Browsing by Subject "CORD BLOOD"

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  • Knight, Anna K.; Craig, Jeffrey M.; Theda, Christiane; Baekvad-Hansen, Marie; Bybjerg-Grauholm, Jonas; Hansen, Christine S.; Hollegaard, Mads V.; Hougaard, David M.; Mortensen, Preben B.; Weinsheimer, Shantel M.; Werge, Thomas M.; Brennan, Patricia A.; Cubells, Joseph F.; Newport, D. Jeffrey; Stowe, Zachary N.; Cheong, Jeanie L. Y.; Dalach, Philippa; Doyle, Lex W.; Loke, Yuk J.; Baccarelli, Andrea A.; Just, Allan C.; Wright, Robert O.; Tellez-Rojo, Mara M.; Svensson, Katherine; Trevisi, Letizia; Kennedy, Elizabeth M.; Binder, Elisabeth B.; Iurato, Stella; Räikkönen, Katri; Lahti, Jari M. T.; Pesonen, Anu-Katriina; Kajantie, Eero; Villa, Pia M.; Laivuori, Hannele; Hämäläinen, Esa; Park, Hea Jin; Bailey, Lynn B.; Parets, Sasha E.; Kilaru, Varun; Menon, Ramkumar; Horvath, Steve; Bush, Nicole R.; LeWinn, Kaja Z.; Tylavsky, Frances A.; Conneely, Karen N.; Smith, Alicia K. (2016)
    Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.
  • Felix, Janine F.; Joubert, Bonnie R.; Baccarelli, Andrea A.; Sharp, Gemma C.; Almqvist, Catarina; Annesi-Maesano, Isabella; Arshad, Hasan; Baiz, Nour; Bakermans-Kranenburg, Marian J.; Bakulski, Kelly M.; Binder, Elisabeth B.; Bouchard, Luigi; Breton, Carrie V.; Brunekreef, Bert; Brunst, Kelly J.; Burchard, Esteban G.; Bustamante, Mariona; Chatzi, Leda; Munthe-Kaas, Monica Cheng; Corpeleijn, Eva; Czamara, Darina; Dabelea, Dana; Smith, George Davey; De Boever, Patrick; Duijts, Liesbeth; Dwyer, Terence; Eng, Celeste; Eskenazi, Brenda; Everson, Todd M.; Falahi, Fahimeh; Fallin, M. Daniele; Farchi, Sara; Fernandez, Mariana F.; Gao, Lu; Gaunt, Tom R.; Ghantous, Akram; Gillman, Matthew W.; Gonseth, Semira; Grote, Veit; Gruzieva, Olena; Haberg, Siri E.; Herceg, Zdenko; Hivert, Marie-France; Holland, Nina; Holloway, John W.; Hoyo, Cathrine; Hu, Donglei; Huang, Rae-Chi; Huen, Karen; Jarvelin, Marjo-Riitta; Jima, Dereje D.; Just, Allan C.; Karagas, Margaret R.; Karlsson, Robert; Karmaus, Wilfried; Kechris, Katerina J.; Kere, Juha; Kogevinas, Manolis; Koletzko, Berthold; Koppelman, Gerard H.; Kupers, Leanne K.; Ladd-Acosta, Christine; Lahti, Jari; Lambrechts, Nathalie; Langie, Sabine A. S.; Lie, Rolv T.; Liu, Andrew H.; Magnus, Maria C.; Magnus, Per; Maguire, Rachel L.; Marsit, Carmen J.; McArdle, Wendy; Melen, Erik; Melton, Phillip; Murphy, Susan K.; Nawrot, Tim S.; Nistico, Lorenza; Nohr, Ellen A.; Nordlund, Bjorn; Nystad, Wenche; Oh, Sam S.; Oken, Emily; Page, Christian M.; Perron, Patrice; Pershagen, Goran; Pizzi, Costanza; Plusquin, Michelle; Räikkönen, Katri; Reese, Sarah E.; Reischl, Eva; Richiardi, Lorenzo; Ring, Susan; Roy, Ritu P.; Rzehak, Peter; Schoeters, Greet; Schwartz, David