Establishment of oral microbiome in very low birth weight infants during the first weeks of life and the impact of oral diet implementation.

Very low birth weight (VLBW) infants, mostly preterm, have many barriers to feeding directly from the mother's breast, and need to be fed alternatively. Feeding is a major influencer in oral microbial colonization, and this colonization in early life is crucial for the promotion of human health. Therefore, this research aimed to observe the establishment of oral microbiome in VLBW infants during their first month of life through hospitalization, and to verify the impact caused by the implementation of oral diet on the colonization of these newborns. We included 23 newborns followed during hospitalization and analyzed saliva samples collected weekly, using 16S rRNA gene sequencing. We observed a significant decrease in richness and diversity and an increase in dominance over time (q-value < 0.05). The oral microbiome is highly dynamic during the first weeks of life, and beta diversity suggests a microbial succession in early life. The introduction of oral diet does not change the community structure, but affects the abundance, especially of Streptococcus. Our results indicate that although time is related to significant changes in the oral microbial profile, oral feeding benefits genera that will remain colonizers throughout the host's life.

Limits of therapeutic intervention in a tertiary neonatal intensive care unit in patients with major congenital anomalies in Brazil.

AIM: Major congenital anomalies are an important cause of death in the neonatal intensive care unit (NICU). Therapeutic interventions and the suspension of those already in place often raise ethical dilemmas in neonatal care. METHODS: We analysed treatments-such as ventilatory support, vasoactive drugs, antibiotics, sedation/or analgesia, central venous access and other invasive procedures-offered up to 48 h before death to all newborns with major congenital anomalies over a 3-year period in a NICU in Brazil. We also gathered information contained in medical records concerning conversations with the families and decisions to limit therapeutic interventions. RESULTS: We enrolled 74 newborns who were hospitalised from 1 January 2015 to 31 December 2017. A total of 81.1% had central venous access, 74.3% were on ventilatory support, 56.8% received antibiotics and 43.2% used some sedative/analgesic drugs in their final moments. Conversations were registered in medical records in 76% of cases, and 46% of the families chose therapeutic intervention limits. Those who chose to limit therapeutic interventions asked for less exposure to vasoactive drugs (P = 0.003) and antibiotics (P = 0.003), as well as fewer invasive procedures (P = 0.046). There was no change in ventilatory support (P = 0.66), and palliative extubation was not performed for any patient. CONCLUSIONS: The therapeutic intervention was mainly characterised by maintenance of the current treatment when a terminal situation was identified with no introduction of new treatments that could increase suffering. The families' approach proved to be essential for making difficult decisions in the NICU.

Association between ventilatory settings and pneumothorax in extremely preterm neonates.

OBJECTIVES: Pneumothorax is a catastrophic event associated with high morbidity and mortality, and it is relatively common in neonates. This study aimed to investigate the association between ventilatory parameters and the risk of developing pneumothorax in extremely low birth weight neonates. METHODS: This single-center retrospective cohort study analyzed 257 extremely low birth weight neonates admitted to a neonatal intensive care unit between January 2012 and December 2017. A comparison was carried out to evaluate the highest value of positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), and driving pressure (DP) in the first 7 days of life between neonates who developed pneumothorax and those who did not. The primary outcome was pneumothorax with chest drainage necessity in the first 7 days of life. A matched control group was created in order to adjust for cofounders associated with pneumothorax (CRIB II score, birth weight, and gestational age). RESULTS: There was no statistically significant difference in PEEP, PIP, and DP values in the first 7 days of life between extremely low birth weight neonates who had pneumothorax with chest drainage necessity and those who did not have pneumothorax, even after adjusting for potential cofounders. CONCLUSIONS: Pressure-related ventilatory settings in mechanically ventilated extremely low birth weight neonates are not associated with a higher risk of pneumothorax in the first 7 days of life.

Prevalence and Outcomes of Congenital Heart Disease in Very Low Birth Weight Preterm Infants: An Observational Study From the Brazilian Neonatal Network Database.

