Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants.
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ABSTRACT:
SUBMITTER: Everson TM
PROVIDER: S-EPMC7574188 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants.
Everson Todd M TM O'Shea T Michael TM Burt Amber A Hermetz Karen K Carter Brian S BS Helderman Jennifer J Hofheimer Julie A JA McGowan Elisabeth C EC Neal Charles R CR Pastyrnak Steven L SL Smith Lynne M LM Soliman Antoine A DellaGrotta Sheri A SA Dansereau Lynne M LM Padbury James F JF Lester Barry M BM Marsit Carmen J CJ
Clinical epigenetics 20201019 1
<h4>Background</h4>Infants born very preterm are more likely to experience neonatal morbidities compared to their term peers. Variations in DNA methylation (DNAm) associated with these morbidities may yield novel information about the processes impacted by these morbidities.<h4>Methods</h4>This study included 532 infants born < 30 weeks gestation, participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants study. We used a neonatal morbidity risk score, which was an additive ...[more]
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Project description:BackgroundPrenatal risk factors are related to poor health and developmental outcomes for infants, potentially via epigenetic mechanisms. We tested associations between person-centered prenatal risk profiles, cumulative prenatal risk models, and epigenome-wide DNA methylation (DNAm) in very preterm neonates.MethodsWe studied 542 infants from a multi-center study of infants born < 30 weeks postmenstrual age. We assessed 24 prenatal risk factors via maternal report and medical record review. Latent class analysis was used to define prenatal risk profiles. DNAm was quantified from neonatal buccal cells using the Illumina MethylationEPIC Beadarray.ResultsWe identified three latent profiles of women: a group with few risk factors (61%) and groups with elevated physical (26%) and psychological (13%) risk factors. Neonates born to women in higher risk subgroups had differential DNAm at 2 CpG sites. Higher cumulative prenatal risk was associated with methylation at 15 CpG sites, 12 of which were located in genes previously linked to physical and mental health and neurodevelopment.ConclusionWe observed associations between prenatal risk factors and DNAm in very preterm infants using both person-centered and cumulative risk approaches. Epigenetics offers a potential biological indicator of prenatal risk exposure.
| S-EPMC8434712 | biostudies-literature
Project description:ImportanceSevere morbidity in very preterm infants is associated with profound clinical implications on development and life-course health. However, studies of racial/ethnic disparities in severe neonatal morbidities are scant and suggest that these disparities are modest or null, which may be an underestimation resulting from the analytic approach used.ObjectiveTo estimate racial/ethnic differences in severe morbidities among very preterm infants.Design, setting, and participantsThis population-based retrospective cohort study was conducted in New York City, New York, using linked birth certificate, mortality data, and hospital discharge data from January 1, 2010, through December 31, 2014. Infants born before 24 weeks' gestation, with congenital anomalies, and with missing data were excluded. Racial/ethnic disparities in very preterm birth morbidities were estimated through 2 approaches, conventional analysis and fetuses-at-risk analysis. The conventional analysis used log-binomial regression to estimate the relative risk of 4 severe neonatal morbidities for the racial/ethnic groups. For the fetuses-at-risk analysis, Cox proportional hazards regression with death as competing risk was used to estimate subhazard ratios associating race/ethnicity with each outcome. Estimates were adjusted for sociodemographic factors and maternal morbidities. Data were analyzed from September 5, 2017, to May 21, 2018.Main outcomes and measuresFour morbidity outcomes were defined using International Classification of Diseases, Ninth Revision, diagnosis and procedure codes: necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity.ResultsIn total, 582 297 infants were included in this study. Of these infants, 285 006 were female (48.9%) and 297 291 were male (51.0%). Using the conventional approach in the very preterm birth subcohort, black compared with white infants had an increased risk of only bronchopulmonary dysplasia (adjusted risk ratio [aRR], 1.34; 95% CI, 1.09-1.64) and a borderline increased risk of necrotizing enterocolitis (aRR, 1.39; 95% CI, 1.00-1.93). Hispanic infants had a borderline increased risk of necrotizing enterocolitis (aRR, 1.39; 95% CI, 0.98-1.96), and Asian infants had an increased risk of retinopathy of prematurity (aRR, 1.85; 95% CI, 1.15-2.97). In the fetuses-at-risk analysis, black infants had a 4.40 times higher rate of necrotizing enterocolitis (95% CI, 2.98-6.51), a 2.73 times higher rate of intraventricular hemorrhage (95% CI, 1.63-4.57), a 4.43 times higher rate of bronchopulmonary dysplasia (95% CI, 2.88-6.81), and a 2.98 times higher rate of retinopathy of prematurity (95% CI, 2.01-4.40). Hispanic infants had an approximately 2 times higher rate for all outcomes, and Asian infants had increased risk only for retinopathy of prematurity (adjusted hazard ratio, 2.43; 95% CI, 1.43-4.11).Conclusions and relevanceIn this study, racial/ethnic disparities in neonatal morbidities among very preterm infants appear to be sizable, but may have been underestimated in previous studies, and may have implications for the future. Understanding these racial/ethnic disparities is important, as they may contribute to inequalities in health and development later in the child's life.
