Phenotypic differences in leucocyte populations among healthy preterm and full-term newborns.

The immune system of neonates has been considered functionally immature, and due to their high susceptibility to infections, the aim of this study was to analyse the phenotypic differences in leucocyte populations in healthy preterm and full-term newborns. We evaluated the absolute numbers and frequencies of dendritic cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2) and full-term (Group 3) newborns and in healthy adults, as controls, by flow cytometry. The analyses revealed statistically higher absolute cell numbers in neonates compared with adults due to the characteristic leucocytosis of neonates. We observed a lower frequency of CD80(+) myeloid and plasmacytoid DCs in Group 1 and reduced expression of TLR-4 on myeloid DCs in all neonates compared with adults. TLR-2(+) monocytes were reduced in Group 1 compared with Groups 2 and 3, and TLR-4(+) monocytes were reduced in Groups 1 and 2 compared with Group 3. The frequencies and numbers of naïve CD4(+) T and CD19(+) B cells were higher in the three groups of neonates compared with adults, while CD4(+) effector and effector memory T cells and CD19(+) memory B cells were elevated in adults compared with neonates, as expected. Our study provides reference values for leucocytes in cord blood from term and preterm newborns, which may facilitate the identification of immunological deficiencies in protection against extracellular pathogens.

Complement profile in neonates of different gestational ages.

Blood levels of regulators of the complement system in preterm babies were reported in few studies only. The aim of this study was to set up a complement profile in premature and term babies focusing on the development of blood levels of MBL, key regulatory proteins and on classical pathway activity, which may allow an estimation of potential susceptibility to infection. Complement activity (CH50), levels of mannan-binding lectin (MBL), complement regulators (factors H and I, C1 inhibitor, properdin) and C3a as marker of complement activation were assessed in three groups of healthy newborns: (1) prematures (≤34 weeks); (2) late prematures (>34-<37 weeks) and (3) term neonates (≥37 weeks). CH50 increased with gestational age with lower titres in cord blood than in day 5 post-delivery venous blood. MBL concentrations were not significantly different among groups. Quantitative and functional C1 inhibitor were below adult normal range in prematures <34 weeks and lower in cord blood as compared to day 5. Factor I, factor H and properdin remained below adult values in all groups. Low C3a levels excluded that low complement titres were due to activation-induced consumption. These results demonstrate the relative immaturity of the complement system and its regulation, especially in premature infants.

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia.

OBJECTIVE: Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. METHODS: Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. RESULTS: Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 ± 2.4 weeks in the FETO group and at 37.4 ± 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the received-treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). CONCLUSION: FETO improves neonatal survival in cases with isolated severe CDH.

Necrotizing fasciitis in a newborn infant: a case report.

We report the case of a one-day-old newborn infant, female, birth weight 1900 g, gestational age 36 weeks presenting with necrotizing fasciitis caused by E. coli and Morganella morganii. The newborn was allowed to fall into the toilet bowl during a domestic delivery. The initial lesion was observed at 24 hours of life on the left leg at the site of the venipuncture for the administration of hypertonic glucose solution. Despite early treatment, a rapid progression occurred resulting in a fatal outcome. We call attention to the risk presented by this serious complication in newborns with a contaminated delivery, and highlight the site of the lesion and causal agents.

Monitoring the treatment of sepsis with vancomycin in term newborn infants.

UNLABELLED: A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. PURPOSE: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique, SBT by the macro-broth dilution method, and MIC by diffusion test in agar. RESULTS: Thirteen newborn infants (59.1%) had adequate peak vancomycin serum concentrations (20 - 40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 microg/mL). Only 48% had adequate trough concentrations (5 - 10 mg/mL), and seven (28%) had a potential nephrotoxicity risk (>10 microg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses.

[Extracorporeal membrane oxygenation (ECMO) in a neonate with respiratory distress due to meconium aspiration syndrome: Effect of the administration of exogenous surfactant] / Circulação extracorpórea prolongada (ECMO) em recém-nascido com insuficiência respiratória por Síndrome de Aspiração Meconial: efeitos da administração de surfactante exógeno.

OBJECTIVES: To present the clinical outcome of a newborn with severe respiratory distress secondary to meconium aspiration syndrome and treated by extracorporeal membrane oxygenation (ECMO); and to present the effect of the use of exogenous surfactant in this case and the cost of the procedure. METHODS: Case report of a newborn with meconium aspiration syndrome and treated at the neonatal ICU of the Instituto da Criança Prof. Pedro de Alcantara, Hospital das Clínicas of the Universidade de São Paulo. RRESULTS: ECMO was carried out for 5 days with no clinical or mechanical complications. On the 4th day of ECMO, we administered porcine exogenous surfactant; a significant improvement in lung compliance was observed and the newborn was decannulated shortly after that. Treatment costs were compatible with the situation of healthcare in Brazil for treatment of critically ill newborn patients. CONCLUSIONS: ECMO is indicated in cases of neonatal respiratory distress not responding to other treatments. The technique should be made available in neonatal Intensive Care Units (ICUs) of tertiary hospitals according to well-established protocols. The use of exogenous surfactant apparently allowed for earlier decannulation of the patient and should be considered in similar cases. The treatment costs do justify the organizing of ECMO teams in this type of ICUs.

