Administration time of caffeine in preterm infants: systematic review and meta-analysis.

To assess the ideal time for caffeine administration in preterms, identifying its effects and safety. Study Design: Meta-analysis conducted including preterms <32 weeks GA or BW < 1500 g, comparing caffeine administration time: <24 x ≥24HOL, <48 x ≥48HOL, <72 x ≥72HOL. 18 studies included 76.998 patients. The median age of starting caffeine was the first 24 HOL. In the overall comparisons, there was reduction in patent ductus arteriosus (OR 0.71 [0.55, 0. 92]; low evidence), retinopathy of prematurity (OR 0.71 [0.54, 0.93]; moderate evidence), severe brain injury (OR 0.79 [0.70, 0.91]; moderate evidence), bronchopulmonary dysplasia (BPD) (OR 0.69 [0.59, 0.81]; moderate evidence), composite outcome of BPD or death (OR 0.76 [0.66, 0.88]; moderate evidence). Mortality increase was found (OR 1.20 [1.12, 1.29], very low evidence).Caffeine in the first 24 HOL has benefits in reducing morbidities associated with prematurity. Mortality finding is potentially due to survival bias.

Association between type of feeding at hospital discharge and nutritional status of Brazilian very preterm infants: a multicenter study.

OBJECTIVES: To examine trends over time in diet and size of very preterm infants, and associations of diet with size at hospital discharge/transfer. METHODS: The authors studied 4062 surviving very preterm infants born < 32 weeks' gestational age and < 1500 g between January 2012 and December 2020 from 12 Brazilian Neonatal Intensive Care Units. Diet type at discharge/transfer was classified as exclusive human milk, exclusive formula, or mixed. Outcomes were weight and head circumference at hospital discharge and the change in each from birth to discharge. The authors used linear regression to estimate adjusted associations of diet type with infant size, overall, and stratified by fetal growth category (small vs. appropriate for gestational age). The authors also examined trends in diet and infant size at discharge over the years. RESULTS: Infants' mean gestational age at birth was 29.3 weeks, and the mean birth weight was 1136 g. Diet at discharge/transfer was exclusive human milk for 22 %, mixed for 62 %, and exclusive formula for 16 %. Infant size in weight and head circumference were substantially below the growth chart reference for all diets. Infants fed human milk and mixed diets were lighter and had smaller heads at discharge/transfer than infants fed formula only (weight z: -2.0, -1.8, and -1.5; head z: -1.3, -1.2 and -1.1 for exclusive human milk, mixed and exclusive formula respectively). CONCLUSION: Results suggest high human milk use but gaps in nutrient delivery among hospitalized Brazilian very preterm infants, with little evidence of improvement over time.

Parent-Guided Developmental Intervention for Infants With Very Low Birth Weight: A Randomized Clinical Trial.

