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1.
BMJ Open ; 9(8): e027344, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383698

RESUMO

OBJECTIVE: The objective of the study was to compare pregnancy outcomes according to maternal antiretroviral treatment (ART) regimens. DESIGN: A retrospective cohort study. PARTICIPANTS AND SETTINGS: Clinical data was extracted from ART exposed pregnancies of HIV-infected Ethiopian women attending antenatal care follow-up in public health facilities in Addis Ababa between February 2010 and October 2016. OUTCOMES: The primary outcomes evaluated were preterm birth, low birth weight and small-for-gestational-age. RESULTS: A total 1663 of pregnancies exposed to ART were included in the analyses. Of these pregnancies, 17% resulted in a preterm birth, 19% in low birth weight and 32% in a small-for-gestational-age baby. Compared with highly active antiretroviral therapy (HAART) initiated during pregnancy, zidovudine monotherapy was less likely to result in preterm birth (adjusted OR 0.35, 95% CI 0.19 to 0.64) and low birth weight (adjusted OR 0.48, 95% CI 0.24 to 0.94). We observed no differential risk of preterm birth, low birth weight and small-for-gestational-age, when comparing women who initiated HAART during pregnancy to women who initiated HAART before conception. The risk for preterm birth was higher in pregnancies exposed to nevirapine-based HAART (adjusted OR 1.44, 95% CI 1.06 to 1.96) compared with pregnancies exposed to efavirenz-based HAART. Comparing nevirapine-based HAART with efavirenz-based HAART indicated no strong evidence of increased risk of low birth weight or small-for-gestational-age. CONCLUSIONS: We observed a higher risk of preterm birth among women who initiated HAART during pregnancy compared with zidovudine monotherapy. Pregnancies exposed to nevirapine-based HAART also had a greater risk of preterm births compared with efavirenz-based HAART.

2.
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.

3.
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.

4.
Eur J Epidemiol ; 34(7): 637-649, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037572

RESUMO

Ecological observations suggest an inverse relationship between smoking in pregnancy and celiac disease (CD) in offspring. While individual-level analyses have been inconsistent, they have mostly lacked statistical power or refined assessments of exposure. To examine the association between pregnancy-related smoking and CD in the offspring, as well as its consistency across data sets, we analyzed: (1) The Norwegian Mother and Child Cohort (MoBa) of 94,019 children, followed from birth (2000-2009) through 2016, with 1035 developing CD; (2) a subsample from MoBa (381 with CD and 529 controls) with biomarkers; and (3) a register-based cohort of 536,861 Norwegian children, followed from birth (2004-2012) through 2014, with 1919 developing CD. Smoking behaviors were obtained from pregnancy questionnaires and antenatal visits, or, in the MoBa-subsample, defined by measurement of cord blood cotinine. CD and potential confounders were identified through nationwide registers and comprehensive parental questionnaires. Sustained smoking during pregnancy, both self-reported and cotinine-determined, was inversely associated with CD in MoBa (multivariable-adjusted [a] OR = 0.61 [95%CI, 0.46-0.82] and aOR = 0.55 [95%CI, 0.31-0.98], respectively); an inverse association was also found with the intensity of smoking. These findings differed from those of our register-based cohort, which revealed no association with sustained smoking during pregnancy (aOR = 0.97 [95%CI, 0.80-1.18]). In MoBa, neither maternal smoking before or after pregnancy, nor maternal or paternal smoking in only early pregnancy predicted CD. In a carefully followed pregnancy cohort, a more-detailed smoking assessment than oft-used register-based data, revealed that sustained smoking during pregnancy, rather than any smoking exposure, predicts decreased likelihood of childhood-diagnosed CD.

5.
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.

