Bronchopulmonary dysplasia: temporal trend from 2010 to 2019 in the Brazilian Network on Neonatal Research.

OBJECTIVE: To evaluate the temporal trend of bronchopulmonary dysplasia (BPD) in preterm infants who survived to at least 36 weeks' post-menstrual age (PMA) and BPD or death at 36 weeks' PMA, and to analyse variables associated with both outcomes. DESIGN: Retrospective cohort with data retrieved from an ongoing national registry. SETTING: 19 Brazilian university public hospitals. PATIENTS: Infants born between 2010 and 2019 with 23-31 weeks and birth weight 400-1499 g. MAIN OUTCOME MEASURES: Temporal trend was evaluated by Prais-Winsten model and variables associated with BPD in survivors or BPD or death were analysed by logistic regression. RESULTS: Of the 11 128 included infants, BPD in survivors occurred in 22%, being constant over time (annual per cent change (APC): -0.80%; 95% CI: -2.59%; 1.03%) and BPD or death in 45%, decreasing over time (APC: -1.05%; 95% CI: -1.67%; -0.43%). Being male, small for gestational age, presenting with respiratory distress syndrome, air leaks, needing longer duration of mechanical ventilation, presenting with treated patent ductus arteriosus and late-onset sepsis were associated with an increase in the chance of BPD. For the outcome BPD or death, maternal bleeding, multiple gestation, 5-minute Apgar <7, late-onset sepsis, necrotising enterocolitis and intraventricular haemorrhage were added to the variables reported above as increasing the chance of the outcome. CONCLUSION: The frequency of BPD in survivors was constant and BPD or death decreased by 1.05% at each study year. These results show some improvement in perinatal care in Brazilian units which resulted in a reduction of BPD or death, but further improvements are still needed to reduce BPD in survivors.

Oxidative status in colostrum and mature breast milk related to gestational age and fetal growth.

INTRODUCTION: The effect of gestational age and fetal growth on the oxidant/antioxidant status of breast milk is poorly understood. OBJECTIVE: To evaluate the oxidative stress biomarkers in colostrum and mature milk according to gestational age and fetal growth. METHOD: A longitudinal study with mothers of premature and term infants, born in a tertiary referral hospital between 2014-2018. Inclusion criteria: postpartum women with a singleton pregnancy, who intended to exclusively breastfeed. Exclusion criteria: maternal diabetes, use of medication, drug addiction, congenital infection or malformation, mastitis, and failure to collect colostrum. Four groups were formed according to gestational age and birth weight (appropriate and small): Preterm small (n = 37), Preterm appropriate (n = 99), Full-term small (n = 65), and Full-term appropriate (control, n = 69). The colostrum samples were collected between 24-72 h and the mature milk was sampled in the 4th week of lactation for malondialdehyde (biomarker for lipid peroxidation) and Glutathione peroxidase, Catalase, and Superoxide dismutase measurements. The data were compared among groups using the Chi-square test or Fisher's exact test, one-way analysis of variance followed by Wald's Distribution test and repeated measures analysis of variance. RESULTS: We found a lower malondialdehyde level in colostrum in preterm groups and term small for gestational age, and the antioxidant enzymes Superoxide dismutase and Catalase activities were higher for preterm compared to term groups. The malondialdehyde levels differed in mature milk samples (Full-term small > Full-term appropriate > Preterm small > Preterm appropriate). The malondialdehyde levels increased during lactation in all groups except Preterm appropriate, and the levels of Catalase decreased in preterm groups. CONCLUSION: The oxidative status in breast milk is influenced by gestational age and fetal growth, which increased antioxidant defense for preterm infants and decreased oxidative stimuli for small for gestational age infants. These findings contribute to encouraging breastfeeding for newborns.

Temporal trends in intraventricular hemorrhage in preterm infants: A Brazilian multicenter cohort.

BACKGROUND: Intraventricular hemorrhage (IVH) is a serious problem in preterm infants. Brazilian national data are unknown. OBJECTIVE: To evaluate the incidence and temporal trend of IVH in very low birth weight (VLBW) preterm infants of 18 centers of the Brazilian Network on Neonatal Research. STUDY DESIGN: National prospective multicenter cohort study including inborn VLBW preterm infants aged 230/7- 336/7 weeks' gestation, admitted between 2013 and 2018. The center with the mean incidence rate was used as reference. We applied two adjustments models using perinatal variables, and perinatal + neonatal diseases. RESULTS: Of 6,420 infants, 1951/30.4% (range 27.1-33.8%) had IVH and the disease showed a significant trend towards an overall increase in incidence over time (p = 0.003), especially in three centers. Severe IVH (grade III or IV) occurred in 32.2% (range 29.2-34.5%) of those affected by IVH, with a stable incidence. After adjustments for perinatal variables, the differences persisted among centers: for global IVH, 7 centers had significantly lower rates (OR ranging from 0.31 to 0.62), and 2 presented rates higher than the reference center (OR ranging from 2.00 to 12.46) for severe HIV. Considering perinatal and neonatal variables, 6 centers had significantly lower rates (OR ranging from 0.36 to 0.60) for global IVH than the reference center and 3 had statistically higher rates (OR 1.72, 1.86 and 11.78) for severe forms. CONCLUSION: The incidence rate of IVH in this Brazilian cohort was high and it revealed an increasing trend towards over time. The severe IVH rate was also worrisome.