Importance: Early interventions improve neurodevelopmental outcomes after preterm birth, but few studies of early intervention have focused on preterm infants whose families reside in low- or middle-income countries (LMICs). Objective: To evaluate whether parent-guided early intervention improves the neurodevelopmental outcomes of preterm infants in an LMIC. Design, Setting, and Participants: This randomized clinical trial was performed at a high-risk obstetric referral hospital in Brazil, with outcome evaluations by examiners masked to randomization group. Eligibility criteria were (1) birth at the study hospital, (2) residence within 40 km of the birth hospital, and (3) gestational age of less than 32 weeks or birth weight of less than 1500 g. Of 138 enrolled infants, 19 died after randomization and 19 withdrew from the study; all other enrollees (50 per randomization group) were evaluated for the primary outcome. Data were collected from January 1, 2016, to May 31, 2022, and analyzed from June 10 to July 31, 2022. Interventions: On postnatal day 7, infants were randomized to usual care, consisting of support for lactation, kangaroo care, and routine developmental therapies, or to a parent-guided enhanced developmental intervention, consisting of usual care plus infant massage and enhanced visual stimulation, auditory stimulation, social interactions, and support for motor development, instructed by developmental therapists. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development-Third Edition score at 18 months of age adjusted for prematurity. Results: Among the 100 infants included in the analysis, mean (SD) gestational age was 28.4 (2.2) weeks, and 57 (57%) were male. The mean (SD) gestational age for the intervention group was 28.3 (2.3) weeks; for the usual care group, 28.5 (2.2) weeks. Female infants accounted for 21 infants (42%) of the intervention group and 22 (44%) of the usual care group; male infants, 29 (58%) and 28 (56%), respectively. The enhanced developmental intervention group had higher cognitive scores at 18 months of corrected age (mean [SD], 101.8 [11.9] vs 97.3 [13.5]; mean difference, 4.5 [95% CI, 0.1-8.9]). Conclusions and Relevance: In this randomized clinical trial of a parent-guided developmental intervention for early cognitive function of very preterm or very low birth weight infants implemented in an LMIC, the intervention improved very preterm infants' neurodevelopmental outcomes at 18 months of adjusted age. Parent-guided early intervention can improve neurodevelopmental outcome of very preterm infants born in LMICs. Trial Registration: ClinicalTrials.gov Identifier: NCT02835612.

Antibiotics and beyond: Unraveling the dynamics of bronchopulmonary dysplasia in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care. Prenatal inflammation and neonatal sepsis contribute to the multifactorial nature of BPD. A potential association between empirical antibiotic therapy and BPD risk has been proposed due to microbiota dysbiosis in very low birth weight premature infants. METHODS: A single centered retrospective cohort study of preterm infants (24-32 weeks gestation) from 2014 to 2021. The study compared groups that received empirical antibiotics in the first days of life and those that did not receive any antibiotic in the first days of life. The primary outcomes studied were BPD, death, and the combined outcome of BPD/death. Statistical analysis employed t-tests, Mann-Whitney U, Chi-square, and logistic regression. RESULTS: Of 454 preterm infants, 61.5% received antibiotics. This group had lower gestational age, birth weight, and Apgar scores. Antibiotic use was associated with higher incidence of BPD (35.5% vs. 10.3%), death (21.5% vs. 8.6%), and combined outcomes (54.5% vs. 18.3%). In multivariate analysis, antibiotic use independently associated with BPD (OR 2.58, p < 0.001) and combined outcome BPD/death (OR 2.06, p < 0.02). Antenatal corticosteroids provided protection against BPD, but not mortality. CONCLUSION: This study suggests an association between early empirical antibiotic use and BPD in preterm infants, emphasizing the need for judicious antibiotic practices in neonatal care.

Developmental coordination disorder in preterm children: A systematic review and meta-analysis.

This study aimed to review the prevalence of developmental coordination disorder (DCD) in individuals born preterm and systematically explore this prevalence according to gestational age and different assessment cut-offs and compare it to full-term peers. The eligibility criteria were observational and experimental studies reporting the prevalence of DCD in preterm individuals. A systematic search was performed in databases from inception until March 2022. Two independent reviewers performed the selection. Study quality assessment was performed using the checklists from Joanna Briggs Institute (JBI). Data analysis was performed on Excel and Review Manager Software 5.4. Among the 1774 studies identified, 32 matched the eligibility criteria. The pooled estimate rate of the DCD rate in preterm was 21% (95% confidence interval [CI] 17.8-24.3). The estimate rates were higher as gestational age decreased, and preterm children are two times more likely to have DCD than their full-term peers risk ratio (RR) 2.2 (95% CI 1.77-2.79). The limitation was high heterogeneity between studies; the assessment tools, cut-off points and age at assessment were diverse. This study provided evidence that preterm children are at higher risk for DCD than full-term children, and the risks increased as gestational age decreased.

Whole genome sequencing as a first-tier diagnostic test for infants in neonatal intensive care units: A pilot study in Brazil.

In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first-tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X-linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting.

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.

