Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

Newborn infants have a high disposition to develop systemic inflammatory response syndromes (SIRSs) upon inflammatory or infectious challenges. Moreover, there is a considerable trafficking of hematopoietic cells to tissues already under noninflammatory conditions. These age-specific characteristics suggest a hitherto unappreciated crucial role of the vascular endothelium during the neonatal period. Here, we demonstrate that healthy neonates showed already strong endothelial baseline activation, which was mediated by a constitutively increased production of TNF-α. In mice, pharmacological inhibition of TNF-α directly after birth prevented subsequent fatal SIRS but completely abrogated the recruitment of leukocytes to sites of infection. Importantly, in healthy neonates, blocking TNF-α at birth disrupted the physiologic leukocyte trafficking, which resulted in persistently altered leukocyte profiles at barrier sites. Collectively, these data suggest that constitutive TNF-α-mediated sterile endothelial activation in newborn infants contributes to the increased risk of developing SIRS but is needed to ensure the postnatal recruitment of leukocytes to organs and interfaces.-Bickes, M. S., Pirr, S., Heinemann, A. S., Fehlhaber, B., Halle, S., Völlger, L., Willers, M., Richter, M., Böhne, C., Albrecht, M., Langer, M., Pfeifer, S., Jonigk, D., Vieten, G., Ure, B., von Kaisenberg, C., Förster, R., von Köckritz-Blickwede, M., Hansen, G., Viemann, D. Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

Antibiotic regimens for the empirical treatment of newborn infants with necrotising enterocolitis.

BACKGROUND: Although the exact aetiology of necrotising enterocolitis (NEC) remains unknown, research suggests that it is multifactorial; suspected pathophysiological mechanisms include immaturity, intestinal ischaemia, disruption of intestinal mucosal integrity, formula feeding, hyperosmolar load to the intestine, infection and bacterial translocation. Various antibiotic regimens have been widely used in the treatment of NEC. OBJECTIVES: To compare the efficacy of different antibiotic regimens on mortality and the need for surgery in neonates with NEC. SEARCH METHODS: Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2012), Oxford Database of Perinatal Trials, MEDLINE (1966 to February 2012), EMBASE (1980 to February 2012) and CINAHL (1982 to February 2012). SELECTION CRITERIA: All randomised and quasi-randomised controlled trials where antibiotic regimens were used for treatment of NEC. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion was assessed independently by each review author. The criteria and standard methods of the Cochrane Neonatal Review Group were used to assess the methodological quality of the included trials. MAIN RESULTS: Two trials met the inclusion criteria. Faix 1988 randomised 42 premature infants with radiological diagnosis of NEC. Infants were randomised to receive either intravenous ampicillin and gentamicin or ampicillin, gentamicin and clindamycin. Hansen 1980 randomised 20 infants with NEC to receive intravenous ampicillin and gentamicin with or without enteral gentamicin.In the study by Faix 1988, there were no statistical differences in mortality (RR 1.10; 95% CI 0.32 to 3.83) or bowel perforation (RR 2.20; 95% CI 0.45 to 10.74) between the two groups although there was a trend towards higher rate of strictures in the group that received clindamycin (RR 7.20; 95% CI 0.97 to 53.36).The Hansen 1980 study showed no statistically significant difference in death, bowel perforation or development of strictures. AUTHORS' CONCLUSIONS: There was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC. There were concerns about adverse effects following the usage of clindamycin, related to the development of strictures. To address this issue a large randomised controlled trial needs to be performed.

Long-chain polyunsaturated fatty acid supplementation in preterm infants.

BACKGROUND: The n-3 and n-6 essential fatty acids alpha linolenic acid (ALA) and linoleic acid (LA) are the precursors of the n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are essential nutrients for preterm infants, who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina. OBJECTIVES: The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to preterm infants. SEARCH STRATEGY: Trials were identified by MEDLINE (February 2007), Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007) and by checking reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed. DATA COLLECTION AND ANALYSIS: Fifteen randomised trials assessing the clinical effects of feeding formula supplemented with LCPUFA were included in the review. MAIN RESULTS: Of the fifteen randomised trials included in the review, four of these were not classified as of high quality, due to low follow-up, uncertainty regarding concealment of patient allocation and randomisation, and problems with assessment methodology. VISUAL ACUITY: Visual acuity over the first year was measured by Teller or Lea acuity cards in eight studies, by VEP in six studies and by ERG in two studies. Most studies found no significant differences in any visual assessment between supplemented and control infants. DEVELOPMENT: Most of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24 months post-term with three out of seven studies reporting some benefit of LCPUFA in different populations of supplemented infants at different postnatal ages. Meta-analysis of BSID of four studies at 12 months (N = 364) and three studies at 18 months (N = 494) post-term showed no significant effect of supplementation on neurodevelopment. Carlson 1992 and Carlson 1996 demonstrated lower novelty preferences (possibly predictive of lower intelligence) in the supplemented compared with the control group. The investigators however concluded that supplemented infants may have more rapid visual information processing given that they had more looks and each look was of shorter duration. GROWTH: Four out of thirteen studies reported benefits of LCPUFA on growth of supplemented infants at different postnatal ages. Two trials (Carlson 1992; Carlson 1996) suggested that LCPUFA supplemented infants grow less well than controls, possibly due to a reduction in AA levels that occurs when n-3 supplements are used without n-6 supplements. Recent trials with addition of AA to the supplement have reported no significant negative effect on growth. Fewtrell 2002 reported mild reductions in length and weight z scores at 18 months. Contrary to these results, meta-analysis of five studies (Uauy 1990; Carlson 1996; Hansen 1997; Vanderhoof 1999; Innis 2002) showed increased weight and length at two months post-term in supplemented infants. Meta-analysis of four studies at 12 months (N = 271) and two studies at 18 months (N = 396) post-term showed no significant effect of supplementation on weight, length or head circumference. SIDE EFFECTS: Uauy 1992 reported no significant effect of LCPUFA supplementation on bleeding time and red cell membrane fragility. AUTHORS' CONCLUSIONS: Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. When the results of the RCT's are pooled, no clear long-term benefits were demonstrated for infants receiving formula supplemented with LCPUFA. There was no evidence that supplementation of formula with n-3 and n-6 LCPUFA impaired the growth of preterm infants.

