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1.
Hum Reprod ; 36(4): 1074-1082, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33592626

RESUMO

STUDY QUESTION: Is the growth pattern of children conceived by ART different compared to naturally conceived children. SUMMARY ANSWER: Both ART and underlying parental subfertility may contribute to differences in early childhood growth between children conceived with and without the use of ART. WHAT IS KNOWN ALREADY: Children conceived by ART weigh less and are shorter at the time of delivery. The extent to which differences in growth according to mode of conception persist during childhood, and the role of underlying parental subfertility, remains unclear. STUDY DESIGN, SIZE, DURATION: We conducted a prospective study population-based study. We studied 81 461 children participating in the Norwegian Mother, Father and Child Cohort Study (MoBa) and 544 113 adolescents screened for military conscription. PARTICIPANTS/MATERIALS, SETTING, METHODS: Conception by ART as registered in the Medical Birth Registry. We compared maternally reported length/height and weight among children in MoBa from mid-pregnancy to age 7 according to mode of conception using mixed-effects linear regression. Differences in self-reported height and weight at 17 years of age at screening for military conscription were assessed with linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: At birth, children conceived by ART were shorter (boys -0.3 cm; 95% CI, -0.5 to -0.1), girls -0.4 cm; 95% CI, -0.5 to -0.3) and lighter (boys -113 grams; 95% CI, -201 to -25, girls -107 grams; 95% CI, -197 to -17). After birth, children conceived by ART grew more rapidly, achieving both greater height and weight at age 3. Children conceived by ART had a greater height up to age 7, but did not have a greater height or weight by age 17. Naturally conceived children of parents taking longer time to conceive had growth patterns similar to ART children. Children born after frozen embryo transfer had larger ultrasound measures and were longer and heavier the first 2 years than those born after fresh embryo transfer. LIMITATIONS, REASONS FOR CAUTIONS: Selection bias could have been introduced due to the modest participation rate in the MoBa cohort. Our reliance on self-reported measures of length/height and weight could have introduced measurement error. WIDER IMPLICATIONS OF THE FINDINGS: : Our findings provide reassurance that offspring conceived by ART are not different in height, weight or BMI from naturally conceived once they reach adolescence. STUDY FUNDING/COMPETING INTEREST(S): Research Council of Norway; Medical Research Council; National Institute of Environmental Health Sciences. The authors have no competing interest. TRIAL REGISTRATION NUMBER: N/A.

2.
Br J Psychiatry ; : 1-6, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448259

RESUMO

BACKGROUND: Some psychiatric disorders have been associated with increased risk of miscarriage. However, there is a lack of studies considering a broader spectrum of psychiatric disorders to clarify the role of common as opposed to independent mechanisms. AIMS: To examine the risk of miscarriage among women diagnosed with psychiatric conditions. METHOD: We studied registered pregnancies in Norway between 2010 and 2016 (n = 593 009). The birth registry captures pregnancies ending in gestational week 12 or later, and the patient and general practitioner databases were used to identify miscarriages and induced abortions before 12 gestational weeks. Odds ratios of miscarriage according to 12 psychiatric diagnoses were calculated by logistic regression. CONCLUSIONS: A wide range of psychiatric disorders were associated with increased risk of miscarriage. The heightened risk of miscarriage among women diagnosed with psychiatric disorders highlights the need for awareness and surveillance of this risk group in antenatal care.

