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1.
Eur J Epidemiol ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451995

RESUMO

Self-selection into prospective cohort studies and loss to follow-up can cause biased exposure-outcome association estimates. Previous investigations illustrated that such biases can be small in large prospective cohort studies. The structural approach to selection bias shows that general statements about bias are not possible for studies that investigate multiple exposures and outcomes, and that inverse probability of participation weighting (IPPW) but not adjustment for participation predictors generally reduces bias from self-selection and loss to follow-up. We propose to substantiate assumptions in structural models of selection bias through calculation of genetic correlations coefficients between participation predictors, outcome, and exposure, and to estimate a lower bound for bias due to self-selection and loss to follow-up by comparing effect estimates from IPP weighted and unweighted analyses. This study used data from the Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway. Using the example of risk factors for ADHD, we find that genetic correlations between participation predictors, exposures, and outcome suggest the presence of bias. The comparison of exposure-outcome associations from regressions with and without IPPW revealed meaningful deviations. Assessment of selection bias for entire multi-exposure multi-outcome cohort studies is not possible. Instead, it has to be assessed and controlled on a case-by-case basis.

2.
Aging (Albany NY) ; 11(16): 5876-5894, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31461406

RESUMO

Telomere length is associated with age-related diseases and is highly heritable. It is unclear, however, to what extent epigenetic modifications are associated with leukocyte telomere length (LTL). In this study, we conducted a large-scale epigenome-wide association study (EWAS) of LTL using seven large cohorts (n=5,713) - the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins. Our stratified analysis suggests that EWAS findings for women of African ancestry may be distinct from those of three other groups: males of African ancestry, and males and females of European ancestry. Using a meta-analysis framework, we identified DNA methylation (DNAm) levels at 823 CpG sites to be significantly associated (P<1E-7) with LTL after adjusting for age, sex, ethnicity, and imputed white blood cell counts. Functional enrichment analyses revealed that these CpG sites are near genes that play a role in circadian rhythm, blood coagulation, and wound healing. Weighted correlation network analysis identified four co-methylation modules associated with LTL, age, and blood cell counts. Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes.

3.
Int J Hyg Environ Health ; 222(8): 1059-1067, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327570

RESUMO

A number of prospective cohort studies are ongoing worldwide to investigate the impact of foetal and neonatal exposures to chemical substances on child health. To assess multiple exposure (mixture) effects and low prevalence health outcomes it is useful to pool data from several studies and conduct mega-data-analysis. To discuss a path towards data harmonization, representatives from several large-scale birth cohort studies and a biomonitoring programme formed a collaborative group, the Environment and Child Health International Birth Cohort Group (ECHIBCG). In this study, an intra-laboratory trial was performed to harmonize existing blood lead measurements within the groups' studies. Then, decentralized analyses were conducted in individual countries' laboratories to evaluate blood lead levels (BLL) in each study. The measurements of pooled BLL samples in French, German and three Japanese laboratories resulted in an overall mean blood lead concentration of 8.66 µg l-1 (95% confidence interval: 8.59-8.72 µg l-1) with 3.0% relative standard deviation. Except for China's samples, BLL from each study were comparable with mean concentrations below or close to 10 µg l-1. The decentralized multivariate analyses revealed that all models had coefficients of determination below 0.1. Determinants of BLL were current smoking, age >35 years and overweight or obese status. The three variables were associated with an increase in BLL in each of the five studies, most strongly in France by almost 80% and the weakest effect being in Norway with only 15%; for Japan, with the far largest sample (~18,000), the difference was 36%. This study successfully demonstrated that the laboratory analytical methods were sufficiently similar to allow direct comparison of data and showed that it is possible to harmonize the epidemiological data for joint analysis. This exercise showed the challenges in decentralized data analyses and reinforces the need for data harmonization among studies.

