Comparison of New Bronchopulmonary Dysplasia Definitions on Long-Term Outcomes in Preterm Infants.

OBJECTIVE: To compare the discriminative performances of the 2018 National Institutes of Health (NIH) and the 2019 Jensen definitions of bronchopulmonary dysplasia (BPD) with the 2001 NIH definition on adverse neurodevelopmental and respiratory outcomes at 2 years and 5 years corrected age. STUDY DESIGN: In this single-center retrospective cohort study, outcomes of infants born at <30 weeks of gestational age were collected. The 3 definitions of BPD were compared by adding the different definitions to the National Institute of Child Health and Human Development's outcome prediction model for neurodevelopmental impairment (NDI) or death. Discriminative performance was compared for both outcomes at 2 years and 5 years corrected age by calculating the areas under the receiver operating characteristic curve and z-statistics. RESULTS: The presence of BPD and its severity were determined in 584 infants. There were considerable shifts in BPD grading among the different definitions. At both time points, all BPD definition models had comparable discriminating power for NDI and respiratory morbidity, with one exception. Compared with the 2001 NIH definition, the 2018 NIH definition had less predictive power for the neurologic outcome at 2 years corrected age. CONCLUSIONS: Our comparison of the 3 BPD definitions shows similar discriminative performance on long term neurodevelopmental and respiratory outcomes at 2 years and 5 years corrected age.

Severity of Bronchopulmonary Dysplasia and Neurodevelopmental Outcome at 2 and 5 Years Corrected Age.

OBJECTIVE: To evaluate the association between bronchopulmonary dysplasia (BPD) severity and risk of neurodevelopmental impairment (NDI) at 2 years and 5 years corrected age and to examine whether this association changes over time. STUDY DESIGN: This single-center retrospective cohort study included patients with a gestational age <30 weeks surviving to 36 weeks postmenstrual age, divided into groups according to BPD severity. NDI was defined as having cognitive or motor abilities below -1 SD, cerebral palsy, or a hearing or a visual impairment. The association was assessed using a multivariate logistic regression model analysis, adjusting for known confounders for NDI, and mixed-model analysis. RESULTS: Of the 790 surviving infants (15% diagnosed with mild BPD, 9% with moderate BPD, and 10% with severe BPD), 88% and 82% were longitudinally assessed at 2 years and 5 years corrected age, respectively. The mixed-model analysis showed a statistically significant increase in NDI at all levels of BPD severity compared with infants with no BPD, and a 5-fold increased risk in NDI was seen from 2 years to 5 years corrected age in all degrees of BPD severity. The strength of this association between NDI and BPD severity did not change over time. CONCLUSIONS: Increased BPD severity is associated with increased risk of NDI at both 2 years and 5 years corrected age. The absolute incidence of NDI increased significantly from 2 years to 5 years corrected age for all BPD severity categories, but this increased risk was similar at both time points in each category.

Risk Factors for Neurodevelopmental Impairment at 2- and 5-Years Corrected Age in Preterm Infants with Established Bronchopulmonary Dysplasia.

INTRODUCTION: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). METHODS: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks' postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. RESULTS: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57-0.95; aOR 0.70, 95% CI 0.54-0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09-9.61; aOR 5.44, 95% CI 1.62-18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11-5.57). CONCLUSION: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI.

Association between bronchopulmonary dysplasia severity and its risk factors and long-term outcomes in three definitions: a historical cohort study.

OBJECTIVE: To compare the association of the severity categories of the 2001-National Institutes of Health (NIH), the 2018-NIH and the 2019-Jensen bronchopulmonary dysplasia (BPD) definitions with neurodevelopmental and respiratory outcomes at 2 and 5 years' corrected age (CA), and several BPD risk factors. DESIGN: Single-centre historical cohort study with retrospective data collection. SETTING: Infants born between 2009 and 2015 at the Amsterdam University Medical Centers, location Amsterdam Medical Center. PATIENTS: Preterm infants born at gestational age (GA) <30 weeks and surviving up to 36 weeks' postmenstrual age. INTERVENTIONS: Perinatal characteristics, (social) demographics and comorbidities were collected from the electronic patient records. MAIN OUTCOME MEASURES: The primary outcomes were neurodevelopmental impairment (NDI) or late death, and respiratory morbidity at 2 and 5 years' CA. Using logistic regression and Brier scores, we investigated if the ordinal grade severity is associated with incremental increase of adverse long-term outcomes. RESULTS: 584 preterm infants (median GA: 28.1 weeks) were included and classified according to the three BPD definitions. None of the definitions showed a clear ordinal incremental increase of risk for any of the outcomes with increasing severity classification. No significant differences were found between the three BPD definitions (Brier scores 0.169-0.230). Respiratory interventions, but not GA, birth weight or small for GA, showed an ordinal relationship with BPD severity in all three BPD definitions. CONCLUSION: The severity classification of three BPD definitions showed low accuracy of the probability forecast on NDI or late death and respiratory morbidity at 2 and 5 years' CA, with no differences between the definitions.

