Weight and neuro-psycho-motor development in children discharged from neonatal intensive care unit

Background: Low birth weight affects child growth and development, requiring the intensive use of health services. There are conversely proportional associations between prematurity and academic performance around the world. In this study we evaluated factors involved in weight and neuropsychomotor profile in one and two years old discharged from Intensive Care Units (ICU). Methods/Design: We investigated 203 children from the ICU who were followed for 24 +/- 4 months. The research was conducted by collecting data from medical records of patients in a Follow-up program. We investigated the following variables: inadequate weight at one year old; inadequate weight at two years old and a severe neurological disorder at two years old. Results: We observed increase of almost 20% in the proportion of children which weighted between the 10th and 90th percentiles and decrease of around 40% of children below the 15th percentile, from one to two years old. In almost 60% of the cases neuropsychomotor development was normal at 2 years old, less than 15% of children presented abnormal development. Variables that remained influential for clinical outcome at 1 and 2 years old were related to birth weight and gestational age, except for hypoglycemia. Neurological examination was the most influential variable for severe neurological disturbance. Conclusion: Hypoglycemia was considered a new fact to explain inadequate weight. The results, new in Brazil and difficult in terms of comparison, could be used to identify risk factors and for a better approach of newborn discharged from ICUs.

Does the neonatal clinical risk for illness severity influence pain reactivity and recovery in preterm infants?

Background: The biobehavioural pain reactivity and recovery of preterm infants in the neonatal period may reflect the capacity of the central nervous system to regulate neurobiological development. Objective: The aim of the present study was to analyse the influence of the neonatal clinical risk for illness severity on biobehavioural pain reactivity in preterm infants. Methods: Fifty-two preterm infants were allocated into two groups according to neonatal severity of illness, as measured by the Clinical Risk Index for Babies (CRIB). The low clinical risk (LCr) group included 30 neonates with CRIB scores <4, and the high clinical risk (HCr) group included 22 neonates with CRIB scores >= 4. Pain reactivity was assessed during a blood collection, which was divided into five phases (baseline, antisepsis, puncture, recovery-dressing and recovery-resting). Behavioral pain reactivity was measured using the scores, and magnitude of responses in Neonatal Facial Coding System (NFCS) and Sleep-Wake States Scale (SWS). The heart rate was continuously recorded. Results: The HCr demonstrated a higher magnitude of response on the SWS score from the baseline to the puncture phase than the LCr. Also, the HCr exhibited a higher mean heart rate and minimum heart rate than the LCr in the recovery-resting phase. In addition, the HCr exhibited a higher minimum heart rate from the baseline to the recovery-resting phase than the LCr. Conclusion: The infants exhibiting a high neonatal clinical risk showed high arousal during the puncture procedure and higher physiological reactivity in the recovery phase.

Etiological diagnosis reduces the use of antibiotics in infants with bronchiolitis

OBJECTIVE: Acute bronchiolitis is a leading cause of infant hospitalization and is most commonly caused by respiratory syncytial virus. Etiological tests are not required for its diagnosis, but the influence of viral screening on the therapeutic approach for acute bronchiolitis remains unclear. METHODS: A historical cohort was performed to assess the impact of viral screening on drug prescriptions. The study included infants up to one year of age who were hospitalized for bronchiolitis. Virus screening was performed using immunofluorescence assays in nasopharyngeal aspirates. The clinical data were obtained from the patients' medical records. Therapeutic changes were considered to be associated with viral screening when made within 24 hours of the release of the results. RESULTS: The frequency of prescriptions for beta agonists, corticosteroids and antibiotics was high at the time of admission and was similar among the 230 patients. The diagnosis of pneumonia and otitis was associated with the introduction of antibiotics but did not influence antibiotics maintenance after the results of the virus screening were obtained. Changes in the prescriptions were more frequent for the respiratory syncytial virus patients compared to patients who had negative viral screening results (p=0.004), especially the discontinuation of antibiotics (p<0.001). The identification of respiratory syncytial virus was associated with the suspension of antibiotics (p=0.003), even after adjusting for confounding variables (p=0.004); however, it did not influence the suspension of beta-agonists or corticosteroids. CONCLUSION: The identification of respiratory syncytial virus in infants with bronchiolitis was independently associated with the discontinuation of antibiotics during hospitalization.