| S-EPMC6248139 | biostudies-literature
Project description:DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early-life stress and neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm, and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth<33 weeks gestation) and healthy controls (birth>37 weeks), and a genome-wide analysis of DNAm was performed; diffusion magnetic resonance imaging (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components (PC) analysis was used to investigate the contribution of MRI features and clinical variables to variance in DNAm. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants compared with controls; 10 of these have neural functions. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 PCs; corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.
| S-EPMC5068883 | biostudies-literature
Project description:Little is known about the association between body proportionality at birth and neonatal outcomes in preterm infants. Body mass index (BMI) is one of the weigh-for-length ratios that represent body proportionality. The objective of this study was to examine whether BMI at birth affects neonatal outcomes in preterm infants. We assessed 3115 preterm (< 30 weeks), very low birth weight (< 1500 g) infants born between January 2013 and December 2016 and registered in the Korean Neonatal Network database. Using gender-specific BMI for gestational age curves, z-scores of BMI at birth were calculated. Low-, normal-, and high-BMI were defined as BMI z-scores of less than - 1, from - 1 to 1, and greater than 1, respectively. Neonatal morbidities and mortality in low- and high-BMI groups were compared to those in normal-BMI group. The low-BMI group had an increased risk of bronchopulmonary dysplasia, bronchopulmonary dysplasia or death, and necrotizing enterocolitis after adjusting for baseline characteristics and the birth weight z-score. High-BMI group had comparable neonatal outcomes to those of normal-BMI group. Low BMI at birth was associated with an increased risk of bronchopulmonary dysplasia and necrotizing enterocolitis, whereas High BMI at birth was not associated with adverse neonatal outcomes.
| S-EPMC8458459 | biostudies-literature
Project description:DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early life stress and life-course neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth < 32 weeks’ gestation) and healthy controls (birth > 37 weeks), and a genome-wide analysis of DNAm was performed; diffusion MRI (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components analysis was used to investigate the contribution of MRI features and key clinical variables to variance in DNAm. Differentially methylated regions were found within 25 gene bodies and 61 promoters of protein-coding genes in preterm infants compared with controls; 10 of these are associated with neural development or function. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 principal components (PC); corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. The differentially methylated regions identified provide several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.
2016-04-27 | GSE72120 | GEO
Project description:Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.
| S-EPMC10902402 | biostudies-literature
Project description:BackgroundSerratia spp. are opportunistic, multidrug resistant, Gram-negative pathogens, previously described among preterm infants in case reports or outbreaks of infection. We describe Serratia late-onset infection (LOI) in very preterm infants in a large, contemporary, nationally representative cohort.MethodsIn this secondary analysis of prospectively collected data of preterm infants born 401-1500 grams and/or 22-29 weeks gestational age from 2018 to 2020 at 774 Vermont Oxford Network members, LOI was defined as culture-confirmed blood and/or cerebrospinal fluid infection > 3 days after birth. The primary outcome was incidence of Serratia LOI. Secondary outcomes compared rates of survival and discharge morbidities between infants with Serratia and non-Serratia LOI.ResultsAmong 119,565 infants, LOI occurred in 10,687 (8.9%). Serratia was isolated in 279 cases (2.6% of all LOI; 2.3 Serratia infections per 1000 infants). Of 774 hospitals, 161 (21%) reported at least one Serratia LOI; 170 of 271 (63%) cases occurred at hospitals reporting 1 or 2 Serratia infections, and 53 of 271 (20%) occurred at hospitals reporting ≥5 Serratia infections. Serratia LOI was associated with a lower rate of survival to discharge compared with those with non-Serratia LOI (adjusted relative risk 0.88, 95% CI: 0.82-0.95). Among survivors, infants with Serratia LOI had higher rates of tracheostomy, gastrostomy and home oxygen use compared with those with non-Serratia LOI.ConclusionsThe incidence of Serratia LOI was 2.3 infections per 1000 very preterm infants in this cohort. Lower survival and significant morbidity among Serratia LOI survivors highlight the need for recognition and targeted prevention strategies for this opportunistic nosocomial infection.
