Acquisition of motor abilities up to independent walking in very low birth weight preterm infants

Objective: To determine chronological and corrected ages at acquisition of motor abilities up to independent walking in very low birth weight preterms and to determine up to what point it is necessary to use corrected age.Methods: This was a longitudinal study of preterms with birth weight < 1,500 g and gestational age <= 34 weeks, free from neurosensory sequelae, selected at the high-risk infants follow-up clinic at the Hospital das Clinicas, Faculdade de Medicine de Botucatu, Universidade Estadual Paulista (UNESP) in Botucatu, Brazil, between 1998 to 2003, and assessed every 2 months until acquisition of independent walking.Results: Nine percent of the 155 preterms recruited were excluded from the study, leaving a total of 143 patients. The mean gestational age was 30 +/- 2 weeks, birth weight was 1,130 +/- 222 g, 59% were female and 44% were small for gestational age. Preterms achieved head control in their second month, could sit independent at 7 months and walked at 12.8 months' corrected age, corresponding to the 4th, 9th and 15th months of chronological age. There were significant differences between chronological age and corrected age for all motor abilities. Preterms who were small for their gestational age acquired motor abilities later, but still within expected limits.Conclusions: Very low birth weight preterms, free from neurosensory disorders, acquired their motor abilities within the ranges expected for their corrected ages. Corrected age should be used until independent walking is achieved.

Red Blood Cell Transfusions are Independently Associated with Intra-Hospital Mortality in Very Low Birth Weight Preterm Infants

Objective To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality.Study design Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions.Results of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 +/- 3.4, with 2.1 +/- 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions.Conclusion Transfusion was associated with increased death, and transfusion guidelines should consider risks and benefits of transfusion. (J Pediatr 2011; 159: 371-6).

Alkaline ribonuclease activity in maternal serum and in serum of newborns from birth up to thirty days of age. A study made with full-term appropriate-, full-term small- and preterm appropriate-for-gestational-age infants

We have studied the alkaline ribonuclease (RNase) activity in maternal serum and serum of full-term small- (T-SGA), full-term appropriate- (T-AGA) and preterm appropriate-for-gestational age (PT-AGA) newborns. A significantly lower level of RNase was observed in T-AGA and T-SGA newborns on the 30th day of age and in PT-AGA newborns on the 15th and 30th days of age, as compared to other T-AGA, T-SGA and PT-AGA groups of infants at birth. RNase activity was significantly higher in cord blood than in the maternal blood in all categories studied. Moreover, in preterm newborns, RNase activity in cord blood was significantly higher in those presenting a lower gestational age. We did not observe any significant difference in RNase levels in the cord blood of newborns from the 3 categories studied. The same results were observed concerning maternal blood. We, therefore, conclude that RNase activity in cord blood or in maternal blood is not a very statisfactory indicator of fetal malnutrition.

Practices related to late-onset sepsis in very low-birth weight preterm infants

Objective: To understand the practices related to late-onset sepsis (LOS) in the centers of the Brazilian Neonatal Research Network, and to propose strategies to reduce the incidence of LOS.Methods: This was a cross-sectional descriptive multicenter study approved by the Ethics Committee. Three questionnaires regarding hand hygiene, vascular catheters, and diagnosis/treatment of LOS were sent to the coordinator of each center. The center with the lowest incidence of LOS was compared with the others.Results: All 16 centers answered the questionnaires. Regarding hand hygiene, 87% use chlorhexidine or 70% alcohol; alcohol gel is used in 100%; 80% use bedside dispensers (50% had one dispenser for every two beds); practical training occurs in 100% and theoretical training in 70% of the centers, and 37% train once a year. Catheters: 94% have a protocol, and 75% have a line insertion team. Diagnosis/treatment: complete blood count and blood culture are used in 100%, PCR in 87%, hematological scores in 75%; oxacillin and aminoglycosides is the empirical therapy in 50% of centers. Characteristics of the center with lowest incidence of LOS: stricter hand hygiene; catheter insertion and maintenance groups; use of blood culture, PCR, and hematological score for diagnosis; empirical therapy with oxacillin and aminoglycoside.Conclusion: The knowledge of the practices of each center allowed for the identification of aspects to be improved as a strategy to reduce LOS, including: alcohol gel use, hand hygiene training, implementation of catheter teams, and wise use of antibiotic therapy. (C) 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Growth of preterm low birth weight infants until 24 months corrected age: effect of maternal hypertension