[Use of blood and blood components and derivatives in newborn infants] / Uso de sangue, hemocomponentes e hemoderivados no recém-nascido.

OBJECTIVE: To describe the current rationale for the transfusion of blood, blood components, and plasma derivatives in term and preterm infants. SOURCES: Selection of relevant medical articles published within the last ten years. SUMMARY OF THE FINDINGS: Peculiar characteristics and special care concerning exchange transfusion, transfusion of red blood cells, platelets, granulocytes, and fresh frozen plasma were described. The recommendations for the use of hematopoietic growth factors, and plasma derivatives such as fibronectin, immunoglobulins, and albumin were also evaluated. CONCLUSIONS: The authors comment on the recommendations and contraindication of blood transfusions, and warn against the limitations and hazards involved.

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.

Infecçäo por Chlamydia trachomatis no período neonatal: aspectos clínicos e laboratoriais. Experiência de uma década: 1987-1998 / Chlamydia trachomatis infection in neonatal period: clinical and laboratorial aspects. Experience of a decade: 1987-1998

A infecção por C. trachomatis é adquirida pelo recém-nascido (RN) principalmente durante sua passagem pelo canal parto; 25 por cento a 50 por cento destes deverão desenvolver conjuntivite e 10 por cento a 20 por cento pneumonia. Objetivos. Verificar a incidência de infecção ocular por C. trachomatis nos RN internados com diagnóstico de conjuntivite, num período de 10 anos. - Observar a associação entre infecção ocular é pneumonia intersticial - Estudar os aspectos epidemiológicos e os métodos utilizados para o diagnóstico laboratorial. Casuística e Metodologia. Foram analisados os RN internados com diagnóstico de conjuntivite e/ ou pneumonia interticial internados na UCINE no período de 1987-1998. Os métodos de diagnóstico utilizados foram: a pesquisa direta do agente etiológico em raspado de conjuntiva, radiografia de tórax, sorologia para C. trachomatis no sangue pelo método de imunofluorescência para anticorpos IgG e IgM. Resultados. Estudamos as características de 20 RN que apresentaram infecção por C. trachomatis: 15 eram de termo (75 por cento) e cinco, pré-termos (25 por cento); houve predominância da infecção no sexo feminino (60 por cento); a pneumonia esteve presente em 15 dos 20 RN (75 por cento) e 12 apresentaram associação de conjuntivite e pneumonia. Não houve relação significante entre tipo de parto, idade materna, número de parceiros e a infecção, sendo que o antecedente materno de leucorreia esteve presente em 50 por cento dos casos. O diagnóstico sorológico esteve relacionado com a presença de pneumonia e a pesquisa direita com a conjuntivite. A incidência de conjuntivite por C. trachomatis entre os RN internados com esse diagnóstico durante o período de estudo foi de 17/100 (17 por cento). Conclusões. A. C. trachomatis é um importante agente patogênico e sua pesquisa é muito importante em RN com conjuntivite e/ou pneumonia intersticial mesmo na ausência de fatores de risco para doença sexualmente transmissível. A pesquisa direta em raspado de conjuntiva e o exame sorológico se mostraram importantes como métodos auxiliares do diagnóstico.

[Chlamydia trachomatis infection in the neonatal period: clinical and laboratory aspects. Experience of a decade: 1987-1998]. / Infecção por Chlamydia trachomatis no período neonatal: aspectos clínicos e laboratoriais. Experiência de uma década: 1987-1998.

UNLABELLED: Chlamydia trachomatis infection is adquired by the newborn infant during the delivery, 25 to 50% of them may develop conjunctivitis and 10 to 20% pneumonia. BACKGROUND: To verify the incidence of ocular infection by C. trachomatis in the newborn infants with conjunctivitis. To observe the association between ocular infection and intersticial pneumonia.-Study the epidemiological aspects and laboratorial methods of criterial diagnosis. CASUISTICS AND METHODS: We studied the newborn infants admitted in the intensive neonatal care with diagnostic of conjunctivitis and/or interstitial pneumonia during the period of ten years. The diagnostic methods were direct exam of etiologic agent in conjunctival material, X ray chest and serologic test by imunofluorescence method for IgG and IgM antibodies. RESULTS: We studied the clinical characteristics of 20 newborns infants with chlamydial trachomatis infection: 15 (75%) were terms newborns and 5 (25%) pre-terms. We observed the predominance of infection in females (60%); pneumonia was observed in 15/20 (75%) and 12 of them had both: conjunctivitis and pneumonia. We did not observe significant association among type of delivery, age of the mother, number of partner and infection. Leukorrhea was present em 50% of the mothers The serologic test was positive in 100% of the newborn with pneumonia and none with conjunctivitis alone, and the direct exam in conjuntival material was positive in newborns with conjunctivitis. The incidence of C. trachomatis in the newborns admitted in this period with conjunctivitis were 17/100 (17%). CONCLUSION: Chlamydia trachomatis is an important pathogenical agent and the research of it is essential in newborn infants with conjunctivitis and/or interstitial pneumonia even there were not risk factors for sexually transmitted diseases. The direct exam of conjunctival material and serologic test are very important to diagnosis.

