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Objective To investigate if preterm neonates developed systemic hypertension after intravitreal bevacizumab for retinopathy of prematurity. Methods Patients who received treatment between January 1, 2011 and January 31, 2019 were eligible for inclusion. Patients with pre-existing hypertension, congenital eye disease, or who were discharged within 72 h of treatment were excluded. Charts were reviewed for baseline data, co-morbidities, and the development of systemic hypertension within 4 weeks post treatment. Results After exclusions, 64 patients were analyzed. New-onset systemic hypertension was identified in 44 (69%) infants. There were no statistical differences in the demographic characteristics or presence of co-morbidities between the hypertensive and non-hypertensive groups. Of those who developed hypertension, the majority presented within the first week post treatment (55%). Conclusions The majority of infants who received intravitreal bevacizumab developed new-onset systemic hypertension after treatment. Further studies may explore hypertension as a potential side effect of bevacizumab in the neonatal population.

Antibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the routine early antibiotic use in symptomatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 h after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.Trial Registration This project is registered at clinicaltrials.gov under the name “Antibiotic ‘Dysbiosis’ in Preterm Infants” with trial number NCT02784821.

Objectives To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7 weeks of gestational age and to assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age. Study design The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models. Results One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age. Conclusions Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.

To investigate if preterm neonates developed systemic hypertension after intravitreal bevacizumab for retinopathy of prematurity.Patients who received treatment between January 1, 2011 and January 31, 2019 were eligible for inclusion. Patients with pre-existing hypertension, congenital eye disease, or who were discharged within 72 h of treatment were excluded. Charts were reviewed for baseline data, co-morbidities, and the development of systemic hypertension within 4 weeks post treatment.After exclusions, 64 patients were analyzed. New-onset systemic hypertension was identified in 44 (69%) infants. There were no statistical differences in the demographic characteristics or presence of co-morbidities between the hypertensive and non-hypertensive groups. Of those who developed hypertension, the majority presented within the first week post treatment (55%).The majority of infants who received intravitreal bevacizumab developed new-onset systemic hypertension after treatment. Further studies may explore hypertension as a potential side effect of bevacizumab in the neonatal population.

Within a randomized prospective pilot study of preterm infants born at less than 33 weeks&rsquo, gestation, weekly fecal samples from 19 infants were collected and metabolomic analysis was performed. The objective was to evaluate for differences in fecal metabolites in infants exposed to antibiotics vs. not exposed to antibiotics in the first 48 h after birth. Metabolomics analysis was performed on 123 stool samples. Significant differences were seen in the antibiotics vs. no antibiotics groups, including pathways related to vitamin biosynthesis, bile acids, amino acid metabolism, and neurotransmitters. Early antibiotic exposure in preterm infants may alter metabolites in the intestinal tract of preterm infants. Broader multi-omic studies that address mechanisms will guide more prudent antibiotic use in this population.

Patent ductus arteriosus is associated with multiple comorbidities in premature infants, however a causal link or strategy to decrease these morbidities has not been found. The association between the patent ductus arteriosus and morbidities has biologic plausibility as, like any cardiac mixing lesion, a significant systemic to pulmonic shunt may lead to pulmonary over-circulation and systemic hypoperfusion. Understanding the underlying pathophysiology of associated morbidities in the setting of a patent ductus arteriosus may aid in risk stratifying infants and offer a patient targeted approach to infants with a pathological ductal shunt. While the deleterious impact of increased pulmonary blood flow maybe easier to identify, the impact on end-organ perfusion is more challenging. In this review, we will discuss the pathophysiology of a hemodynamically significant patent ductus arteriosus in premature infants, impact on end-organ perfusion and associated morbidities, and novel modalities to assess shunt volume and effect on end-organ perfusion.

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22–26 months corrected gestational age (cGA) compared with those randomized to placebo. STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs. placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine [SCr]/ cystatin C values at days 0, 7, 9 and 14). At 22–26 months cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) 30 mg/g, 23% had a systolic blood pressure (SBP) >95(th) percentile for age, and 40% had a diastolic blood pressure (DBP) >95(th) percentile for age. SBP >90(th) percentile occurred less often among recipients of erythropoietin (p95(th) percentile or DBP >90(th) or >95(th) percentiles. CONCLUSIONS: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22–26 months cGA. Recombinant erythropoietin (rhEpo) may protect ELGANs against long-term elevated SBP, but does not appear to protect from AKI, low eGFR, albuminuria or elevated DBP at 22–26 months cGA.

ObjectiveWe aim to assess the feasibility of a pragmatic randomized trial of antibiotics vs. no antibiotics in symptomatic premature infants after birth. Most premature infants are exposed to antibiotics after birth without evidence of benefit or harm for this practice. No study to date has attempted to randomize premature infants to antibiotics vs no antibiotics after birth.Study DesignInfants Results186 subjects were enrolled (98 infants and 88 mothers) were enrolled over a 2-year period. 56% of infants (n=55) were randomized; 48% of infants randomized to the no antibiotics arm were switched and received antibiotics within the first 48 hours after birth. Serious adverse events were not significantly different between the randomization arms.ConclusionThis is the first prospective randomized trial of antibiotics vs no antibiotics after birth in symptomatic premature infants. The results of this trial establish a framework of feasibility for a larger multicentered trial that is needed to evaluate the risks and benefits of routine antibiotic exposure in premature infants.

Antibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the Routine Early Antibiotic use in SymptOmatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 hours after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered betweenVeillonellaand the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.

We enrolled 98 infants (gestational age

Enteral feeding and composition play a chief role in the prevention and treatment of necrotizing enterocolitis (NEC). In the face of decades of research on this fatal disease, the exact mechanism of disease is still poorly understood. There is established evidence that providing mother's own breast milk and standardization of feeding regimens leads to a decreased risk for NEC. More recent studies have focused on the provision of donor human milk or an exclusive human milk diet in the endeavor to prevent NEC while still maintaining adequate nutrition to the premature infant. There is growing literature on the provision of specific human milk components and its effect on the incidence of NEC.

To use a large current prospective cohort of infants29 weeks to compare bronchopulmonary dysplasia (BPD) rates in black and white infants.The Prematurity and Respiratory Outcome Program (PROP) enrolled 835 infants born in 2011-2013 at29 weeks of gestation; 728 black or white infants survived to 36 weeks postmenstrual age (PMA). Logistic regression was used to compare BPD outcomes (defined as supplemental oxygen requirement at 36 weeks PMA) between the races, adjusted for gestational age (GA), antenatal steroid use, intubation at birth, and surfactant use at birth.Of 707 black or white infants with available BPD outcomes, BPD was lower in black infants (38% vs 45%), even though they were of significantly lower GA. At every GA, BPD was more common in white infants. The aOR for BPD was 0.60 (95% CI, 0.42-0.85; P = .004) for black infants compared with white infants after adjusting for GA. Despite the lower rate of BPD, black infants had a higher rate of first-year post-prematurity respiratory disease (black, 79%; white, 63%).In this large cohort of recently born preterm infants at29 weeks GA, compared with white infants, black infants had a lower risk of BPD but an increased risk of persistent respiratory morbidity.