RESUMO
OBJECTIVE: This study aimed to compare the efficacy of osteopathic manipulative therapy (OMTh) versus light touch therapy (LTT) in reducing cranial asymmetries in infants with nonsynostotic plagiocephaly (NSP). STUDY DESIGN: A prospective, parallel-group, single-center, LTT-controlled randomized clinical trial was conducted in the Department of Neonatology of Sant'Anna Hospital in Turin, Italy, from September 6, 2016 to February 20, 2020. We enrolled infants of 1 to 6 months of age with NSP, who were then randomly assigned to the study group (repositioning therapy plus six sessions of OMTh) or the control group (repositioning therapy plus six sessions of LTT). The outcome was the reduction of the oblique diameter difference index (ODDI) score <104%, which was assessed at the end of the intervention protocol (at 3 months) and at 1 year of age. RESULTS: A total of 96 infants were randomized, 48 in the OMTh group and 48 in the LTT group, with mean ages of 3.1 versus 3.2 months, and baseline ODDI score of 110.2 versus 108.7%. In the OMTh group, a significant reduction of the ODDI score <104%, compared with the LTT group, was observed in the intension-to-treat (ITT) and per-protocol (PP) analyses. The ITT analysis revealed an ODDI score <104% in the OMTh group at 3 months (risk difference: 0.41; 95% confidence interval [CI]: 0.25-0.53; p < 0.001) and at the follow-up at 1 year of age (risk difference: 0.47; 95% CI: 0.31-0.64; p < 0.001). The PP analysis at 3 months reported a risk difference of 0.44 (95% CI: 0.27-0.60; p < 0.001), and at 1 year of age, a risk difference of 0.54 (95% CI: 0.36-0.72; p < 0.001). CONCLUSION: In infants with NSP, a course of six OMTh sessions significantly reduced cranial asymmetries at both the 3-month and 1-year follow-up assessments, compared with LTT. This study is registered with ClinicalTrial.gov (identifier: NCT03970395; www. CLINICALTRIALS: gov ). KEY POINTS: · OMTh plus repositioning therapy significantly decreased the risk and severity of NSP compared with LTT.. · OMTh reduced mild and moderate cranial asymmetries.. · The role of OMTh in severe cranial asymmetries should be investigated in a multicenter trial..
Assuntos
Osteopatia , Plagiocefalia não Sinostótica , Humanos , Lactente , Osteopatia/métodos , Plagiocefalia não Sinostótica/terapia , Estudos Prospectivos , Fototerapia , Itália , Resultado do TratamentoRESUMO
OBJECTIVE: We analyzed the fungal ecology of a neonatal intensive care unit (NICU) over a period of 20 consecutive years following the introduction of routine fluconazole prophylaxis for all very low birth weight (VLBW; <1,500 g at birth) preterm babies. The aim was to detect the possible appearance of any ecological shifts toward the emergence of native fluconazole-resistant (NFR) fungal species. STUDY DESIGN: This was a retrospective analysis of clinical and microbiological data of VLBW preterm neonates admitted to a large tertiary NICU in Italy from 1997 to 2016 and surviving more than 3 days. Colonization and infection incidence rates, both for fluconazole-sensitive Candida spp and NFR Candida spp, were calculated for each year. We compared the first 4-year period without prophylaxis (1997-2000) with the last 16-year period with use of routine fluconazole prophylaxis (2000-2016). RESULTS: Overall, the incidence of fungal colonization significantly decreased after the introduction of prophylaxis (from 43.4% to 16.5%) as well as the systemic fungal infection incidence (from 16% to 3.7%). The proportion of colonization and infection by NFR Candida spp, on the other hand, did not increase, remaining stable throughout the 16 years of exposure to fluconazole. During the prophylaxis period, 42 of 1,172 VLBW neonates were colonized by NFR species (3.6%), and of them 11 developed a systemic infection (0.9%). During the preprophylaxis period, colonization by these particular species affected 11 of 285 VLBW neonates (3.8%), and a systemic infection involved 4 neonates (1.4%). CONCLUSION: Fluconazole prophylaxis is effective in decreasing Candida colonization and systemic infections in preterm neonates in NICU and did not cause emergence or shifts toward NFR Candida spp over a 16-year surveillance period.