[Bacterial endocarditis as a complication of neonatal sepsis: case report]. / Endocardite bacteriana como complicação de sepse neonatal--relato de caso.

The authors reported on a 11 day-old child, admitted in Neonatal Intensive Care Unit for multiple congenital malformations, who had sepsis and bacterial endocarditis. Among the risk factors for endocarditis were outstanding: the central venous catheterism, hemoculture with growth of Staphylococcus aureus and mechanical ventilation. The diagnosis was made in the 61st day after admission owing to the presence of persistent fever and appearance of systolic murmur. The echocardiogram revealed a thrombus in the right atrium measuring 1.9 x 0.7 mm. Antibiotic therapy and surgical resection being performed, with clinical improvement. On the 125st day after admission the patient died owing sepsis and cerebral abscess. At necropsy, heart malformations were not observed. The authors concluded to be very important the knowledge of the potential risks of invasive procedures currently used to care for critically ill newborns. The clinical suspicion of endocarditis should be considered in all neonates with sepsis and receiving intensive care for long time.

[Immunological indicators (IgM and C-reactive protein) in neonatal infections]. / Indicadores imunológicos (IgM e proteína C-reativa) nas infecções neonatais.

UNLABELLED: Sepsis in the neonatal age is associated with risk factors for infections and with the immunological state of the newborn infant. BACKGROUND: Verify if IgM and C-reactive protein were indicators of infection in newborn infants with risk factors. MATERIAL AND METHODS: We studied 57 newborn infants that had: premature rupture of amniotic membranes associated ou no with clinical amniotics or with urinary tract infection. They were classified in three gestational age groups (< 34 weeks, between 34-36 6/7 and (37 weeks) Sepsis diagnosis was made through clinical and laboratorial criterious and we also included: IgM and C-reactive protein obtained of the newborn at birth and at fifth day of life. RESULTS: Sepsis diagnosis was made in 18 (31.5%) of 57 newborn infants, 13 (22.8%) with early sepsis and 5 (8.7%) with late sepsis. The infection had statistical association with gestational age and with weight at birth. The gestational group < 34 weeks was more infected and in this group the number of newborn that died had association with infection. We did not observed association in the three groups studied between infection and sex. There were significant differences of levels of IgM between infected and not infected newborn infants in the same group of gestational age, this difference was more evident in the fifth day. There were association between levels of C-reactive protein > 10 mg/L and infection in the three groups studied. CONCLUSION: C-reactive protein was the better indicator of infection at birth and in the fifth day of life and this was very important for the clinical evolution of the infection and in the late sepsis was the first prove that was altered.

Indicadores imunológicos (IgM e proteína C-reativa) nas infecçöes neonatais / Immunological indicators (IgM and C-reactive protein) in neonatal infections

A sepse, no período neonatal, está associada com a presença de fatores de risco para infecçao e com o estado imunológico do recém-nascido. Objetivo. Verificar, em recém-nascidos com fatores de risco para infecçao, o papel da proteína C reativa (PCR) e da imunoglobulina M (IgM) como indicadores de infecçao. Casuística e Metodologia. Foram estudados 57 recém-nascidos que apresentavam, como fatores de risco para infecçao: ruptura prematura de membranas, associada ou nao a amniotite clínica ou a infecçao de trato urinário. Estes foram classificados em três grupos, de acordo com a idade gestacional <34 semanas, entre 34-36 6/7 semanas e (>37 semanas). O diagnóstico de infecçao foi baseado em critérios clínicos e laboratoriais, e foram incluídos entre os métodos de diagnóstico e dosagem de PCR e de IgM. Os exames laboratoriais foram colhidos ao nascimento e no quinto dia de vida. Resultados. Dos 57 recém-nascidos estudados, 18 (31,5 por cento) apresentaram sepse, sendo 13 (22,8 por cento) a forma precoce e cinco (8,7 por cento) a forma tardia. Houve associaçao estatisticamente significante entre idade gestacional, peso e presença de infecçao, constituindo o grupo com idade gestacional inferior a 34 semanas o mais acometido e o que apresentou também maior número de óbitos relacionados com o processo infeccioso. Nao se observou associaçao estatisticamente significante entre sexo e infecçao nos três grupos estudados. Em relaçao à IgM, houve diferença estatisticamente significante entre níveis séricos médios de IgM dos RNs infectados que se mostraram superiores aos dos nao-infectados nos três grupos de idade gestacional, tanto ao nascimento como no quinto dia, sendo esta diferença mais evidente no quinto dia. Constatou-se forte associaçao estatística entre níveis de PCR > 10mg/litro e presença de infecçao nos três grupos estudados. Conclusoes. Nesta casuística, a PCR foi o melhor indicador de infecçao, revelando-se esta prova confiável para seguimento clínico no quinto dia de vida, e naqueles casos que apresentaram infecçao tardia foi a primeira prova a se mostrar alterada.

