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1.
Epigenomics ; 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31536415

RESUMO

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

3.
Pediatr Pulmonol ; 54(10): 1557-1566, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273956

RESUMO

Diagnosing asthma and deciding treatment are difficult in young children. An inappropriate and too high prescription rate of inhaled corticosteroids (ICS) is suggested, but how airway symptoms are associated with prescriptions of asthma medication is less known. We studied how strongly wheeze, lower respiratory tract infections (LRTI), and atopic diseases are associated with dispensing of asthma medications during early childhood. We used data from the Norwegian Mother and Child Cohort Study and the Norwegian Prescription Database at four age-intervals (0-6, 6-18, 18-36 months, and 3-7 years). Primary outcomes were dispensed asthma medications (no medication, short-acting ß-2 agonist, or ICS). Relative risks (RRs) and average attributable fractions (AAFs) were estimated. Both wheeze and LRTI were positively associated with both medication groups (0-6 months: no data on wheeze). The RRs and AAFs were higher for wheeze than LRTI. For ICS, the AAFs (95% CI) for wheeze vs LRTI were: 6 to 18 months: 69.2 (67.2, 71.2)% vs 10.4 (9.0, 11.8)%, 18 to 36 months: 33.0 (30.5, 35.5)% vs 10.0 (8.0, 12.0)%, and 3 to 7 years: 33.7 (31.0, 36.5)% vs 1.2 (0.5, 1.9)%. Except at 3 to 7 years of age, the AAFs were lower for atopic diseases than for LRTI and wheeze. Atopic diseases modified the associations between wheeze and ICS at 18 to 36 months and between LRTI or wheeze and ICS at 3 to 7 years. In conclusion, both wheeze and LRTI were associated with prescriptions of asthma medications in young children, with the strongest associations seen for wheeze. Atopic diseases contributed to these associations only in the oldest age groups.

4.
Nat Commun ; 10(1): 2548, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186427

RESUMO

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.


Assuntos
Metilação de DNA/genética , DNA/sangue , Interação Gene-Ambiente , Estudos de Coortes , Epigênese Genética , Feminino , Sangue Fetal , Genótipo , Humanos , Recém-Nascido , Masculino , Gravidez , Fatores de Risco
5.
Scand J Med Sci Sports ; 29(10): 1636-1646, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31220367

RESUMO

OBJECTIVES: High maternal pre-pregnancy body mass index (BMI), high birth weight, and rapid infant weight gain are associated with increased risk of childhood obesity. We examined whether moderate-to-vigorous physical activity (MVPA) or vigorous physical activity (VPA) in 9- to 12-year-olds modified the associations between these early life risk factors and subsequent body composition and BMI. METHODS: We used data from a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), including 445 children with available data on accelerometer assessed physical activity (PA). All participants had data on BMI, 186 of them provided data on body composition (dual energy X-ray absorptiometry (DXA)). We used multiple regression analyses to examine the modifying effect of PA by including interaction terms. RESULTS: Maternal pre-pregnancy BMI and infant weight gain were more strongly related to childhood body composition in boys than in girls. Higher VPA attenuated the association between maternal pre-pregnancy BMI and BMI in boys (low VPA: B = 0.32, 95% CI = 0.22, 0.41; high VPA B = 0.22, 95% CI = 0.12, 0.31). Birth weight was unrelated to childhood body composition, and there was no effect modification by PA. PA attenuated the associations between infant weight gain and childhood fat mass (low MVPA: B = 2.32, 95% CI = 0.48, 4.17; high MVPA: B = 1.00, 95% CI = 0.10, 1.90) and percent fat (low MVPA: B = 3.35, 95% CI = 0.56, 6.14; high MVPA: B = 1.41, 95% CI = -0.06, 2.87) in boys, but not girls. CONCLUSION: Findings from this study suggest that MVPA and VPA may attenuate the increased risk of an unfavorable body composition and BMI due to high maternal pre-pregnancy BMI and rapid infant weight gain in boys, but not in girls.