Assuntos
Antifúngicos/uso terapêutico , Candida/isolamento & purificação , Candidíase/prevenção & controle , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Doenças do Prematuro/prevenção & controle , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Candida/efeitos dos fármacos , Candidíase/diagnóstico , Candidíase/epidemiologia , Contagem de Colônia Microbiana , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Itália , Masculino , Testes de Sensibilidade Microbiana , Estudos RetrospectivosRESUMO
BACKGROUND: Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. AIM: To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. STUDY DESIGN: This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. RESULTS: (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). CONCLUSION: Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS.
Assuntos
Anti-Infecciosos/uso terapêutico , Fórmulas Infantis/química , Doenças do Prematuro/prevenção & controle , Recém-Nascido Prematuro , Lactoferrina/uso terapêutico , Leite Humano/química , Sepse/prevenção & controle , Animais , Bovinos , Humanos , Recém-Nascido , Modelos Logísticos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. STUDY DESIGN: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. RESULTS: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. CONCLUSION: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. TRIAL REGISTRATION: isrctn.org: ISRCTN53107700.
Assuntos
Enterocolite Necrosante/prevenção & controle , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Lactoferrina/administração & dosagem , Probióticos/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Sepse/prevenção & controle , Administração Oral , Suplementos Nutricionais , Enterocolite Necrosante/epidemiologia , Ácido Gástrico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Itália , Lacticaseibacillus rhamnosus , Nova Zelândia , Fatores de Risco , Sepse/epidemiologiaRESUMO
Decline and resurgence of breastfeeding (BF) characterized last century. Several factors influencing BF outcome were identified. Despite the huge literature on BF, no data on its matrilineal transmission are available. BF practice was prospectively followed in 2546 Italian mothers. Lactation and BF outcome were related, besides to known factors interfering with BF, to the occurrence of previous maternal and paternal BF. Recalls of grandmaternal and grand-grandmaternal BF behaviours allowed the construction of familiar pedigrees of BF across three generations. Having been breastfed was the strongest factor addressing successful BF establishment (odds ratio (OR) 9.33; 95% confidence interval (CI) 7.40-11.84; p < 0.0001) and BF duration (at 6 months: OR 3.79; 95% CI 3.11-4.64; p < 0.0001). The hazard ratio for breastfed vs non-breastfed mothers was 0.46 (95% CI 0.41-0.50; log-rank p < 0.0001). The rate of BF failures was fivefold higher in non-breastfed mothers, mostly occurring during lactogenesis when the let-down reflex becomes essential. CONCLUSION: At any generation, mothers are likely to have daughters repeating their BF experience. Differently from the intergenerational effects of environmental factors responsible for the BF secular trend, this trait is transgenerationally transmitted and reversible, with temporal and clinical features of lactation failure. Accordingly, we speculate that epigenetic mechanisms might alter offspring's oxytocinergic receptor signalling. WHAT IS KNOWN: Several cultural and socio-demographic factors are known to influence breastfeeding outcome. The generational effects of breastfeeding itself have not been investigated so far. WHAT IS NEW: Maternal breastfeeding is the most important factor addressing daughters' breastfeeding outcome. This behavior is transmitted transgenerationally, with features suggesting epigenetic mechanisms.
