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Search Results: 1 - 10 of 472447 matches for " Eric A. Steegers "
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Periconceptional Maternal Folic Acid Use of 400 μg per Day Is Related to Increased Methylation of the IGF2 Gene in the Very Young Child
Régine P. Steegers-Theunissen,Sylvia A. Obermann-Borst,Dennis Kremer,Jan Lindemans,Cissy Siebel,Eric A. Steegers,P. Eline Slagboom,Bastiaan T. Heijmans
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007845
Abstract: Countries worldwide recommend women planning pregnancy to use daily 400 μg of synthetic folic acid in the periconceptional period to prevent birth defects in children. The underlying mechanisms of this preventive effect are not clear, however, epigenetic modulation of growth processes by folic acid is hypothesized. Here, we investigated whether periconceptional maternal folic acid use and markers of global DNA methylation potential (S-adenosylmethionine and S-adenosylhomocysteine blood levels) in mothers and children affect methylation of the insulin-like growth factor 2 gene differentially methylation region (IGF2 DMR) in the child. Moreover, we tested whether the methylation of the IGF2 DMR was independently associated with birth weight.
Work-Related Maternal Risk Factors and the Risk of Pregnancy Induced Hypertension and Preeclampsia during Pregnancy. The Generation R Study
Jaap Jan Nugteren, Claudia A. Snijder, Albert Hofman, Vincent W. V. Jaddoe, Eric A. P. Steegers, Alex Burdorf
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039263
Abstract: Objective To study the associations between physically demanding work and occupational exposure to chemicals and hypertensive disorders during pregnancy within a large birth cohort study, the Generation R Study. Methods Associations between occupational characteristics and hypertensive disorders during pregnancy were studied in 4465 pregnant woman participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002–2006). Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment), were included if they conducted paid employment, had a spontaneously conceived singleton live born pregnancy, and did not suffer from pre-existing hypertension (n = 4465). Questions on physical demanding work were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on manually handling loads of 25 kg or more, long periods of standing or walking, night shifts, and working hours. To assess occupational exposure to chemicals, job titles and task descriptions were linked to a job-exposure-matrix (JEM), an expert judgment on exposure to chemicals at the workplace. Information on hypertensive disorders during pregnancy was obtained from medical records. Results We observed no consistent associations between any of the work related risk factors, such as long periods of standing or walking, heavy lifting, night shifts, and working hours, nor exposure to chemicals with hypertensive disorders during pregnancy. Conclusion This prospective birth cohort study suggests that there is no association of hypertensive disorders during pregnancy with physically demanding work or exposure to chemicals. However, the low prevalence of PIH and PE, combined with the low prevalence of occupational risk factors limit the power for inference and larger studies are needed to corroborate or refute these findings.
A Common Genetic Variant at 15q25 Modifies the Associations of Maternal Smoking during Pregnancy with Fetal Growth: The Generation R Study
Elisabeth T. M. Leermakers, H. Rob Taal, Rachel Bakker, Eric A. P. Steegers, Albert Hofman, Vincent W. V. Jaddoe
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034584
Abstract: Objective Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics. Methods This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy. Results Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences ?0.23 mm (95%CI ?0.45 to ?0.00) and ?0.41 mm (95%CI ?0.69 to ?0.13), respectively] and a smaller birth length [difference ?2.61 mm (95%CI ?5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference ?33 grams (95%CI ?55 to ?10)], and tended to be associated with birth weight [difference ?38 grams (95%CI ?89 to 13)]. This association persisted after adjustment for smoking quantity. Conclusions Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene – fetal smoke exposure interactions.
