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Full-term low birth weight infants have differentially hypermethylated DNA related to immune system and organ growth: a comparison with full-term normal birth weight infants.

ABSTRACT: Low birth weight (LBW) is a major public health issue as it increases the risk of noncommunicable diseases throughout life. However, the genome-wide DNA methylation patterns of full-term LBW infants (FT-LBWs) are still unclear. This exploratory study aimed to analyze the DNA methylation differences in FT-LBWs compared with those in full-term normal birth weight infants (FT-NBWs) whose mothers were nonsmokers and had no complications. Initially, 702 Japanese women with singleton pregnancies were recruited. Of these, four FT-LBWs and five FT-NBWs were selected as references for DNA methylation analysis, and 862,260 CpGs were assessed using Illumina Infinium MethylationEPIC BeadChip. Gene ontology enrichment analysis was performed using DAVID v6.8 software to identify the biological functions of hyper- and hypomethylated DNA in FT-LBWs. 483 hyper-differentially methylated genes (DMGs) and 35 hypo-DMGs were identified in FT-LBW promoter regions. Hyper-DMGs were annotated to 11 biological processes; "macrophage differentiation" (e.g., CASP8), "apoptotic mitochondrial changes" (e.g., BH3), "nucleotide-excision repair" (e.g., HUS1), and "negative regulation of inflammatory response" (e.g., NLRP12 and SHARPIN). EREG was classified into "ovarian cumulus expansion" within the "organism growth and organization" category. Our data imply that LBW might be associated with epigenetic modifications, which regulate the immune system and cell maturation.

SUBMITTER: Hayashi I

PROVIDER: S-EPMC7126402 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Full-term low birth weight infants have differentially hypermethylated DNA related to immune system and organ growth: a comparison with full-term normal birth weight infants.

Hayashi Ikuyo I Yamaguchi Ken K Sumitomo Masahiro M Takakura Kenji K Nagai Narumi N Sakane Naoki N

BMC research notes 20200403 1

<h4>Objective</h4>Low birth weight (LBW) is a major public health issue as it increases the risk of noncommunicable diseases throughout life. However, the genome-wide DNA methylation patterns of full-term LBW infants (FT-LBWs) are still unclear. This exploratory study aimed to analyze the DNA methylation differences in FT-LBWs compared with those in full-term normal birth weight infants (FT-NBWs) whose mothers were nonsmokers and had no complications. Initially, 702 Japanese women with singleton ...[more]

PMID: 32245519

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Project description:BackgroundLow birth weight (LBW) is one of the leading causes of adverse perinatal outcomes and is closely related to neonatal disease and death. The incidence of LBW has been increasing. The aim of this study was to investigate the current incidence rate and factors affecting low birth weight infants and perinatal outcomes of full-term low birth weight infants in mainland China.MethodsThis paper describes a retrospective analysis of children born in 39 hospitals of different types in 14 different provinces, municipalities, and autonomous regions in seven districts within China throughout 2011. The data were first collected in hardcopy format and then entered into computer network databases. Data covering a total of 112,441 cases were collected. Cases were excluded if data were incomplete and in the case of miscarriage before 24 weeks of gestation, multiple pregnancies, or induction of labor due to fetal malformation, intrauterine death, and other reasons, leaving a total of 101,163 cases. SPSS 18.0 and SAS 9.2 statistical packages were used to analyze the collected data.ResultsAccording to this research, the incidence of LBW in mainland China was 6.1%, which is higher than the 5.87% reported in 2000, and it varied across different areas. The incidence of LBW was significantly higher in tertiary care hospitals than in secondary care hospitals. LBW was found to be associated with maternal age of less than 20 years, low level of maternal education, previous histories of adverse pregnancies, and with pregnancy comorbidities and complications, such as hypertensive disorders during pregnancy, anemia, oligohydramnios, premature rupture of membranes, and gestational diabetes. The rates of stillbirths, severe neonatal asphyxia, and deaths among full-term LBW infants were 2.42%, 0.83%, and 3.49%, respectively. The rates of stillbirths and neonatal deaths among full-term LBW infants born by caesarean section were 0.5% and 1.0%, respectively, which was lower than vaginal delivery.ConclusionsThe incidence of LBW has increased in China. LBW is a leading cause of adverse pregnancy outcomes. Health care during pregnancy and management of high-risk factors for LBW may reduce the incidence of LWB and the death rate of LBW infants.