6.
J Urol ; : 101097JU0000000000000360, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31145033

RESUMO

PURPOSE: To examine the prospective associations between physical activity and a range of lower urinary tract symptoms (LUTS) in parous middle-aged women. MATERIALS AND METHODS: We used prospectively collected data on women participating in the Avon Longitudinal Study of Parents and Children. Physical activity levels were self-reported at mean age of 37.2 years (SD 4.6) and translated into metabolic-equivalents hours per week (MET hours/week). Women reported symptoms of LUTS (stress incontinence, urgency incontinence and mixed incontinence) after 3 (n=4126) and 11.5 (n=2770) years of follow-up. RESULTS: Prevalence of any LUTS after 3 and 11.5 years of follow-up (mean ages 40.5 years and 49.3 years) was 15% and 23%, respectively. Women in the highest category of physical activity (≥43.2 MET hours/week) had lower odds of stress incontinence (adjusted OR (aOR)=0.51; 95% CI 0.32, 0.80) compared to women in the lowest category (0 MET hours/week) after 3 years of follow-up. After 11.5 years of follow-up, women in the highest category of physical activity had lower odds of stress incontinence (aOR= 0.56; 95%CI: 0.39, 0.82), urgency incontinence (aOR= 0.34; 95%CI: 0.20, 0.67) and mixed incontinence (aOR= 0.34; 95%CI: 0.19, 0.63) when compared to women in the lowest physical activity category. CONCLUSION: Greater physical activity is associated with reduced odds of LUTS, especially stress incontinence, among middle-aged parous women. Further research is necessary to examine the impact of different types of physical activity on LUTS.

7.
Nat Commun ; 10(1): 1893, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015461

RESUMO

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.


Assuntos
Peso ao Nascer/genética , DNA/metabolismo , Epigênese Genética , Genoma Humano , Adolescente , Adulto , Índice de Massa Corporal , Criança , Ilhas de CpG , DNA/genética , Metilação de DNA , Feminino , Desenvolvimento Fetal/genética , Feto , Ácido Fólico/sangue , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Fumar/sangue , Fumar/genética
8.
BMJ ; 364: l869, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894356

RESUMO

OBJECTIVES: To estimate the burden of miscarriage in the Norwegian population and to evaluate the associations with maternal age and pregnancy history. DESIGN: Prospective register based study. SETTING: Medical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register. PARTICIPANTS: All Norwegian women that were pregnant between 2009-13. MAIN OUTCOME MEASURE: Risk of miscarriage according to the woman's age and pregnancy history estimated by logistic regression. RESULTS: There were 421 201 pregnancies during the study period. The risk of miscarriage was lowest in women aged 25-29 (10%), and rose rapidly after age 30, reaching 53% in women aged 45 and over. There was a strong recurrence risk of miscarriage, with age adjusted odds ratios of 1.54 (95% confidence interval 1.48 to 1.60) after one miscarriage, 2.21 (2.03 to 2.41) after two, and 3.97 (3.29 to 4.78) after three consecutive miscarriages. The risk of miscarriage was modestly increased if the previous birth ended in a preterm delivery (adjusted odds ratio 1.22, 95% confidence interval 1.12 to 1.29), stillbirth (1.30, 1.11 to 1.53), caesarean section (1.16, 1.12 to 1.21), or if the woman had gestational diabetes in the previous pregnancy (1.19, 1.05 to 1.36). The risk of miscarriage was slightly higher in women who themselves had been small for gestational age (1.08, 1.04 to 1.13). CONCLUSIONS: The risk of miscarriage varies greatly with maternal age, shows a strong pattern of recurrence, and is also increased after some adverse pregnancy outcomes. Miscarriage and other pregnancy complications might share underlying causes, which could be biological conditions or unmeasured common risk factors.


Assuntos
Aborto Espontâneo/epidemiologia , Idade Materna , Aborto Habitual/epidemiologia , Aborto Espontâneo/etiologia , Adulto , Fatores Etários , Feminino , Humanos , Pessoa de Meia-Idade , Noruega/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Recidiva , Sistema de Registros , História Reprodutiva , Medição de Risco/métodos , Fatores de Risco , Natimorto/epidemiologia , Adulto Jovem
9.
Lancet ; 393(10180): 1527-1535, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30827781