Midwives unable to overcome language barriers in prenatal care
Mirjam P. Fransen,Hajo I.J.Wildschut,Johan P. Mackenbach,Eric A.P. Steegers
Italian Journal of Public Health , 2012, DOI: 10.2427/7531
Abstract: Background: the present study aims to explore to what extent midwives experience barriers in providing information about prenatal screening for Down syndrome to women from diverse ethnic backgrounds, and to assess their competences to overcome these barriers. Methods: midwives from 24 Dutch midwifery practices in Rotterdam completed a structured webbased questionnaire (n=57). Data were obtained on perceived ethnic-related differences and barriers in providing information on prenatal screening, preparedness to provide cultural competent care, and the use of translated materials and professional translators. A group interview was conducted to further explore the results emerging from the questionnaire (n=23). Results: almost all midwives (95%) experienced barriers in informing women from non-Western ethnic backgrounds about prenatal screening. Midwives especially felt incompetent to provide information to pregnant women that hardly speak and understand Dutch. In total 58% of the midwives reported that they never used translated information materials and 88% never used professional interpreters in providing information on prenatal screening. The main reasons for this underutilization were unawareness of the availability of translated materials and unfamiliarity with the use of professional interpreters. Conclusions: although language barriers were reported to be the main difficulty in providing cultural competent care to patients from diverse ethnic backgrounds, only a minority of the midwives used translated materials or professional interpreters. In order to enable all pregnant women to make an informed decision whether or not to participate in prenatal screening, midwives’ competences to address language barriers should be increased.
Angiogenic Factors in Women Ten Years after Severe Very Early Onset Preeclampsia
Ingrid P. M. Gaugler-Senden, Jouke T. Tamsma, Chris van der Bent, Ron Kusters, Eric A. P. Steegers, Christianne J. M. de Groot
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043637
Abstract: Background Women with a history of mainly severe and early onset preeclampsia have an increased risk of future cardiovascular disease. During these complicated pregnancies increased levels of anti-angiogenic factors can be found. We hypothesize that women with a history of severe very early onset preeclampsia still have increased levels of these biomarkers years after this pregnancy, resulting in increased risk for cardiovascular disease. Methods Twenty women with severe early onset preeclampsia before 24 weeks' gestation, who delivered between 1993–2003 in a tertiary referral centre and twenty matched controls with uncomplicated pregnancies and healthy term infants, were addressed for participation in the study. Venous plasma samples were analyzed for basic fibroblast growth factor (bFGF), placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), E- and P-selectin, soluble intercellular adhesion molecule-3 (sICAM-3) and thrombomodulin by ELISA. Results Sixteen case subjects and 18 control subjects consented participation. The median time interval index pregnancy to study was 9.4 and 9.7 years for cases and controls, respectively. Median levels for cases-controls (p-value) were not different; bFGF: 17.43–11.11 pg/mL (0.33), sFlt-1: 102.98–101.92 pg/ml (0.84), PLGF: 3.57–4.20 pg/mL (0.38), VEGF: 64.05–45.72 pg/mL (0.73), E-selectin: 5.11–4.68 ng/mL (0.20), P-selectin: 85.35–71.69 ng/mL (0.69), sICAM-3: 0.42–0.63 ng/mL (0.41) and Thrombomodulin: 0.92–0.93 ng/mL (0.59). Conclusion There were no differences in angiogenic biomarkers between women with a history of severe early onset preeclampsia versus uncomplicated pregnancy almost 10 years later, suggesting that these angiogenic factors will not contribute to the early detection of women at risk for future cardiovascular disease.
Glucocorticoid receptor gene polymorphisms do not affect growth in fetal and early postnatal life. The Generation R Study
Miranda JJ Geelhoed, Eric AP Steegers, Jan W Koper, Elisabeth FC van Rossum, Henriette A Moll, Hein Raat, Henning Tiemeier, Albert Hofman, Vincent WV Jaddoe
BMC Medical Genetics , 2010, DOI: 10.1186/1471-2350-11-39
Abstract: This study was embedded in a population-based prospective cohort study from fetal life onwards. The studied glucocorticoid receptor gene polymorphisms included BclI (rs41423247), TthIIII (rs10052957), GR-9β (rs6198), N363S (rs6195) and R23K (rs6789 and6190). Fetal growth was assessed by ultrasounds in second and third trimester of pregnancy. Anthropometric measurements in early childhood were performed at birth and at the ages of 6, 14 and 24 months postnatally. Analyses focused on weight, length and head circumference. Analyses were based on 2,414 healthy, Caucasian children.Glucocorticoid receptor gene polymorphisms were not associated with fetal weight, birth weight and early postnatal weight. Also, no associations were found with length and head circumference. Neither were these polymorphisms associated with the risks of low birth weight or growth acceleration from birth to 24 months of age.We found in a large population-based cohort no evidence for an effect of known glucocorticoid receptor gene polymorphisms on fetal and early postnatal growth characteristics. Further systematic searches for common genetic variants by means of genome-wide association studies will enable us to obtain a more complete understanding of what genes and polymorphisms are involved in growth in fetal life and infancy.Glucocorticoids are important regulators of growth, development and metabolism. The effects of these hormones, including cortisol, are mediated by glucocorticoid receptors. The sensitivity to glucocorticoids is known to show a large interindividual variation [1]. Polymorphisms in the glucocorticoid receptor gene have been suggested to contribute to this difference in sensitivity and thereby to differences in growth, development and metabolism. These glucocorticoid receptor gene variants may also explain part of the previously demonstrated associations between growth characteristics in early life and metabolic disease, including type 2 diabetes, in adult life [2,3].Four dif
The Association of Neighborhood Social Capital and Ethnic (Minority) Density with Pregnancy Outcomes in the Netherlands
Vera L. N. Sch?lmerich, ?zcan Erdem, Gerard Borsboom, Halleh Ghorashi, Peter Groenewegen, Eric A. P. Steegers, Ichiro Kawachi, Semiha Denkta?
