: Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O2 dependency at 28 days/death in azithromycin-treated patients regardless of the detection of Ureaplasma in blood. CONCLUSIONS: Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O2 dependency at 28 days/death in mechanically ventilated preterm neonates.

Outcome and Feasibility after 7 Years of Therapeutic Hypothermia in Southern Brazil.

OBJECTIVE: This study aimed to describe the experience with a protocol of therapeutic hypothermia (TH) in southern Brazil. STUDY DESIGN: Newborns with gestational age > 35 weeks with evidence of perinatal asphyxia plus moderate or severe encephalopathy were recruited between March 2011 and November 2017. Whole-body hypothermia for 72 hours, starting within the first 6 hours of life was used. Survivors underwent magnetic resonance imaging (MRI) and electroencephalogram (EEG). The primary outcome was death during hospitalization and neurodevelopment assessed using the Bayley Scales of Infant Development III (BSID III) at 12 months of age. RESULTS: A total of 72 newborns were treated (41 with moderate encephalopathy and 31 with severe encephalopathy), of whom 16 died. MRI was performed in 56 patients, and 24 presented some alterations. Fifty-three patients had an EEG: 11 normal, 20 mildly altered, 12 moderately altered, and 10 severely altered. Forty patients were evaluated through BSID III: 45% presented with some delay in neurodevelopment, 8 (20%) had motor retardation, 15 (37.5%) had language delay, and 13 (32.5%) had a delay in cognitive development. CONCLUSION: Mortality and adverse events were similar to those described in large randomized controlled trials. TH is a safe and an effective method of neurologic protection in asphyxiated newborns in a developing country when performed adequately.

The vaginal microbial communities of healthy expectant Brazilian mothers and its correlation with the newborn's gut colonization.

The female lower genital tract harbors a complex microbial community essential for homeostasis and health. During pregnancy, the female body undergoes unique hormonal changes that contribute to weight gain as well as modulations in immune function that can affect microbiota composition. Several studies have described the vaginal microbiota of pregnant women from the USA, Europe and Mexico. Here we expand our knowledge about the vaginal microbial communities during the third trimester to healthy expectant Brazilian mothers. Vaginal samples were collected from patients delivering at the Hospital de Clínicas de Porto Alegre, Brazil. Microbial DNA was isolated from samples and the V4 region of the 16S rRNA gene was amplified and sequenced using the PGM Ion Torrent. Brazilian pregnant women presented three distinct types of microbial community at the time of labor. Two microbial communities, Cluster 1 and Cluster 3, presented an overall dominance of Lactobacillus while Cluster 2 tended to present higher diversity and richness, with the presence of Pseudomonas, Prevotella and other vaginosis related bacteria. About half of the Brazilian mothers sampled here had dominance of L. iners. The proportion of mothers without dominance of any Lactobacillus was higher in Brazil (22%) compared to UK (2.4%) and USA, where this community type was not detected. The vaginal microbiota showed significant correlation with the composition of the babies' gut microbiota (p-value = 0.002 with a R2 of 15.8%). Mothers presenting different vaginal microbiota shared different microorganisms with their newborns, which would reflect on initial colonizers of the developing newborns' gut.

Influence of own mother's milk and different proportions of formula on intestinal microbiota of very preterm newborns.

OBJECTIVE: To determine the differences in preterm infants' stool microbiota considering the use of exclusive own mother's milk and formula in different proportions in the first 28 days of life. METHODS: The study included newborns with GA ≤ 32 weeks divided in 5 group according the feeding regimen: 7 exclusive own mother's milk, 8 exclusive preterm formula, 16 mixed feeding with >70% own mother's milk, 16 mixed feeding with >70% preterm formula, and 15 mixed 50% own mother's milk and preterm formula. Exclusion criteria: congenital infections, congenital malformations and newborns of drug addicted mothers. Stools were collected weekly during the first 28 days. Microbial DNA extraction, 16S rRNA amplification and sequencing were performed. RESULTS: All groups were similar in perinatal and neonatal data. There were significant differences in microbial community among treatments. Approximately 37% of the variation in distance between microbial communities was explained by use of exclusive own mother´s milk only compared to other diets. The diet composed by exclusive own mother´s milk allowed for greater microbial richness (average of 85 OTUs) while diets based on preferably formula, exclusive formula, preferably maternal milk, and mixed of formula and maternal milk presented an average of 9, 29, 23, and 25 OTUs respectively. The mean proportion of the genus Escherichia and Clostridium was always greater in those containing formula than in the those with maternal milk only. CONCLUSIONS: Fecal microbiota in the neonatal period of preterm infants fed with exclusive own mother's milk presented increased richness and differences in microbial composition from those fed with different proportions of formula.

Low Microbial Diversity and Abnormal Microbial Succession Is Associated with Necrotizing Enterocolitis in Preterm Infants.