RESUMO

BACKGROUND: WHO recommends that women wait at least 2 years after a livebirth and at least 6 months after a miscarriage or induced abortion before conceiving again, to reduce the risk of adverse birth outcomes in the subsequent pregnancy. No recommendation exists for the optimal interval after a stillbirth. We investigated the association between interpregnancy interval after stillbirth and birth outcomes in the subsequent pregnancy. METHODS: In this international cohort study, we used data from birth records from Finland (1987-2016), Norway (1980-2015), and Western Australia (1980-2015). Consecutive singleton pregnancies in women whose most recent pregnancy had ended in stillbirth of at least 22 weeks' gestation were included in the analysis. Interpregnancy interval was defined as the time between the end of pregnancy (delivery date) and the start of the next pregnancy (delivery date of next pregnancy minus gestational age at birth). We calculated odds ratios (ORs) for stillbirth, preterm birth, and small-for-gestational-age birth by interpregnancy interval by country, adjusted for maternal age, parity, decade of delivery, and gestational length of the previous pregnancy. A fixed-effects meta-analysis was used to estimate pooled ORs. FINDINGS: We identified 14 452 births in women who had a stillbirth in the previous pregnancy; median interpregnancy interval after stillbirth was 9 months (IQR 4-19). 9109 (63%) women conceived within 12 months of the stillbirth. Of the 14 452 births, 228 (2%) were stillbirths, 2532 (18%) were preterm births, and 1284 (9%) were small-for-gestational-age births. Compared with an interpregnancy interval of 24-59 months, intervals shorter than 12 months were not associated with increased odds of subsequent stillbirth (pooled adjusted OR 1·09 [95% CI 0·63-1·91] for <6 months; 0·90 [0·47-1·71] for 6-11 months), preterm birth (0·91 [0·75-1·11] for <6 months; 0·91 [0·74-1·11] for 6-11 months), or small-for-gestational-age birth (0·66 [0·51-0·85] for <6 months; 0·64 [0·48-0·84] for 6-11 months). Further, we noted no difference in the association between interpregnancy interval and birth outcomes by gestational length of the previous stillbirth. INTERPRETATION: Conception within 12 months of a stillbirth was common and was not associated with increased risk of adverse outcomes in the subsequent pregnancy. These findings could be used when counselling women who are planning future pregnancies after a stillbirth and for informing future recommendations for pregnancy spacing in a high-income setting. FUNDING: National Health and Medical Research Council (Australia), and Research Council of Norway.


Assuntos
Intervalo entre Nascimentos , Internacionalidade , Complicações na Gravidez/epidemiologia , Natimorto , Austrália , Estudos de Coortes , Feminino , Finlândia , Humanos , Noruega , Gravidez
10.
BMJ Open ; 9(1): e027941, 2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30700492

RESUMO

INTRODUCTION: Short interpregnancy interval (IPI) has been linked to adverse pregnancy outcomes. WHO recommends waiting at least 2 years after a live birth and 6 months after miscarriage or induced termination before conception of another pregnancy. The evidence underpinning these recommendations largely relies on data from low/middle-income countries. Furthermore, recent epidemiological investigations have suggested that these studies may overestimate the effects of IPI due to residual confounding. Future investigations of IPI effects in high-income countries drawing from large, population-based data sources are needed to inform IPI recommendations. We aim to assess the impact of IPIs on maternal and child health outcomes in high-income countries. METHODS AND ANALYSIS: This international longitudinal retrospective cohort study will include more than 18 million pregnancies, making it the largest study to investigate IPI in high-income countries. Population-based data from Australia, Finland, Norway and USA will be used. Birth records in each country will be used to identify consecutive pregnancies. Exact dates of birth and clinical best estimates of gestational length will be used to estimate IPI. Administrative birth and health data sources with >99% coverage in each country will be used to identify maternal sociodemographics, pregnancy complications, details of labour and delivery, birth and child health information. We will use matched and unmatched regression models to investigate the impact of IPI on maternal and infant outcomes, and conduct meta-analysis to pool results across countries. ETHICS AND DISSEMINATION: Ethics boards at participating sites approved this research (approval was not required in Finland). Findings will be published in peer-reviewed journals and presented at international conferences, and will inform recommendations for optimal IPI in high-income countries. Findings will provide important information for women and families planning future pregnancies and for clinicians providing prenatal care and giving guidance on family planning.

