Early Empiric Antibiotic Use Is Associated With Delayed Feeding Tolerance in Preterm Infants: A Retrospective Analysis.

The causative factors of neonatal feeding intolerance are poorly understood, but potentially related to clinical practices such as empiric antibiotic usage. The objective of this study was to evaluate whether early empiric antibiotic exposure negatively affects preterm infants' enteral feeding tolerance. Data from infants without risk factors for sepsis, 500 to 1499 g birth weight and 24 to 34 weeks gestational age were analyzed. The primary outcomes were the empiric antibiotic exposure effects on the infants' total parenteral nutrition usage duration and prevalence of necrotizing enterocolitis (NEC). Among the 901 infants included, 67 were exposed to early empiric antibiotic. A 50% increase in parenteral nutrition usage duration and a 4-fold greater prevalence of NEC was seen in the early empiric antibiotic-exposed neonates, when compared with control infants (P < 0.01). Early empiric antibiotic exposure appears to negatively influence preterm infant feeding tolerance and possibly contributes to NEC.

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus / Efeitos da abordagem terapêutica da persistência de canal arterial sobre a evolução neonatal de recém-nascidos de extremo baixo peso

OBJECTIVE: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. METHODS: This was a multicentric cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. Outcomes: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Statistics: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) ...

OBJETIVO: Analisar os efeitos da terapêutica adotada para o canal arterial (CA) em recém-nascidos (RN) < 1.000gadmitidos em unidades neonatais (UN) da Rede Brasileira de Pesquisas Neonatais (RBPN), sobre os desfechos: óbito, displasia broncopulmonar (DBP), hemorragia intraventricular grave (HIVIII/IV), retinopatia da prematuridade cirúrgica (ROPcir), enterocolite necrosante cirúrgica (ECNcir) e o desfecho combinado óbito e DBP. MÉTODOS: Estudo multicêntrico, de coorte, coleta de dados retrospectiva, incluindo RN de 16 UN da RBPN de 01/01/2010 a 31/12/2011, PN < 1.000 g, idade gestacional (IG) < 33 semanas e diagnóstico ecocardiográfico de PCA. Excluídos: óbitos ou transferências até o terceiro dia de vida, infecções congênitas ou malformações. Grupos:G1 - conservadora (sem intervenção medicamentosa ou cirúrgica), G2 - farmacológica (indometacina ou ibuprofeno) e G3 - cirúrgico (com ou sem tratamento farmacológico anterior). Analisou-se: uso de esteroide antenatal, parto cesárea, PN, IG, Apgar5' < 4, sexo masculino, SNAPPE II, síndrome do dDesconforto respiratório (SDR), sepse tardia, ventilação mecânica (VM), surfactante < 2 horas de vida, tempo de VM e os desfechos: óbito, dependência de oxigênio com 36 semanas (DBP36s), HIV III/IV, ROPcir, ECNcir e óbito/DBP36s. Estatística: Teste t-Student, Qui-Quadrado ou teste Exato de Fisher. Testes de Regressão Binária Logística e Regressão Múltipla Stepwise Backward. MedCalc (Medical Calculator) software, versão 12.1.4.0.p < 0,05. RESULTADOS: Foram selecionados 1.097 RN e 494 foram incluídos: G1-187 (37,8%), G2-205 (41,5%) e G3-102 (20,6%). Verificou-se: maior mortalidade (51,3%) no G1 e menor no G3(14,7%); maior frequência DBP36s (70,6%) e ROPcir (23,5%) ...

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

OBJECTIVE: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. METHODS: This was a multicentric, cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. OUTCOMES: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. STATISTICS: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2 (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34; 95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks. CONCLUSION: The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks.

Non-nutritive sucking evaluation in preterm newborns and the start of oral feeding: a multicenter study.