Objective: To evaluate the growth pattern of low birth weight preterm infants born to hypertensive mothers, the occurrence of growth disorders, and risk factors for inadequate growth at 24 months of corrected age (CA).Methods: Cohort study of preterm low birth weight infants followed until 24 months CA, in a university hospital between January 2009 and December 2010. Inclusion criteria: gestational age < 37 weeks and birth weight of 1,500-2,499g. Exclusion criteria: multiple pregnancies, major congenital anomalies, and loss to follow up in the 2nd year of life. The following were evaluated: weight, length, and BMI. Outcomes: growth failure and risk of overweight at 0, 12, and 24 months CA. Student's t-test, Repeated measures ANOVA (RM-ANOVA), and multiple logistic regression were used.Results: A total of 80 preterm low birth weight infants born to hypertensive mothers and 101 born to normotensive mothers were studied. There was a higher risk of overweight in children of hypertensive mothers at 24 months; however, maternal hypertension was not a risk factor for inadequate growth. Logistic regression showed that being born small for gestational age and inadequate growth in the first 12 months of life were associated with poorer growth at 24 months.Conclusion: Preterm low birth weight born infants to hypertensive mothers have an increased risk of overweight at 24 months CA. Being born small for gestational age and inadequate growth in the 1st year of life are risk factors for growth disorders at 24 months CA. (C) 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units

Preterm infants in neonatal intensive care units frequently receive red blood cells (RBC) transfusions due to the anemia of prematurity. A number of variables related to gestational age, severity of illness and transfusion practices adopted in the neonatal unit where the neonate was born may contribute to the prescription of RBC transfusions. This study aimed to analyse the frequency and factors associated with RBC transfusions in very-low-birth-weight preterm infants. A prospective cohort of 4283 preterm infants (gestational age: 29.9 ± 2.9 weeks; birth weight: 1084 ± 275 g) carried out at 16 university hospitals in Brazil between January 2009 and December 2011 was analysed. Factors associated with RBC transfusions were evaluated using univariate and multiple logistic regression analysis. A total of 2208 (51.6%) infants received RBC transfusions (variation per neonatal unit: 34.1% to 66.4%). RBC transfusions were significantly associated with gestational age (OR: -1.098; 95%CI: -1.12 to -1.04), SNAPPE II score (1.01; 1.00-1.02), apnea (1.69; 1.34-2.14), pulmonary hemorrhage (2.65; 1.74-4.031), need for oxygen at 28 days of life (1.56; 1.17-2.08), clinical sepsis (3.22; 2.55-4.05), necrotising enterocolitis (3.80; 2.26-6.41), grades III/IV intraventricular hemorrhage (1.64; 1.05-2.58), mechanical ventilation (2.27; 1.74-2.97), use of umbilical catheter (1.86; 1.35-2.57), parenteral nutrition (2.06; 1.27-3.33), >60 days of hospitalization (5.29; 4.02-6.95) and the neonatal unit where the neonate was born. The frequency of RBC transfusions varied among neonatal intensive care units. Even after adjusting for adverse health conditions and therapeutic interventions, the neonatal unit continued to influence transfusion practices in very-low birth-weight infants.

Selenium and vitamin A and E in the nutrition of very low-birth weight preterm infants

Deficient antioxidant defenses in preterm infants have been implicated in diseases such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage. The antioxidant properties of selenium, vitamin A, and vitamin E make these elements important in the nutrition of Very Low-Birth Weight (VLBW) infants. Selenium is a component of glutathione peroxidase, an enzyme that prevents the production of free radicals. The decrease in plasma selenium in VLBW infants in the first month after birth makes evident that preterm infants have low selenium store and require supplementation by parenteral and enteral nutrition. A meta-analysis, with only three trials, showed that selenium supplementation did not affect mortality, and the incidence of neonatal chronic lung disease or retinopathy of prematurity, but was associated with a reduction in lateonset sepsis. Most VLBW infants and extremely Low-Birth Weight Infants (ELBW) are born with low vitamin A stores and need vitamin A supplementation by intramuscular or enteral route. Low plasma retinol concentrations increase the risk of chronic lung disease/bronchopulmonary dysplasia and long-term respiratory disabilities in preterm infants. There is evidence that vitamin A supplementation decreases the mortality or oxygen requirement at one month of age, and oxygen requirement at 36 weeks’ postmenstrual age. Vitamin E blocks natural peroxidation of polyunsaturated fatty acids from lipid layers of cell membranes. VLBW infants have a decrease in plasma concentrations in the first month after birth suggesting the need of vitamin E supplementation. A meta-analysis on vitamin E supplementation concluded that vitamin E did not affect mortality, risk of bronchopulmonary dysplasia, and necrotizing enterocolitis but reduced the risk of intraventricular hemorrhage and increased the risk of sepsis. Serum vitamin E concentrations higher than 3.5 mg/dL are associated with a decrease in the risk of severe retinopathy of prematurity, and blindness, but also with an increase in neonatal sepsis. Caution is recommended with the supplementation of high doses of parenteral vitamin E and supplementation that increases serum levels above 3.5 mg/dL. In conclusion: although it is known that preterm infants are deficient in selenium, vitamin A and E, more studies are required to determine the best way to supplement and the impact of supplementation on neonatal outcome.