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095873
Abstract: Background Perinatal morbidity rates are relatively high in the Netherlands, and significant inequalities in perinatal morbidity and mortality can be found across neighborhoods. In socioeconomically deprived areas, ‘Western’ women are particularly at risk for adverse birth outcomes. Almost all studies to date have explained the disparities in terms of individual determinants of birth outcomes. This study examines the influence of neighborhood contextual characteristics on birth weight (adjusted for gestational age) and preterm birth. We focused on the influence of neighborhood social capital – measured as informal socializing and social connections between neighbors – as well as ethnic (minority) density. Methods Data on birth weight and prematurity were obtained from the Perinatal Registration Netherlands 2000–2008 dataset, containing 97% of all pregnancies. Neighborhood-level measurements were obtained from three different sources, comprising both survey and registration data. We included 3.422 neighborhoods and 1.527.565 pregnancies for the birth weight analysis and 1.549.285 pregnancies for the premature birth analysis. Linear and logistic multilevel regression was performed to assess the associations of individual and neighborhood level variables with birth weight and preterm birth. Results We found modest but significant neighborhood effects on birth weight and preterm births. The effect of ethnic (minority) density was stronger than that of neighborhood social capital. Moreover, ethnic (minority) density was associated with higher birth weight for infants of non-Western ethnic minority women compared to Western women (15 grams; 95% CI: 12,4/17,5) as well as reduced risk for prematurity (OR 0.97; CI 0,95/0,99). Conclusions Our results indicate that neighborhood contexts are associated with birth weight and preterm birth in the Netherlands. Moreover, ethnic (minority) density seems to be a protective factor for non-Western ethnic minority women, but not for Western women. This helps explain the increased risk of Western women in deprived neighborhoods for adverse birth outcomes found in previous studies.
DNA Methylation of IGF2DMR and H19 Is Associated with Fetal and Infant Growth: The Generation R Study
Marieke I. Bouwland-Both, Nina H. van Mil, Lisette Stolk, Paul H. C. Eilers, Michael M. P. J. Verbiest, Bastiaan T. Heijmans, Henning Tiemeier, Albert Hofman, Eric A. P. Steegers, Vincent W. V. Jaddoe, Régine P. M. Steegers-Theunissen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081731
Abstract: Changes in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case children born small-for-gestational age (SGA, birth weight <-2SDS) and 471 control children. Fetal growth was assessed with serial ultrasound measurements. Information on birth outcomes was retrieved from medical records. Infant weight was assessed at three and six months. Methylation was assessed in DNA extracted from umbilical cord white blood cells. Analyses were performed using linear mixed models with DNA methylation as dependent variable. The DNA methylation levels of IGF2DMR and H19 in the control group were, median (90% range), 53.6% (44.5–61.6) and 30.0% (25.6–34.2) and in the SGA group 52.0% (43.9–60.9) and 30.5% (23.9–32.9), respectively. The MTHFR region was found to be hypomethylated with limited variability in the control and SGA group, 2.5% (1.4–4.0) and 2.4% (1.5–3.8), respectively. SGA was associated with lower IGF2DMR DNA methylation (β = ?1.07, 95% CI ?1.93; ?0.21, P-value = 0.015), but not with H19 methylation. A weight gain in the first three months after birth was associated with lower IGF2DMR DNA methylation (β = ?0.53, 95% CI ?0.91; ?0.16, P-value = 0.005). Genetic variants in the IGF2/H19 locus were associated with IGF2DMR DNA methylation (P-value<0.05), but not with H19 methylation. Furthermore, our results suggest a possibility of mediation of DNA methylation in the association between the genetic variants and SGA. To conclude, IGF2DMR and H19 DNA methylation is associated with fetal and infant growth.