N-glycome profiling of Bothrops jararaca newborn and adult venoms

Glycosylation is an important post-translational modification of snake venom proteins and contributes to venom proteome complexity. Many snake venom components are known to be glycosylated, however, very little is known about the carbohydrate structures present in venom glycoproteins. Previous studies showed that the ontogenetic shift in diet, from ectothermic prey in early life to endothermic prey in adulthood, and shift in animal size are associated with changes in the venom proteome of the snake Bothrops jararaca. In this study we explored the composition of the N-glycome released from newborn and adult B. jararaca venom proteins. We used an ion trap mass spectrometer (IT-MS) to disassemble glycan structures based on the use of several pathways of MS (MSn) and demonstrate the presence of some structural isomers in both newborn and adult venom B. jararaca N-glycans. The main N-glycans identified in both venoms are of the hybrid/complex type however some mannose-rich type structures were also detected. The N-glycan composition of newborn and adult venoms did not vary indicating that differences in the utilization of the N-glycosylation motif could be the explanation for the differences in the glycosylation levels indicated by the differential electrophoretic profiles previously reported for B. jararaca newborn and adult venoms. (C) 2011 Elsevier B.V. All rights reserved.

Cost-effectiveness of introducing the 10-valent pneumococcal conjugate vaccine into the universal immunisation of infants in Brazil

Background Cost-effectiveness studies have been increasingly part of decision processes for incorporating new vaccines into the Brazilian National Immunisation Program. This study aimed to evaluate the cost-effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) in the universal childhood immunisation programme in Brazil. Methods A decision-tree analytical model based on the ProVac Initiative pneumococcus model was used, following 25 successive cohorts from birth until 5 years of age. Two strategies were compared: (1) status quo and (2) universal childhood immunisation programme with PCV10. Epidemiological and cost estimates for pneumococcal disease were based on National Health Information Systems and literature. A 'top-down' costing approach was employed. Costs are reported in 2004 Brazilian reals. Costs and benefits were discounted at 3%. Results 25 years after implementing the PCV10 immunisation programme, 10 226 deaths, 360 657 disability-adjusted life years (DALYs), 433 808 hospitalisations and 5 117 109 outpatient visits would be avoided. The cost of the immunisation programme would be R$10 674 478 765, and the expected savings on direct medical costs and family costs would be R$1 036 958 639 and R$209 919 404, respectively. This resulted in an incremental cost-effectiveness ratio of R$778 145/death avoided and R$22 066/DALY avoided from the society perspective. Conclusion The PCV10 universal infant immunisation programme is a cost-effective intervention (1-3 GDP per capita/DALY avoided). Owing to the uncertain burden of disease data, as well as unclear long-term vaccine effects, surveillance systems to monitor the long-term effects of this programme will be essential.

Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates

Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+ CD25+ Foxp3+ T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-gamma-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods.

Birth in Brazil: national survey into labour and birth

Background: Caesarean section rates in Brazil have been steadily increasing. In 2009, for the first time, the number of children born by this type of procedure was greater than the number of vaginal births. Caesarean section is associated with a series of adverse effects on the women and newborn, and recent evidence suggests that the increasing rates of prematurity and low birth weight in Brazil are associated to the increasing rates of Caesarean section and labour induction. Methods: Nationwide hospital-based cohort study of postnatal women and their offspring with follow-up at 45 to 60 days after birth. The sample was stratified by geographic macro-region, type of the municipality and by type of hospital governance. The number of postnatal women sampled was 23,940, distributed in 191 municipalities throughout Brazil. Two electronic questionnaires were applied to the postnatal women, one baseline face-to-face and one follow-up telephone interview. Two other questionnaires were filled with information on patients' medical records and to assess hospital facilities. The primary outcome was the percentage of Caesarean sections (total, elective and according to Robson's groups). Secondary outcomes were: post-partum pain; breastfeeding initiation; severe/near miss maternal morbidity; reasons for maternal mortality; prematurity; low birth weight; use of oxygen use after birth and mechanical ventilation; admission to neonatal ICU; stillbirths; neonatal mortality; readmission in hospital; use of surfactant; asphyxia; severe/near miss neonatal morbidity. The association between variables were investigated using bivariate, stratified and multivariate model analyses. Statistical tests were applied according to data distribution and homogeneity of variances of groups to be compared. All analyses were taken into consideration for the complex sample design. Discussion: This study, for the first time, depicts a national panorama of labour and birth outcomes in Brazil. Regardless of the socioeconomic level, demand for Caesarean section appears to be based on the belief that the quality of obstetric care is closely associated to the technology used in labour and birth. Within this context, it was justified to conduct a nationwide study to understand the reasons that lead pregnant women to submit to Caesarean sections and to verify any association between this type of birth and it's consequences on postnatal health.

