NEOage clocks - epigenetic clocks to estimate post-menstrual and postnatal age in preterm infants.
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ABSTRACT:
SUBMITTER: Graw S
PROVIDER: S-EPMC8580352 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo examine the environmental effects on cytosine methylation of preterm infant's DNA, because early life experiences are considered to influence the physiological and mental health of an individual through epigenetic modification of DNA.DesignA prospective cohort study, comparison of epigenetic differences in the glucocorticoid receptor (GR) gene between healthy term and preterm infants.SettingNeonatal Intensive Care Unit in a Japanese University Hospital.ParticipantsA cohort of 40 (20 term and 20 preterm) infants was recruited on the day of birth, and peripheral blood was obtained from each infant at birth and on postnatal day 4.Main outcome measuresThe methylation rates in the 1-F promoter region of the GR gene using the Mquant method.ResultsThe methylation rate increased significantly between postnatal days 0 and 4 in preterm infants but remained stable in term infants. Thus, the methylation rate was significantly higher in preterm than in term infants at postnatal day 4. Several perinatal parameters were significantly correlated with this change in the methylation rate. Logistic regression analysis revealed that methylation rates at postnatal day 4 predicted the occurrence of later complications that required glucocorticoid administration during the neonatal period. No gene polymorphism was detected within the GR promoter region analysed.ConclusionsAlthough further large-scale studies are needed to detect the environmental factors that explain the difference in epigenetic modification among infants after birth, our data show that the postnatal environment influences epigenetic programming of GR expression through methylation of the GR gene promoter in premature infants, which may result in relative glucocorticoid insufficiency during the postnatal period.
| S-EPMC4120337 | biostudies-literature
Project description:Preterm birth is associated with medical problems affecting the neuroendocrine system, altering cortisol levels resulting in negative effects on newborn neurobehavior. Newborn neurobehavior is regulated by DNA methylation of NR3C1 and HSD11B2.Determine if methylation of HSD11B2 and NR3C1 is associated with neurobehavioral profiles in preterm infants.Neurobehavior was measured before discharge from the hospital in 67 preterm infants. Cheek swabs were collected for DNA extraction.Infants with the high-risk neurobehavioral profile showed more methylation than infants with the low-risk neurobehavioral profile at CpG3 for NR3C1 and less methylation of CpG3 for HSD11B2. Infants with these profiles were more likely to have increased methylation of NR3C1 and decreased methylation of HSD11B2 at these CpG sites.Preterm birth is associated with epigenetic differences in genes that regulate cortisol levels related to high-risk neurobehavioral profiles.
| S-EPMC5551936 | biostudies-other
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.
| S-EPMC6443302 | biostudies-literature
Project description:The human pan-tissue epigenetic clock is widely used for estimating age across the entire lifespan, but it does not lend itself well to estimating gestational age (GA) based on placental DNAm methylation (DNAm) data. We replicate previous findings demonstrating a strong correlation between GA and genome-wide DNAm changes. Using substantially more DNAm arrays (n=1,102 in the training set) than a previous study, we present three new placental epigenetic clocks: 1) a robust placental clock (RPC) which is unaffected by common pregnancy complications (e.g., gestational diabetes, preeclampsia), and 2) a control placental clock (CPC) constructed using placental samples from pregnancies without known placental pathology, and 3) a refined RPC for uncomplicated term pregnancies. These placental clocks are highly accurate estimators of GA based on placental tissue; e.g., predicted GA based on RPC is highly correlated with actual GA (r>0.95 in test data, median error less than one week). We show that epigenetic clocks derived from cord blood or other tissues do not accurately estimate GA in placental samples. While fundamentally different from Horvath's pan-tissue epigenetic clock, placental clocks closely track fetal age during development and may have interesting applications.