OBJECTIVES: To evaluate the prevalence of congenital heart disease and their outcomes in a Brazilian cohort of very low birth weight preterm infants. DESIGN: Post hoc analysis of data from the Brazilian Neonatal Network database, complemented by retrospective data from medical charts and a cross-sectional survey. SETTING: Twenty public tertiary-care university hospitals. PATIENTS: A total of 13,955 newborns weighing from 401 to 1,499 g and between 22 and 36 weeks of gestational age, born from 2010 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of congenital heart disease was 2.45% (95% CI, 2.20-2.72%). In a multivariate regression analysis, risk factors associated with congenital heart disease were maternal diabetes (relative risk, 1.55; 95% CI, 1.11-2.20) and maternal age above 35 years (relative risk, 2.09; 95% CI, 1.73-2.51), whereas the protection factors were maternal hypertension (relative risk, 0.54; 95% CI, 0.43-0.69), congenital infection (relative risk, 0.45; 95% CI, 0.21-0.94), and multiple gestation (relative risk, 0.73; 95% CI, 0.55-0.97). The pooled standardized mortality ratio in patients with congenital heart disease was 2.48 (95% CI, 2.22-2.80), which was significantly higher than in patients without congenital heart disease (2.08; 95% CI, 2.03-2.13). However, in multiple log-binomial regression analyses, only the presence of major congenital anomaly, gestational age (< 29 wk; relative risk, 2.32; 95% CI, 2.13-2.52), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20; relative risk, 3.76; 95% CI, 3.41-4.14) were independently associated with death, whereas the effect of congenital heart disease was spotted only when a conditional inference tree approach was used. CONCLUSIONS: The overall prevalence of congenital heart disease in this cohort of very low birth weight infants was higher and with higher mortality than in the general population of live births. The occurrence of a major congenital anomaly, gestational age (< 29 wk), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20) were significantly and independently associated with death, whereas the association of congenital heart disease and death was only evident when a major congenital anomaly was present.

Association between ventilatory settings and pneumothorax in extremely preterm neonates

OBJECTIVES: Pneumothorax is a catastrophic event associated with high morbidity and mortality, and it is relatively common in neonates. This study aimed to investigate the association between ventilatory parameters and the risk of developing pneumothorax in extremely low birth weight neonates. METHODS: This single-center retrospective cohort study analyzed 257 extremely low birth weight neonates admitted to a neonatal intensive care unit between January 2012 and December 2017. A comparison was carried out to evaluate the highest value of positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), and driving pressure (DP) in the first 7 days of life between neonates who developed pneumothorax and those who did not. The primary outcome was pneumothorax with chest drainage necessity in the first 7 days of life. A matched control group was created in order to adjust for cofounders associated with pneumothorax (CRIB II score, birth weight, and gestational age). RESULTS: There was no statistically significant difference in PEEP, PIP, and DP values in the first 7 days of life between extremely low birth weight neonates who had pneumothorax with chest drainage necessity and those who did not have pneumothorax, even after adjusting for potential cofounders. CONCLUSIONS: Pressure-related ventilatory settings in mechanically ventilated extremely low birth weight neonates are not associated with a higher risk of pneumothorax in the first 7 days of life.

Vaginal progesterone for the prevention of preterm birth in twin gestations: a randomized placebo-controlled double-blind study.

OBJECTIVE: The purpose of this study was to investigate the use of vaginal progesterone for the prevention of preterm delivery in twin pregnancies. STUDY DESIGN: We conducted a prospective, randomized, double-blind, placebo-controlled trial that involved 390 naturally conceived twin pregnancies among mothers with no history of preterm delivery who were receiving antenatal care at a single center. Women with twin pregnancies between 18 and 21 weeks and 6 days' gestation were assigned randomly to daily vaginal progesterone (200 mg) or placebo ovules until 34 weeks and 6 days' gestation. The primary outcome was the difference in mean gestational age at delivery; the secondary outcomes were the rate of spontaneous delivery at <34 weeks' gestation and the rate of neonatal composite morbidity and mortality in the treatment and nontreatment groups. RESULTS: The baseline characteristics were similar in both groups. The final analysis included 189 women in the progesterone group and 191 in the placebo group. No difference (P = .095) in the mean gestational age at delivery was observed between progesterone (35.08 ± 3.19 [SD]) and placebo groups (35.55 ± 2.85). The incidence of spontaneous delivery at <34 weeks' gestation was 18.5% in the progesterone group and 14.6% in the placebo group (odds ratio, 1.32; 95% confidence interval, 0.24-2.37). No difference in the composite neonatal morbidity and mortality was observed between the progesterone (15.5%) and placebo (15.9%) groups (odds ratio, 1.01; 95% confidence interval, 0.58-1.75). CONCLUSION: In nonselected twin pregnancies, vaginal progesterone administration does not prevent preterm delivery and does not reduce neonatal morbidity and death.