4.
Sci Rep ; 9(1): 9519, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266998

RESUMO

Maternal fever during pregnancy is associated with several adverse child outcomes. We investigated associations between maternal fever and ADHD among offspring, as well as the sub-dimensions of ADHD - inattention and hyperactivity/impulsivity. Data came from the Norwegian Mother and Child Cohort Study, including more than 114,000 children. Information about children's ADHD diagnoses was obtained from the Norwegian Patient Register. Mothers reported on inattention and hyperactivity/impulsivity symptoms in questionnaires at 8 years. Logistic regression analysis showed that children exposed to maternal fever in the first trimester received an ADHD diagnosis more often than unexposed children (Odds Ratio (OR) = 1.31, 95% confidence interval (CI) = 1.06-1.61). For children exposed twice or more in the first trimester, the OR was 2.64 (CI = 1.36-5.14). Linear regression analysis showed elevated inattention symptoms among children exposed to fever in the first (Cohen's d = 0.09, CI = 0.03-0.15) and second (Cohen's d = 0.05, CI = 0.01-0.09) trimester. Results were similar whether the mother had taken acetaminophen for their fever or not. Hyperactivity/impulsivity symptoms were not related to maternal fever. The results indicate that maternal fever in early pregnancy may be a risk factor for ADHD, and particularly for inattention problems. This risk is neither mitigated nor inflated by use of acetaminophen.

5.
Aging (Albany NY) ; 11(12): 4238-4253, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235674

RESUMO

The human pan-tissue epigenetic clock is widely used for estimating age across the entire lifespan, but it does not lend itself well to estimating gestational age (GA) based on placental DNAm methylation (DNAm) data. We replicate previous findings demonstrating a strong correlation between GA and genome-wide DNAm changes. Using substantially more DNAm arrays (n=1,102 in the training set) than a previous study, we present three new placental epigenetic clocks: 1) a robust placental clock (RPC) which is unaffected by common pregnancy complications (e.g., gestational diabetes, preeclampsia), and 2) a control placental clock (CPC) constructed using placental samples from pregnancies without known placental pathology, and 3) a refined RPC for uncomplicated term pregnancies. These placental clocks are highly accurate estimators of GA based on placental tissue; e.g., predicted GA based on RPC is highly correlated with actual GA (r>0.95 in test data, median error less than one week). We show that epigenetic clocks derived from cord blood or other tissues do not accurately estimate GA in placental samples. While fundamentally different from Horvath's pan-tissue epigenetic clock, placental clocks closely track fetal age during development and may have interesting applications.

6.
Int J Cancer ; 2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054169

RESUMO

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case-control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97-10.68; insecticides HR = 2.86, 95% CI = 0.99-8.23; animals HR = 3.89, 95% CI = 1.18-12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12-5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31-0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.

7.
JAMA ; 321(17): 1702-1715, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063572

RESUMO

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação , Complicações na Gravidez , Resultado da Gravidez , Adulto , Peso ao Nascer , Cesárea/estatística & dados numéricos , Diabetes Gestacional , Feminino , Humanos , Hipertensão Induzida pela Gravidez , Recém-Nascido , Obesidade , Gravidez , Nascimento Prematuro
8.
J Am Heart Assoc ; 8(6): e011615, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30857459

RESUMO

Background Evidence linking individual-level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies. Methods and Results Women recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996-2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000-2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non-folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80-1.22), 1.08 (95% CI , 0.93-1.25), and 1.07 (95% CI , 0.97-1.19), respectively. For initiation of folic acid in the preconception period weeks -4 to -1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI , 1.00-1.25), 1.09 (95% CI , 0.95-1.25), 0.98 (95% CI , 0.86-1.12), and 0.97 (95% CI , 0.78-1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results. Conclusions Folic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.

9.
Paediatr Perinat Epidemiol ; 33(2): 164-171, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30920006

RESUMO

BACKGROUND: Socio-economic disparities in preterm delivery have often been attributed to socially patterned smoking habits. However, most existing studies have used methods that potentially give biased estimates of the mediating effect of smoking. We used a contemporary mediation approach to study to which extent smoking during pregnancy mediates educational disparities in preterm delivery. METHODS: We performed a comparative analysis of data from three large birth cohort studies: the Danish National Birth Cohort (DNBC), the Dutch Generation R Study, and the Norwegian Mother and Child Cohort Study (MoBa). Risk of preterm delivery by maternal education is reported as risk differences and decomposed into a part explained by smoking and a part explained by other pathways. RESULTS: Proportions of preterm singleton deliveries were 4.8%-4.9% in all three cohorts. Total effects of maternal education were 2.0 (95% confidence interval [CI] 1.4, 2.5), 3.2 (95% CI 0.8, 5.2) and 2.0 (95% CI 0.9, 3.0) excess preterm deliveries per 100 singleton deliveries in DNBC, Generation R and MoBa when comparing primary/lower secondary education to an academic degree or equivalent. Smoking mediated, respectively, 22%, 10% and 19% of the excess risk in the DNBC, Generation R and MoBa cohorts. Adjustment for potential misclassification of smoking only increased mediated proportions slightly. CONCLUSIONS: Smoking during pregnancy explains part of educational disparities in preterm delivery, but the mediated proportion depends on the educational gradient in smoking, emphasising that educational disparities in preterm birth may be mediated by different risk factors in different countries.