Cytokine Levels in Neonates: Unveiling the Impact of Perinatal Inflammation on Prematurity.

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-ß [TGF-ß]) were evaluated. RESULTS: Premature newborns exhibited higher levels of IL-6, IL-8, and IL-10, while TNF-α and TGF-ß 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.

The Influence of Early Nutrition on Neurodevelopmental Outcomes in Preterm Infants.

Premature infants, given their limited reserves, heightened energy requirements, and susceptibility to nutritional deficits, require specialized care. AIM: To examine the complex interplay between nutrition and neurodevelopment in premature infants, underscoring the critical need for tailored nutritional approaches to support optimal brain growth and function. DATA SOURCES: PubMed and MeSH and keywords: preterm, early nutrition, macronutrients, micronutrients, human milk, human milk oligosaccharides, probiotics AND neurodevelopment or neurodevelopment outcomes. Recent articles were selected according to the authors' judgment of their relevance. Specific nutrients, including macro (amino acids, glucose, and lipids) and micronutrients, play an important role in promoting neurodevelopment. Early and aggressive nutrition has shown promise, as has recognizing glucose as the primary energy source for the developing brain. Long-chain polyunsaturated fatty acids, such as DHA, contribute to brain maturation, while the benefits of human milk, human milk oligosaccharides, and probiotics on neurodevelopment via the gut-brain axis are explored. This intricate interplay between the gut microbiota and the central nervous system highlights human milk oligosaccharides' role in early brain maturation. CONCLUSIONS: Individualized nutritional approaches and comprehensive nutrient strategies are paramount to enhancing neurodevelopment in premature infants, underscoring human milk's potential as the gold standard of nutrition for preterm infants.

Autopsy in a Neonatal Intensive Care Unit: pathological and clinical agreement

Abstract Objectives To evaluate neonatal autopsy rates at a tertiary hospital in southern Brazil ascertain the level of agreement between premortem and postmortem diagnosis. Methods The authors reviewed all neonatal autopsies performed over a 10-year period and described the percentage of neonates who died and underwent autopsy. The authors tested for agreement between autopsy findings and the cause of death as defined by the neonatologist. Agreement between clinical diagnosis and autopsy findings was classified using the modified Goldman criteria. Additional findings at autopsy were grouped by organ system. Linear regression and multiple comparisons were used for statistical analyses. Results During the study period, 382 neonates died at the Neonatal Intensive Care Unit (NICU). Consent to perform an autopsy was obtained for 73 (19.1%). The complete agreement between autopsy findings and the neonatologist's premortem diagnosis was found in 48 patients (65.8%). Additional findings were obtained at autopsy in 25 cases (34.2%). In 5 cases (6.9%), the autopsy findings contributed to subsequent genetic counseling. Seven autopsies (9.6%) revealed a diagnosis that would have changed patient management if established premortem. The autopsy rate increased by an average of 1.87% each year. Conclusion Despite a high level of agreement between clinical diagnosis and pathological findings, autopsies provided relevant data regarding the cause of death, providing additional clinical information to neonatologists and allowing genetic counseling of family members.

Translating Neonatal Resuscitation Guidelines Into Practice in Brazil.