Differences in walking attainment ages between low-risk preterm and healthy full-term infants

Objective: To compare gross motor development of preterm infants (PT) without cerebral palsy with healthy full-term (FT) infants, according to Alberta Infant Motor Scale (AIMS); to compare the age of walking between PT and FT; and whether the age of walking in PT is affected by neonatal variables. Methods: Prospective study compared monthly 101 PT and 52 FT, from the first visit, until all AIMS items had been observed. Results: Mean scores were similarity in their progression, except from the eighth to tenth months. FT infants were faster in walking attainment than PT. Birth weight and length and duration of neonatal nursery stay were related to walking delay. Conclusion: Gross motor development between PT and FT were similar, except from the eighth to tenth months of age. PT walked later than FT infants and predictive variables were birth weight and length, and duration of neonatal intensive unit stay.

In Vitro Effects of Bevacizumab Treatment on Newborn Rat Retinal Cell Proliferation, Death, and Differentiation

PURPOSE. Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on cell death, proliferation, and differentiation in newborn rat retina. METHODS. Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared. RESULTS. No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS. Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue. (Invest Ophthalmol Vis Sci. 2012;53:7904-7911) DOI:10.1167/iovs.12-10283

Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a "roadmap" for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH.

Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors

Abstract Background Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. Methods Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. Results We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. Conclusions Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.

Birth defects in newborns and stillborns: an example of the Brazilian reality

Abstract Background This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects. Methods For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases. Result The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death. Conclusions The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments.

What types of unintentional injuries kill our children? Do infants die of the same types of injuries? A systematic review

The objective of this study was to review mortality from external causes (accidental injury) in children and adolescents in systematically selected journals. This was a systematic review of the literature on mortality from accidental injury in children and adolescents. We searched the Pubrvled, Latin-American and Caribbean Health Sciences and Excerpta Medica databases for articles published between July of 2001 and June of 2011. National data from official agencies, retrieved by manual searches, were also reviewed. We reviewed 15 journal articles, the 2011 edition of a National Safety Council publication and 2010 statistical data from the Brazilian National Ministry of Health Mortality Database. Most published data were related to high-income countries. Mortality from accidental injury was highest among children less than 1 year of age. Accidental threats to breathing (non-drowning threats) constituted the leading cause of death among this age group in the published articles. Across the pediatric age group in the surveyed studies, traffic accidents were the leading cause of death, followed by accidental drowning and submersion. Traffic accidents constitute the leading external cause of accidental death among children in the countries understudy. However, infants were vulnerable to external causes, particularly to accidental non-drowning threats to breathing, and this age group had the highest mortality rates for external causes. Actions to reduce such events are suggested. Further studies investigating the occurrence of accidental deaths in low-income countries are needed to improve the understanding of these preventable events.

Pain in preterm infants: effects of sex, gestational age, and neonatal illness severity

Neonates hospitalized in a neonatal intensive care unit are exposed to many painful and stressful procedures. Biobehavioral pain reactivity in preterm infants during the neonatal period may reflect the capacity of the central nervous system to regulate arousal and neurobiological organization. We review empirical studies on the effects of sex, gestational age, and neonatal illness severity on pain reactivity in children born preterm. A literature search was conducted using PubMed, Institute of Scientific Information Web of Science, PsycINFO, Latin American and Caribbean Health Sciences Literature, and Scientific Electronic Library Online databases. Additionally, a special search was performed in online journals that publish pain studies including Pain, Early Human Development, European Journal of Pain, and Pain Management Nursing. The literature search covered the period from 2004 to 2009. Data were extracted according to predefined inclusion and exclusion criteria. Of the 18 studies reviewed, 16 analyzed gestational age, 13 examined neonatal illness severity, and eight focused on sex. Most of the studies analyzed more than one of these three variables. The majority of the studies found effects of gestational age (n = 14) and neonatal illness severity (n = 11) on pain responses. Only two studies found an influence of sex on infant pain responses. In conclusion, gestational age and neonatal illness severity influence pain responses in infants born preterm. Further studies should be conducted to examine the influence of sex on pain responses.