Prediction of intrauterine death and severe preterm delivery in twin pregnancies discordant for major fetal abnormality.

OBJECTIVE: To investigate predictors of spontaneous fetal death and preterm delivery in twin pregnancies with one fetus affected by a major structural malformation. STUDY DESIGN: Retrospective study (1999-2012) conducted at a tertiary teaching hospital involving 51 twin pregnancies (dichorionic=31, monochorionic diamniotic=15, monochorionic monoamniotic=4, not established=1) with a major fetal abnormality, enrolled before 26 weeks and managed expectantly. PRIMARY OUTCOMES: spontaneous fetal death, and/or delivery before 32 weeks. Prediction was examined with stepwise logistic regression analysis, and independent variables included: maternal age, gestational age at diagnosis, chorionicity, fetal gender, number and type of fetal abnormalities. Significance level was set at 0.15. RESULTS: Fetal abnormalities were diagnosed at a mean gestation of 21.5±3.7 weeks: cardiac abnormalities were observed in 31.4% of abnormal fetuses, abdominal wall defects in 29.4%, central nervous system 21.5%, spine 17.6%, effusions 17.6%, noncardiac thoracic abnormalities 15.7%, genital and urinary system 13.7%, limbs and soft tissue 3.9%, intestinal 1.9% and facial defects 1.9%. Fetal death occurred in 15 (29.4%) abnormal fetuses and was significantly correlated with the number of fetal malformations (p=0.02, OR=2.54, 95% CI=1.14-5.62), presence of effusion/hydrops (p=0.06, OR=4.7, 95% CI=0.95-24) and monochorionic placenta (p=0.11, OR=2.8, 95% CI=0.78-9.8). Normal co-twin fetal death occurred in four cases (7.8%) and was related to monochorionic pregnancies (p=0.14, OR=5.8, 95% CI=0.56-61). Delivery before 32 weeks was observed in 14 (27.5%) pregnancies and was related to presence of effusion/hydrops (p=0.04, OR=5.5, 95% CI=1.07-28). CONCLUSION: Spontaneous fetal death and/or delivery before 32 weeks in twin pregnancies with one fetus affected by a major structural malformation are related to the number of abnormalities diagnosed and presence of fetal effusion or hydrops.

Should we measure fetal omphalocele diameter for prediction of perinatal outcome?

OBJECTIVE: To evaluate the fetal omphalocele diameter/abdominal circumference ratio (OD/AC) as a predictor of adverse perinatal outcome. METHODS: Analysis involving 47 singleton pregnancies with fetal omphalocele, normal karyotype and absence of other major abnormalities. The OD/AC ratio was determined antenatally by ultrasound and the best cutoff for the prediction of neonatal death was determined by receiver operating characteristic curve analysis. Additional secondary outcomes included need for oral intubation in the first 24 h of life, two-step surgery or use of synthetic mesh, reoperation, parenteral feeding and need for respiratory assistance >21 days, time to first oral feed, and time to hospital discharge. RESULTS: Fetal OD/AC did not change significantly with gestational age. Postnatal death occurred in 10 (21.3%) cases and the best cutoff for prediction was an OD/AC ratio ≥0.26. In pregnancies with the first ultrasound evaluation performed before 31 weeks' gestation and an OD/AC ≥0.26, the likelihood ratio for needing intubation in the first 24 h of life was 2.6 (95% CI: 1.2-5.7), needing two-step surgery or use of mesh was 4.9 (95% CI: 1.9-14.4), and postnatal death was 4 (95% CI: 1.9-7.5). CONCLUSION: A fetal ultrasound OD/AC ratio ≥0.26 is associated with increased postnatal morbidity and mortality.