Longchain polyunsaturated fatty acid supplementation in preterm infants.

BACKGROUND: The n-3 and n-6 essential fatty acids alpha linolenic acid (ALA) and linoleic acid (LA) are the precursors of the n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are essential nutrients for preterm infants who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina. OBJECTIVES: The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to preterm infants. SEARCH STRATEGY: Trials were identified by MEDLINE (October 2003), Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003) and by checking reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed. DATA COLLECTION AND ANALYSIS: Eleven randomised trials assessing the clinical effects of feeding formula supplemented with LCPUFA were included in the review. MAIN RESULTS: Of the eleven randomised trials included in the review, two of these were not classified as of high quality despite blinded assessment and complete follow-up, due to problems with assessment methodology. VISUAL ACUITY: Visual acuity over the first year was measured by Teller acuity cards in six studies, by VEP in four studies and by ERG in two studies. Most studies found no significant differences in any visual assessment between supplemented and control infants. DEVELOPMENT: Most of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24 months postterm and shown no significant effect following supplementation. Meta-analysis of BSID of three studies (Fewtrell 2002, O'Connor 2001, van Wezel 2002) shows no significant effect of supplementation on development. Carlson 1993 and Carlson 1996 demonstrated lower novelty preferences (possibly predictive of lower intelligence) in the supplemented compared with the control group. The investigators however concluded that supplemented infants may have more rapid visual information processing given that they had more looks and each look was of shorter duration. GROWTH: Most trials have reported no significant effect of LCPUFA supplementation on growth of preterm infants. Two trials (Carlson 1993, Carlson 1996) suggest that LCPUFA supplemented infants grow less well than controls, possibly due to a reduction in AA levels which occurs when n-3 supplements are used without n-6 supplements. Recent trials with addition of AA to the supplement have reported no significant effect on growth. Fewtrell 2002 reported mild reductions in length and weight z scores at 18 months. Contrary to these results, the meta-analysis of five studies (Uauy 1992, Carlson 1996, Hansen 1997, Vanderhoof 1999, Innis 2002) showed increased weight and length at two months post-term in supplemented infants. SIDE EFFECTS: Uauy 1992 reported no significant effect of LCPUFA supplementation on bleeding time and red cell membrane fragility. REVIEWER'S CONCLUSIONS: Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. No long-term benefits were demonstrated for infants receiving formula supplemented with LCPUFA. There was no evidence that supplementation of formula with n-3 and n-6 LCPUFA impaired the growth of preterm infants.

Long-chain polyunsaturated fatty acid supplementation in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: The n-3 and n-6 essential fatty acids alpha linolenic acid and linoleic acid are the precursors of the n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are essential nutrients for preterm infants who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina. The aim of this review is to assess whether supplementation of infant formula with LCPUFA is safe and of benefit to preterm infants. SEARCH STRATEGY: Trials were identified by MEDLINE and by checking reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed. DATA COLLECTION AND ANALYSIS: Eight randomised trials were identified. Five were assessed as being of high quality and one is awaiting assessment. Problems with the remaining two included a change in assessment methodology mid-study (Memphis 1996) and assessment methodology that deviated from generally accepted international standards (Bologna 1996). MAIN RESULTS: Studies from Dallas (Uauy et al 1990, Birch et al 1992, Hoffman & Uauy 1992, Uauy et al 1994) and Memphis (Carlson et al 1991, Carlson et al 1992, Carlson et al 1993, Werkman & Carlson 1996) suggest that early visual development is better in formula-fed infants who receive a LCPUFA supplement compared with those fed standard formula. However, the effects were not long-term, with no differences detected between groups after 4 months of age. The Bologna group (Fadelli et al 1996) reported some differences in the visual evoked potential at 3 months post-term but their methodology was questionable making interpretation of the data difficult. In the largest study (the Mead Johnson study, Hansen et al 1997), no difference in visual acuity was demonstrated between LCPUFA supplemented and control infants at 2 and 4 months post-term. The Memphis studies used the Fagan Infantest (Fagan 1970) to measure infant development and demonstrated lower novelty preferences (possibly predictive of lower intelligence) in preterm infants supplemented with LCPUFA. However, the supplemented infants had more looks at the novel stimulus and each look was of shorter duration which may represent more rapid visual information processing. Normalised weight (expressed as SD from the mean for age) was lower in preterm infants who were fed supplemented formula in the Memphis studies. No difference in growth between supplemented and control infants was documented in the Dallas, Bologna, Alberta (Clandinin et al 1997) and Wyeth (Vanderhoof et al 1997) studies while the Mead Johnson study documented higher weights in supplemented infants compared with controls at two months post-term. The Dallas study documented little effect of LCPUFA supplements on bleeding time and membrane fragility. REVIEWER'S CONCLUSIONS: No long-term benefit has been demonstrated for preterm infants receiving formula supplemented with LCPUFA. There is some evidence that n-3 LCPUFA supplementation of formula increases the early rate of visual maturation in preterm infants. Supplementation of formula with n-3 and n-6 LCPUFA does not impair the growth of preterm infants.