Maternal TLR4 and NOD2 Gene Variants, Pro-Inflammatory Phenotype and Susceptibility to Early-Onset Preeclampsia and HELLP Syndrome
Bas B. van Rijn, Arie Franx, Eric A. P. Steegers, Christianne J. M. de Groot, Rogier M. Bertina, Gerard Pasterkamp, Hieronymus A. M. Voorbij, Hein W. Bruinse, Mark Roest
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001865
Abstract: Background Altered maternal inflammatory responses play a role in the development of preeclampsia and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. We examined whether allelic variants of the innate immune receptors Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 2 (NOD2), that impair the inflammatory response to endotoxin, are related to preeclampsia and HELLP syndrome. Methods and Findings We determined five common mutations in TLR4 (D299G and T399I) and NOD2 (R702W, G908R and L1007fs) in 340 primiparous women with a history of early-onset preeclampsia, of whom 177 women developed HELLP syndrome and in 113 women with a history of only uneventful pregnancies as controls. In addition, we assessed plasma levels of pro-inflammatory biomarkers C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, fibrinogen and von Willebrand factor in a subset of 214 women included at least six months after delivery. After adjustment for maternal age and chronic hypertension, attenuating allelic variants of TLR4 were more common in women with a history of early-onset preeclampsia than in controls (OR 2.9 [95% CI 1.2–6.7]). Highest frequencies for TLR4 variants were observed in women who developed HELLP syndrome (adjusted OR 4.1 [95% CI 1.7–9.8]). In addition, high levels of interleukin-6 and fibrinogen were associated with a history of early-onset preeclampsia. Combined positivity for any of the TLR4 and NOD2 allelic variants and high levels of interleukin-6 was 6.9-fold more common in women with a history of early-onset preeclampsia (95% CI 2.1–23.2) compared to controls. Conclusions We observed an association of common TLR4 and NOD2 gene variants, and pro-inflammatory phenotype with a history of early-onset preeclampsia and HELLP syndrome. These findings suggest involvement of the maternal innate immune system in severe hypertensive disorders of pregnancy.
Heritability Estimates of Body Size in Fetal Life and Early Childhood
Dennis O. Mook-Kanamori, Catharina E. M. van Beijsterveldt, Eric A. P. Steegers, Yurii S. Aulchenko, Hein Raat, Albert Hofman, Paul H. Eilers, Dorret I. Boomsma, Vincent W. V. Jaddoe
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039901
Abstract: Background The objective was to estimate the heritability for height and weight during fetal life and early childhood in two independent studies, one including parent and singleton offsprings and one of mono- and dizygotic twins. Methods This study was embedded in the Generation R Study (n = 3407, singletons) and the Netherlands Twin Register (n = 33694, twins). For the heritability estimates in Generation R, regression models as proposed by Galton were used. In the Twin Register we used genetic structural equation modelling. Parental height and weight were measured and fetal growth characteristics (femur length and estimated fetal weight) were measured by ultrasounds in 2nd and 3rd trimester (Generation R only). Height and weight were assessed at multiple time-points from birth to 36 months in both studies. Results Heritability estimates for length increased from 2nd to 3rd trimester from 13% to 28%. At birth, heritability estimates for length in singletons and twins were both 26% and 27%, respectively, and at 36 months, the estimates for height were 63% and 72%, respectively. Heritability estimates for fetal weight increased from 2nd to 3rd trimester from 17% to 27%. For birth weight, heritability estimates were 26% in singletons and 29% in twins. At 36 months, the estimate for twins was 71% and higher than for singletons (42%). Conclusions Heritability estimates for height and weight increase from second trimester to infancy. This increase in heritability is observed in singletons and twins. Longer follow-up studies are needed to examine how the heritability develops in later childhood and puberty.
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