BACKGROUND AND OBJECTIVES: The Brazilian Neonatal Resuscitation Program releases guidelines based on local interpretation of international consensus on science and treatment recommendations. We aimed to analyze whether guidelines for preterm newborns were applied to practice in the 20 Brazilian Network on Neonatal Research centers of this middle-income country. METHODS: Prospectively collected data from 2014 to 2020 were analyzed for 8514 infants born at 230/7 to 316/7 weeks' gestation. The frequency of procedures was evaluated by gestational age (GA) category, including use of a thermal care bundle, positive pressure ventilation (PPV), PPV with a T-piece resuscitator, maximum fraction of inspired oxygen (Fio2) concentration during PPV, tracheal intubation, chest compressions and medications, and use of continuous positive airway pressure in the delivery room. Logistic regression, adjusted by center and year, was used to estimate the probability of receiving recommended treatment. RESULTS: For 3644 infants 23 to 27 weeks' GA and 4870 infants 28 to 31 weeks' GA, respectively, the probability of receiving care consistent with guidelines per year increased, including thermal care (odds ratio [OR], 1.52 [95% confidence interval (CI) 1.44-1.61] and 1.45 [1.38-1.52]) and PPV with a T-piece (OR, 1.45 [95% CI 1.37-1.55] and 1.41 [1.32-1.51]). The probability of receiving PPV with Fio2 1.00 decreased equally in both GA groups (OR, 0.89; 95% CI, 0.86-0.93). CONCLUSIONS: Between 2014 and 2020, the resuscitation guidelines for newborns <32 weeks' GA on thermal care, PPV with a T-piece resuscitator, and decreased use of Fio2 1.00 were translated into clinical practice.

Autopsy in a Neonatal Intensive Care Unit: pathological and clinical agreement.

OBJECTIVES: To evaluate neonatal autopsy rates at a tertiary hospital in southern Brazil ascertain the level of agreement between premortem and postmortem diagnosis. METHODS: The authors reviewed all neonatal autopsies performed over a 10-year period and described the percentage of neonates who died and underwent autopsy. The authors tested for agreement between autopsy findings and the cause of death as defined by the neonatologist. Agreement between clinical diagnosis and autopsy findings was classified using the modified Goldman criteria. Additional findings at autopsy were grouped by organ system. Linear regression and multiple comparisons were used for statistical analyses. RESULTS: During the study period, 382 neonates died at the Neonatal Intensive Care Unit (NICU). Consent to perform an autopsy was obtained for 73 (19.1%). The complete agreement between autopsy findings and the neonatologist's premortem diagnosis was found in 48 patients (65.8%). Additional findings were obtained at autopsy in 25 cases (34.2%). In 5 cases (6.9%), the autopsy findings contributed to subsequent genetic counseling. Seven autopsies (9.6%) revealed a diagnosis that would have changed patient management if established premortem. The autopsy rate increased by an average of 1.87% each year. CONCLUSION: Despite a high level of agreement between clinical diagnosis and pathological findings, autopsies provided relevant data regarding the cause of death, providing additional clinical information to neonatologists and allowing genetic counseling of family members.

Meconium microbiota predicts clinical early-onset neonatal sepsis in preterm neonates.

BACKGROUND: Early-onset neonatal sepsis (EONS) remains one of the leading causes of morbidity and mortality related to premature birth, and its diagnosis remains difficult. Our goal was to evaluate the intestinal microbiota of the first meconium of preterm newborns and ascertain whether it is associated with clinical EONS. METHODS: In a controlled, prospective cohort study, samples of the first meconium of premature infants with a gestational age (GA) ≤32 weeks was obtained at Hospital de Clínicas de Porto Alegre and DNA was isolated from the samples. 16S rDNA based microbiota composition of preterm infants with a clinical diagnosis of EONS was compared to that of a control group. RESULTS: 40 (48%) premature infants with clinical diagnosis of EONS and 44 (52%) without EONS were included in the analysis. The most abundant phylum detected in both groups, Proteobacteria, was more prevalent in the sepsis group (p = .034). 14% of variance among bacterial communities (p = .001) correlated with EONS. The genera most strongly associated with EONS were Paenibacillus, Caulobacter, Dialister, Akkermansia, Phenylobacterium, Propionibacterium, Ruminococcus, Bradyrhizobium, and Alloprevotella. A single genus, Flavobacterium, was most strongly associated with the control group. CONCLUSION: These findings suggest that the first-meconium microbiota is different in preterm neonates with and without clinical EONS.

Early Detection of Cognitive, Language, and Motor Delays for Low-Income Preterm Infants: A Brazilian Cohort Longitudinal Study on Infant Neurodevelopment and Maternal Practice.