Assuntos
Aleitamento Materno/estatística & dados numéricos , Adulto , Epigenômica , Feminino , Humanos , Itália , Lactação/fisiologia , Linhagem , Estudos ProspectivosRESUMO
Osteopathic medicine is a form of complementary and alternative medicine. Osteopathic practitioners treat patients of all ages: according to the Osteopathic International Alliance's 2012 survey, about one-third of all treated patients are aged between 31 and 50 years and nearly a quarter (23.4%) are pediatric patients, with 8.7% of them being younger than 2 years. In 2013 a systematic review evaluated the effectiveness of osteopathic manipulative treatment (OMT) in pediatric patients with different underlying disorders, but due to the paucity and low methodological quality of the primary studies the results were inconclusive. The aim of this review is therefore to update the evidence concerning OMT in perinatal and pediatric disorders and to assess its clinical impact. Most published studies favor OMT, but the generally small sample sizes in these studies cannot support ultimate conclusions about the efficacy of osteopathic therapy in pediatric age. In turn, clinical trials of OMT in premature infants might represent an important step in the osteopathic research because they can address both cost-effectiveness issues, and an innovative, multidisciplinary approach to the management of specific pediatric diseases cared for by the same, common health care system. The available studies in neonatal settings provide evidence that OMT is effective in reducing the hospital length of stay of the treated infants, therefore, suggesting that robust cost-effectiveness analyses should be included in the future clinical trials' design to establish new possible OMT-shared strategies within the health care services provided to newborns.
Assuntos
Cólica/terapia , Recém-Nascido Prematuro , Osteopatia/métodos , Plagiocefalia não Sinostótica/terapia , Análise Custo-Benefício , Humanos , Lactente , Recém-Nascido , Medicina Osteopática , Pediatria , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Human milk feeding protects against oxidative stress-induced damage in preterm neonates, including severe multifactorial diseases such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). The carotenoids, which are not found in formula milk, might play a key role in these actions. METHODS: A multicenter, double-blind, randomized controlled trial was conducted in three tertiary Italian neonatal intensive care units. All preterm infants < 32(+6) weeks' gestational age were eligible and were randomized to a single, oral, daily 0.5-mL dose of carotenoid supplementation (0.14 mg lutein + 0.0006 mg zeaxanthin) or placebo (5% glucose solution) from birth till 36 weeks' corrected gestational age. Primary outcomes were threshold ROP, NEC > second stage, and BPD. Surveillance for detection of these diseases and for intolerance/adverse effects was performed. RESULTS: No treatment-related adverse effect was documented in the 229 analyzed infants, whose clinical/demographical characteristics were similar in the two groups. Threshold ROP incidence did not significantly differ in treated (6.2%) versus not treated infants (10.3%; p = 0.18). The same occurred for NEC (1.7% versus 5.1%; p = 0.15) and BPD (4.5% versus 10.3%; p = 0.07). Noteworthy, the progression rate from early ROP stages to threshold ROP was decreased by 50% (0.30 versus 0.44; p = 0.23). CONCLUSION: Lutein/zeaxanthin supplementation in preterm infants is well tolerated. No significant effect was seen on threshold ROP, NEC, or BPD. The decreasing trends of these outcomes in the treatment group need to be assessed and confirmed on larger sample-sizes.
Assuntos
Displasia Broncopulmonar/prevenção & controle , Suplementos Nutricionais , Enterocolite Necrosante/prevenção & controle , Luteína/uso terapêutico , Retinopatia da Prematuridade/prevenção & controle , Xantofilas/uso terapêutico , Progressão da Doença , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Terapia Intensiva Neonatal , Luteína/efeitos adversos , Masculino , Xantofilas/efeitos adversos , ZeaxantinasRESUMO
Neonatal sepsis causes a huge burden of morbidity and mortality and includes bloodstream, urine, cerebrospinal, peritoneal, and lung infections as well as infections starting from burns and wounds, or from any other usually sterile sites. It is associated with cytokine - and biomediator-induced disorders of respiratory, hemodynamic, and metabolic processes. Neonates in the neonatal intensive care unit feature many specific risk factors for bacterial and fungal sepsis. Loss of gut commensals such as Bifidobacteria and Lactobacilli spp., as occurs with prolonged antibiotic treatments, delayed enteral feeding, or nursing in incubators, translates into proliferation of pathogenic microflora and abnormal gut colonization. Prompt diagnosis and effective treatment do not protect septic neonates form the risk of late neurodevelopmental impairment in the survivors. Thus prevention of bacterial and fungal infection is crucial in these settings of unique patients. In this view, improving neonatal management is a key step, and this includes promotion of breast-feeding and hygiene measures, adoption of a cautious central venous catheter policy, enhancement of the enteric microbiota composition with the supplementation of probiotics, and medical stewardship concerning H2 blockers with restriction of their use. Additional measures may include the use of lactoferrin, fluconazole, and nystatin and specific measures to prevent ventilator associated pneumonia.