Twenty-five years of fetal echocardiography in conjoined twins: lessons learned.

BACKGROUND: The aim of this study was to determine the accuracy of prenatal echocardiography in the diagnosis of intracardiac malformations and the degree of cardiac fusion in conjoined twins presenting to a single center over a 25-year period. METHODS: The study group included 53 sets of conjoined twins from 1987 to 2012, including 38 thoracopagus, six parapagus, six omphalo-ischiopagus, two omphalopagus, and one cephalopagus. Twins were classified according to the degree of cardiac fusion: separate hearts and pericardium (group A, n = 10), separated hearts and common pericardium (group B, n = 2), fused atria and separated ventricles (group C, n = 2), and fused atria and ventricles (group D, n = 39). Postmortem examination was possible in 68 individual cases (98 deaths [69.3%]). RESULTS: Cardiac defects were diagnosed in 47 sets of twins (88.6%). In 10 (18.8%), only one fetus was affected, and in 37 (69.8%), both fetuses were affected (n = 84/106 [79.2%]). There was a high predominance of right-sided lesions (63.0% [53 fetuses in 84 affected]) including pulmonary atresia or stenosis (35.7%), tricuspid atresia (11.9%), and hypoplastic or small right ventricle (21.4%). Autopsy findings added information to fetal echocardiographic findings in nine sets of twins (25.7%). Three pairs classified antenatally in groups A, B, and D were confirmed by autopsy in groups B, C, and C, respectively. CONCLUSIONS: This study demonstrates that specialized fetal echocardiography is not a perfect diagnostic tool but is sensitive enough to establish prognosis in the counseling process. Because of complexity, such evaluations should be performed only at tertiary centers by specialists who are familiar with the peculiarities of this rare malformation. The predominance of right-sided lesions is not only an interesting finding, but this information has essential importance in terms of shortening examination times, allowing a more focused analysis of the fetal heart.

Novel treatment immediately after myelomeningocele repair applying low-level laser therapy in newborns: a pilot study.

BACKGROUND/AIMS: The use of low-level laser therapy (LLLT) in neurosurgery is still hardly disseminated and there are situations in which the effects of this therapeutic tool would be extremely relevant in this medical field. The aim of the present study is to analyze the effect of LLLT on tissue repair after the corrective surgical incision in neonates with myelomeningocele, in an attempt to diminish the incidence of postoperative dehiscences following surgical repair performed immediately after birth. MATERIALS AND METHODS: Prospective pilot study with 13 patients submitted to surgery at birth who received adjuvant treatment with LLLT (group A). A diode laser CW, λ = 685 nm, p = 21 mW, was applied punctually along the surgical incision, with 0.19 J delivered per point, accounting for a total of 4-10 J delivered energy per patient, according to the surgical wound area and then compared with the results obtained in 23 patients who underwent surgery without laser therapy (group B). RESULTS: This pilot study disclosed a significant decline in dehiscences of the surgical wounds in neonates who were submitted to LLLT (7.69 vs. 17.39%). CONCLUSION: This new adjuvant therapeutic modality with LLLT aided the healing of surgical wounds, preventing morbidities, as well as shortening the period of hospital stay, which implies a reduction of costs for patients and for the institution.

Effects of the use of fortified raw maternal milk on very low birth weight infants / Efeitos do uso de aditivo no leite humano cru da própria mãe em recém-nascidos pré-termo de muito baixo peso