A.; Sebert, Sylvain; Snieder, Harold; Sorensen, Thorkild I. A.; Starling, Anne P.; Sunyer, Jordi; ATaylor, Jack; Tiemeier, Henning; Ullemar, Vilhelmina; Vafeiadi, Marina; Van Ijzendoorn, Marinus H.; Vonk, Judith M.; Vriens, Annette; Vrijheid, Martine; Wang, Pei; Wiemels, Joseph L.; Wilcox, Allen J.; Wright, Rosalind J.; Xu, Cheng-Jian; Xu, Zongli; Yang, Ivana V.; Yousefi, Paul; Zhang, Hongmei; Zhang, Weiming; Zhao, Shanshan; Agha, Golareh; Relton, Caroline L.; Jaddoe, Vincent W. V.; London, Stephanie J. (2018)
  • Summanen, Milla; Seikku, Laura; Rahkonen, Petri; Stefanovic, Vedran; Teramo, Kari; Andersson, Sture; Kaila, Kai; Rahkonen, Leena (2017)
    Background: Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. Objectives: To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B. Methods: The study population consisted of 140 singleton, term neonates: 113 controls and 27 with birth asphyxia (2/3 criteria met: umbilical artery pH
  • Vehmeijer, Florianne O. L.; Kuepers, Leanne K.; Sharp, Gemma C.; Salas, Lucas A.; Lent, Samantha; Jima, Dereje D.; Tindula, Gwen; Reese, Sarah; Qi, Cancan; Gruzieva, Olena; Page, Christian; Rezwan, Faisal; Melton, Philip E.; Nohr, Ellen; Escaramis, Georgia; Rzehak, Peter; Heiskala, Anni; Gong, Tong; Tuominen, Samuli T.; Gao, Lu; Ross, Jason P.; Starling, Anne P.; Holloway, John W.; Yousefi, Paul; Aasvang, Gunn Marit; Beilin, Lawrence J.; Bergstrom, Anna; Binder, Elisabeth; Chatzi, Leda; Corpeleijn, Eva; Czamara, Darina; Eskenazi, Brenda; Ewart, Susan; Ferre, Natalia; Grote, Veit; Gruszfeld, Dariusz; Haberg, Siri E.; Hoyo, Cathrine; Huen, Karen; Karlsson, Robert; Kull, Inger; Langhendries, Jean-Paul; Lepeule, Johanna; Magnus, Maria C.; Maguire, Rachel L.; Molloy, Peter L.; Monnereau, Claire; Mori, Trevor A.; Oken, Emily; Räikkönen, Katri; Rifas-Shiman, Sheryl; Ruiz-Arenas, Carlos; Sebert, Sylvain; Ullemar, Vilhelmina; Verduci, Elvira; Vonk, Judith M.; Xu, Cheng-jian; Yang, Ivana; Zhang, Hongmei; Zhang, Weiming; Karmaus, Wilfried; Dabelea, Dana; Muhlhausler, Beverly S.; Breton, Carrie; Lahti, Jari; Almqvist, Catarina; Jarvelin, Marjo-Riitta; Koletzko, Berthold; Vrijheid, Martine; Sorensen, Thorkild I. A.; Huang, Rae-Chi; Arshad, Syed Hasan; Nystad, Wenche; Melen, Erik; Koppelman, Gerard H.; London, Stephanie J.; Holland, Nina; Bustamante, Mariona; Murphy, Susan K.; Hivert, Marie-France; Baccarelli, Andrea; Relton, Caroline L.; Snieder, Harold; Jaddoe, Vincent W. V.; Felix, Janine F. (2020)
    Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P <1.06 x 10(-7), with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P-enrichment = 1; childhood P-enrichment = 2.00 x 10(-4); adolescence P-enrichment = 2.10 x 10(-7)). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.