OBJECTIVES: The assessment of early sucking by preterm infants provides information on the ability of these infants to efficiently and safely receive nutrients via an oral route (oral feeding). To analyze the application and reliability of an instrument in assessing non-nutritive sucking that indicates a capacity for oral feeding in the routine care of different neonatal units. METHODS: A multicenter, prospective cohort study was conducted in seven neonatal units. A non-nutritive sucking assessment with a formulary validated by Neiva et al (2008) (variables evaluated: rooting reaction; easy initiation of sucking; labial sealing; tongue central groove; peristaltic tongue movements; jaw raising and lowering movements; labial, tongue and jaw coordination; sucking strength; sucking rhythm; bites; excessive jaw excursion; stress signals) was applied to 199 pre-term newborns, who had a chronological age ≥ 2 days and were clinically stable. These infants were divided into two groups based on their corrected gestational age at the first assessment, as follows: Group I-infants with a gestational age ≤ 33 weeks and Group II-infants with a gestational age between 34 and 36 6/7 weeks. RESULTS: The mean gestational age was 31.66±2 weeks, and the mean birth weight was 1494 ± 373 g. The mean scores on the non-nutritive sucking assessment were 46 ± 25 in Group I and 49 ± 24 in Group II. The beginning of oral feeding was successful in 43 (67.2%) infants in Group I and 64 (81%) infants in Group II (p = 0.089). CONCLUSION: The method identified preterm infants who were able to feed orally based on 33 points in the non-nutritive sucking assessment and a corrected gestational age of 32 weeks or more. The corrected gestational age was the most important factor in predicting the success of oral feeding.

Non-nutritive sucking evaluation in preterm newborns and the start of oral feeding: a multicenter study

OBJECTIVES: The assessment of early sucking by preterm infants provides information on the ability of these infants to efficiently and safely receive nutrients via an oral route (oral feeding). To analyze the application and reliability of an instrument in assessing non-nutritive sucking that indicates a capacity for oral feeding in the routine care of different neonatal units. METHODS: A multicenter, prospective cohort study was conducted in seven neonatal units. A non-nutritive sucking assessment with a formulary validated by Neiva et al (2008) (variables evaluated: rooting reaction; easy initiation of sucking; labial sealing; tongue central groove; peristaltic tongue movements; jaw raising and lowering movements; labial, tongue and jaw coordination; sucking strength; sucking rhythm; bites; excessive jaw excursion; stress signals) was applied to 199 pre-term newborns, who had a chronological age ≥ 2 days and were clinically stable. These infants were divided into two groups based on their corrected gestational age at the first assessment, as follows: Group I-infants with a gestational age ≤ 33 weeks and Group II-infants with a gestational age between 34 and 36 6/7 weeks. RESULTS: The mean gestational age was 31.66±2 weeks, and the mean birth weight was 1494 ± 373 g. The mean scores on the non-nutritive sucking assessment were 46 ± 25 in Group I and 49 ± 24 in Group II. The beginning of oral feeding was successful in 43 (67.2%) infants in Group I and 64 (81%) infants in Group II (p = 0.089). CONCLUSION: The method identified preterm infants who were able to feed orally based on 33 points in the non-nutritive sucking assessment and a corrected gestational age of 32 weeks or more. The corrected gestational age was the most important factor in predicting the success of oral feeding. .

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.

Respostas pulmonares à restrição nutricional e à hiperoxia em coelhos prematuros / Pulmonary responses to nutritional restriction and hyperoxia in premature rabbits

OBJETIVOS: Este modelo experimental foi desenvolvido para analisar os efeitos da restrição nutricional e da hiperoxia, durante 11 dias, sobre o peso e a morfometria pulmonares, em coelhos prematuros. MÉTODOS: Após cesárea, coelhos New Zealand White com idade gestacional de 28 dias foram randomizados nos seguintes grupos: dieta controle e ar ambiente, dieta controle e hiperoxia (> 95 por cento O2), restrição nutricional e ar ambiente e restrição nutricional e hiperoxia (>95 por cento O2). A restrição nutricional foi obtida com uma redução em 30 por cento de todos os nutrientes da dieta controle. As lâminas de pulmão foram coradas com hematoxilina-eosina, resorcina-orceína modificada e picrosírius, sendo posteriormente realizada a análise morfométrica RESULTADOS: Observou-se um menor ganho de peso no grupo restrição nutricional e hiperoxia (p < 0,001) a partir do quarto dia e, no grupo restrição nutricional e ar ambiente (p < 0,001), a partir do sexto dia de vida, em relação aos respectivos grupos controles. A restrição nutricional reduziu o número de alvéolos (p < 0,001) e o depósito de colágeno (p < 0,001). A hiperoxia produziu uma redução do número de alvéolos (p < 0,001) e do depósito de colágeno (p < 0,001), além de maiores intercepto linear médio (p < 0,05) e espessamento de septos inter-alveolares (p < 0,001). A restrição nutricional associada à hiperoxia intensificou a redução do número de alvéolos (p < 0,001) e do depósito de colágeno (p < 0,001). CONCLUSÕES: A restrição nutricional intensificou as alterações morfométricas pulmonares produzidas pela hiperoxia, especialmente em relação à alveolização e depósito de colágeno.

