Dataset Information

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure.

ABSTRACT: Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention.

SUBMITTER: Younge NE

PROVIDER: S-EPMC6546715 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure.

Younge Noelle E NE Newgard Christopher B CB Cotten C Michael CM Goldberg Ronald N RN Muehlbauer Michael J MJ Bain James R JR Stevens Robert D RD O'Connell Thomas M TM Rawls John F JF Seed Patrick C PC Ashley Patricia L PL

Scientific reports 20190603 1

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa incl ...[more]

PMID: 31160673

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Project description:BackgroundThere is no consensus with regard to which charts are most suitable for monitoring the postnatal growth of preterm infants.ObjectiveWe aimed to assess the strategies used to develop existing postnatal growth charts for preterm infants and their methodologic quality.DesignA systematic review of observational longitudinal studies, having as their primary objective the creation of postnatal growth charts for preterm infants, was conducted. Thirty-eight items distributed in 3 methodologic domains ("study design," "statistical methods," and "reporting methods") were assessed in each study. Each item was scored as a "low" or "high" risk of bias. Two reviewers independently selected the studies, assessed the risk of bias, and extracted data. A total quality score [(number of "low risk" of bias marks/total number of items assessed) × 100%] was calculated for each study. Median (range, IQR) quality scores for each methodologic domain and for all included studies were computed.ResultsSixty-one studies met the inclusion criteria. Twenty-seven (44.3%) of the 61 studies scored ≥50%, of which 10 scored >60% and only 1 scored >66%. The median (range, IQR) quality score for the 61 included studies was 47% (26-75%, 34-56%). The scores for the domains study design, statistical methods, and reporting methods were 44% (19-67%, 33-52%), 25% (0-88%, 13-38%), and 33% (0-100%, 0-33%), respectively. The most common shortcomings were observed in items related to anthropometric measures (the main variable of interest), gestational age estimation, follow-up duration, reporting of postnatal care and morbidities, assessment of outliers, covariates, and chart presentation.ConclusionsThe overall methodologic quality of existing longitudinal studies was fair to low. To overcome these problems, the Preterm Postnatal Follow-up Study, 1 of the 3 main components of The International Fetal and Newborn Growth Consortium for the 21st Century Project, was designed to construct preterm postnatal growth standards from a prospective cohort of "healthy" pregnancies and preterm newborns without evidence of fetal growth restriction.

Project description:Background: Sleep is an important determinant of brain development in preterm infants. Its temporal organization varies with gestational age (GA) and post-menstrual age (PMA) but little is known about how sleep develops in very preterm infants. The objective was to study the correlation between the temporal organization of quiet sleep (QS) and maturation in premature infants without severe complications during their neonatal hospitalization. Methods: Percentage of time spent in QS and average duration of time intervals (ADI) spent in QS were analyzed from a cohort of newborns with no severe complications included in the Digi-NewB prospective, multicentric, observational study in 2017-19. Three groups were analyzed according to GA: Group 1 (27-30 weeks), Group 2 (33-37 weeks), Group 3 (>39 weeks). Two 8-h video recordings were acquired in groups 1 and 2: after birth (T1) and before discharge from hospital (T2). The annotation of the QS phases was performed by analyzing video recordings together with heart rate and respiratory traces thanks to a dedicated software tool of visualization and annotation of multimodal long-time recordings, with a double expert reading. Results are expressed as median (interquartile range, IQR). Correlations were analyzed using a linear mixed model. Results: Five newborns were studied in each group (160 h of recording). Median time spent in QS increased from 13.0% [IQR: 13-20] to 28.8% [IQR: 27-30] and from 17.0% [IQR: 15-21] to 29.6% [IQR: 29.5-31.5] in Group 1 and 2, respectively. Median ADI increased from 54 [IQR: 53-54] to 288 s [IQR: 279-428] and from 90 [IQR: 84-96] to 258 s [IQR: 168-312] in Group 1 and 2. Both groups reach values similar to that of group 3, respectively 28.2% [IQR: 24.5-31.3] and 270 s [IQR: 210-402]. The correlation between PMA and time spent in QS or ADI were, respectively 0.73 (p < 10-4) and 0.46 (p = 0.06). Multilinear analysis using temporal organization of QS gave an accurate estimate of PMA (r 2 = 0.87, p < 0.001). Conclusion: The temporal organization of QS is correlated with PMA in newborns without severe complication. An automated standardized continuous behavioral quantification of QS could be interesting to monitor during the hospitalization stay in neonatal units.

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Project description:BackgroundGrowth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term.Material/methodsInfants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)-1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age.ResultsIn total, 49 infants (median [range] GA 25.4 [22.9-27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, β = 0.90), white matter (p = 0.007, β = 0.33), cortical gray matter (p = 0.002, β = 0.43), deep gray matter (p = 0.008, β = 0.05), and cerebellar (p = 0.006, β = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors.ConclusionsEndogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants.ImpactHigh serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants. IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood. Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).

Dataset Information

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure.

Publications

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure.

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