Perinatal factors associated with early deaths of preterm infants born in Brazilian Network on Neonatal Research centers

Objective: To evaluate perinatal factors associated with early neonatal death in preterm infants with birth weights (BW) of 400-1,500 g.Methods: A multicenter prospective cohort study of all infants with BW of 400-1,500 g and 23-33 weeks of gestational age (GA), without malformations, who were born alive at eight public university tertiary hospitals in Brazil between June of 2004 and May of 2005. Infants who died within their first 6 days of life were compared with those who did not regarding maternal and neonatal characteristics and morbidity during the first 72 hours of life. Variables associated with the early deaths were identified by stepwise logistic regression.Results: A total of 579 live births met the inclusion criteria. Early deaths occurred in 92 (16%) cases, varying between centers from 5 to 31%, and these differences persisted after controlling for newborn illness severity and mortality risk score (SNAPPE-II). According to the multivariate analysis, the following factors were associated with early intrahospital neonatal deaths: gestational age of 23-27 weeks (odds ratio - OR = 5.0; 95%CI 2.7-9.4), absence of maternal hypertension (OR = 1.9; 95%CI 1.0-3.7), 5th minute Apgar 0-6 (OR = 2.8; 95%CI 1.4-5.4), presence of respiratory distress syndrome (OR = 3.1; 95%CI 1.4-6.6), and network center of birth.Conclusion: Important perinatal factors that are associated with early neonatal deaths in very low birth weight preterm infants can be modified by interventions such as improving fetal vitality at birth and reducing the incidence and severity of respiratory distress syndrome. The heterogeneity of early neonatal rates across the different centers studied indicates that best clinical practices should be identified and disseminated throughout the country.

Sepsis and Neutropenia in Very Low Birth Weight Infants Delivered of Mothers with Preeclampsia

Objective To study the association between maternal preeclampsia and neonatal sepsis in very low birth weight newborns.Study design We studied all infants with birth weights between 500 g and 1500 g who were admitted to 6 neonatal intensive care units of the Brazilian Network on Neonatal Research for 2 years. Exclusion criteria were major malformations, death in the delivery room, and maternal chronic hypertension. Absolute neutrophil count was performed in the first 72 hours of life.Results A total of 911 very low birth weight infants (preeclampsia, 308; non-preeclampsia, 603) were included. The preeclampsia group had significantly higher gestational age, more cesarean deliveries, antenatal steroid, central catheters, total parenteral nutrition, and neutropenia, and less rupture of membranes >18 hours and mechanical ventilation. Both groups had similar incidences of early sepsis (4.6% and 4.2% in preeclampsia and non-preeclampsia groups, respectively) and late sepsis (24% and 22.1% in preeclampsia and non-preeclampsia groups, respectively). Vaginal delivery and neutropenia were associated with multiple logistic regressions with early sepsis, and mechanical ventilation, central catheter, and total parenteral nutrition were associated with late sepsis. Death was associated with neutropenia in very preterm infants.Conclusions Preeclampsia did not increase neonatal sepsis in very low birth weight infants, and death was associated with neutropenia in very preterm infants. (J Pediatr 2010; 157: 434-8).

Antenatal corticosteroid use and clinical evolution of preterm newborn infants

Objectives: To describe the use of antenatal corticosteroid and clinical evolution of preterm babies. Methods: An observational prospective cohort study was carried out. All 463 pregnant women and their 514 newborn babies with gestational age ranging from 23 to 34 weeks, born at the Brazilian Neonatal Research Network units, were evaluated from August 1 to December 31, 2001. The data were obtained through maternal interview, analysis of medical records, and follow-up of the newborn infants. Data analysis was performed with the use of chi-square, t Student, Mann-Whitney, and ANOVA tests and multiple logistic regression, with level of significance set at 5%. Results: Treatment was directly associated with the number of prenatal visits, with maternal hypertension and with the antenatal use of tocolytic agents. Babies from treated pregnant women presented better Apgar scores at the 1st and 5th minute, reduced need for intervention in the delivery room and lower SNAPPE II. They were born with higher birth weight, longer gestational age and needed less surfactant use, ventilation, and oxygenation time. After multiple logistic regression, the use of antenatal corticosteroid independently improved birth conditions, decreased ventilation time, being related to increased occurrence of neonatal sepsis. Conclusions: The use of corticosteroid was associated with better prenatal care and birth conditions, better preterm evolution but higher risk of infection. Copyright © 2004 by Sociedade Brasileira de Pediatria.