| S-EPMC6628997 | biostudies-literature
Project description:BackgroundWeight z scores at 36 weeks of postmenstrual age (PMA) define postnatal growth failure (PGF) and malnutrition. This study aimed to determine weight z scores at 36 weeks PMA that are associated with adverse cognitive outcomes at 2 years of age.MethodsIn this retrospective cohort study, 350 infants 24-26 weeks of gestation born between 2006 and 2014 and followed at 2 years were included. Weight z scores at birth and at 36 weeks PMA were calculated using the INTERGROWTH-21st growth curves. The primary outcome was cognitive delay at 2 years of age (Bayley-III cognitive score < 85).ResultsNeither the traditional definition of PGF (z score below -1.3) nor the recently proposed definition of malnutrition (z score decline of 1.2 or greater) was associated with cognitive delay. Both a weight z score below -1.0 at 36 weeks PMA (RR: 1.65; 95% CI: 1.10-2.49; p < 0.05) and a decline below -1.0 in weight z score from birth to 36 weeks PMA (RR: 1.40; 95% CI: 1.00-1.94; p < 0.05) were associated with a higher risk of cognitive delay.ConclusionWith optimal cutoffs, INTERGROWTH-21st weight z scores can predict the risk of cognitive delay.ImpactNew growth curves generated with longitudinal data could overcome some limitations of traditional growth curves generated with cross-sectional data. When these new growth curves are used to assess the growth of preterm infants, alternative definitions for postnatal growth alterations may be needed. This study examines the association between postnatal growth alterations defined by the INTEGROWTH-21st growth curves and adverse cognitive outcomes at 2 years of age. With alternative definitions of postnatal growth failure and malnutrition, the INTERGROWTH-21st growth curves can help establish the association between postnatal growth of extremely preterm infants and adverse neurodevelopmental outcomes in early childhood.
| S-EPMC7965787 | biostudies-literature
Project description:In preterm infants, poor postnatal growth is associated with adverse neurocognitive outcomes; conversely, rapid postnatal growth is supposedly harmful for future development of metabolic diseases.In this systematic review, observational studies reported consistent positive associations between postnatal weight or head growth and neurocognitive outcomes; however, there was limited evidence from the few intervention studies. Evidence linking postnatal weight gain to later adiposity and other cardiovascular disease risk factors in preterm infants was also limited.
| S-EPMC5054880 | biostudies-other
Project description:Historically, postnatal corticosteroids have been used to prevent and treat bronchopulmonary dysplasia (BPD), a significant cause of morbidity and mortality in preterm infants. Administering dexamethasone to prevent BPD in the first 7 days post-birth has been associated with increasing risk for cerebral palsy, while early inhaled corticosteroids appear to be associated with an increased risk of mortality. Neither medication is presently recommended to prevent BPD. New evidence suggests that prophylactic hydrocortisone, when initiated in the first 48 hours post-birth, at a physiological dose, and in the absence of indomethacin, improves survival without BPD, with no adverse neurodevelopmental effects at 2 years. This therapy may be considered by clinicians for infants at highest risk for BPD. Routine dexamethasone therapy for all ventilator-dependent infants is not recommended, but after the first week post-birth, clinicians may consider a short course of low-dose dexamethasone (0.15 mg/kg/day to 0.2 mg/kg/day) for individual infants at high risk for, or with evolving, BPD. There is no evidence that hydrocortisone is an effective or safe alternative to dexamethasone for treating evolving or established BPD. Current evidence does not support inhaled corticosteroids for the treatment of BPD.
| S-EPMC7395322 | biostudies-literature
Project description:BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.
| S-EPMC5511508 | biostudies-literature
Project description:IntroductionHuman nephrogenesis is typically completed by 36 weeks gestation; however, it is impacted by preterm birth. Early studies suggested that nephrogenesis persisted for ≤40 postnatal days in preterm infants. However, the postmenstrual age (PMA) of the preterm infants who survived >40 days was uncertain. In this study, we sought to reexamine postnatal kidney development in preterm infants surviving >40 days.MethodsHuman kidney samples were obtained from an institutional biobank. Samples were considered controls if survival was ≤4 days after birth with PMA of 30 to ≤36 weeks. Kidneys from preterm neonates with postnatal survival >40 days and PMA of 30 to ≤36 weeks were compared to controls. We counted glomerular generations, measured nephrogenic zone widths (NZW), and performed immunofluorescence (IF) with SIX1 and RET. We compared kidney weights and quantified the cross-sectional area of proximal (lotus tetragonolobus lectin [LTL], SL22A2), distal (SLC12A3, KCNJ10), and glomerular (nephrin) markers using IF.ResultsSeven preterm infants surviving >40 days and 8 controls were analyzed. Four of 7 preterm infants had histologic and molecular evidence of nephrogenesis. Cessation of nephrogenesis in preterm infants occurred 2 weeks earlier than PMA-matched controls with attenuated expression of both SIX1 and RET. We found increased kidney weight-to-body weight ratio, increased distal tubular cross-sectional staining in the superficial nephrons, and distal tubular hypertrophy and hyperplasia in the preterm infant kidneys.ConclusionOur study supports that nephrogenesis in preterm infants persists longer than previously thought with evidence of early nephron stress, placing importance on the neonatal environment.
| S-EPMC10851065 | biostudies-literature
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.
| S-EPMC7536325 | biostudies-literature