6.
Hypertension ; 74(2): 375-383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230546

RESUMO

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

7.
Prev Med ; 125: 49-54, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31077724

RESUMO

INTRODUCTION: Women who experience severe nausea and vomiting in early pregnancy are less likely to participate in leisure-time physical activity (LTPA) during pregnancy. Whether LTPA before pregnancy is associated with hyperemesis gravidarum (HG) has not yet been studied. The aim of the study was to estimate associations between prepregnancy LTPA and HG in pregnancy. METHODS: We present data from 37,442 primiparous women with singleton pregnancies enrolled in The Norwegian Mother and Child Cohort Study. Prepregnancy LTPA was self-reported by questionnaire in pregnancy week 17. HG was reported in week 30 and defined as prolonged nausea and vomiting in pregnancy requiring hospitalisation before the 25th gestational week. We estimated the crude and adjusted associations between LTPA and HG using multiple logistic regression. We assessed effect modification by prepregnancy BMI or smoking by stratified analysis and interaction terms. RESULTS: A total of 398 (1.1%) women developed HG. Before pregnancy 56.7% conducted LTPA at least 3 times weekly, while 18.4% of women conducted LTPA less than once a week. Compared to women reporting LTPA 3 to 5 times weekly, women reporting no LTPA before pregnancy had an increased odds of HG (adjusted odds ratio (aOR) 1.69; 95% confidence interval (CI), 1.20 to 2.37). LTPA-HG associations differed by prepregnancy BMI but not by prepregnancy smoking. DISCUSSION: Lack of LTPA before pregnancy was associated with an increased odds of HG. Due to few cases of HG and thereby low statistical power, one need to be cautious when interpreting the results of this study.

8.
Thorax ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514789

RESUMO

BACKGROUND: It remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (ART). OBJECTIVE: Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between ART and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis. METHODS: We used data from national Norwegian health registries (n=474 402) and the Norwegian Mother and Child Cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings. RESULTS: ART offspring had greater asthma risk, the adjusted relative risk (aRR) was 1.20 (95% CI 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% CI 1.14 to 1.76) in MoBa. The sibling analysis yielded similar associations, although the CI included the null value. The elevated asthma risk among ART offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, aRR 1.22 (95% CI 0.95 to 1.57). Asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an aRR of 1.07 (95% CI 1.03 to 1.11) for one, aRR 1.18 (95% CI 1.10 to 1.26) for two and aRR 1.24 (95% CI 1.12 to 1.37) for three or more. CONCLUSION: Our findings indicate that both parental subfertility and characteristics related to the ART procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis.

9.
Braz J Phys Ther ; 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-30017257

RESUMO

BACKGROUND: Abdominal strength training before and during pregnancy has been recommended to enhance normal vaginal birth by enabling increased force needed for active pushing. However, to date there is little research addressing this hypothesis. OBJECTIVE: To investigate whether nulliparous pregnant women reporting regular abdominal strength training prior to and at two time points during pregnancy have reduced risk of cesarean section, instrumental assisted vaginal delivery and third- and fourth-degree perineal tears. METHODS: Analysis of 36124 nulliparous pregnant women participating in the Norwegian Mother and Child Cohort Study during the period 1999-2009 who responded to questions regards the main exposure; regular abdominal strength training. Data on delivery outcomes were retrieved from the Medical Birth Registry of Norway. Logistic regression analyses were used to evaluate the association between exposure and outcome before pregnancy and at gestational weeks 17 and 30. RESULTS: Amongst participants, 66.9% reported doing abdominal strength training exercises before pregnancy, declining to 31.2% at gestational week 30. The adjusted odds ratios were 0.97 (95% CI 0.79-1.19) for acute cesarean section, among those training with the same frequency before and during pregnancy compared to those that never trained. The results were similar for instrumental assisted vaginal delivery and third- and fourth-degree perineal tear. CONCLUSION: There was no association between the report of regular abdominal strength training before and during pregnancy and delivery outcomes in this prospective population-based cohort.

10.
BMJ ; 361: k2167, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925546

RESUMO

OBJECTIVE: To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. DESIGN: One and two sample mendelian randomisation analyses. SETTING: Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). PARTICIPANTS: 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. EXPOSURES: Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. MAIN OUTCOME MEASURES: Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. RESULTS: In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. CONCLUSIONS: No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.

11.
Am J Clin Nutr ; 107(5): 789-798, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29722838

RESUMO

Background: Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective: The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design: We studied 61,676 school-age children (born during 2002-2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results: Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions: Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233.