Minerals in the nutrition of extremely low birth weight infants

Objective: To review the literature on the role of calcium, phosphorus and trace elements in the nutrition of extremely low birth weight infants, considering their importance for metabolism, bone mineralization and as dietary components. Sources of data: MEDLINE, the Cochrane Database of Systematic Reviews and books on nutrition were searched between 1994 and 2004. Original research studies and reviews were selected. Summary of the findings: Extremely preterm infants are frequently growth-restricted at hospital discharge as a consequence of difficulties in the provision of adequate nutrition. The long-term effects of this growth restriction need to be determined. There is a paucity of studies about the role of minerals, especially micronutrients, in the nutrition of extremely preterm infants. The principal focus of this review was on calcium and phosphorus metabolism, bone mineralization and parenteral and enteral supplementation. A critical evaluation of post-discharge nutrition and its influence upon growth and bone mineralization was presented. Selenium and zinc requirements and the role of selenium as an antioxidant with possible effects on free radical diseases of the preterm infant were discussed. Conclusions: Extremely preterm infants have low mineral reserves and, as a consequence, may have deficiencies in the postnatal period if they do not receive parenteral or enteral supplementation. More studies are needed to elucidate the actual requirements and the appropriate supplementation of micronutrients. There are controversies about the outcome and the influence of post-discharge nutrition on bone disease of prematurity. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Growth and developmental outcomes of the extremely preterm infant

Objetive: To provide information for pediatricians and neonatologists to create realistic outcome expectations and thus help plan their actions. Sources of data: Searches were made of the Cochrane Library, MEDLINE, and Lilacs databases. Summary of the findings: The assessment of growth and development over the first 2-3 years must adjust chronological age with respect of the degree of prematurity. There is special concern regarding the prognoses of small for gestational age preterm infants, and for those with bronchopulmonary dysplasia. Attention must be directed towards improving the nutrition of extremely low birth weight infants during their first years of life; these infants have high prevalence levels of failure to catch-up on growth, diseases and rehospitalizations during their first 2 years. They are frequently underweight and shorter than expected during early childhood, but delayed catch-up growth may occur between 8 and 14 years. Extremely low birth weight infants are at increased risk of neurological abnormalities and developmental delays during their first years of life. Educational, psychological, and behavioral problems are frequent during school years. Teenage and adult outcomes show that although some performance differences persist, social integration is not impaired. Conclusions: The growth and neurodevelopment of all ELBW infants must be carefully monitored after discharge, to ensure that children and their families receive adequate support and intervention to optimize prognoses. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Hypothermia and Early Neonatal Mortality in Preterm Infants

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Frequência de retinopatia da prematuridade em recém-nascidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

OBJETIVOS: Determinar a frequência de retinopatia da prematuridade no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP-USP) e verificar a associação da retinopatia da prematuridade com fatores de risco conhecidos. MÉTODOS: Foi realizada análise prospectiva de 70 pacientes, nascidos no HCFMRP-USP, com peso inferior a 1.500 gramas, no período de um ano. Os pacientes foram divididos em dois grupos (Retinopatia da prematuridade e Normal) para realização de análise estatística com relação a fatores de risco conhecidos. Adotou-se nível de significância de 5%. RESULTADOS: A frequência de retinopatia da prematuridade foi de 35,71% entre os pré-termos estudados. Os fatores pesquisados que apresentaram relação de risco para o desenvolvimento da doença foram: peso (p=0,001), idade gestacional (p=0,001), escore SNAPPE II (p=0,008), uso de oxigenoterapia por intubação (p=0,019) e por pressão positiva de vias aéreas (p=0,0017), múltiplas transfusões sanguíneas (p=0,01) e uso de diuréticos (p=0,01). CONCLUSÃO: A frequência de retinopatia da prematuridade foi de 35,71% entre os prétermos nascidos com menos de 1.500 g. Vários fatores de risco foram identificados nos recém-nascidos do HCFMRP-USP, sendo constatado que crianças mais pré-termos apresentam formas mais graves de retinopatia da prematuridade.