  • Merid, Simon Kebede; Novoloaca, Alexei; Sharp, Gemma C.; Kupers, Leanne K.; Kho, Alvin T.; Roy, Ritu; Gao, Lu; Annesi-Maesano, Isabella; Jain, Pooja; Plusquin, Michelle; Kogevinas, Manolis; Allard, Catherine; Vehmeijer, Florianne O.; Kazmi, Nabila; Salas, Lucas A.; Rezwan, Faisal I.; Zhang, Hongmei; Sebert, Sylvain; Czamara, Darina; Rifas-Shiman, Sheryl L.; Melton, Phillip E.; Lawlor, Debbie A.; Pershagen, Goran; Breton, Carrie V.; Huen, Karen; Baiz, Nour; Gagliardi, Luigi; Nawrot, Tim S.; Corpeleijn, Eva; Perron, Patrice; Duijts, Liesbeth; Nohr, Ellen Aagaard; Bustamante, Mariona; Ewart, Susan L.; Karmaus, Wilfried; Zhao, Shanshan; Page, Christian M.; Herceg, Zdenko; Jarvelin, Marjo-Riitta; Lahti, Jari; Baccarelli, Andrea A.; Anderson, Denise; Kachroo, Priyadarshini; Relton, Caroline L.; Bergstrom, Anna; Eskenazi, Brenda; Soomro, Munawar Hussain; Vineis, Paolo; Snieder, Harold; Bouchard, Luigi; Jaddoe, Vincent W.; Sorensen, Thorkild I. A.; Vrijheid, Martine; Arshad, S. Hasan; Holloway, John W.; Haberg, Siri E.; Magnus, Per; Dwyer, Terence; Binder, Elisabeth B.; DeMeo, Dawn L.; Vonk, Judith M.; Newnham, John; Tantisira, Kelan G.; Kull, Inger; Wiemels, Joseph L.; Heude, Barbara; Sunyer, Jordi; Nystad, Wenche; Munthe-Kaas, Monica C.; Raikkonen, Katri; Oken, Emily; Huang, Rae-Chi; Weiss, Scott T.; Anto, Josep Maria; Bousquet, Jean; Kumar, Ashish; Soderhall, Cilla; Almqvist, Catarina; Cardenas, Andres; Gruzieva, Olena; Xu, Cheng-Jian; Reese, Sarah E.; Kere, Juha; Brodin, Petter; Solomon, Olivia; Wielscher, Matthias; Holland, Nina; Ghantous, Akram; Hivert, Marie-France; Felix, Janine F.; Koppelman, Gerard H.; London, Stephanie J.; Melen, Erik (2020)
    Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
  • BIOS Consortium; Reese, Sarah E.; Xu, Cheng-Jian; den Dekker, Herman T.; Lahti, Jari; Kajantie, Eero; Kere, Juha; Räikkönen, Katri (2019)
    Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate <0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate <0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.
  • Howe, Caitlin G.; Cox, Bianca; Fore, Ruby; Jungius, James; Kvist, Tuomas; Lent, Samantha; Miles, Harriet E.; Salas, Lucas A.; Rifas-Shiman, Sheryl; Starling, Anne P.; Yousefi, Paul; Ladd-Acosta, Christine; Baccarelli, Andrea; Binder, Elisabeth B.; Chatzi, Vaia Lida; Czamara, Darina; Dabelea, Dana; DeMeo, Dawn L.; Ghantous, Akram; Herceg, Zdenko; Kajantie, Eero; Lahti, Jari M. T.; Lawlor, Debbie A.; Litonjua, Augusto; Nawrot, Tim S.; Nohr, Ellen A.; Oken, Emily; Pizzi, Costanza; Plusquin, Michelle; Räikkönen, Katri; Relton, Caroline L.; Sharp, Gemma C.; Sorensen, Thorkild I. A.; Sunyer, Jordi; Vrijheid, Martine; Zhang, Weiming; Hivert, Marie-France; Breton, Carrie V. (2020)
    OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.