OBJETIVO: Comparar o ganho pôndero-estatural e a frequência de complicações clínicas em recém-nascidos pré-termo com peso inferior a 1.500 g, alimentados exclusivamente com leite humano cru da própria mãe com e sem aditivo até atingirem o peso de 1.800 g. MÉTODOS: Ensaio clínico prospectivo randomizado duplo-cego em 40 recém-nascidos pré-termo com peso de nascimento < 1.500 g e ≤ 34 semanas, internados em unidade de terapia intensiva neonatal no período de agosto de 2005 a abril de 2007. Foram randomizados em 2 grupos: controle (leite humano puro) e intervenção (leite humano com aditivo). A fortificação foi feita no leite humano cru ordenhado no momento da oferta, quando a dieta atingiu 100 mL/kg/dia (até os neonatos atingirem peso de 1.800 g). Foram comparados ganho de peso diário, crescimento e perímetro cefálico semanalmente, variáveis nutricionais e complicações clínicas. RESULTADOS: A fortificação resultou em melhor crescimento, com ganho de 1,09 e 0,87 cm/semana (p = 0,003) e perímetro cefálico observado de 0,73 e 1,02 cm/semana (p = 0,0001), respectivamente grupo intervenção e controle. O ganho de peso foi de 24,4 e 21,2 g/dia (p = 0,075). Quanto às complicações clínicas observadas, não houve diferença significante. CONCLUSÕES: O uso de aditivo no leite humano cru da própria mãe proporcionou melhor crescimento, com aumento significativo do comprimento e do perímetro cefálico.

OBJECTIVE: To compare the weight and height gain and the frequency of clinical complications in preterm newborns weighing less than 1,500 g, exclusively fed human milk or fortified human milk until reaching 1,800 g. METHODS: Prospective double-blind randomized controlled trial involving 40 preterm infants weighing < 1,500 g at birth and ≤ 34 weeks of gestational age, admitted to a neonatal intensive care unit from August 2005 to April 2007. Preterm infants were randomized into two groups: control (human milk) and intervention (fortified human milk). Fortifiers were added to manually expressed human milk when feeding volume reached 100 mL/kg/day until newborns reached 1,800 g. Daily weight gain, weekly length and head circumference gain, nutritional variables and clinical complications were compared. RESULTS: Human milk fortification resulted in better growth, with length gain of 1.09 and 0.87 cm/week (p = 0.003) and head circumference gain of 0.73 and 1.02 cm/week (p = 0.0001), respectively, for intervention and control groups. The weight gain was 24.4 and 21.1 g/day (p = 0.075). There were no significant clinical complications. CONCLUSIONS: Human milk fortification resulted in better growth, significant increase in length and head circumference.

Effects of the use of fortified raw maternal milk on very low birth weight infants.

OBJECTIVE: To compare the weight and height gain and the frequency of clinical complications in preterm newborns weighing less than 1,500 g, exclusively fed human milk or fortified human milk until reaching 1,800 g. METHODS: Prospective double-blind randomized controlled trial involving 40 preterm infants weighing < 1,500 g at birth and

Ductus venosus Doppler and postnatal outcomes in fetuses with absent or reversed end-diastolic flow in the umbilical arteries.

OBJECTIVE: To evaluate the relationship between ductus venosus Doppler findings on the day of delivery and postnatal outcomes in pregnancies with absent or reversed end-diastolic (ARED) flow in the umbilical arteries. STUDY DESIGN: Postnatal outcomes of 103 newborns of pregnancies with a diagnosis of ARED flow on Doppler velocimetry of the umbilical arteries were analyzed retrospectively between January 1997 and December 2004. Single pregnancies and fetuses without malformations were included. The cases were divided into two groups according to the flow during atrial contraction (a-wave) in the ductus venosus on the day of delivery: group A, 20 cases with absent or reversed flow in the ductus venosus and group B, 83 cases with positive flow. The results were analyzed statistically using the chi-square test, Fisher's exact test and the Mann-Whitney U test with the level of significance set at 5%. RESULTS: All newborns were delivered by cesarean section. Gestational age was similar in the two groups (group A: 30 weeks and group B: 30.9 weeks, P=0.23). Absent or reversed ductus venosus flow was associated with the following adverse postnatal outcomes: lower birthweight (P<0.001), lower Apgar scores in the first (P=0.001) and fifth minute (P=0.001), a higher frequency of orotracheal intubation (P=0.001) and pH at birth less than 7.20 (P<0.001), pulmonary hemorrhage (P=0.03), thrombocytopenia (P=0.02), hypoglycemia (P=0.01), intracranial hemorrhage (P=0.02), and postnatal death (P=0.007). CONCLUSION: The study of ductus venosus flow may provide additional information regarding the best time for interruption of pregnancies with ARED flow in the umbilical arteries characterized by extreme prematurity.

