Dataset Information

Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD).

ABSTRACT:

Aim

To characterize postnatal changes in serum insulin-like growth factor-1 (IGF-I) in relation to development of bronchopulmonary dysplasia (BPD) in very preterm infants.

Methods

Longitudinal study of 108 infants with mean (SD) gestational age (GA) 27.2 (2.2) weeks. Weekly serum samples of IGF-I were analysed from birth until postmenstrual age (PMA) 36 weeks. Multivariate models were developed to identify independent predictors of BPD.

Results

Postnatal mean IGF-I levels at postnatal day (PND) 3-21 were lower in infants with BPD compared with infants with no BPD (16 vs. 26 ?g/L, p < 0.001). Longitudinal postnatal change in IGF-I levels (IGF-I regression coefficient (?)), PNDs 3-21, was lower in infants with BPD compared with infants with no BPD (0.28 vs. 0.97, p = 0.002) and mean IGF-I during PMA 30-33 weeks was lower in infants with BPD as compared with infants without BPD (22 vs. 29 ?g/L, p < 0.001). In a binomial multiple regression model, lower GA, male gender and lower mean serum IGF-I levels during PND 3-21 were the most predictive risk factors associated with BPD (r(2) = 0.634, p < 0.001).

Conclusion

Lower IGF-I concentrations during the first weeks after very preterm birth are associated with later development of BPD.

SUBMITTER: Lofqvist C

PROVIDER: S-EPMC3569611 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD).

Löfqvist Chatarina C Hellgren Gunnel G Niklasson Aimon A Engström Eva E Ley David D Hansen-Pupp Ingrid I

Acta paediatrica (Oslo, Norway : 1992) 20120910 12

<h4>Aim</h4>To characterize postnatal changes in serum insulin-like growth factor-1 (IGF-I) in relation to development of bronchopulmonary dysplasia (BPD) in very preterm infants.<h4>Methods</h4>Longitudinal study of 108 infants with mean (SD) gestational age (GA) 27.2 (2.2) weeks. Weekly serum samples of IGF-I were analysed from birth until postmenstrual age (PMA) 36 weeks. Multivariate models were developed to identify independent predictors of BPD.<h4>Results</h4>Postnatal mean IGF-I levels a ...[more]

PMID: 22924869

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Project description:Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and a key contributor to the large health care burden associated with prematurity, longer hospital stays, higher hospital costs, and frequent re-hospitalizations of affected patients through the first year of life and increased resource utilization throughout childhood. This disease is associated with abnormal pulmonary function that may lead to BPD-associated pulmonary hypertension (PH), a major contributor to neonatal mortality and morbidity. In the absence of any definitive treatment options, this life-threatening disease is associated with high resource utilization during and after neonatal intensive care unit (NICU) stay. The goal of this study was to test the safety and efficacy of a small molecule derivative of chitin, AVR-48, as prophylactic therapy for preventing experimental BPD in a mouse model. Two doses of AVR-48 were delivered either intranasally (0.11 mg/kg), intraperitoneally (10 mg/kg), or intravenously (IV) (10 mg/kg) to newborn mouse pups on postnatal day (P)2 and P4. The outcomes were assessed by measuring total inflammatory cells in the broncho-alveolar lavage fluid (BALF), chord length, septal thickness, and radial alveolar counts of the alveoli, Fulton's Index (for PH), cell proliferation and cell death by immunostaining, and markers of inflammation by Western blotting and ELISA. The bioavailability and safety of the drug were assessed by pharmacokinetic and toxicity studies in both neonatal mice and rat pups (P3-P5). Following AVR-48 treatment, alveolar simplification was improved, as evident from chord length, septal thickness, and radial alveolar counts; total inflammatory cells were decreased in the BALF; Fulton's Index was decreased and lung inflammation and cell death were decreased, while angiogenesis and cell proliferation were increased. AVR-48 was found to be safe and the no-observed-adverse-effect level (NOAEL) in rat pups was determined to be 100 mg/kg when delivered via IV dosing with a 20-fold safety margin. With no reported toxicity and with a shorter half-life, AVR-48 is able to reverse the worsening cardiopulmonary phenotype of experimental BPD and BPD-PH, compared to controls, thus positioning it as a future drug candidate.