Central diabetes insipidus as a complication of neonatal pathology: report of three cases.

Three patients, 11, 17 and 41 days old with various degrees of central nervous system (CNS) lesions developed central diabetes insipidus as a complication of hypothalamic damage. Two of the children had congenital CNS malformations including meningomyelocele, hydrocephalus, and prosencephaly, while the third child presented Streptococcus agalactiae meningitis, complicated with CNS hemorrhage and hypertensive dilatation of the lateral ventricles. All of them fulfilled the criteria for central diabetes insipidus, reaching high levels of serum sodium and osmolality, along with hypotonic urine. The responses to intranasal arginine-vasopressin were prompt, normalizing the serum levels of sodium and increasing urinary osmolality, allowing a better metabolic balance, avoiding continuing damage to the already compromised CNS. The neonatologist must be aware of the possibility of this kind of complication even in a normal child with CNS infection. Imaging studies showing hemorrhage in the region of the posterior hypothalamus must be a sign that this type of complication is able to occur.

[Immunological behavior (IgG, IgM, IgA) and total complement (CH50) of newborns infants with risk factors for early onset sepsis. Comparative analysis of newborns with and without infection]. / Comportamento imunológico (IgG, IgM, IgA) e complemento total (CH 50) de recém-nascidos com fatores de risco para sepse precoce. Análise comparativa entre recém-nascidos com e sem infecção.

Immunological behavior (IgG, IgM, IgA) and total Complement (CH50) of newborns infants with risk factors for early onset sepsis. Comparative analysis between newborns with and without infection. Rev. Hosp. Clín. Fac. Med. S. Paulo, 53(6): 303-310, 1998. The objective of this study was to verify the immunological behavior of the newborn infant in front of an infection. We studied 60 newborn infants that had risk factors for early onset sepsis (premature rupture membranes, clinic amnionitis or tract urinary infection) from de immunological and infection point of view. They were classified into three gestational age groups: < 34 weeks, between 34 and 36 6/7 weeks and > or = 37 weeks. Sepsis diagnosis was done through clinical and laboratorial data and we also included the followings exams: Immunological types (IgG, IgM, IgA) and total complement (CH50) obtained from the newborn at birth and on the fifth day of life. We could verify that 15 newborns (25%) presented early sepsis. There was a statistical association between perinatal asfixia and infection in the group with gestational age < 34 weeks and this same group presented statistical association between infection and death. The serical levels of IgG and CH50 were directly related to the gestational age and there were significant statistical differences between levels of IgG, IgM and total Complement between infected and not infected newborns within the same group os gestional age. We observed that the infection was associated to low levels of IgG and CH50, at birth and on the fifth day, mainly in the group of infected newborns with gestional age < 34 weeks, being this group, therefore, the one that would mostly benefit from an immunological support in front of and infection.

Exchange transfusion in newborn infants with perinatal hemolytic disease. Efficacy of the procedure.

A study was conducted on 115 full-term newborn infants with fetal-maternal ABO or Rh incompatibility submitted to exchange transfusion (EXT) due to hyperbilirubinemia. Donor blood was preserved in sodium citrate-sodium phosphate-dextrose-adenine (CPDA-1) and stored for a maximum of 48 hours. The volume of blood exchange was equivalent to two blood volumes of the infant and the procedure took approximately two hours. The following results were obtained with respect to bilirubins: 1) EXT let to a 44.03% reduction in indirect bilirubin in the ABO group and to a 43.40% reduction in the Rh group, thus demonstrating the efficacy of this procedure. 2) EXT was indicated earlier and in the presence of lower indirect bilirubin levels in the Rh group, which was also the group which required more frequent repetition of EXT (44.40% as opposed to 17.10% for the Rh group. 3) In both the ABO and Rh groups, the indirect bilirubin value that most closely approached the level for EXT indication was that obtained 3 hours post-EXT (least significant percent difference).