| S-EPMC9846441 | biostudies-literature
Project description:To determine the association between direct costs for the initial neonatal intensive care unit hospitalization and 4 potentially preventable morbidities in a retrospective cohort of very low birth weight (VLBW) infants (birth weight <1500 g).The sample included 425 VLBW infants born alive between July 2005 and June 2009 at Rush University Medical Center. Morbidities included brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and late-onset sepsis. Clinical and economic data were retrieved from the institution's system-wide data and cost accounting system. A general linear regression model was fit to determine incremental direct costs associated with each morbidity.After controlling for birth weight, gestational age, and sociodemographic characteristics, the presence of brain injury was associated with a $12048 (P = .005) increase in direct costs; necrotizing enterocolitis, with a $15 440 (P = .005) increase; bronchopulmonary dysplasia, with a $31565 (P < .001) increase; and late-onset sepsis, with a $10055 (P < .001) increase. The absolute number of morbidities was also associated with significantly higher costs.This study provides collective estimates of the direct costs incurred during neonatal intensive care unit hospitalization for these 4 morbidities in VLBW infants. The incremental costs associated with these morbidities are high, and these data can inform future studies evaluating interventions aimed at preventing or reducing these costly morbidities.
| S-EPMC3584449 | biostudies-other
Project description:ImportanceRacial and ethnic minorities receive lower-quality health care than white non-Hispanic individuals in the United States. Where minority infants receive care and the role that may play in the quality of care received is unclear.ObjectiveTo determine the extent of segregation and inequality of care of very low-birth-weight and very preterm infants across neonatal intensive care units (NICUs) in the United States.Design, setting, and participantsThis cohort study of 743 NICUs in the Vermont Oxford Network included 117 982 black, Hispanic, Asian, and white infants born at 401 g to 1500 g or 22 to 29 weeks' gestation from January 2014 to December 2016. Analysis began January 2018.Main outcomes and measuresThe NICU segregation index and NICU inequality index were calculated at the hospital level as the Gini coefficients associated with the Lorenz curves for black, Hispanic, and Asian infants compared with white infants, with NICUs ranked by proportion of white infants for the NICU segregation index and by composite Baby-MONITOR (Measure of Neonatal Intensive Care Outcomes Research) score for the NICU inequality index.ResultsInfants (36 359 black [31%], 21 808 Hispanic [18%], 5920 Asian [5%], and 53 895 white [46%]) were segregated among the 743 NICUs by race and ethnicity (NICU segregation index: black: 0.50 [95% CI, 0.46-0.53], Hispanic: 0.58 [95% CI, 0.54-0.61], and Asian: 0.45 [95% CI, 0.40-0.50]). Compared with white infants, black infants were concentrated at NICUs with lower-quality scores, and Hispanic and Asian infants were concentrated at NICUs with higher-quality scores (NICU inequality index: black: 0.07 [95% CI, 0.02-0.13], Hispanic: -0.10 [95% CI, -0.17 to -0.04], and Asian: -0.26 [95% CI, -0.32 to -0.19]). There was marked variation among the census regions in weighted mean NICU quality scores (range: -0.69 to 0.85). Region of residence explained the observed inequality for Hispanic infants but not for black or Asian infants.Conclusions and relevanceBlack, Hispanic, and Asian infants were segregated across NICUs, reflecting the racial segregation of minority populations in the United States. There were large differences between geographic regions in NICU quality. After accounting for these differences, compared with white infants, Asian infants received care at higher-quality NICUs and black infants, at lower-quality NICUs. Explaining these patterns will require understanding the effects of sociodemographic factors and public policies on hospital quality, access, and choice for minority women and their infants.
| S-EPMC6503514 | biostudies-literature
Project description:Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain-related stress in the neonatal intensive care unit (NICU) in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24-32 weeks' gestational age). Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary-adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant's stress may be brain-protective.
| S-EPMC3820298 | biostudies-literature