Nosocomial infection in newborns by Pichia anomala in a Brazilian intensive care unit.

Disseminated candidiasis is the most common nosocomial fungal infection, and Candida albicans has been reported to account for 50% to more than 70% of cases of invasive candidiasis. However, recent reports have also suggested the emergence of infections caused by non-albicans species. In addition, less-common pathogenic yeasts (Malassezia, Trichosporon, Rhodotorula, Debaryomyces and Pichia) have recently been reported, with increased frequency, as causes of nosocomial infections with high mortality. This article describes two cases of fungemia caused by Pichia anomala in newborns that occurred in an intensive care unit (ICU), in November 2004 at the Instituto da Criança (Pediatric Institute) of the Hospital das Clínicas of the School of Medicine, São Paulo University, Brazil. The principal factors related to virulence (proteinase and phospholipase) and the susceptibility of the isolated strains to antifungal agents were also evaluated, and the biotype of each strain was determined through the use of an epidemiological marker (killer biotype).

TNF-alpha and IL-6 in the diagnosis of bacterial and aseptic meningitis in children.

The objective of this study was to analyze the usefulness of tumor necrosis factor-alpha and interleukin-6 cerebrospinal fluid concentrations for the differential diagnosis between bacterial and aseptic meningitis in children and in the prognostic evaluation. A cross-sectional study was performed on 35 children between 1 month and 12 years of age with suspected meningitis. Cytokines determination was performed by enzyme-linked immunosorbent assay technique. The Mann-Whitney test and Spearman's correlation coefficients were used for statistical analysis. Six children presented bacterial meningitis, 13 aseptic, and 16 had no meningitis. The tumor necrosis factor-alpha concentrations were significantly higher in the bacterial meningitis group as compared with the aseptic group (P = 0.001) and among groups with and without meningitis (P = 0.000). There was correlation between tumor necrosis factor-alpha and cerebrospinal fluid leukocytes (P = 0.019), protein (P = 0.000), and glucose (P = 0.038). There was no association between cytokines and complications of the meningitis. The tumor necrosis factor-alpha concentrations in the cerebrospinal fluid were useful markers for distinguishing bacterial from aseptic meningitis and were demonstrated to be useful in evaluating the intensity of the inflammatory process in the central nervous system.

Vancomycin monitoring in term newborns: comparison of peak and trough serum concentrations determined by high performance liquid chromatography and fluorescence polarization immunoassay

INTRODUCTION: Peak and trough serum concentrations of vancomycin were determined in term newborn infants with confirmed or suspected Staphylococcus sp sepsis by high performance liquid chromatography and flourescence polarization immunoassay. OBJECTIVE: To statistically compare the results of the high performance liquid chromatography and flourescence polarization immunoassay techniques for measuring serum vancomycin concentrations. METHODS: Eighteen peak and 20 trough serum samples were assayed for vancomycin concentrations using high performance liquid chromatography and flourescence polarization immunoassay from October 1995 to October 1997. RESULTS: The linear correlation coefficients for high performance liquid chromatography and flourescence polarization immunoassay were 0.27 (peak, P = 0.110) and 0.26 (trough, P = 0.1045) respectively, which were not statistically significant. CONCLUSION: There was wide variation in serum vancomycin concentrations determined by high performance liquid chromatography as compared with those determined by flourescence polarization immunoassay. There was no recognizable pattern in the variability; in an apparently random fashion, the high performance liquid chromatography measurement was sometimes substantially higher than the flourescence polarization immunoassay measurement, and at other times it was substantially lower

Brain abscess by citrobacter diversus in infancy: case report

Citrobacter diversus is closely related to brain abscess in newborn infants. We describe a case of brain abscess by this bacteria in a newborn infant and his clinical and cranial computed tomographic evaluation until the fourth month of life and discuss therapeutic management of this patient