3.
Mol Psychiatry ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414500

RESUMO

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

4.
Eur J Epidemiol ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492547

RESUMO

A few studies indicate that women with prolonged time-to-pregnancy (TTP) have an increased risk of cardiovascular disease (CVD). This has not been studied in men. We evaluated CVD risk by self-reported TTP among parous women (n = 64,064) and men (n = 50,533) participating in the Norwegian Mother, Father and Child Cohort Study. TTP was categorized as 0-3 (reference), 4-12 and > 12 months. CVD diagnosed between 2008 and 2017 were available from the national patient and general practitioner databases. Risk of CVD by TTP was estimated using Cox regression adjusting for baseline age, education, BMI, smoking, diabetes, and number of offspring in both sexes, and history of endometriosis, ovarian cysts, preterm birth and pre-eclampsia for women. Mean age was 33 for women and 35 for men at baseline (years). The rate of any CVD was 24 per 1000 person years among women and 22 per 1000 person years among men. Longer TTP was associated with increased rate of CVD among women, with adjusted hazard ratios (HRs) of 1.07 (95% CI: 1.03, 1.09) for TTP 4-12 months and 1.14 (1.08, 1.20) for TTP > 12 months. Among men, respective HRs for CVD were 1.06 (1.00, 1.10) for TTP 4-12 months and 1.07 (1.01, 1.14) for TTP > 12 months. We observed sex-differences in the relationship with CVD subtypes but none were statistically significant. In conclusion, both men and women with a prolonged TTP had a small increased risk of CVD, clinical significance of which is unclear. Further studies are necessary to investigate in detail what underlying causes of prolonged TTP might be reflected in the increased risk of CVD. Longer follow-up is required to confirm these preliminary findings.

5.
BJOG ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232573

RESUMO

OBJECTIVE: To investigate the effect of interpregnancy interval (IPI) on preterm birth (PTB) according to whether the previous birth was preterm or term. DESIGN: Cohort study. SETTING: USA (California), Australia, Finland, Norway (1980-2017). POPULATION: Women who gave birth to first and second (N=3,213,855) singleton livebirths. METHODS: Odds ratios (ORs) for PTB according to IPIs were modelled using logistic regression with prognostic score stratification for potential confounders. Within-site ORs were pooled by random-effects meta-analysis. OUTCOME MEASURE: PTB (gestational age<37 weeks). RESULTS: Absolute risk of PTB for each IPI ranged from 3-6% after previous term and 17-22% after previous PTB. ORs for PTB differed between previous term and preterm births in all countries (P-for-interaction≤0.001). For women with a previous term birth, pooled ORs were increased for IPI <6months (1.50, 95%CI 1.43-1.58); 6-11months (1.10, 95%CI 1.04-1.16); 24-59months (1.16, 95%CI 1.13-1.18); and ≥60months (1.72, 95%CI 1.60-1.86), compared to 18-23months. For previous PTB, ORs were increased for <6months (1.30, 95%CI 1.18-1.42) and ≥60months (1.29, 95%CI 1.17-1.42), but were less than ORs among women with a previous term birth (P<0.05). CONCLUSIONS: Associations between IPI and PTB are modified by whether the previous pregnancy was preterm. ORs for short and long IPIs were higher among women with a previous term birth than a previous PTB, which for short IPI is consistent with the maternal depletion hypothesis. Given high risk of recurrence and assuming a causal association between IPI and PTB, IPI remains a potentially modifiable risk factor for women with previous PTB.

6.
Genome Med ; 12(1): 105, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239103

RESUMO

BACKGROUND: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. METHODS: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. RESULTS: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7). CONCLUSIONS: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

7.
BMC Genomics ; 21(1): 747, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109080

RESUMO

BACKGROUND: Epigenetic clocks have been recognized for their precise prediction of chronological age, age-related diseases, and all-cause mortality. Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC). Thus, it remains unclear to what extent EPIC contributes to increased precision and accuracy in the prediction of chronological age. RESULTS: We developed three blood-based epigenetic clocks for human adults using EPIC-based DNA methylation (DNAm) data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Gene Expression Omnibus (GEO) public repository: 1) an Adult Blood-based EPIC Clock (ABEC) trained on DNAm data from MoBa (n = 1592, age-span: 19 to 59 years), 2) an extended ABEC (eABEC) trained on DNAm data from MoBa and GEO (n = 2227, age-span: 18 to 88 years), and 3) a common ABEC (cABEC) trained on the same training set as eABEC but restricted to CpGs common to 450 K and EPIC. Our clocks showed high precision (Pearson correlation between chronological and epigenetic age (r) > 0.94) in independent cohorts, including GSE111165 (n = 15), GSE115278 (n = 108), GSE132203 (n = 795), and the Epigenetics in Pregnancy (EPIPREG) study of the STORK Groruddalen Cohort (n = 470). This high precision is unlikely due to the use of EPIC, but rather due to the large sample size of the training set. CONCLUSIONS: Our ABECs predicted adults' chronological age precisely in independent cohorts. As EPIC is now the dominant platform for measuring DNAm, these clocks will be useful in further predictions of chronological age, age-related diseases, and mortality.