11.
Int J Infect Dis ; 82: 89-95, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30802623

RESUMO

OBJECTIVE: To compare health outcomes following initiation of antiretroviral therapy (ART) for asymptomatic HIV-infected pregnant women at different CD4 levels. METHODS: We analyzed data from 706 asymptomatic HIV-infected Ethiopian women initiating ART during pregnancy between February 2012 and October 2016. The outcomes evaluated were CD4 gain, CD4 normalization (CD4 count ≥750cells/mm3) and occurrence of HIV-related clinical events after twelve months of treatment. RESULT: On average, CD4 count (cells/mm3) increased from 391 (95% CI: 372-409) at baseline to 523 (95% CI: 495-551) after twelve months of treatment. Rate of CD4 gain was higher among women with baseline CD4 between 350 and 499 compared to CD4 ≥500 (207 versus 6, p<0.001). But women with baseline CD4 between 350 and 499 could not catch up with women with CD4 ≥500. Women with baseline CD4 ≥500 had significantly higher likelihood of achieving CD4 normalization as compared to those with CD4 between 350 and 499 (AOR=0.32, 95% CI: 0.13-0.76). No strong evidence of differential risk in the occurrence of HIV-related clinical events. CONCLUSION: Starting ART for asymptomatic HIV-infected women with CD4 count ≥500cells/mm3 was beneficial to preserve or recover immunity after 12 months of treatment in a resource limited setting.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Doenças Assintomáticas , Contagem de Linfócito CD4 , Esquema de Medicação , Etiópia , Feminino , Infecções por HIV/virologia , Humanos , Gravidez , Cuidado Pré-Natal , Carga Viral , Adulto Jovem
12.
J Allergy Clin Immunol ; 143(6): 2062-2074, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30579849

RESUMO

BACKGROUND: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. OBJECTIVE: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. METHODS: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. RESULTS: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. CONCLUSION: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.

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.
Int J Epidemiol ; 47(6): 1855-1864, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30339246

RESUMO

Background: Limited evidence suggests that exposure to maternal smoking in utero or early life might be associated with chronic obstructive pulmonary disease (COPD), but whether this is independent of later own smoking remains unclear. Our objective was to examine the independent and combined association of maternal and own smoking with adult lung function and COPD. Methods: We used UK Biobank to examine associations of maternal smoking around delivery, and pack-years of own smoking, with lung function (n = 502 626) and hospitalization/death from COPD (n = 433 863). We calculated the additive interaction between maternal and own smoking on the outcomes of interest, and estimated the association with maternal smoking within categories of own smoking. Results: There was no strong evidence that maternal smoking influenced adult lung health among never smokers. Exposure to both maternal and own smoking was associated with lower Forced expiratory volume (FEV1)/ forced vital capacity (FVC) and greater risk of hospitalization/death from COPD than expected from their independent associations. For FEV1/FVC, the mean difference according to maternal smoking was -0.02 (-0.06, 0.02), -0.01 (-0.05, 0.03), -0.11 (-0.16, -0.05) and -0.11 (-0.19, -0.04) among women who smoked ≤10, 11-20, 21-30 and >30 pack-years, respectively. The association between maternal smoking and COPD also varied by pack-years of own smoking, with a hazard ratio of 2.25 (1.30, 3.89) for ≤10 years, 1.23 (0.80, 1.89) for 11-20 years, 1.30 (0.85, 2.01) for 21-30 years and 1.14 (0.91, 1.43) for >30 years. Conclusions: Our findings indicate an excess reduction in FEV1/FVC and risk of COPD due to maternal smoking that is heterogeneous across levels of own smoking.

16.
Epidemiology ; 29(6): 848-856, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30074542

RESUMO

BACKGROUND: A few prospective studies suggest an association between maternal smoking during pregnancy and lower risk of type 1 diabetes. However, the role of unmeasured confounding and misclassification remains unclear. METHODS: We comprehensively evaluated whether maternal smoking in pregnancy predicts lower risk of childhood-onset type 1 diabetes in two Scandinavian pregnancy cohorts (185,076 children; 689 cases) and a Norwegian register-based cohort (434,627 children; 692 cases). We measured cord blood cotinine as an objective marker of nicotine exposure during late pregnancy in 154 cases and 476 controls. We also examined paternal smoking during pregnancy, in addition to environmental tobacco smoke exposure the first 6 months of life, to clarify the role of characteristics of smokers in general. RESULTS: In the pregnancy cohorts, maternal smoking beyond gestational week 12 was inversely associated with type 1 diabetes, pooled adjusted hazard ratio (aHR) 0.66 (95% CI = 0.51, 0.85). Similarly, in the Norwegian register-based cohort, children of mothers who still smoked at the end of pregnancy had lower risk of type 1 diabetes, aHR 0.65 (95% CI = 0.47, 0.89). Cord blood cotinine ≥30 nmol/L was also associated with reduced risk of type 1 diabetes, adjusted odds ratio 0.42 (95% CI = 0.17, 1.0). We observed no associations of paternal smoking during pregnancy, or environmental tobacco smoke exposure, with childhood-onset type 1 diabetes. CONCLUSION: Maternal sustained smoking during pregnancy is associated with lower risk of type 1 diabetes in children. This sheds new light on the potential intrauterine environmental origins of the disease.