Aim: This study examined the neurodevelopment trajectories, the prevalence of delays, and the risks and protective factors (adverse outcomes, environment, and maternal factors) associated with cognitive, motor, and language development for preterm infants from 4- to 24-months. Method: We assessed 186 preterm infants (24.7% extremely preterm; 54.8% very preterm; 20.4% moderate/late preterm) from 4- to 24-months using the Bayley Scales of Infant Development - III. Maternal practices and knowledge were assessed using the Daily Activities of Infant Scale and the Knowledge of Infant Development Inventory. Birth risks and adverse outcomes were obtained from infant medical profiles. Results: A high prevalence of delays was found; red flags for delays at 24-months were detected at 4- and 8-months of age. The neurodevelopmental trajectories showed steady scores across time for cognitive composite scores for extremely- and very-preterm infants and for language composite scores for the extremely- and moderate/late-preterm; a similar trend was observed for the motor trajectories of moderate/late preterm. Changes over time were restricted to motor composite scores for extremely- and very-preterm infants and for cognitive composite scores for moderate/late preterm; declines, stabilization, and improvements were observed longitudinally. Positive, strong, and significant correlations were for the neurodevelopment scores at the first year of life and later neurodevelopment at 18 and 24 months. The cognitive, language, and motor composite scores of extremely and very preterm groups were associated with more risk factors (adverse outcomes, environment, and maternal factors). However, for moderate/late preterm infants, only APGAR and maternal practices significantly explained the variance in neurodevelopment. Discussion: Although adverse outcomes were strongly associated with infant neurodevelopment, the environment and the parents' engagement in play and breastfeeding were protective factors for most preterm infants. Intervention strategies for preterm infants should start at 4- to 8-months of age to prevent unwanted outcomes later in life.

Does ADHD worsen inhibitory control in preschool children born very premature and/or with very low birth weight?

INTRODUCTION: Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW. METHODS: 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children - Present and Lifetime Version (K-SADS-PL). IC was measured with Conners' Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P).Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times. CONCLUSIONS: ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children's EFs are already so impaired that there is not much room for additional impairments imposed by ADHD.

Does ADHD worsen inhibitory control in preschool children born very premature and/or with very low birth weight?

Abstract Introduction Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/hyperactivity disorder (ADHD). Objective To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW. Methods 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children - Present and Lifetime Version (K-SADS-PL). IC was measured with Conners' Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P).Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times. Conclusions ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children's EFs are already so impaired that there is not much room for additional impairments imposed by ADHD.

Meconium microbiome and its relation to neonatal growth and head circumference catch-up in preterm infants.

The purpose was identify an association between meconium microbiome, extra-uterine growth restriction, and head circumference catch-up. MATERIALS AND METHODS: Prospective study with preterm infants born <33 weeks gestational age (GA), admitted at Neonatal Unit and attending the Follow-Up Preterm Program of a tertiary hospital. Excluded out born infants; presence of congenital malformations or genetic syndromes; congenital infections; HIV-positive mothers; and newborns whose parents or legal guardians did not authorize participation. Approved by the institution's ethics committee. Conducted 16S rRNA sequencing using PGM Ion Torrent meconium samples for microbiota analysis. RESULTS: Included 63 newborns, GA 30±2.3 weeks, mean weight 1375.80±462.6 grams, 68.3% adequate weight for GA at birth. Polynucleobacter (p = 0.0163), Gp1 (p = 0.018), and Prevotella (p = 0.038) appeared in greater abundance in meconium of preterm infants with adequate birth weight for GA. Thirty (47.6%) children reached head circumference catch-up before 6 months CA and 33 (52.4%) after 6 months CA. Salmonella (p<0.001), Flavobacterium (p = 0.026), and Burkholderia (p = 0.026) were found to be more abundant in meconium in the group of newborns who achieved catch-up prior to 6th month CA. CONCLUSION: Meconium microbiome abundance was related to adequacy of weight for GA. Meconium microbiome differs between children who achieve head circumference catch-up by the 6th month of corrected age or after this period.

