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Objective: This study aimed to investigate the association between variations in cytokine levels in the first 72 hours of life and prematurity., Study Design: In this prospective study, we examined the cytokine levels of 110 newborns in the first 72 hours of life. The participants were divided into two groups based on gestational age (66 very preterm and 44 term newborns), and cytokine levels (interleukin [IL]-6, IL-8, and IL-10, tumor necrosis factor-α [TNF-α], and transforming growth factor-β [TGF-β]) were evaluated., Results: Premature newborns exhibited higher levels of IL-6, IL-8, and IL-10, while TNF-α and TGF-β levels were lower comparing to term newborns. Even after adjusting for maternal and peripartum factors, the significant differences persisted., Conclusion: Our study underscores significant cytokine profile differences between full-term and very preterm newborns in early life. Elevated IL-6 and IL-8 levels in preterm infants suggest potential perinatal inflammation links to prematurity., Key Points: · There is a direct association between cytokine levels and prematurity.. · Knowledge of the variation of cytokines in newborns enhances personalized interventions.. · Cytokine levels are early associated with gestational age., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to describe the experience with a protocol of therapeutic hypothermia (TH) in southern Brazil., Study Design: Newborns with gestational age > 35 weeks with evidence of perinatal asphyxia plus moderate or severe encephalopathy were recruited between March 2011 and November 2017. Whole-body hypothermia for 72 hours, starting within the first 6 hours of life was used. Survivors underwent magnetic resonance imaging (MRI) and electroencephalogram (EEG). The primary outcome was death during hospitalization and neurodevelopment assessed using the Bayley Scales of Infant Development III (BSID III) at 12 months of age., Results: A total of 72 newborns were treated (41 with moderate encephalopathy and 31 with severe encephalopathy), of whom 16 died. MRI was performed in 56 patients, and 24 presented some alterations. Fifty-three patients had an EEG: 11 normal, 20 mildly altered, 12 moderately altered, and 10 severely altered. Forty patients were evaluated through BSID III: 45% presented with some delay in neurodevelopment, 8 (20%) had motor retardation, 15 (37.5%) had language delay, and 13 (32.5%) had a delay in cognitive development., Conclusion: Mortality and adverse events were similar to those described in large randomized controlled trials. TH is a safe and an effective method of neurologic protection in asphyxiated newborns in a developing country when performed adequately., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To verify the prevalence of systemic arterial hypertension (SAH) and to identify possible early predictors of SAH at ages 2 and 4 years in very low birth weight (VLBW) infants., Study Design: This is a prospective cohort study including inborn children with birth weight (BW) <1,500 g. Arterial blood pressure measurements were performed at 2 and 4 years. Model 1 compared children with and those without SAH at age 4. Model 2 compared children who had SAH at ages 2 and 4 with the others. SAH was diagnosed if the systolic or/and diastolic pressures were above the 95th percentile., Results: A total of 198 patients were included during the 5-year study period, of whom 56% had SAH at age 4. In model 1, white matter injury (WMI) and catch-up growth at age 2 were predictors of SAH at age 4. In model 2, bronchopulmonary dysplasia, WMI, catch-up growth at age 2, and BW were predictors of SAH at 2 and 4 years. SAH at age 2 was an independent risk factor for SAH at age 4. After a multivariate analysis of model 2, BW and catch-up growth were associated with SAH., Conclusion: Prevalence of SAH was high in VLBW infants; it was associated with low BW and catch-up growth at age 2., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Phototherapy in neonates for treatment of pathological jaundice is an effective therapeutic tool that is widely used in neonatal units. Over the past years, a greater concern has emerged about the effects on the immune and inflammatory system and its potential genotoxic and side effects, especially the late ones, possibly associated with childhood diseases, showing that this treatment is not as harmless as previously believed. Numerous studies assessing these possible adverse effects of phototherapy on neonates have been published over the past years. Through this review, we seek to analyze what we know about the side effects of phototherapy in the neonatal period. The main causes of jaundice, phototherapy techniques, acute and late side effects, and effects on the immune and inflammatory system were reviewed. It was concluded that phototherapy is not a treatment free of side effects and further studies need to be conducted to elucidate its harmful effects on