Effects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial.

Broad-spectrum antibiotics for suspected early-onset neonatal sepsis (sEONS) may have pronounced effects on gut microbiome development and selection of antimicrobial resistance when administered in the first week of life, during the assembly phase of the neonatal microbiome. Here, 147 infants born at ≥36 weeks of gestational age, requiring broad-spectrum antibiotics for treatment of sEONS in their first week of life were randomized 1:1:1 to receive three commonly prescribed intravenous antibiotic combinations, namely penicillin + gentamicin, co-amoxiclav + gentamicin or amoxicillin + cefotaxime (ZEBRA study, Trial Register NL4882). Average antibiotic treatment duration was 48 hours. A subset of 80 non-antibiotic treated infants from a healthy birth cohort served as controls (MUIS study, Trial Register NL3821). Rectal swabs and/or faeces were collected before and immediately after treatment, and at 1, 4 and 12 months of life. Microbiota were characterized by 16S rRNA-based sequencing and a panel of 31 antimicrobial resistance genes was tested using targeted qPCR. Confirmatory shotgun metagenomic sequencing was executed on a subset of samples. The overall gut microbial community composition and antimicrobial resistance gene profile majorly shift directly following treatment (R2 = 9.5%, adjusted p-value = 0.001 and R2 = 7.5%, adjusted p-value = 0.001, respectively) and normalize over 12 months (R2 = 1.1%, adjusted p-value = 0.03 and R2 = 0.6%, adjusted p-value = 0.23, respectively). We find a decreased abundance of Bifidobacterium spp. and increased abundance of Klebsiella and Enterococcus spp. in the antibiotic treated infants compared to controls. Amoxicillin + cefotaxime shows the largest effects on both microbial community composition and antimicrobial resistance gene profile, whereas penicillin + gentamicin exhibits the least effects. These data suggest that the choice of empirical antibiotics is relevant for adverse ecological side-effects.

[A premature neonate with a right pre-auricular swelling]. / Een prematuur met een pre-auriculaire zwelling.

We present a 14-day-old premature born girl with a temperature of 37.8°C and a swelling and redness of the right parotid gland. Laboratory tests revealed a CRP of 79 mg/l and ultrasound examination confirmed a parotitis. Treatment with augmentin i.v. resolved the condition.

Correlation between clinical and histologic findings in the human neonatal hippocampus after perinatal asphyxia.

Hypoxic ischemic encephalopathy after perinatal asphyxia is a major cause of mortality and morbidity in infants. Here, we evaluated pathologic changes in the hippocampi of a cohort of 16 deceased full-term asphyxiated infants who died from January 2000 to January 2009. Histochemical and immunocytochemical results for glial and neuronal cells were compared between cases with or without seizures and to adult and sudden infant death syndrome cases (n = 3 each). All asphyxiated infants displayed neuronal cell damage and reactive glial changes. Strong aquaporin-4 immunoreactivity was seen on astroglial cells within hippocampi in 50% of cases. In patients with seizures, the expression of metabotropic glutamate receptors was increased in glial cells. Cases with seizures displayed increased microglial activation and greater expression of the inflammatory markers interleukin 1ß and complement 1q compared with those in cases without seizures. All cases with seizures displayed alterations in the blood-brain barrier, as assessed by immunohistochemistry for albumin. These findings confirm the complex cascade of cellular and molecular changes occurring in the human neonatal hippocampus after perinatal asphyxia. These changes may contribute to seizure development leading to secondary brain damage. These data may aid in the development of therapeutic targets for neonatal seizures.