Pulmonary responses to nutritional restriction and hyperoxia in premature rabbits.

OBJECTIVES: To analyze the effects of nutritional restriction and hyperoxia on lung weight and pulmonary morphometry in premature rabbits during the first 11 days of life. METHODS: New Zealand White rabbits were delivered by C-section at 28 days' gestational age and randomized into four groups: control diet and room air, control diet and hyperoxia (> or = 95% O2), nutritional restriction and room air and nutritional restriction and hyperoxia (> or = 95% O2). Nutritional restriction was achieved by reducing all nutrients by 30% in comparison with the control diet. Lung tissue slides were stained with hematoxylin-eosin, modified resorcin-orcein and picrosirius, before morphometric analysis was performed. RESULTS: From the fourth day onwards, less weight was gained by the nutritional restriction and hyperoxia group (p < 0.001), and from the sixth day on, by the nutritional restriction and room air group (p < 0.001), in comparison with their respective control groups. Nutritional restriction decreased alveoli number (p < 0.001) and collagen deposition (p < 0.001). Hyperoxia was responsible for reductions in number of alveoli (p < 0.001) and collagen deposition (p < 0.001), in addition to higher mean linear intercept values (p < 0.05) and thickening of alveolar septa (p < 0.001). When nutritional restriction was associated with hyperoxia, the reductions in number of alveoli (p < 0.001) and of collagen deposition (p < 0.001) intensified. CONCLUSIONS: Nutritional restriction intensified the changes of pulmonary architecture findings caused by hyperoxia, in particular through alterations to alveolarization and collagen deposition.

Effects of corticosteroids in very low birth weight newborns dependent on mechanical ventilation.

UNLABELLED: Corticosteroids have been used in bronchopulmonary dysplasia prevention because of their antiinflammatory effects. Among their effects is a decrease in the incidence of bronchopulmonary dysplasia. However, short- and long-term side effects have been detected in preterm newborns. PURPOSE: To analyze the effects of corticosteroids on bronchopulmonary dysplasia, length of stay, mortality, growth, as well as the adverse effects in very low birth weight newborns between 10 and 14 days of life and dependent on mechanical ventilation. METHODS: Cohort study. All newborns with a birth weight under 1500 g, mechanical ventilation-dependent between 10 and 14 days of life, during the period January 2000 and June 2001 were included (n = 38). They were divided into 2 groups: Group I with corticosteroids (n = 16) and Group II without corticosteroids (n = 22). Dexamethasone administration: from the 10th day of life, d1-d3, 0.3 mg/kg/d; d4-d6, 0.2 mg/kg/d; d7-d9, 0.1 mg/kg/d. Respiratory evolution, bronchopulmonary dysplasia (oxygen dependence at 28 days of life), growth pattern and the presence of adverse effects were analyzed. RESULTS: The incidence of bronchopulmonary dysplasia was 6.5% (Group I) and 30% (Group II), P = .07. A decrease in growth was detected in Group I compared with Group II (change in weight: Group I--47 g/week, Group II--85.5 g/week, P = .06; change in head circumference: Group I--0.75 cm/week, Group II--1 cm/week, P = .05). CONCLUSION: Use of corticosteroids in very low birth weight infants dependent on mechanical ventilation during the first 10 to 14 days of life did not affect the respiratory evolution and occurrence of bronchopulmonary dysplasia, but the velocity of growth was reduced.

Effects of corticosteroids in very low birth weight newborns dependent on mechanical ventilation