neonates., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective:  The objective of this study was to investigate the neurodevelopment and growth of very low birth weight (BW) preterm infants, at 8 and 18 months corrected age (CA), compared with full term in Brazil., Methods:  Prospective cohort study including 83 preterm infants with BW ≤ 1,500 g and gestational age ≤ 32 weeks, and 52 full-term control infants. Preterm infants free from significant sensory and motor disability, and from congenital anomalies were included. Alberta infant motor scale (AIMS) and Brunet-Lèzini scale (BLS) were used to evaluate the neurodevelopment at 8 and 18 months. Anthropometric measurements were collected to evaluate the growth in both age groups., Results:  At 8 months CA, preterm infants scored significantly lower in total AIMS score ( p  = 0.001). At 18 months, they scored significantly lower on the stand subscale from AIMS ( p  = 0.040) and exhibited poor psychomotor development in the BLS ( p  = 0.006). The nutritional status showed significant differences between the groups, in both age groups ( p  < 0.001). There were positive correlations between nutritional status and AIMS ( r  = 0.420; p  < 0.001) and BLS ( r  = 0.456; p  < 0.001) at 8 months, and between head circumference and BLS ( r  = 0.235; p  < 0.05) at 8 months and AIMS ( r  = 0.258; p  < 0.05) at 18 months., Conclusion:  Very low BW preterm infants at 8 and 18 months CA showed significant differences in the neurodevelopment and growth pattern when compared with their full-term peers., Competing Interests: Conflict of Interest: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction  Bronchopulmonary dysplasia (BPD) is a frequent, long-term complication in very low-birth-weight (VLBW) newborns. Its etiology is multifactorial and the oxidative stress is one of its main causes. Breast milk (BM) reduces oxidative stress and provides antioxidant protection, therefore, BM may have a protective effect against BPD. Objectives  This study aims to assess the possible protective effects of BM on BPD. Methods  This is a cohort study including infants with a birth weight below 1,500 g and/or gestational age of less than 32 weeks, born between January 2011 and October 2014. BPD was defined as the need for supplementary oxygen for 28 days or more. Results  The incidence of BPD was 29.1%. The median amount of BM received by the patients in the first 6 weeks of life was significantly higher in patients without BPD (10.8 mL/kg/day) than in those with BPD (2.3 mL/kg/day). The amount of BM received was inversely associated with the incidence of BPD, even after multivariate analysis. The cutoff point at which the protective effect emerged was an average amount of 7 mL/kg/day of BM during the first 42 days of life. Conclusion  Feeding VLBW infants with BM is associated with a lower risk of developing BPD., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Bronchopulmonary dysplasia (BPD) is associated with changes in pulmonary angiogenesis. However, the role of the vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer, an antiangiogenic factor, remains unknown in this disease., Objective: To compare VEGF/PlGF levels in preterm infants with and without BPD., Methods: This study was approved by the Institutional Review Board. Preterm neonates with birth weight <2,000 g and gestational age ≤ 34 weeks were included. Exclusion criteria were: neonates transferred from other institutions after 72 hours of life; death before blood collection; presence of major congenital malformations, inborn errors of metabolism, and early sepsis; and mothers with multiple pregnancies, TORCH infections, HIV infection, or autoimmune diseases. BPD was defined as the need for oxygen therapy for a period equal to or greater than 28 days, accompanied by radiographic changes compatible with the disease. Blood was collected from neonates in the first 72 hours of life. VEGF/PlGF levels were measured using the enzyme-linked immunosorbent assay method. The chi-square test, t-test, Mann-Whitney test, analysis of variance, and Kruskal-Wallis test were used for statistical analysis. Variables found to be significant in the univariate analysis were included in the multivariate analysis., Results: Seventy-three patients were included (19 with BPD, 43 without BPD, and 11 neonates who died in the first 28 days of life), with a mean (SD) gestational age of 30.32 (2.88) weeks and birth weight of 1,288 (462) g. Median VEGF/PlGF levels were higher in the groups with BPD and death in the first 28 days of life than in the group without BPD (16.46 [IQR, 12.19-44.57] and 20.64 [IQR, 13.39-50.22], respectively, vs. 9.14 [IQR, 0.02-20.64] pg/mL], p < 0.001). Higher VEGF/P1GF levels remained associated with BPD and death in the first 28 days of life in the multivariate analysis., Conclusion: Higher plasma VEGF/PlGF levels were found in preterm neonates with BPD and in those who died in the first 28 days of life, suggesting an important role