Assuntos
Infecção Hospitalar/prevenção & controle , Unidades de Terapia Intensiva Neonatal , Sepse/prevenção & controle , Anti-Infecciosos/uso terapêutico , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/normas , Contraindicações , Fluconazol/uso terapêutico , Antagonistas dos Receptores H2 da Histamina , Humanos , Recém-Nascido , Lactoferrina/uso terapêutico , Leite Humano , Nistatina/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Probióticos/uso terapêuticoRESUMO
BACKGROUND: Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates. METHODS: During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing. RESULTS: Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect. CONCLUSIONS: Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).
Assuntos
Antifúngicos/uso terapêutico , Candidíase/prevenção & controle , Fluconazol/uso terapêutico , Doenças do Prematuro/prevenção & controle , Recém-Nascido de muito Baixo Peso , Candida/isolamento & purificação , Candidíase/epidemiologia , Candidíase/mortalidade , Colestase/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Masculino , Testes de Sensibilidade MicrobianaRESUMO
An episode of sepsis occurs in 20 to 40% of all preterm patients, and such figures have been reported constantly increasing in Neonatal Intensive Care Units. Neonatal sepsis include bloodstream, urine, cerebrospinal, peritoneal infections, infections starting from burns and wounds, or from any other usually sterile sites. Many specific risk factors account for the increased risk of sepsis, including employment of broad-spectrum antibiotics selecting resistant microflora, parenteral nutrition, acid inhibitors and steroids, as well as the systematic and long-lasting use of invasive management. In preterm neonates, loss of gut commensals such as bifidobacteria and lactobacilli, due to the difficulties in oral feeding, or a slower acquisition of them, translates into an increased susceptibility to pathogenic gut colonization. Prompt diagnosis, effective treatment, and specific prophylaxis with antibacterial and antifungal drugs are the milestones of management of these life-threatening events. This article discusses the recent advances in prevention and shows how fluconazole for prevention of fungal sepsis, probiotics for prevention of necrotizing enterocolitis, and bovine lactoferrin for prevention of bacterial sepsis may be considered as effective preventive strategies.
Assuntos
Doenças do Prematuro/prevenção & controle , Sepse/prevenção & controle , Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Humanos , Recém-Nascido , Lactoferrina/uso terapêutico , Probióticos/uso terapêuticoRESUMO
The aim of this study is to evaluate the possibility of increasing the use of standardised parenteral nutrition (PN) as a replacement of individualized parenteral nutrition in the neonatal intensive care unit (NICU). The standardisation of the PN formulations has the potential to improve nutrient intakes, quality control, cost effectiveness and reduce prescription errors. In our hospital the individualized PN solutions are made by Chemists for premature babies born during the working days. We have been using standardised PN formulations for about two years for the preterm infants born during the weekend. The use of SPN is currently limited to the weekend, until our Chemists can prepare the IPN.In this study we describe the case of a sick low birth weight baby for whom we used for the first time the bags of a standardised PN "ready to use" since the sixth day of life for thirteen consecutive days. The baby was not a very low birth weight, but he needed parenteral nutrition because he was relatively unstable and he had a poor feeding tolerance. As result of the study, the baby growth was regular and the SPN were well tolerated. No adverse effects were reported.