Evaluation of the effectiveness of antenatal corticoid in preterm twin and single pregnancies: a multicenter cohort study.

BACKGROUND: The effects of antenatal corticosteroids (ANSs) on twins are not well established. OBJECTIVE: To determine the impact of ANS use according to the number of fetuses. METHODS: Retrospective cohort study of newborns between 23 and 33 weeks of gestational age, birth weight from 400 to 1499 g, without malformations, delivered at 20 public university hospitals from 2010 to 2014.Exposed group: Received ANS (any time, any dose) and no exposed group: no received ANS. Analysis of birth conditions and clinical outcomes. Association of variables, relative risks, and 95% confidence intervals estimated from the adjustment of log-binomial regression models. RESULTS: About 7165 premature infants were analyzed: 5167 singleton, 937 twins, and 104 triplets. Characteristics of gestations with one, two, or three fetuses not receiving ANS were similar. Reduced hemodynamic instability in single and twins gestations in the first 72 h were observed (Adj R2 Twins = 0.78; 95% CI = 0.69-0.86) (Adj R2 Singles = 0.79; 95% CI = 0.62-0.99). Reduced peri-intraventricular hemorrhage (Adj R2 Twins = 0.54; 95% CI = 0.36-0.78) (Adj R2 singles = 0.54; 95% CI = 0.36-0.78); and early sepsis reduction on single and triplex gestations (Adj R2 triplex = 0.51; 95% CI = 0.27-0.94) (Adj single R2 = 0.51; 95% CI = 0.27-0.94) were observed. CONCLUSIONS: This study demonstrates ANS produces an important protective factor for severe intraventricular hemorrhage and hemodynamic instability in single and multiple pregnancies. ANS had a protective effect on death and birth conditions improvement just in single gestations. Regarding respiratory aspects was not observed the protective effect in the single or multiple gestations.

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.

Late-onset sepsis in very low birth weight infants: a Brazilian Neonatal Research Network Study.

BACKGROUND: Late-onset sepsis (LOS) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants. AIM: To determine the incidence, risk factors and etiology of LOS. METHODS: LOS was investigated in a multicenter prospective cohort of infants at eight public university neonatal intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of gestational age, 400-1499 g birth weight, who survived >3 days. RESULTS: Of 1507 infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with LOS were more likely to die. The majority of infections (76%) were caused by Gram-positive organisms. Independent risk factors for proven LOS were use of central venous catheter and mechanical ventilation, age at the first feeding and number of days on parenteral nutrition and on mechanical ventilation. CONCLUSION: LOS incidence and mortality are high in Brazilian VLBW infants. Most risk factors are associated with routine practices at NICU.

Hypothermia and early neonatal mortality in preterm infants.

OBJECTIVE: To evaluate intervention practices associated with hypothermia at both 5 minutes after birth and at neonatal intensive care unit (NICU) admission and to determine whether hypothermia at NICU admission is associated with early neonatal death in preterm infants. STUDY DESIGN: This prospective cohort included 1764 inborn neonates of 22-33 weeks without malformations admitted to 9 university NICUs from August 2010 through April 2012. All centers followed neonatal International Liaison Committee on Resuscitation recommendations for the stabilization and resuscitation in the delivery room (DR). Variables associated with hypothermia (axillary temperature <36.0 °C) 5 minutes after birth and at NICU admission, as well as those associated with early death, were analyzed by logistic regression. RESULTS: Hypothermia 5 minutes after birth and at NICU admission was noted in 44% and 51%, respectively, with 6% of early neonatal deaths. Adjusted for confounding variables, practices associated with hypothermia at 5 minutes after birth were DR temperature <25 °C (OR 2.13, 95% CI 1.67-2.28), maternal temperature at delivery <36.0 °C (OR 1.93, 95% CI 1.49-2.51), and use of plastic bag/wrap (OR 0.53, 95% CI 0.40-0.70). The variables associated with hypothermia at NICU admission were DR temperature <25 °C (OR 1.44, 95% CI 1.10-1.88), respiratory support with cold air in the DR (OR 1.40, 95% CI 1.03-1.88) and during transport to NICU (OR 1.51, 95% CI 1.08-2.13), and cap use (OR 0.55, 95% CI 0.39-0.78). Hypothermia at NICU admission increased the chance of early neonatal death by 1.64-fold (95% CI 1.03-2.61). CONCLUSION: Simple interventions, such as maintaining DR temperature >25 °C, reducing maternal hypothermia prior to delivery, providing plastic bags/wraps and caps for the newly born infants, and using warm resuscitation gases, may decrease hypothermia at NICU admission and improve early neonatal survival.