of this substance in pulmonary vascular development., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborns remains unknown., Objective: This study aims to measure vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels in preterm neonates born to mothers with PE., Methods: Neonates with birth weight<2,000 g and gestational age≤34 weeks were included and divided into the following two groups: born to mothers with PE and without PE. Blood was collected from neonates within the first 72 hours of life. VEGF and sFlt-1 levels were measured using the enzyme-linked immunosorbent assay method., Results: A total of 88 neonates were included (37 born to mothers with PE and 51 born to mothers without PE), with a mean gestational age of 29.12±2.96 weeks and birth weight of 1,223.80±417.48 g. In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age., Conclusion: Higher sFlt-1 and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Aim: To assess the influence of gestational age and perinatal nutrition on development at 24 months' corrected age in a cohort of very low-birth-weight preterm infants., Methods: One hundred twenty-five very low-birth-weight preterm infants admitted to a neonatal intensive care unit within the first 48 hours of life were studied. The infants were classified as born small for gestational age (SGA) and still SGA at discharge (SGA/SGA); born adequate for gestational age (AGA) and SGA at discharge (AGA/SGA); and born AGA and still AGA age at discharge (AGA/AGA). The Bayley Scales of Infant and Toddler Development III (BSID-III) were used for assessment of neurodevelopment at 24 months' corrected age., Results: Fifty-six infants were classified as SGA/SGA, 55 as AGA/SGA, and 14 as AGA/AGA with no difference in BSID-III among the groups. By multiple linear regression analysis, the variables associated to better neurodevelopment outcome were higher gestational age and absence of grade III/IV periventricular/intraventricular hemorrhage., Conclusion: Immaturity is the most important variable associated with better neurodevelopment outcome in very preterm infants., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Aim: To evaluate bone metabolism in newborn preterm infants before and after a physical therapy protocol., Method: This randomized controlled clinical trial included 30 newborn preterm infants with gestational age ≤ 35 weeks and appropriate weight for gestational age, who were randomized into control group (CG) and physiotherapy group (PG). The PG protocol consisted of 15 minutes of daily passive movements with gentle joint compression 5 days a week. Daily data were obtained on feeding and body weight. Measurements of bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were collected before and after intervention in both groups. The analysis of covariance test was performed to compare the means of both groups., Results: At baseline, gestational age and corrected gestational age, birth weight, and gender were similar between both groups. Nutrient supply, length of total parenteral nutrition, and mechanical ventilation were also similar. BAP level increase in PG was 22.44 ± 3.49 U/L, whereas in CG was 2.87 ± 3.99 U/L (p = 0.003). There was a reduction of DPD levels in PG of 28.21 ± 11.05 nmol/mmol, and an increase of 49.95 ± 11.05 nmol/mmol (p < 0.001) in GC., Conclusion: The benefits of prevention and treatment of metabolic bone disease of prematurity, in addition to an adequate diet, should include these passive exercises with gentle joint compressions to improve the quality of premature infant's bones., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We sought to determine cytokine response in term and late preterm newborn infants on phototherapy. Twenty newborn infants with gestational age > or = 35 weeks and birth weight > or = 2000 g in the first week of life had serum interleukin (IL)-6, IL-8, IL-10, IL-1beta, and tumor necrosis factor (TNF)-alpha measured immediately prior to and after 24 hours on phototherapy. Exclusion criteria were newborns with severe congenital malformations, congenital infections, birth asphyxia, sepsis, hemolytic anemia that required blood transfusion, maternal-infant Rh incompatibility and those who required exchange transfusion or intravenous immunoglobulin treatment for hyperbilirubinemia. Median IL-6 concentrations significantly decreased after 24 hours on phototherapy (18.3 pg/mL and 7.85 pg/mL, respectively, p = 0.005). IL-6 concentrations decreased in 17 out of the 20 newborns. There were no statistical differences in IL-8, IL-10, IL-1beta, and TNF-alpha concentrations before and after 24 hours on phototherapy. There was a statistically significant correlation between IL-6 decline and irradiance (r = 0.57, p = 0.009). The finding that serum IL-6 decreases in newborn under phototherapy suggests that phototherapy possibly has an anti-inflammatory effect, although the clinical implications of this study deserve further studies., (Copyright Thieme Medical Publishers.)