17.
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.

18.
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.

19.
J Am Heart Assoc ; 7(4)2018 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-29440004

RESUMO

BACKGROUND: Previous studies of age at menarche and cardiometabolic health report conflicting findings, and only a few could account for childhood characteristics. We aimed to estimate the associations of age at menarche with cardiovascular risk factors in unrelated women and within sister groups, under the assumption that within-sibship estimates will be better adjusted for shared genetics and early life environment. METHODS AND RESULTS: Our study included 7770 women, from 5984 sibships, participating in the GS:SFHS (Generation Scotland: Scottish Family Health Study). We used fixed- and between-effects linear regression to estimate the associations within sister groups and between unrelated individuals, respectively. Within sibships, the mean difference between sisters with early menarche (≤11 years) and sisters with menarche at 12 to 13 years was 1.73 mm Hg (95% confidence interval [CI], -0.41 to 3.86) for systolic blood pressure, 1.26 mm Hg (95% CI, -0.02 to 2.55) for diastolic blood pressure, -0.06 nmol/L (95% CI, -0.11 to -0.02) for high-density lipoprotein, 0.20 nmol/L (95% CI, 0.08-0.32) for non-high-density lipoprotein, -0.34% (95% CI, -1.98 to 1.30) for glucose, 1.60 kg/m2 (95% CI, 0.92-2.28) for body mass index, and 2.75 cm (95% CI, 1.06-4.44) for waist circumference. There was weak evidence of associations between later menarche (14-15 or ≥16 years) and lower body mass index, waist circumference, and blood pressure. We found no strong evidence that estimates from within- and between-sibship analyses differed (all P values >0.1). The associations with other cardiovascular risk factors were attenuated after adjustment for adult body mass index. CONCLUSIONS: Our results suggest that confounding by shared familial characteristics is unlikely to be a major driver of the association between early menarche and adverse cardiometabolic health but do not exclude confounding by individual-level characteristics.

20.
J Pediatr ; 195: 182-189.e2, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29397158

RESUMO

OBJECTIVES: To study whether the duration of breastfeeding and time for introduction of complementary foods was associated with the risk of childhood asthma. STUDY DESIGN: We used data from the Norwegian Mother and Child Study, a nationwide prospective cohort study that recruited pregnant women from across Norway between 1999 and 2008. Children with complete data of breastfeeding up to 18 months and current age >7 years were eligible (n = 41 020). Asthma as the primary outcome was defined based on ≥2 dispensed asthma medications at age 7 years registered in the Norwegian Prescription Database. We used log-binomial regression models to obtain crude relative risks (RRs) in the main analysis, and adjusted for selected confounders in multivariable analyses. RESULTS: For duration of any breastfeeding, 5.9% of infants breastfed <6 months (adjusted RR [aRR] 1.05, 0.93-1.19) and 4.6% breastfed 6-11 months (aRR 0.96, 0.87-1.07) had dispensed asthma medications at age 7 years compared with 4.6% of infants breastfed ≥12 months (Ptrend .62). Infants still breastfed at 6 months, but introduced to complementary foods <4 months and 4-6 months, had an aRR of 1.15 (0.98-1.36) and 1.09 (0.94-1.27) respectively, compared with infants fully breastfed for 6 months (Ptrend .09). Ages at introduction of solids or formula separately were not significant predictors (Ptrend .16 and .08, respectively). CONCLUSIONS: We found no association between duration of breastfeeding or age of introduction to complementary foods and asthma at age 7 years.

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