Avaliaçäo antropométrica e perfil plasmático de ácidos graxos de recém-nascidos pré-termo submetidos a duas dietas isocalóricas e com diferentes composiçoes lipídicas / Anthropometric evaluation and plasm fatty acids profile of preterm newborn infants subjected 2 isocaloric diets of different lipid composition

Este trabalho analisou o perfil de ácidos graxos plamáticos eo crescimento somático de 20 recém-nascidos pré-termos, com idade gestacional entre 30 a 35 semanas, admitidos no Berçário do Hospital das Clínicas da Faculdade de Medicina de Ribeiräo Preto da Universidade de Säo Paulo, submetidos, por um período de aproximadamente 20 dias, a duas dietas isocalóricas e com diferentes composiçöes liídicas. Um grupo de 10 crianças GRUPO L.D.S. usou uma dieta contendo 0,5% das calorias totais (54,5 mg/100 cal) como ácido linoléico (C18:2) e relaçäo PS=0,053. Os outros 10 recém-nascidos GRUPO L.D.O. foram colocados numa dieta contendo 10,5% das calorias totais (1171mg/100 kcal) como ácido linoléico (C18:2) e a relaçäo P/S = 0,508. Os grupos no período imediato antes da instituiçäo das dietas em estudo apresentaram valores plasmáticos dos ácidos linoléico (C18:2) e aracdônico (20:4) semelhantes entre si e superiores aos limites mínimos normais estabelecidos por WIESE etalii (1958) e HANSEN ET ALII (1963), refletindo reservas corporais e dietas semelhantes previamente ao estudo. Após o uso da dieta no GRUPO L.D.S. houve uma queda significante (p < 0,05) dos níveis plasmáticos ácidos C16:0 (palmítico), C16:1 (palmitoléico) e C18:1 (oléico) se elevaram significantemente (p < 0,05). As alteraçöes encontradas foram semelhantes as relatadas em diversos trabalhos da literatura e poderiam ser considerados como evidências bioquímicas de deficiência de ácidos graxos essenciais. No GRUPO L.D.O. após o uso da dieta verificamos uma queda nos níveis plasmáticos do ácido aracdônico (C20:4 a níveis inferiores aos mínimos normais estabelecidos na literatura em 90% dos recém-nascidos pré-termos, mas a queda foi menor do que a verificada no GRUPO L.D.S. (p < 0,,5). O ácido linoléico (C18:2) apresentou elevaçäo no seu nível plasmático em 50% dos pré-termos estudados e nos outros 50% os valores foram semelhantes ou ligeiramente inferiores ao período prédieta, mas todos apresentaram níveis superiores aos limites mínimos normais e aos do GRUPO L.D.S. (p , 0,05). Os niveis plasmticos elevados de C18:2 no GRUPO L.D.O. após o uso da dieta com elevado conteúdo de ácido linoléico concordam com a melhor absorçäo de gorduras verificada neste grupo em relaçäo ao GRUPO L.D.S. (p < 0,05)...

Hanseniase e gravidez: prognostico materno-fetal / ?

O autor estudou 196 gestacoes em 151 pacientes com hanseniase, no Hospital Padre Bento, Guarulhos, da Secretaria da Saude de Sao Paulo, no periodo de janeiro de 1965 a junho de 1984. As pacientes foram seguidas no ambulatorio de Pre-Natal deste hospital e internadas quando apresentaram complicacoes da gravidez ou da hanseniase. A morbidade materna foi aumentada na hanseniase pelas altas prevalencias de anemia, infeccao urinaria, infeccao puerperal, amniorrexe prematura, dibates mellitus e hipertensao arterial. A morbidade perinatal foi aumentada na hanseniase pelas altas prevalencias de prematuridade (27,84 por cento), de baixo peso (39,93 por cento) e infeccao neo-natal (8,52 por cento). A incidencia de parto cesareo foi aumentada (51,43 por cento). A associacao hanseniase e gravidez e de alto risco, necessitando pre-natal cuidadoso e correto acompanhamento clinco-obstetrico e pediatrico