Assuntos
Recém-Nascido Prematuro , Nutrição Parenteral , Ingestão de Alimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Masculino , Nutrição Parenteral/efeitos adversos , Soluções de Nutrição Parenteral/administração & dosagem , Soluções de Nutrição Parenteral/efeitos adversosRESUMO
BACKGROUND: It is controversial whether thrombocytopenia is suggestive of one (or more) causative agents of neonatal sepsis: a low platelet count has been related in turn to Gram-positive, Gram-negative or fungal sepsis. METHODS: A retrospective, cohort study on 514 very low-birthweight (VLBW) neonates admitted over a 9 year period to a large tertiary neonatal intensive care unit (NICU) in Italy was carried out. Through database search, data on platelet counts, sepsis, clinical course, and microbiological culture were collected and analyzed. Statistical analysis was performed to look for significant association between thrombocytopenia and sepsis caused by different (Gram-positive, Gram-negative or fungal) organisms. RESULTS: Sepsis diagnosed on microbiological criteria occurred in 197 of 514 VLBW neonates (38.3%), and thrombocytopenia (at least one finding of platelet count <80,000/mm(3)) was detected in 34 (17.2%) of the 197 septic infants. Thrombocytopenia occurred in 10 of 51 neonates with fungal sepsis (19.6%), and in 24 of 146 with bacterial sepsis (16.4%; P = 0.37). The difference was not significant when clustering for sepsis caused by Gram-positive (nine thrombocytopenic of 51 with Gram-positive sepsis, 17.6%; P = 0.40) and Gram-negative organisms (15/95, 15.7%; P = 0.22), or when considering only coagulase-negative Staphylococcus sepsis (6/37, 16.2%; P = 0.25). CONCLUSIONS: In contrast with previous reports, thrombocytopenia might not be an organism-specific marker of sepsis. Caution should be maintained in relating a low platelet count to any infectious agent (or group of agents) in preterm VLBW neonates.
Assuntos
Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Positivas/sangue , Recém-Nascido de muito Baixo Peso , Sepse/microbiologia , Trombocitopenia/microbiologia , Candidíase/sangue , Candidíase/epidemiologia , Comorbidade , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Contagem de Plaquetas , Estudos Retrospectivos , Sepse/sangue , Sepse/epidemiologia , Trombocitopenia/epidemiologiaRESUMO
CONTEXT: Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants. OBJECTIVE: To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates. DESIGN, SETTING, AND PATIENTS: Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis. INTERVENTION: Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates <1000 g at birth). MAIN OUTCOME MEASURE: First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid. RESULTS: Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred. CONCLUSION: Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN53107700.
Assuntos
Doenças do Prematuro/prevenção & controle , Recém-Nascido de muito Baixo Peso , Lacticaseibacillus rhamnosus , Lactoferrina/administração & dosagem , Probióticos/uso terapêutico , Sepse/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Terapia Intensiva Neonatal , Modelos Logísticos , Masculino , Fatores de Risco , Sepse/mortalidadeRESUMO
BACKGROUND: We have previously demonstrated efficacy against fungal colonization and infection of fluconazole prophylaxis that was routinely administered since 2001 in our ICU for preterm infants <1500 g at birth (VLBW). With prolonged use, concerns exist for the emergence of acquired fungal resistance and of Candida subspecies that are natively fluconazole-resistant (NFR), mostly Candida glabrata and Candida krusei. METHODS: We evaluated retrospectively all clinical and surveillance fungal isolates obtained from VLBW infants in our NICU during a 10-year period (1997-2006). Each fungal isolate was speciated, infants colonized or infected with NFR-Candida spp were identified and the incidence rates of colonization and infection by these fungal species were calculated. A comparison was made of the 6-year (2001-2006) prophylaxis period with the 4-year (1997-2000) preprophylaxis period. RESULTS: Overall, colonization by NFR-Candida spp ranged between 2.8% and 6.6% of VLBW infants yearly admitted, without any increasing trend during the study period. There were 18 of 434 (4.1%) neonates colonized by these species. Five episodes of systemic fungal infections caused by NFR-Candida spp occurred (incidence rate, 1.1%). No significant differences were detected when compared with the preprophylaxis period, when 11 of 295 infants (3.7%) were colonized by NFR-Candida spp and 4 episodes of infection occurred (1.4%) (P = 0.84 and 0.76, respectively). CONCLUSIONS: Fluconazole prophylaxis administered to VLBW neonates in 4- to 6-week courses after birth does not lead to the emergence of natively fluconazole-resistant Candida spp.
