Browsing by Subject "Gestational age"

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  • Haftorn, Kristine L; Lee, Yunsung; Denault, William R P; Page, Christian M; Nustad, Haakon E; Lyle, Robert; Gjessing, Håkon K; Malmberg, Anni; Magnus, Maria C; Næss, Øyvind; Czamara, Darina; Räikkönen, Katri; Lahti, Jari; Magnus, Per; Håberg, Siri E; Jugessur, Astanand; Bohlin, Jon (BioMed Central, 2021)
    Abstract Background Gestational age is a useful proxy for assessing developmental maturity, but correct estimation of gestational age is difficult using clinical measures. DNA methylation at birth has proven to be an accurate predictor of gestational age. Previous predictors of epigenetic gestational age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC). Our aims here were to build an epigenetic gestational age clock specific for the EPIC array and to evaluate its precision and accuracy using the embryo transfer date of newborns from the largest EPIC-derived dataset to date on assisted reproductive technologies (ART). Methods We built an epigenetic gestational age clock using Lasso regression trained on 755 randomly selected non-ART newborns from the Norwegian Study of Assisted Reproductive Technologies (START)—a substudy of the Norwegian Mother, Father, and Child Cohort Study (MoBa). For the ART-conceived newborns, the START dataset had detailed information on the embryo transfer date and the specific ART procedure used for conception. The predicted gestational age was compared to clinically estimated gestational age in 200 non-ART and 838 ART newborns using MM-type robust regression. The performance of the clock was compared to previously published gestational age clocks in an independent replication sample of 148 newborns from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restrictions (PREDO) study—a prospective pregnancy cohort of Finnish women. Results Our new epigenetic gestational age clock showed higher precision and accuracy in predicting gestational age than previous gestational age clocks (R2 = 0.724, median absolute deviation (MAD) = 3.14 days). Restricting the analysis to CpGs shared between 450 K and EPIC did not reduce the precision of the clock. Furthermore, validating the clock on ART newborns with known embryo transfer date confirmed that DNA methylation is an accurate predictor of gestational age (R2 = 0.767, MAD = 3.7 days). Conclusions We present the first EPIC-based predictor of gestational age and demonstrate its robustness and precision in ART and non-ART newborns. As more datasets are being generated on the EPIC platform, this clock will be valuable in studies using gestational age to assess neonatal development.
  • Girchenko, Polina; Lahti, Jari; Czamara, Darina; Knight, Anna K; Jones, Meaghan J; Suarez, Anna; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M; Reynolds, Rebecca M; Kobor, Michael S; Smith, Alicia K; Binder, Elisabeth B; Räikkönen, Katri (BioMed Central, 2017)
    Abstract Background A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjögren’s syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity.
  • Girchenko, Polina; Lahti, Jari; Czamara, Darina; Knight, Anna K.; Jones, Meaghan J.; Suarez Figueiredo, Anna; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M.; Reynolds, Rebecca M.; Kobor, Michael S.; Smith, Alicia K.; Binder, Elisabeth B.; Räikkönen, Katri (2017)
    Background: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results: DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjogren's syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions: Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity.
  • Martikainen, Silja (Helsingfors universitet, 2010)
    This thesis examines the associations between personality traits and sleep quantity and quality in young adults. Additionally the possible effects of birth status on these associations are examined. The data used in this thesis is part of a birth cohort study (Helsinki Study of Very Low Birth Weight Adults). The personality traits are based on the five-factor model of personality. The sleep quantity and quality are based on actigraphy assessments. Four hypothesis were made about the personality and sleep associations: (1) neuroticism is related to a lesser quality of sleep, (2) there will be more significant associations between personality traits and sleep quality than between personality traits and sleep quantity, (3) the Very Low Birth Weight (VLBW) as well as, (4) the Small for Gestational Age (SGA) status will affect the associations. Linear regressions were used to study the associations between personality traits and sleep quality and quantity. Whenever an association was significant, it was tested whether this association was moderated first, by the VLBW and second, by the SGA status of the participant. The results were mostly in line with previous research especially demonstrating the negative association between neuroticism and the quality of sleep and suggesting that vulnerability to stress decreases sleep quality. Also it was found that agreeableness and conscientiousness were associated with better sleep quality and extraversion was associated with lower sleep quantity. In addition SGA status moderated the personality and sleep associations. It is proposed that there are two factors behind the interaction. First, prenatally developing mechanisms have an effect on the development of sleep as well as personality. Second, differences in the postnatal environment, for instance the parenting practices, can account for this finding. Future research could focus especially on what kind of prenatal disturbances SGA infants have in the development of mechanisms related to sleep and personality. Also focusing on the differences in parental interaction might shed more light on the results.
  • 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.
  • Merid, Simon K; Novoloaca, Alexei; Sharp, Gemma C; Küpers, 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, Göran; Breton, Carrie V; Huen, Karen; Baiz, Nour; Gagliardi, Luigi; Nawrot, Tim S; Corpeleijn, Eva; Perron, Patrice; Duijts, Liesbeth; Nohr, Ellen A; 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; Bergström, Anna; Eskenazi, Brenda; Soomro, Munawar H; Vineis, Paolo; Snieder, Harold; Bouchard, Luigi; Jaddoe, Vincent W; Sørensen, Thorkild I A; Vrijheid, Martine; Arshad, S. H; Holloway, John W; Håberg, 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; Räikkönen, Katri; Oken, Emily; Huang, Rae-Chi; Weiss, Scott T; Antó, Josep M; Bousquet, Jean; Kumar, Ashish; Söderhäll, 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; Melén, Erik (BioMed Central, 2020)
    Abstract 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 × 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.
  • Heliövaara, Arja; Vuola, P.; Hukki, J.; Leikola, J. (2016)
    The purpose of this study was to evaluate perinatal features and the rate of cesarean section in children with non-syndromic sagittal synostosis and to compare these with the official statistics. The birth data of 36 consecutive children (25 boys) operated on using cranial vault remodeling because of primary sagittal synostosis were analyzed retrospectively from hospital records. The children were born between 2007 and 2011, and the surgery was performed before the age of 1 year. The official statistics of all Finnish newborns from the year 2010 (n = 61 371) were used as a reference. Chi-square and Fisher's exact tests were used in statistical analyses. The average gestational age of the newborns with sagittal synostosis was 39.8 weeks (reference 39.7 weeks). The average birth weight was 3565.8 g (3540 g) for boys and 3197.2 g (3427 g) for girls, and the average lengths at birth are 51 cm (50.4 cm) and 49.4 cm (49.6 cm), respectively. The average head circumference was 36 cm for both sexes (35.2 and 34.6 cm for reference boys and girls). The mean age of mothers was 30.5 years (30.1 years). The rate of cesarean section was significantly increased 30.5 % (reference 16.6 %), and the rate of suction cup delivery was increased 13.9 % (9 %). In addition, a prolonged or difficult delivery was reported in three childbirths. Newborns with non-syndromic sagittal synostosis appear to be of average birth size and gestational age. The incidences of perinatal complications and cesarean sections were increased with problems occurring in more than half of the childbirths.