Project description:IMPORTANCE:Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but in very low-birth-weight (VLBW) infants can cause pneumonitis and sepsislike illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown. OBJECTIVE:To investigate the association between postnatal CMV infection and bronchopulmonary dysplasia (BPD) and mortality in a large multicenter cohort of VLBW infants. DESIGN, SETTING, AND PARTICIPANTS:Conducted between October 2014 and June 2015, this propensity-matched retrospective cohort study involved 101,111 hospitalized VLBW (<1500 g) infants at 348 neonatal intensive care units in the United States from 1997 to 2012. We matched infants with postnatal CMV infection 1:1 to comparison infants using propensity scores, and we used Poisson regression to examine the effect of postnatal CMV on the combined risk for death or BPD at 36 weeks' postmenstrual age. To describe features of postnatal CMV infection, we extracted clinical and laboratory data from 7 days before until 7 days after infants met criteria for postnatal CMV. EXPOSURES:Postnatal CMV infection was defined as a diagnosis of CMV or detection of CMV from blood, urine, cerebrospinal fluid, or respiratory secretions on or after day of life 21. Infants with a CMV diagnosis or virologic detection of CMV prior to day of life 21 were not considered to have postnatal infection. MAIN OUTCOMES AND MEASURES:The primary outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS:Of 101,111 infants, 328 (0.3%) had postnatal CMV infection. We matched a comparison infant to 303 CMV-infected infants (92%) for a final cohort of 606 infants. The median gestational age and birth weight of this cohort were 25 weeks and 730 g, respectively. Postnatal CMV infection was associated with an increased risk for death or BPD at 36 weeks' postmenstrual age (risk ratio, 1.21; 95% CI, 1.10-1.32) and BPD (risk ratio, 1.33; 95% CI, 1.19-1.50). Changes in cardiorespiratory status associated with postnatal CMV infection included a new requirement for vasopressor medications (9%; n?=?29), intubation for mechanical ventilation (15%; n?=?49), a new oxygen requirement (28%; n?=?91), and death (1.2%; n?=?4). CONCLUSIONS AND RELEVANCE:In VLBW infants, postnatal CMV infection was associated with increased risk for BPD. Further studies are needed to determine the role of preventive measures against CMV in this population.

Project description:BackgroundBronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD.MethodsCord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (non-BPD, n = 93) was applied to Illumina 450 K methylation arrays. Blood cell-type compositions were estimated using DNA methylation profiles. Multivariable robust regression analysis elucidated CpGs associated with BPD risk. cDNA microarray analysis of cord blood RNA identified differentially expressed genes in neonates who later developed BPD.ResultsThe development of BPD and the need for oxygen supplementation were strongly associated with GA (BPD, p < 1.0E-04; O2 supplementation, p < 1.0E-09) and birth weight (BPD, p < 1.0E-02; O2 supplementation, p < 1.0E-07). The estimated nucleated red blood cell (NRBC) percent was negatively associated with birth weight and GA, positively associated with hypomethylation of the tobacco smoke exposure biomarker cg05575921, and high-NRBC blood samples displayed a hypomethylation profile. Epigenome-wide association study (EWAS) identified 38 (Bonferroni) and 275 (false discovery rate 1%) differentially methylated CpGs associated with BPD. BPD-associated CpGs in cord blood were enriched for lung maturation and hematopoiesis pathways. Stochastic epigenetic mutation burden at birth was significantly elevated among those who developed BPD (adjusted p = 0.02). Transcriptome changes in cord blood cells reflected cell cycle, development, and pulmonary disorder events in BPD.ConclusionsWhile results must be interpreted with caution because of the small size of this study, NRBC content strongly impacted DNA methylation profiles in preterm cord blood and EWAS analysis revealed potential insights into biological pathways involved in BPD pathogenesis.

Dataset Information

Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD).

Aim

Methods

Results

Conclusion

Publications

Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD).

Similar Datasets

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