Assuntos
Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/prevenção & controle , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Doenças do Prematuro/prevenção & controle , Unidades de Terapia Intensiva Neonatal , Candida/classificação , Candidíase/microbiologia , Quimioprevenção , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/microbiologia , Recém-Nascido de muito Baixo Peso , Masculino , Testes de Sensibilidade MicrobianaRESUMO
Neutropenia is a major risk factor for bacterial colonization and sepsis in preterm neonates in the neonatal intensive care unit (NICU), but little is known about its relationships with candidal colonization (CC) in these settings. We performed a case-control study on neonates with birth weight of <1500 g admitted to our NICU during a 7-year period (1996-2003, N = 585). Through database search, infants with early-onset neutropenia (EON) (n = 68, group A) were identified and 1:1 matched with controls without EON (n = 68, group B). Microbiologic data from weekly surveillance cultures were examined to determine the presence and intensity of CC. Groups A and B were similar clinically and demographically. All group A neonates recovered from EON before the 8th day of life. Incidence of CC in the 1st month of life (at least 1 site) was significantly higher in group A (61.8% versus 35.3%, P = 0.002) and was not modified by treatment with recombinant granulocyte colony-stimulating factor. The same was true of CC intensity, expressed as the number of sites affected (P = 0.002). Incidence of candidal sepsis, mortality rates, and relative frequencies of the various subspecies of Candida among the isolates did not significantly differ between the 2 groups. In conclusion, EON in preterm neonates is a significant, independent risk factor for CC. Larger, prospective, adequately powered studies should verify whether increased CC related to neutropenia may translate into a similar increased occurrence of candidal sepsis in these settings.
Assuntos
Candidíase , Doenças do Prematuro , Recém-Nascido de muito Baixo Peso , Neutropenia/complicações , Candida/crescimento & desenvolvimento , Candidíase/epidemiologia , Candidíase/microbiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/microbiologia , Unidades de Terapia Intensiva Neonatal , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease with evidence of many associated risk factors. Erythropoietin has been reported to be associated with this disorder in a murine model, as well as in humans in some single-center reports. We reviewed the data from two large tertiary NICUs in Italy to test the hypothesis that the use of erythropoietin may be associated with the development of the most severe stages of ROP in extremely low birth weight (ELBW) neonates. DESIGN/METHODS: Retrospective study by review of patient charts and eye examination index cards on infants with birth weight <1000g admitted to two large tertiary NICUs in Northern Italy (Sant'Anna Hospital NICU in Torino, and Ca' Foncello Hospital Neonatology in Treviso) in the years 2005 to 2007. Standard protocol of administration of EPO in the two NICUs consisted of 250 UI/kg three times a week for 6-week courses (4-week in 1001-1500g infants). Univariate analysis was performed to assess whether the use of EPO was associated with severe (threshold) ROP. A control, multivariate statistical analysis was performed by entering into a logistic regression model a number of neonatal and perinatal variables that - in univariate analysis - had been associated with threshold ROP. RESULTS: During the study period, 211 ELBW infants were born at the two facilities and survived till discharge. Complete data were obtained for 197 of them. Threshold retinopathy of prematurity occurred in 26.9% (29 of 108) of ELBW infants who received erythropoietin therapy, as compared with 13.5% (12 of 89) of those who did not receive erythropoietin (OR 2.35; 95% CI 1.121-4.949; p=0.02 in univariate analysis, and p=0.04 at multivariate logistic regression after controlling for the following variables: birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, vaginal delivery). Use of erythropoietin was not significantly associated with other major sequelae of prematurity (intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis). © 2014 Elsevier Ireland Ltd. All rights reserved. CONCLUSIONS: Use of erythropoietin is an additional, independent predictor of threshold ROP in ELBW neonates. Larger prospective, population-based studies should further clarify the extent of this association.