  • Hauta-alus, Helena H.; Viljakainen, Heli T.; Holmlund-Suila, Elisa M.; Enlund-Cerullo, Maria; Rosendahl, Jenni; Valkama, Saara M.; Helve, Otto M.; Hytinantti, Timo K.; Mäkitie, Outi M.; Andersson, Sture (2017)
    Background: Maternal vitamin D status has been associated with both gestational diabetes mellitus (GDM) and fetal growth restriction, however, the evidence is inconsistent. In Finland, maternal vitamin D status has improved considerably due to national health policies. Our objective was to compare maternal 25-hydroxy vitamin D concentrations [25(OH)D] between mothers with and without GDM, and to investigate if an association existed between maternal vitamin D concentration and infant birth size. Methods: This cross-sectional study included 723 mother-child pairs. Mothers were of Caucasian origin, and infants were born at term with normal birth weight. GDM diagnosis and birth size were obtained from medical records. Maternal 25(OH)D was determined on average at 11 weeks of gestation in pregnancy and in umbilical cord blood (UCB) at birth. Results: GDM was observed in 81 of the 723 women (11%). Of the study population, 97% were vitamin D sufficient [25(OH)D >= 50 nmol/L]. There was no difference in pregnancy 25(OH)D concentration between GDM and non-GDM mothers (82 vs 82 nmol/L, P = 0.99). Regression analysis confirmed no association between oral glucose tolerance test results and maternal 25(OH)D (P > 0.53). Regarding the birth size, mothers with optimal pregnancy 25(OH)D (>= 80 nmol/L) had heavier newborns than those with suboptimal pregnancy 25(OH)D (P = 0.010). However, mothers with optimal UCB 25(OH) D had newborns with smaller head circumference than those with suboptimal 25(OH)D (P = 0.003), which was further confirmed as a linear association (P = 0.024). Conclusions: Maternal vitamin D concentration was similar in mothers with and without GDM in a mostly vitamin D sufficient population. Associations between maternal vitamin D status and birth size were inconsistent. A sufficient maternal vitamin D status, specified as 25(OH)D above 50 nmol/L, may be a threshold above which the physiological requirements of pregnancy are achieved.
  • Kupers, Leanne K.; Monnereau, Claire; Sharp, Gemma C.; Yousefi, Paul; Salas, Lucas A.; Ghantous, Akram; Page, Christian M.; Reese, Sarah E.; Wilcox, Allen J.; Czamara, Darina; Starling, Anne P.; Novoloaca, Alexei; Lent, Samantha; Roy, Ritu; Hoyo, Cathrine; Breton, Carrie; Allard, Catherine; Just, Allan C.; Bakulski, Kelly M.; Holloway, John W.; Everson, Todd M.; Xu, Cheng-Jian; Huang, Rae-Chi; van der Plaat, Diana A.; Wielscher, Matthias; Merid, Simon Kebede; Ullemar, Vilhelmina; Rezwan, Faisal; Lahti, Jari; van Dongen, Jenny; Langie, Sabine A. S.; Richardson, Tom G.; Magnus, Maria C.; Nohr, Ellen A.; Xu, Zongli; Duijts, Liesbeth; Zhao, Shanshan; Zhang, Weiming; Plusquin, Michelle; DeMeo, Dawn L.; Solomon, Olivia; Heimovaara, Joosje H.; Jima, Dereje D.; Gao, Lu; Bustamante, Mariona; Perron, Patrice; Wright, Robert O.; Hertz-Picciotto, Irva; Zhang, Hongmei; Karagas, Margaret R.; Gehring, Ulrike; Marsit, Carmen J.; Beilin, Lawrence J.; Vonk, Judith M.; Jarvelin, Marjo-Riitta; Bergstrom, Anna; Ortqvist, Anne K.; Ewart, Susan; Villa, Pia M.; Moore, Sophie E.; Willemsen, Gonneke; Standaert, Arnout R. L.; Haberg, Siri E.; Sorensen, Thorkild I. A.; Taylor, Jack A.; Räikkönen, Katri; Yang, Ivana; Kechris, Katerina; Nawrot, Tim S.; Silver, Matt J.; Gong, Yun