Assuntos
Gestantes , Nascimento Prematuro/epidemiologia , Fumar/epidemiologia , Adulto , Estudos de Coortes , Dinamarca/epidemiologia , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Recém-Nascido , Países Baixos/epidemiologia , Noruega/epidemiologia , Gravidez , Gestantes/educação , Nascimento Prematuro/etiologia , Fumar/efeitos adversos , Fatores Socioeconômicos
10.
PLoS Med ; 16(2): e1002744, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742624

RESUMO

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

11.
Eur J Epidemiol ; 34(4): 383-396, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30661159

RESUMO

Studies report increased risk of congenital heart defects (CHD) in the offspring of mothers with diabetes, where high blood glucose levels might confer the risk. We explored the association between intake of sucrose-sweetened soft beverages during pregnancy and risk of CHD. Prospective cohort data with 88,514 pregnant women participating in the Norwegian Mother and Child Cohort Study was linked with information on infant CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. Risk ratios were estimated by fitting generalized linear models and generalized additive models. The prevalence of children with CHD was 12/1000 in this cohort (1049/88,514). Among these, 201 had severe and 848 had non-severe CHD (patent ductus arteriosus; valvular pulmonary stenosis; ventricular septal defect; atrial septal defect). Only non-severe CHD was associated with sucrose-sweetened soft beverages. The adjusted risk ratios (aRR) for non-severe CHD was 1.30 (95% CI 1.07-1.58) for women who consumed 25-70 ml/day and 1.27 (95% CI 1.06-1.52) for women who consumed ≥ 70 ml/day when compared to those drinking ≤ 25 ml/day. Dose-response analyses revealed an association between the risk of non-severe CHD and the increasing exposure to sucrose-sweetened soft beverages, especially for septal defects with aRR = 1.26 (95% CI 1.07-1.47) per tenfold increase in daily intake dose. The findings persisted after adjustment for maternal diabetes or after excluding mothers with diabetes (n = 19). Fruit juices, cordial beverages and artificial sweeteners showed no associations with CHD. The findings suggest that sucrose-sweetened soft beverages may affect the CHD risk in offspring.

12.
Int J Cancer ; 144(1): 26-33, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098208

RESUMO

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06-0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.


Assuntos
Ordem de Nascimento , Peso ao Nascer , Idade Paterna , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos
13.
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.

14.
Paediatr Perinat Epidemiol ; 32(6): 568-583, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30466188

RESUMO

BACKGROUND: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples. METHODS: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. RESULTS: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. CONCLUSIONS: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

15.
APMIS ; 126(12): 899-906, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30378168

RESUMO

CMV is the most common cause of congenital infection. During the past few decades, there has been a change in behaviour that possibly has affected the CMV infection rate of mother and child. We investigated 1350 randomly selected pregnant women from the Norwegian Mother and Child Cohort Study using an algorithm for detection of maternal and congenital CMV (cCMV) infection including both serology and nucleic acid amplification assay. The CMV IgG seroprevalence was 54% and 23 (3.7%) mothers seroconverted. Three (0.22%) children had a positive CMV PCR in the umbilical cord blood. The transmission rate was lower than reported in previous studies, probably due to lower sensitivity in plasma compared to saliva and urine. The prevalence of cCMV in the present study was compared with the number registered with the ICD-10 code P.35.1-congenital CMV infection in the Norwegian Patient Register. The number registered was lower than the number of estimated infections. Factors like lower level of education and parity were associated with higher CMV IgG seroprevalence, but no significant difference could be linked to age. In conclusion, in this cohort of pregnant women, a high CMV IgG seroconversion rate was found, while the vertical transmission rate was low.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/isolamento & purificação , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Estudos de Coortes , Citomegalovirus/genética , Citomegalovirus/imunologia , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Noruega/epidemiologia , Reação em Cadeia da Polimerase , Gravidez , Prevalência , Estudos Soroepidemiológicos , Inquéritos e Questionários , Adulto Jovem
16.
BMC Med ; 16(1): 201, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30396358