Despite increased efforts, the diverse etiologies of Necrotizing Enterocolitis (NEC) have remained largely elusive. Clinical predictors of NEC remain ill-defined and currently lack sufficient specificity. The development of a thorough understanding of initial gut microbiota colonization pattern in preterm infants might help to improve early detection or prediction of NEC and its associated morbidities. Here we compared the fecal microbiota successions, microbial diversity, abundance and structure of newborns that developed NEC with preterm controls. A 16S rRNA based microbiota analysis was conducted in a total of 132 fecal samples that included the first stool (meconium) up until the 5th week of life or NEC diagnosis from 40 preterm babies (29 controls and 11 NEC cases). A single phylotype matching closest to the Enterobacteriaceae family correlated strongly with NEC. In DNA from the sample with the greatest abundance of this phylotype additional shotgun metagenomic sequencing revealed Citrobacter koseri and Klebsiella pneumoniae as the dominating taxa. These two taxa might represent suitable microbial biomarker targets for early diagnosis of NEC. In NEC cases, we further detected lower microbial diversity and an abnormal succession of the microbial community before NEC diagnosis. Finally, we also detected a disruption in anaerobic microorganisms in the co-occurrence network of meconium samples from NEC cases. Our data suggest that a strong dominance of Citrobacter koseri and/or Klebsiella pneumoniae, low diversity, low abundance of Lactobacillus, as well as an altered microbial-network structure during the first days of life, correlate with NEC risk in preterm infants. Confirmation of these findings in other hospitals might facilitate the development of a microbiota based screening approach for early detection of NEC.

Diversity and composition of vaginal microbiota of pregnant women at risk for transmitting Group B Streptococcus treated with intrapartum penicillin.

BACKGROUND: Administering intravenous antibiotics during labor to women at risk for transmitting Group B Streptococcus (GBS) can prevent infections in newborns. However, the impact of intrapartum antibiotic prophylaxis on mothers' microbial community composition is largely unknown. We compared vaginal microbial composition in pregnant women experiencing preterm birth at ≤ 32 weeks gestation that received intrapartum antibiotic prophylaxis with that in controls. METHODS: Microbiota in vaginal swabs collected shortly before delivery from GBS positive women that received penicillin intravenously during labor or after premature rupture of membranes was compared to controls. Microbiota was analyzed by 16S rRNA sequencing using the PGM Ion Torrent to determine the effects of penicillin use during hospitalization and GBS status on its composition. RESULTS: Penicillin administration was associated with an altered vaginal microbial community composition characterized by increased microbial diversity. Lactobacillus sp. contributed only 13.1% of the total community in the women that received penicillin compared to 88.1% in the controls. Streptococcus sp. were present in higher abundance in GBS positive woman compared to controls, with 60% of the total vaginal microbiota in severe cases identified as Streptococcus sp. CONCLUSIONS: Vaginal communities of healthy pregnant women were dominated by Lactobacillus sp. and contained low diversity, while Group B Streptococcus positive women receiving intrapartum antibiotic prophylaxis had a modified vaginal microbiota composition with low abundance of Lactobacillus but higher microbial diversity.

Chorioamnionitis and subsequent lung function in preterm infants.

OBJECTIVE: To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants. METHODS: Placenta and membranes were collected from preterm deliveries (<37 weeks gestational age) and evaluated for histological chorioamnionitis (HCA). Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique. RESULTS: Ninety-five infants (43 males) born prematurely (median gestational age 34.2 weeks) were recruited. HCA was detected in 66 (69%) of the placentas, and of these 55(58%) were scored HCA Grade 1, and 11(12%) HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (p = 0.012 for FEF50, p = 0.014 for FEF25-75 and p = 0.32 for FEV0.5). Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows (p<0.01 for FEF50, FEF25-75 and p<0.05 for FEV0.5). Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males. CONCLUSIONS: Our findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease.

Reduced lung function in healthy preterm infants in the first months of life.

RATIONALE: Preterm delivery has been associated with a higher incidence of respiratory morbidity even in infants that do not have significant respiratory disease during the neonatal period. Reduced flows have been reported in children and adolescents born prematurely. OBJECTIVE: The aim of this study was to assess lung function in healthy preterm infants in the first months of life. METHODS: Preterm infants with less than 48 h of supplemental oxygen were recruited. Lung function was assessed by the raised-volume rapid thoracic compression in the first months of life. The control group consisted of full-term infants without a history of respiratory diseases. MEASUREMENTS AND MAIN RESULTS: Sixty-two preterm (29 male) and 27 full-term (10 male) infants were tested. Adjusting for length, age, and sex, we found a mean significant reduction of 92 ml/s (22%) in FEF(50), 73 ml/s (21%) in FEF(25-75), and 19 ml (28%) in FEV(0.5) in the preterm group. These differences in expiratory flows remained significant using another model that adjusts for lung volume (p < 0.01 for FEF(50), FEF(25-75), and FEV(0.5), and p < 0.05 for FEF(75)). In the preterm group, after adjusting for length, male sex, lower gestational age, and increased weight were significantly and independently associated with reduced flows. CONCLUSIONS: Our findings confirm that prematurity is independently associated with reduced lung function and that this is detectable in the first months of life. Male sex, lower gestational age, and weight are important predictors for reduced expiratory flows in this group.