Yun; Richiardi, Lorenzo; Kogevinas, Manolis; Litonjua, Augusto A.; Eskenazi, Brenda; Huen, Karen; Mbarek, Hamdi; Maguire, Rachel L.; Dwyer, Terence; Vrijheid, Martine; Bouchard, Luigi; Baccarelli, Andrea A.; Croen, Lisa A.; Karmaus, Wilfried; Anderson, Denise; de Vries, Maaike; Sebert, Sylvain; Kere, Juha; Karlsson, Robert; Arshad, Syed Hasan; Hämäläinen, Esa; Routledge, Michael N.; Boomsma, Dorret; Feinberg, Andrew P.; Newschaffer, Craig J.; Govarts, Eva; Moisse, Matthieu; Fallin, M. Daniele; Melen, Erik; Prentice, Andrew M.; Kajantie, Eero; Almqvist, Catarina; Oken, Emily; Dabelea, Dana; Boezen, H. Marike; Melton, Phillip E.; Wright, Rosalind J.; Koppelman, Gerard H.; Trevisi, Letizia; Hivert, Marie-France; Sunyer, Jordi; Munthe-Kaas, Monica C.; Murphy, Susan K.; Corpeleijn, Eva; Wiemels, Joseph; Holland, Nina; Herceg, Zdenko; Binder, Elisabeth B.; Smith, George Davey; Jaddoe, Vincent W. V.; Lie, Rolv T.; Nystad, Wenche; London, Stephanie J.; Lawlor, Debbie A.; Relton, Caroline L.; Snieder, Harold; Felix, Janine F. (2019)
    Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,
  • Biobank-based Integrative Omics; Gruzieva, Olena; Xu, Cheng-Jian; Yousefi, Paul; Kere, Juha; Melen, Erik (2019)
    Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. Objectives: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter Methods: We meta-analyzed associations between exposure to PM10 (n=1,949) and PM2.5 (n=1,551) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. Results: Six CpGs were significantly associated [false discovery rate (FDR) Conclusions: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes.
  • Hauta-Alus, Helena H.; Holmlund-Suila, Elisa M.; Kajantie, Eero; Rosendahl, Jenni; Valkama, Saara M.; Enlund-Cerullo, Maria; Andersson, Sture; Mäkitie, Outi (2021)
    Context: The relationship between maternal and infant vitamin D and early childhood growth remains inadequately understood. Objective: This work aimed to investigate how maternal and child 25-hydroxyvitamin D (25[OH]D) and vitamin D supplementation affect growth during the first 2 years of life. Methods: A randomized, double-blinded, single-center intervention study was conducted from pregnancy until offspring age 2 years. Altogether 812 term-born children with complete data were recruited at a maternity hospital. Children received daily vitamin D-3 supplementation of 10 mu g (group 10) or 30 mu g (group 30) from age 2 weeks to 2 years. Anthropometry and growth rate were measured at age 1 and 2 years. Results: Toddlers born to mothers with pregnancy 25(OH)D greater than 125 nmol/L were at 2 years lighter and thinner than the reference group with 25(OH)D of 50 to 74.9 nmol/L (P < .010). Mean 2-year 25(OH)D concentrations were 87 nmol/L in group 10 and 118 nmol/L in group 30 (P < .001). When group 30 was compared with group 10, difference in body size was not statistically significant (P > .053), but group 30 had slower growth in length and head circumference between 6 months and 1 year (P < .047), and more rapid growth in weight and length-adjusted weight between 1 and 2 years (P < .043). Toddlers in the highest quartile of 25(OH)D (> 121 nmol/L) were shorter (mean difference 0.2 SD score [SDS], P = .021), lighter (mean difference 0.4 SDS, P = .001), and thinner (in length-adjusted weight) (mean difference 0.4 SDS, P = .003) compared with the lowest quartile (< 81.2 nmol/L). Conclusion: Vitamin D and early childhood growth may have an inverse U-shaped relationship.