Cord blood cytokine levels in focal early-onset neonatal infection after preterm premature rupture of membranes.

This study aimed to evaluate the levels of pro- and anti-inflammatory cytokines in umbilical cord blood of preterm neonates who developed focal early-onset infection (EOI) after preterm premature rupture of membranes (PPROM). This is a prospective study conducted on 46 preterm infants from mothers with PPROM. The cytokines were measure by flow cytometry. Newborns were classified into two groups as focal EOI (n=19) and non-infected (n=27). Interleukin (IL)-6 and IL-8 levels were higher, whereas IL-10 and IL-12 p70 levels were lower in the EOI when compared to the non-infected group. The best combination of cytokines was IL-6+IL-8, with a diagnostic accuracy of 0.97. Focal EOI after PPROM is associated with increased levels of IL-6 and IL-8 and diminished IL-10 and IL-12 in the cord blood of preterm infants. Combined assessment of IL-6 and IL-8 in cord blood may provide an additional tool for identifying preterm infants who develop EOI after PPROM.

Detection of Oxacillin Resistance in Staphylococcus aureus Isolated from the Neonatal and Pediatric Units of a Brazilian Teaching Hospital.

OBJECTIVE: To determine, by phenotypic and genotypic methods, oxacillin susceptibility in Staphylococcus aureus strains isolated from pediatric and neonatal intensive care unit patients seen at the University Hospital of the Botucatu School of Medicine. METHODS: A total of 100 S. aureus strains isolated from the following materials were studied: 25 blood cultures, 21 secretions, 12 catheters, 3 cannulae and one chest drain from 62 patients in the neonatal unit, and 36 blood cultures, one pleural fluid sample and one peritoneal fluid sample from 38 patients in the pediatric unit. Resistance of the S. aureus isolates to oxacillin was evaluated by the disk diffusion method with oxacillin (1 µg) and cefoxitin (30 µg), agar screening test using Mueller-Hinton agar supplemented with 6 µg/ml oxacillin and 4% NaCl, and detection of the mecA gene by PCR. In addition, the isolates were tested for ß-lactamase production using disks impregnated with Nitrocefin and hyperproduction of ß-lactamase using amoxicillin (20 µg) and clavulanic acid (10 µg) disks. RESULTS: Among the 100 S. aureus strains included in the study, 18.0% were resistant to oxacillin, with 16.1% MRSA being detected in the neonatal unit and 21.0% in the pediatric unit. The oxacillin (1 µg) and cefoxitin (30 µg) disk diffusion methods presented 94.4% and 100% sensitivity, respectively, and 98.8% specificity. The screening test showed 100% sensitivity and 98.8% specificity. All isolates produced ß-lactamase and one of these strains was considered to be a hyperproducer. CONCLUSIONS: The 30 µg cefoxitin disk diffusion method presented the best result when compared to the 1 µg oxacillin disk. The sensitivity of the agar screening test was similar to that of the cefoxitin disk diffusion method and higher than that of the oxacillin disk diffusion method. We observed variations in the percentage of oxacillin-resistant isolates during the study period, with a decline over the last years which might be related to improved nosocomial infection control and the rational use of antibiotics.

Is urine interleukin-8 level a reliable laboratory test for diagnosing late onset sepsis in premature infants?

The present study is aimed to determine serum and urine interleukin-8 (IL-8) levels in premature infants with late onset sepsis (LOS) and to evaluate if urine IL-8 is a useful test for LOS diagnosis. Fifty-six premature infants admitted to the NICU over 1 year had serum and urine IL-8 determined by ELISA. They were divided into three groups: I definite sepsis, II probable sepsis and III non-infected. Results were expressed as mean or median. Differences between groups were assessed by ANOVA, Kruskal-Wallis ANOVA and Dunn's Method. Sensitivity, specificity and positive and negative predictive values were calculated and a receiver operator characteristic curve was constructed to determine serum and urine IL-8 accuracy. There were no differences between groups for birth weight, and gestational and post-natal age. Median serum and urine IL-8 levels were significantly higher in GI and GII: 929 x 906 x 625 pg/ml; P = 0.024, and 249 x 189 x 42 pg/mgCr; P < 0.001. Optimal cut-off point was 625 pg/ml for serum IL-8 with 69% sensitivity and 75 pg/mgCr for urine IL-8 with 92% sensitivity. IL-8 can be determined in urine from premature infants with LOS and is an accurate and feasible diagnosis method.