12.
Epigenomics ; 10(1): 27-42, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29172695

RESUMO

AIM: Alcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero. MATERIALS & METHODS: We meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium. RESULTS: We found no strong evidence of association at either individual CpGs or across larger regions of the genome. CONCLUSION: Our findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Metilação de DNA , Sangue Fetal/metabolismo , Exposição Materna , Troca Materno-Fetal , Adulto , Estudos de Coortes , Feminino , Humanos , Países Baixos/epidemiologia , Noruega/epidemiologia , Gravidez , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
13.
Matern Child Health J ; 22(4): 512-519, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29285630

RESUMO

Objectives Air pollution exposure may contribute to the development of preeclampsia and hypertension during pregnancy. However, the evidence for such a relation is still limited. We investigated the associations between exposure for moderate to low levels of air pollution during pregnancy and preeclampsia and gestational hypertension in selected urban and county areas of Norway. Methods This study used a sub-group of 17,533 women in the Norwegian Mother and Child Cohort Study. Air pollution levels at residential addresses were estimated using land use regression models and back-extrapolated to the period of each pregnancy. Information on preeclampsia and gestational hypertension were obtained from the Medical Birth Registry of Norway and information on lifestyle factors was collected from questionnaires completed by the women during pregnancy. Results Moderate mean levels of NO2 (13.6 ± 6.9 µg/m3) at residential address during pregnancy were not associated with preeclampsia and pregnancy hypertension. We found no statistically significant associations per 10 µg/m3 change in NO2 exposure and preeclampsia (adjusted OR 0.89, 95% CI 0.74, 1.08) or hypertension during pregnancy (adjusted OR 0.91, 95% CI 0.78, 1.06). Conclusions for Practice In this large Norwegian pregnancy cohort, we found no statistically significant associations for moderate to low levels of pregnancy NO2 exposure and preeclampsia or hypertension during pregnancy.

14.
Am J Epidemiol ; 187(6): 1199-1209, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29244063

RESUMO

Prenatal maternal psychosocial stress might influence the development of childhood asthma. Evaluating paternal psychosocial stress and conducting a sibling comparison could provide further insight into the role of unmeasured confounding. We examined the associations of parental psychosocial stress during and after pregnancy with asthma at age 7 years in the Norwegian Mother and Child Cohort Study (n = 63,626; children born in 2000-2007). Measures of psychosocial stress included lifetime major depressive symptoms, current anxiety/depression symptoms, use of antidepressants, anxiolytics, and/or hypnotics, life satisfaction, relationship satisfaction, work stress, and social support. Childhood asthma was associated with maternal lifetime major depressive symptoms (adjusted relative risk (aRR) = 1.19, 95% confidence interval (CI): 1.09, 1.30), in addition to symptoms of anxiety/depression during pregnancy (aRR = 1.17, 95% CI: 1.06, 1.29) and 6 months after delivery (aRR = 1.17, 95% CI: 1.07, 1.28). Maternal negative life events during pregnancy (aRR = 1.10, 95% CI: 1.06, 1.13) and 6 months after delivery (aRR = 1.14, 95% CI: 1.11, 1.18) were also associated with asthma. These associations were not replicated when evaluated within sibling groups. There were no associations with paternal psychosocial stress. In conclusion, maternal anxiety/depression and negative life events were associated with offspring asthma, but this might be explained by unmeasured maternal background characteristics that remain stable across deliveries.

15.
BMJ Open ; 7(12): e015796, 2017 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-29282255

RESUMO

OBJECTIVES: It is unclear whether maternal air pollution exposure during pregnancy induces changes in the developing respiratory system of a child and whether it has consequences for respiratory health in early childhood. We investigated associations between exposure to moderate levels of air pollution during pregnancy and early childhood lower respiratory tract infections (LRTI) and wheezing. METHODS: This study used a subgroup of 17 533 participants in the Norwegian Mother and Child Cohort Study. Air pollution levels at residential addresses were estimated using land use regression models, and back-extrapolated to the period of each pregnancy. Information on LRTI and wheezing and lifestyle factors was collected from questionnaires completed by mothers during pregnancy and when the child was 6 and 18 months of age. RESULTS: Moderate mean levels of NO2 (13.6 µg/m3, range 0.01-60.4) exposure at residential address during pregnancy were not statistically associated with LRTI and wheezing. No association was found per 10 µg/m3 change in NO2 exposure and LRTI before the age of 6 months (adjusted risk ratio (RR) 0.99; 95% CI 0.84 to 1.17), or between 6 and 18 months of age (adjusted RR 1.05; 95% CI 0.94 to 1.16). Similarly, we found no association per 10 µg/m3 change in NO2 exposure and wheezing between 6 and 18 months of age (adjusted RR 1.02; 95% CI 0.97 to 1.07). CONCLUSIONS: There were no statistically significant associations for moderate levels of pregnancy NO2 exposure and respiratory health outcomes during early childhood in overall analyses.