Devido às suas ações anti-inflamatórias, os corticosteróides têm sido utilizados para prevenção de displasia broncopulmonar, sendo descrita, uma redução da incidência desta patologia. No entanto, efeitos adversos a curto e a longo prazo têm sido detectados, em recém-nascidos pré-termo. OBJETIVO: Analisar os efeitos sobre a incidência de displasia broncopulmonar, duração de ventilação mecânica e de internação, mortalidade, crescimento, além dos efeitos adversos dos corticosteróides, administrados entre 10-14 dias de vida, em recém-nascidos de muito baixo peso, dependentes de ventilação mecânica. MÉTODOS: Realizou-se estudo de coorte, incluindo-se todos os recém-nascidos com peso de nascimento < 1500 gramas dependentes de ventilação mecânica, entre 10-14 dias de vida. Foram divididos em: Grupo I - receberam dexametasona (16) e Grupo II - não receberam dexametasona (22). Administrou-se dexametasona, a partir do 10º dia de vida, dias 1 a 3 - 0,3 mg/kg/d, dias 4 a 6 - 0,2 mg/kg/d, dias 7 a 9 - 0,1 mg/kg/d. Analisou-se o desenvolvimento de displasia broncopulmonar (dependência de oxigênio aos 28 dias de vida), efeitos sobre a evolução respiratória e sobre o padrão de crescimento, além da ocorrência de efeitos adversos. RESULTADOS: A incidência de displasia broncopulmonar não diferiu entre os grupos (GI - 62,5%; GII - 22,7%;p = 0,07). Detectou-se desaceleração do crescimento no GI em relação ao GII(D P = 47g/semana, GI e 85,5g/semana, GII; p = 0,06; D PC - 0,75 cm/semana GI e 1cm/semana, no GII; p = 0,05). CONCLUSAO: O uso de corticosteróides, em recém-nascidos pré-termo, entre 10 - 14 dias de vida não reduziu incidência de displasia broncopulmonar e causou uma desaceleração do crescimento.

Magnesium and intrauterine growth restriction.

BACKGROUND: The presence of intrauterine growth restriction (IUGR), could potentially lead to imbalances of Mg homeostasis, which have not yet been fully clarified. OBJECTIVE: To describe, in term newborn (NB) without IUGR, ionized magnesium (iMg) and total magnesium (TMg) concentrations in umbilical cord blood, on the third and seventh days of life and to compare these values with those of term NB with IUGR. METHODS: A prospective study was performed on 70 term NB divided into two groups: Group I-30 NB without IUGR and Group II-40 NB with IUGR. TMg concentrations were determined in sera by a classical colorimetric end point method (Cobas-Mira, Roche), and iMg was determined in whole blood by means of the Stat Profile-M analyzer (NOVA Biomedical). RESULTS: We found that in term NB without IUGR, TMg concentrations increased during the first week of life and were lower than those of NB with IUGR in cord blood (p < 0.05). NB without IUGR had decreased iMg concentrations in comparison to NB with IUGR in all sampling times, i.e., cord blood, third and seventh days of life (p < 0.001). iMg concentrations remained unchanged during the study period. We also found that all NB enrolled in the study presented with low iMg concentrations (reference interval 0.4-0.6 mmol/L). CONCLUSION: The presence of IUGR may influence neonatal levels of magnesium, suggesting an effect on the modulation of this ion homeostasis, during the perinatal period.

Glycemia in newborns of hypertensive mothers according to maternal treatment.

PURPOSE: To evaluate the evolution of glycemic levels in newborns of hypertensive mothers according to maternal treatment. METHODS: Prospective randomized study, including 93 newborns of mothers treated with isradipine (n = 39), atenolol (n = 40), or low sodium diet (control group - n=14). Glycemia was determined at birth (mother and newborn by the oxidase glucose method) and in the 1st, 3rd, 6th, 12th, and 24th hours after birth (newborn by a test strip method). The evolution of glycemia was analyzed in each group (Friedman test). The groups were compared regarding glycemia (Kruskall-Wallis test), and linear regression models were constructed for the analyses (independent variable = maternal glycemia; dependent variables = umbilical cord, 3rd, and 6th hour glycemia). RESULTS: There were no statistically significant differences among the mean blood glucose levels of the 3 groups in any of the assessments. There was a correlation between maternal and umbilical cord blood glucose in the isradipine (r = 0.61; P <.05) and control (r = 0.84; P <.05) groups. Regarding glycemia levels of the mothers and newborns in the third and sixth hours postpartum, this correlation was present only in the control group (maternal x third hour: r = 0.65; P <.05; maternal x sixth hour: r = 0.68; P <.05). There were no correlations in the atenolol group. Hypoglycemia was detected in 51.3% of the isradipine group, 60% of the atenolol group, and 35.7% of the control group, and it was more frequent in the first hour postpartum in all groups. CONCLUSIONS: The results suggest a similar effect of the 3 types of treatment upon newborn glycemia. The correlation analysis suggests that isradipine could have effects upon newborn glycemia only after birth (correlation only in umbilical cord blood), whereas atenolol could act earlier (there was no correlation at any moment). The results also point to the need for glycemic control from the first hour postpartum of newborns of hypertensive mothers whether they have or have not undergone treatment with antihypertensive drugs.