Use of Azithromycin for the Prevention of Lung Injury in Mechanically Ventilated Preterm Neonates: A Randomized Controlled Trial.

INTRODUCTION: Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. METHODS: This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for Ureaplasma. Patients were followed up throughout the hospital stay for the outcomes of death and broncho-pulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). RESULTS: Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O2 dependency at 28 days/death in azithromycin-treated patients regardless of the detection of Ureaplasma in blood. CONCLUSIONS: Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O2 dependency at 28 days/death in mechanically ventilated preterm neonates.

Impact of a pre-feeding oral stimulation program on first feed attempt in preterm infants: Double-blind controlled clinical trial.

OBJECTIVE: To evaluate the effect of an oral stimulation program in preterm on the performance in the first oral feeding, oral feeding skills and transition time from tube to total oral intake. STUDY DESIGNER: Double-blind randomized clinical trial including very preterm newborns. Congenital malformations, intracranial hemorrhage grade III or IV, bronchopulmonary dysplasia, and necrotizing enterocolitis were excluded. Intervention group (GI) received an oral stimulation program of tactile extra-, peri-, and intraoral tactile manipulation once a day for 15 minutes, during a 10-day period. Control group (GII) received sham procedure with same duration of time. Feeding ability was assessed by a speech-language pathologist blinded to group assignment. The classification of infants' oral performance was determined by Oral Feeding Skills (OFS). Neonates were monitored until hospital discharge. RESULTS: Seventy-four (37 in each group) were randomized. Mean gestational ages and birth weights were 30±1.4 and 30±1.5 weeks, and 1,452±330g and 1,457±353g for intervention and control groups, respectively. Infants in the intervention group had significantly better rates than infants in the control group on: mean proficiency (PRO) (41.5%±18.3 vs. 19.9%±11.6 (p<0.001)), transfer rate (RT) (2.3 mL/min and 1.1 mL/min (p<0.001)) and overall transfer (OT) (57.2%±19.7 and 35.0%±15.7 (p<0.001)). Median transition time from tube to oral feeding was 4 (3-11) and 8 (7-13) days in intervention and control groups, respectively (p = 0.003). Intake of breast milk was found to reduce transition time from tube feeds to exclusive oral feeding (p<0.001, HR 1.01, 95%CI 1.005-1.019), but the impact of the study intervention remained significant (p = 0.007, HR 1.97, 95%CI 1.2-3.2). CONCLUSION: Infants who were breast-fed and an oral stimulation program proved beneficial in reducing transition time from tube feeding to oral feeding. TRIAL REGISTRATION: ClinicalTrials.gov number NCT03025815.

Neonatal Adverse Outcomes, Neonatal Birth Risks, and Socioeconomic Status: Combined Influence on Preterm Infants' Cognitive, Language, and Motor Development in Brazil.

BACKGROUND: This study extended previous research by investigating the combined effects of neonatal birth risks, neonatal adverse outcomes, and socioeconomic status on preterm neurodevelopment. METHOD: A total of 184 preterm infants were assessed using the Bayley Scales of Infant Development III in a follow-up clinic in southern Brazil. Structural equation modeling was conducted with 3 latent variables (neonatal birth risks, neonatal adverse outcomes, and socioeconomic status) and 3 outcomes (cognitive, language, and motor development). RESULTS: The analyses showed that neonatal adverse outcomes were associated with infants' cognitive (b = -0.45, P < .001), language (b = -0.23, P = .001), and motor (b = -0.51, P < .001) development. Socioeconomic status also explained the variances (cognitive: b = 0.20, P = .006; language: b = 0.28, P = .001; and motor: b = 0.21, P = .004), whereas neonatal birth risks remained significant only in the motor development (b = 0.15, P = .040). CONCLUSION: This study suggests that the most evident contributors to poor neurodevelopment were adverse outcomes and socioeconomic risk factors.