RESUMO

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

17.
Wellcome Open Res ; 3: 67, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123849

RESUMO

Russia has one of the highest rates of cardiovascular disease in the world. The International Project on Cardiovascular Disease in Russia (IPCDR) was set up to understand the reasons for this. A substantial component of this study was the Know Your Heart Study devoted to characterising the nature and causes of cardiovascular disease in Russia by conducting large cross-sectional surveys in two Russian cities Novosibirsk and Arkhangelsk. The study population was 4542 men and women aged 35-69 years recruited from the general population. Fieldwork took place between 2015-18. There were two study components: 1) a baseline interview to collect information on socio-demographic characteristics and cardiovascular risk factors, usually conducted at home, and 2) a comprehensive health check at a primary care clinic which included detailed examination of the cardiovascular system. In this paper we describe in detail the rationale for, design and conduct of these studies.

18.
J Infect Dis ; 218(12): 1900-1910, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30010913

RESUMO

Background: In 2009, quadrivalent human papillomavirus (HPV) vaccine was introduced in a school-based single-cohort program targeting 12-year-old girls in Norway. We estimated the impact of the Norwegian HPV immunization program. Methods: Three birth cohorts of 17-year-old girls, 2 nonvaccine-eligible cohorts (born 1994 or 1996) and 1 vaccine-eligible cohort (born 1997) were invited to deliver urine samples. The samples were analyzed for 37 HPV genotypes. HPV prevalence was compared between birth cohorts and between vaccinated and unvaccinated girls within and across birth cohorts after linkage to the Norwegian Immunisation Registry. Results: In total, 17749 urine samples were analyzed. A 42% (95% confidence interval [CI], 37%-47%) reduction in any HPV type and 81% (95% CI, 76%-85%) reduction in vaccine types (HPV-6/11/16/18) were observed in the vaccine-eligible cohort compared to the 1994 cohort. Vaccine types were reduced by 54% (95% CI, 39%-66%) and 90% (95% CI, 86%-92%) in unvaccinated and vaccinated girls, respectively, from the 1997 cohort, compared with unvaccinated girls born in 1994. A significant reduction was also observed for several nonvaccine types. Vaccine-type prevalence was reduced by 77% (95% CI, 65%-85%) in vaccinated compared with unvaccinated girls from the 1997 cohort. Conclusions: In this largely HPV-naive population, we observed a substantial reduction in vaccine and nonvaccine types in vaccinated and unvaccinated girls following introduction of HPV vaccination.

19.
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.

20.
Epidemiology ; 29(5): 729-738, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29927819

RESUMO

BACKGROUND: Being overweight constitutes a health risk, and the proportion of overweight and obese children is increasing. It has been argued that road traffic noise could be linked to adiposity through its influence on sleep and stress. Few studies, to our knowledge, have investigated whether noise and adiposity are associated. Most of them were on adults, and we are not aware of any longitudinal study using repeated measures. OBJECTIVES: The present longitudinal study investigated whether road traffic noise exposures in pregnancy (N = 6,963; obs = 22,975) or childhood (N = 6,403; obs = 14,585) were associated with body mass index (BMI) trajectories in children. METHODS: We obtained information on BMI and covariates from questionnaires used in the Norwegian Mother and Child Cohort Study, Statistics Norway, and Medical Birth Registry of Norway. We modeled road traffic noise for the most exposed façade of children's present and historical addresses at 6 time points from pregnancy to age 8. We investigated effects on BMI trajectories using repeated measures and linear mixed models. RESULTS: The results indicated that BMI curves depended on road traffic noise exposure during pregnancy, but not on exposure during childhood. Children in the highest decile of traffic noise exposure had increased BMI, with 0.35 kg/m more than children in the lowest decile, from birth to age 8 years. CONCLUSIONS: The results indicate that exposure to road traffic noise during pregnancy may be associated with children's BMI trajectories. Future studies should investigate this further, using anthropometric measures such as waist-hip ratio and skinfold thickness, in addition to BMI.

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