Assuntos
Eritropoetina/efeitos adversos , Retinopatia da Prematuridade/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Itália , Masculino , Retinopatia da Prematuridade/diagnóstico , Estudos RetrospectivosRESUMO
The diagnosis of congenital CMV is usually guided by a number of specific symptoms and findings. Unusual presentations may occur and diagnosis is challenging due to uncommon or rare features. Here we report the case of two preterm, extremely low birthweight, 28-week gestational age old twin neonates with CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN). They were born to a HIV-positive mother, hence they underwent treatment with zidovudine since birth. Both infants featured severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support, with full recovery after 2 months. Treatment with ganciclovir was not feasible due the concomitant treatment with zidovudine and the risk of severe, fatal toxicity. Therefore administration of intravenous hyperimmune anti-CMV immunoglobulin therapy was initiated. Severe lung involvement at birth and subsequent pulmonary hypertension are rarely described in preterm infants as early manifestations of CMV congenital disease. In the two twin siblings here described, the extreme prematurity and the treatment with zidovudine likely worsened immunosuppression and ultimately required a complex management of the CMV-associated lung involvement.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Hipertensão Pulmonar/diagnóstico , Adulto , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Feminino , Humanos , Hipertensão Pulmonar/complicações , Recém-Nascido , Recém-Nascido Prematuro , GêmeosRESUMO
IMPORTANCE: NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW, <1500 g at birth). Probiotics including lactobacillus rhamnosus GG (LGG) proved effective in preventing NEC in preterm infants in several RCTs. OBJECTIVE: Lactoferrin, a mammalian milk glycoprotein involved in innate immune host defences, can reduce the incidence of NEC in animal models, and its action is enhanced by LGG. We tried to assess whether bovine lactoferrin (BLF), alone or with the probiotic LGG, has a similar effect in human infants, something that has not yet been studied. DESIGN: An international, multicenter, randomized, double-blind, placebo-controlled trial conducted from October 1st, 2007 through July 31st, 2010. SETTING: Thirteen Italian and New Zealand tertiary neonatal intensive care units. PARTICIPANTS: 743 VLBW neonates were assessed until discharge for development of NEC. INTERVENTION: Infants were randomly assigned to receive orally either BLF (100 mg/day) alone (group LF; n = 247) or with LGG (at 6×10(9) CFU/day; group BLF + LGG; n = 238), or placebo (Control group; n = 258) from birth until day 30 of life (45 for neonates <1000 g at birth). MAIN OUTCOME MEASURES: ≥ stage 2 NEC; death-and/or-≥ stage 2 NEC prior to discharge. RESULTS: Demographics, clinical and management characteristics of the 3 groups were similar, including type of feeding and maternal milk intakes. NEC incidence was significantly lower in groups BLF and BLF + LGG [5/247 (2.0%)] and 0/238 (0%), respectively] than in controls [14/258 (5.4%)] (RR = 0.37; 95% CI: 0.136-1.005; p = 0.055 for BLF vs. control; RR = 0.00; p < 0.001 for BLF + LGG vs. control). The incidence of death-and/or-NEC was significantly lower in both treatment groups (4.0% and 3.8% in BLF and BLF + LGG vs. 10.1% in control; RR = 0.39; 95% CI: 0.19-0.80; p = 0.008. RR = 0.37; 95% CI: 0.18-0.77; p = 0.006, respectively). No adverse effects or intolerances to treatment occurred. CONCLUSIONS AND RELEVANCE: Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death-and/or ≥ stage 2 NEC in VLBW neonates. BLF might be a promising strategy to prevent NEC in NICU settings. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical settings. TRIAL REGISTRATION: ISRCTN53107700-http://www.controlled-_trials.com/ISRCTN53107700.