[Pulmonary prognosis in preterm infants]. / Prognóstico pulmonar em prematuros.

OBJECTIVE: The increased survival of preterm infants poses the challenge of dealing with a wide range of chronic pulmonary diseases, including bronchopulmonary dysplasia, Wilson-Mikity syndrome and recurrent wheezing. This article reviews the pulmonary clinical and functional prognosis of preterm newborns in infancy and adolescence. SOURCE OF DATA: MEDLINE search for articles published between 1970 and 2004 that focused on lung growth and function of preterm infants, besides a clinical follow-up of this group. SUMMARY OF THE FINDINGS: Prenatal and postnatal events, such as placental insufficiency, tobacco exposure, infections, oxygen and mechanical ventilation, have an important effect on lung development and can lead to chronic lung diseases, of which bronchopulmonary dysplasia is the most severe complication. However, significant loss of lung function occurs in preterm infants who do not fulfill the criteria for bronchopulmonary dysplasia, and even in those who did not have significant respiratory disease during the neonatal period. The impact of prematurity on the respiratory system of these patients is usually underestimated. Clinically, preterm infants have an increased incidence of pneumonia and bronchiolitis, hospital readmissions due to respiratory diseases, chronic cough and wheezing and bronchial hyperresponsiveness. In adolescence, there is a tendency for normalization of the lung function, but they persist with reduced flows, lower exercise tolerance and bronchial hyperresponsiveness. CONCLUSIONS: Prematurity, the events that cause it and the interventions that follow it permanently change the development of the respiratory system. Studies are necessary to clarify the effect of each of these perinatal insults on the development of the respiratory system.

Prognóstico pulmonar em prematuros / Pulmonary prognosis in preterm infants

OBJETIVO: O aumento da sobrevida de prematuros traz o desafio de lidar com um amplo espectro de doenças pulmonares crônicas, incluindo displasia broncopulmonar, síndrome de Wilson-Mikity e sibilância recorrente. Este artigo discute o prognóstico pulmonar clínico e funcional de prematuros na infância e na adolescência. FONTE DE DADOS: Foi realizada pesquisa no MEDLINE de publicações entre 1970 e 2004 que abordassem função e crescimento pulmonar de prematuros, bem como a evolução clínica dos mesmos. SíNTESE DOS DADOS: Eventos pré e pós-natais como insuficiência placentária, tabagismo, infecções, oxigênio e ventilação mecânica exercem efeitos importantes no desenvolvimento pulmonar, podendo conduzir a doenças pulmonares crônicas, sendo a displasia broncopulmonar a complicação clínica mais severa. No entanto, perdas significativas de função pulmonar também podem ocorrer em prematuros sem critérios de displasia broncopulmonar e que não apresentaram doença respiratória neonatal significativa. Nestes pacientes, o impacto da prematuridade sobre o sistema respiratório é freqüentemente subestimado. Clinicamente, observa-se incidência aumentada de pneumonias e bronquiolites, re-hospitalizações por doenças respiratórias, tosse e sibilância crônicas e hiper-reatividade brônquica. Posteriormente, percebe-se uma tendência à normalização da função pulmonar, mas persistem fluxos reduzidos, menor tolerância a exercícios e hiper-reatividade brônquica. CONCLUSÕES: A prematuridade, os eventos que a provocam e as intervenções que dela decorrem alteram de maneira permanente, em maior ou menor grau, o desenvolvimento do sistema respiratório. São necessários estudos adicionais para esclarecer o efeito de cada um desses insultos perinatais no desenvolvimento do sistema respiratório.

Estudo retrospectivo das colecistectomias convencional e laparoscópica / Retrospective study of conventional and laparoscopic cholecystectomies

Os autores apresentam um estudo retrospectivo de 200 pacientes operados no Hospital Saúde, pelo mesmo cirurgiao, de colecistite calculosa. Desses pacientes, 100 foram operados pela técnica convencional e os demais pela técnica laparoscópica. Foram analisados: tempo cirúrgico e de hospitalizaçao; necessidade de analgésicos potentes e complicaçoes pós-operatórias. Esse estudo permitiu concluir a superioridade, estatisticamente significativa, da cirurgia laparoscópica em relaçao à convencional quanto ao tempo cirúrgico, tempo de hospitalizaçao, necessidade de analgésicos potentes e índice de morbidade.

Síndrome de Dandy-Walker / Dandy-Walker syndrome

Os autores relatam um caso de uma paciente de 2 anos e 4 meses, com sintomas característicos de hipertensao intracraniana e disfunçao cerebelar. Realizada tomografia computadorizada, verificou-se a presença de uma grande coleçao cística na fossa posterior e hidrocefalia triventricular. O diagnóstico definitivo foi de síndrome de Dandy-Walker, opitando-se por um sistema de drenagem ventriculocistoperitoneal. Realiza-se, nesse trabalho, uma breve revisao quanto a sua patogenia e anormalidades associadas. E faz-se, ainda, uma discussao a respeito do método diagnóstico, tratamento e prognóstico desta síndrome.