Assuntos
Poluentes Atmosféricos/análise , Exposição Materna , Dióxido de Nitrogênio/análise , Sons Respiratórios/fisiopatologia , Infecções Respiratórias/epidemiologia , Adulto , Feminino , Humanos , Lactente , Masculino , Noruega , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Estudos Prospectivos , Sons Respiratórios/etiologia , Fatores de Risco
16.
Epigenomics ; 9(3): 253-265, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28234025

RESUMO

AIMS: Assessing whether epigenetic alterations mediate associations between environmental exposures and health outcomes is increasingly popular. We investigate the impact of exposure misclassification in such investigations. MATERIALS & METHODS: We quantify bias and false-positive rates due to exposure misclassification in mediation analysis and assess the performance of the simulation extrapolation method (SIMEX). We evaluate whether DNA-methylation mediates smoking-birth weight relationship in the Norwegian Mother and Child Study birth cohort. RESULTS: Ignoring exposure misclassification increases type I error in mediation analysis. The direct effect is underestimated and, when the mediator is a biomarker of the exposure, as is true for smoking, the indirect effect is overestimated. CONCLUSION: Misclassification correction plus cautious interpretation are recommended for mediation analyses in the presence of exposure misclassification.


Assuntos
Peso ao Nascer/genética , Metilação de DNA , Epigenômica/normas , Retardo do Crescimento Fetal/genética , Estudo de Associação Genômica Ampla/normas , Fumar/epidemiologia , Adulto , Viés , Epigenômica/métodos , Reações Falso-Positivas , Feminino , Retardo do Crescimento Fetal/epidemiologia , Estudo de Associação Genômica Ampla/métodos , Humanos , Recém-Nascido , Fumar/efeitos adversos , Fumar/genética
17.
Am J Epidemiol ; 185(4): 247-258, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28087514

RESUMO

Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994-2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. Atmospheric pollution measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the -5°C to 15°C range, with a plateau afterwards (spline coding, P = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Pressão Atmosférica , Conceitos Meteorológicos , Nascimento Prematuro/etiologia , Europa (Continente) , Humanos , Nascimento Prematuro/induzido quimicamente , Modelos de Riscos Proporcionais , Saúde da População Urbana
19.
Am J Respir Crit Care Med ; 195(2): 221-228, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27518161

RESUMO

RATIONALE: A potential adverse effect of high folate intake during pregnancy on children's asthma development remains controversial. OBJECTIVES: To prospectively investigate folate intake from both food and supplements during pregnancy and asthma at age 7 years when the diagnosis is more reliable than at preschool age. METHODS: This study included eligible children born 2002-2006 from the Norwegian Mother and Child Cohort Study, a population-based pregnancy cohort, linked to the Norwegian Prescription Database. Current asthma at age 7 was defined by asthma medications dispensed at least twice in the year (1,901 cases; n = 39,846) or by maternal questionnaire report (1,624 cases; n = 28,872). Maternal folate intake was assessed with a food frequency questionnaire validated against plasma folate. We used log-binomial and multinomial regression to calculate adjusted relative risks with 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: Risk of asthma was increased in the highest versus lowest quintile of total folate intake with an adjusted relative risk of 1.23 (95% confidence interval, 1.06-1.44) that was similar for maternally reported asthma. Mothers in the highest quintile had a relatively high intake of food folate (median, 308; interquartile range, 241-366 µg/d) and nearly all took at least 400 µg/d of supplemental folic acid (median, 500; interquartile range, 400-600 µg/d). CONCLUSIONS: In this large prospective population-based cohort with essentially complete follow-up, pregnant women taking supplemental folic acid at or above the recommended dose, combined with a diet rich in folate, reach a total folate intake level associated with a slightly increased risk of asthma in children.


Assuntos
Asma/etiologia , Suplementos Nutricionais/efeitos adversos , Ácido Fólico/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/etiologia , Adulto , Asma/epidemiologia , Criança , Feminino , Humanos , Masculino , Noruega/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
20.
Environ Health Perspect ; 125(4): 760-766, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27323799

RESUMO

BACKGROUND: Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable. OBJECTIVES: We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms. METHODS: Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa). RESULTS: This score reliably predicted smoking status in the training set (n = 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set (n = 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracytrain = 82%, accuracytest = 83%). CONCLUSIONS: Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.


Assuntos
Biomarcadores/sangue , Metilação de DNA , Exposição Materna/estatística & dados numéricos , Fumar/epidemiologia , Adulto , Peso ao Nascer , Estudos de Coortes , Cotinina/sangue , Feminino , Sangue Fetal/metabolismo , Humanos , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal
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