Project description:BackgroundStudies have identified relationships between air pollution and birth weight, but have been inconsistent in identifying individual pollutants inversely associated with birth weight or elucidating susceptibility of the fetus by trimester of exposure. We examined effects of prenatal ambient pollution exposure on average birth weight and risk of low birth weight in full-term births.MethodsWe estimated average ambient air pollutant concentrations throughout pregnancy in the neighborhoods of women who delivered term singleton live births between 1996 and 2006 in California. We adjusted effect estimates of air pollutants on birth weight for infant characteristics, maternal characteristics, neighborhood socioeconomic factors, and year and season of birth.Results3,545,177 singleton births had monitoring for at least one air pollutant within a 10 km radius of the tract or ZIP Code of the mother's residence. In multivariate models, pollutants were associated with decreased birth weight; -5.4 grams (95% confidence interval -6.8 g, -4.1 g) per ppm carbon monoxide, -9.0 g (-9.6 g, -8.4 g) per pphm nitrogen dioxide, -5.7 g (-6.6 g, -4.9 g) per pphm ozone, -7.7 g (-7.9 g, -6.6 g) per 10 microg/m3 particulate matter under 10 microm, -12.8 g (-14.3 g, -11.3 g) per 10 microg/m3 particulate matter under 2.5 microm, and -9.3 g (-10.7 g, -7.9 g) per 10 microg/m3 of coarse particulate matter. With the exception of carbon monoxide, estimates were largely unchanged after controlling for co-pollutants. Effect estimates for the third trimester largely reflect the results seen from full pregnancy exposure estimates; greater variation in results is seen in effect estimates specific to the first and second trimesters.ConclusionsThis study indicates that maternal exposure to ambient air pollution results in modestly lower infant birth weight. A small decline in birth weight is unlikely to have clinical relevance for individual infants, and there is debate about whether a small shift in the population distribution of birth weight has broader health implications. However, the ubiquity of air pollution exposures, the responsiveness of pollutant levels to regulation, and the fact that the highest pollution levels in California are lower than those regularly experienced in other countries suggest that precautionary efforts to reduce pollutants may be beneficial for infant health from a population perspective.

Project description:PurposeWhile it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (<37 weeks gestation).MethodsA large retrospective study was conducted using population-based hospital data from January 2015 to December 2019 that included 69,964 cases of singleton infant births with complete paternal age data. The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile). Birth weight percentiles by gestational age were based on those published in the INTERGROWTH-21st neonatal weight-for gestational-age standard. Logistic regression analysis and linear regression model were used to estimate the association between paternal age and infant birth weight.ResultsAdvanced paternal age was associated with a higher risk for a preterm birth [35-44 years: adjusted odds ratio (OR) = 1.13, 95%CI (1.03 to 1.24); >44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35-44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35-44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (<25 years) (OR = 1.32; 95%CI, 1.07 to 1.62) and older (35-44 years) (OR = 1.07; 95% CI, 1.01 to 1.14) fathers in comparison to those who were 25 to 34 years old at the time of delivery.ConclusionsOur study found advanced paternal age increased the risk of SGA among preterm infants and for LGA among term infants. These findings likely reflect a pathophysiology etiology and have important preconception care implications and suggest the need for antenatal monitoring.

Project description:BACKGROUND:The association between gestational weight gain and neonatal body composition has been inconsistent, exposing the need for further research. The aim of this study was to evaluate whether gestational weight gain influences the body composition of full-term newborns and infants up to 4 months old. METHODS:A cohort study was performed with 124 participants divided into categories of gestational weight gain according to the 2009 Institute of Medicine guidelines. The anthropometric and body composition data of newborns and infants acquired using air displacement plethysmography (PeaPod®) were collected at 96?h, 1?month, 2?months and 4?months of life. In the statistical analysis, the chi-square test was used to analyze categorical variables, and ANOVA was used to analyze numerical variables. Univariate analysis was performed, and the absolute and relative frequencies of the categorical variables, as well as mean and standard deviation of the numerical variables, were obtained. Bivariate analysis was performed for the categories of gestational weight gain and gestational and neonatal characteristics. When adjustments to gestational hypertension, gestational diabetes, and pregestational body mass index (BMI) were analyzed by linear regression, gestational weight gain remained a significant variable for newborn percent fat mass. For all analyses, a significance level of 5% was adopted. RESULTS:Gestational weight gain was adequate in 33.8% of the participants, excessive in 41.1% and insufficient in 25%. Women with excessive weight gain had higher pregestational BMIs and a higher incidence of gestational hypertension. Their newborns had a higher body mass, body fat mass in grams and percent fat mass than the infants born to mothers with adequate or insufficient gestational weight gain. No significant differences were observed in body composition at 1, 2 and 4?months of life during infant follow-up. CONCLUSION:Excessive gestational weight gain may alter the body composition of newborns at birth. Further studies are required to better evaluate infant follow-up. TRIAL REGISTRATION:Clinical Trial Registry: NCT00875251 on April 3, 2009.

Project description:Infant formulas have been conventionally prepared with an excess of total protein in order to provide sufficient amounts of essential amino acids to the rapidly growing infant. However, this practice leads to higher than necessary protein intake during early infant development, inducing accelerated growth patterns correlated with the development of chronic diseases later in life. This study was aimed at assessing the safety of an infant formula enriched with bovine alpha-lactalbumin containing a total protein concentration very close to that of human milk, and determining its efficacy in the support of healthy infant growth from the first month to the fourth month of age. Healthy full-term infants ≤40 days of age were randomized in this controlled single blind trial to one of the following infant formulas: IF 1 (containing 1.0 g protein/dL; n = 30), IF 2 (containing 1.3 g protein/dL; n = 24), and IF 3 (containing 1.5 g protein/dL; n = 42). A control group consisting of exclusively breastfed infants (HM; n = 212) was included in the study. Anthropometric measurements and Z-scores were evaluated at baseline, at 1 month of age, and at 4 months of age. Weight gain (g/day) was similar in the IF 1 and the HM groups (p = 0.644), and it was significantly greater in the IF 2 and IF 3 groups than in the HM group. Growth patterns in both breastfed or IF-fed infants were in accordance with the World Health Organization (WHO) growth standards. At four months of age, the mean weight-for-age Z-score (WAZ) adjusted for initial value in the IF 1 group was similar to that of the HM group and significantly lower than that of the IF 2 and IF 3 groups (p = 0.031 and p = 0.014 for IF 2 and IF 3, respectively). Length-for-age (LAZ) adjusted for initial value was similar among all groups at four months of age. From 1 to 4 months of life, IF 1 containing 1.0 g protein/dL promotes growth and weight gain similar to those observed in exclusively breastfed infants. As this is a first approach to studying an IF containing total protein in a level below that recommended by international committees on nutrition, further investigations are needed to support these findings evaluating infant’s metabolic profile and growth in the long term.

Project description:Weaning is associated with increased occurrence of infections and diseases in piglets. Recent findings indicate that weaning induces mitochondrial dysfunction and oxidative stress conditions that more severely impact smaller piglets. The objective of this study was to characterize the molecular mechanisms underlying these physiological consequences and the relation with systemic inflammatory status in both normal and low birth weight (NBW and LBW) piglets throughout the peri-weaning period. To conduct the study, 30 sows were inseminated, and specific piglets from their litters were assigned to one of two experimental groups: NBW (n = 60, 1.73 ± 0.01 kg,) and LBW piglets weighing less than 1.2 kg (n = 60, 1.01 ± 0.01 kg). Then, 10 piglets from each group were selected at 14, 21 (weaning), 23, 25, 29 and 35 days of age to collect organ and plasma samples. Specific porcine RT2 Profiler™ PCR Arrays related to mitochondrial function, oxidative stress, inflammation and apoptosis processes were first used to target genes that are modulated after weaning in NBW piglets (d 23 and d 35 vs. d 14). Expression of selected genes was evaluated by quantitative PCR. These analyses revealed that expression of inflammatory genes CXCL10 and CCL19 increased after weaning in intestinal mucosa, while expression of genes encoding subunits of the mitochondrial respiratory chain was downregulated in liver and kidney of both groups. Interestingly, major modulators of mitophagy (BNIP3), cell survival (BCL2A1) and antioxidant defense system (TXNRD2, GPx3, HMOX1) were found to be highly expressed in NBW piglets. The systemic levels of TNF-α and IL1-β significantly increased following weaning and were higher in NBW piglets. These results provide novel information about the molecular origin of mitochondrial dysfunction and oxidative stress observed in weaned piglets and suggest that clearance of dysfunctional mitochondria, antioxidant defenses and inflammatory response are compromised in LBW piglets.

Dataset Information

Full-term low birth weight infants have differentially hypermethylated DNA related to immune system and organ growth: a comparison with full-term normal birth weight infants.

Publications

Full-term low birth weight infants have differentially hypermethylated DNA related to immune system and organ growth: a comparison with full-term normal birth weight infants.

Similar Datasets

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