8.
Epidemiology ; 31(4): 587-594, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32427635

RESUMO

BACKGROUND: There was a distinct rise in mean birthweights in Norway starting in 1991 that plateaued in 1996-2002 and then declined to previous levels. We investigated whether these changes corresponded to trends in neonatal mortality or other birthweight-associated pregnancy outcomes. We also explored known predictors of birthweight and examined whether these could explain the birthweight trends. METHODS: We calculated mean birthweight for all live births in Norway in each year from 1982 to 2016, together with annual neonatal mortality and proportion of infants born preterm, or with low Apgar score. We stratified mean birthweight over time by factors including parity, gestational age, and Scandinavian versus non-Scandinavian origin of mother, to test robustness of the pattern. In addition, we used multivariable linear regression to obtain adjusted estimates for mean birthweight per year. RESULTS: A 50-g rise and fall of mean birthweights during a 25-year period was not accompanied by corresponding changes in neonatal mortality, preterm births, or Apgar scores. The distinct hump pattern was restricted to term births and was not apparent among infants of mothers born outside Scandinavia. We saw a similar pattern for Sweden but not Finland. Known predictors of birthweight (such as parity, mode of onset of delivery, and marital status) did not explain the hump. CONCLUSIONS: A distinct temporal hump in mean birthweight among Norwegian term births had no obvious explanations. Furthermore, these fluctuations in birthweight were not associated indirectly with adverse outcomes in measures of infant health.

9.
BMC Med ; 18(1): 71, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32200763

RESUMO

BACKGROUND: Age at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner. METHODS: We conducted a Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n = 181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations. RESULTS: Of the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null. CONCLUSIONS: The genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Menarca/fisiologia , Análise da Randomização Mendeliana/métodos , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Epidemiology ; 31(3): 451-458, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31985502

RESUMO

BACKGROUND: Previous studies of early day care attendance and asthma development are inconsistent, which may be explained by inadequate control of confounding and effect modification. We examined the effect of early day care on the risk of asthma taking into account the underlying susceptibility to asthma. METHODS: The study included 55,404 children participating in the Norwegian Mother, Father and Child Cohort Study. Asthma at age 7 was defined by dispensed asthma medications in the Norwegian Prescription Database. We defined a disease risk score (DRS) to account for an underlying susceptibility to asthma including a range of hereditary and nonhereditary predictors of asthma. We assessed confounding and modifying effects of DRS on the association between day care and asthma. RESULTS: Day care before 18 months was associated with a lower risk of asthma by age 7 (adjusted risk ratio [RR] = 0.85; 95% confidence interval [CI] = 0.78, 0.92) when compared with home care. DRS modified the estimated effect of day care on asthma risk. Among the 80% of children with DRS between 0.03 and 0.16, day care was associated with a reduced asthma risk (RRs between 0.79 and 0.87), whereas among 0.5% of children with a high DRS (above 0.28), estimated effect of day care on asthma increased gradually (RR for the highest DRS 2.2; 1.0-4.9). CONCLUSIONS: In our study, among most children, early day care was associated with reduced asthma risk at 7 years, and increased risk in a small group of children with very high underlying susceptibility to asthma.

11.
BMJ Open ; 9(8): e027344, 2019 08 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.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Nascimento Prematuro/epidemiologia , Adulto , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/epidemiologia , Humanos , Incidência , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Estudos Retrospectivos
12.
Hypertension ; 74(2): 375-383, 2019 08.
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.


Assuntos
Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Hipertensão Induzida pela Gravidez/genética , Recém-Nascido Prematuro , Resultado da Gravidez , Adulto , Estudos de Coortes , Epigênese Genética , Feminino , Sangue Fetal , Idade Gestacional , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico , Recém-Nascido , Gravidez
13.
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.


Assuntos
Doença Celíaca/epidemiologia , Cotinina/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/induzido quimicamente , Feminino , Sangue Fetal , Antígenos HLA , Humanos , Masculino , Pessoa de Meia-Idade , Mães , Noruega/epidemiologia , Gravidez , Sistema de Registros , Fatores de Risco , Autorrelato , Fumar/sangue , Abandono do Hábito de Fumar
14.
Prev Med ; 125: 49-54, 2019 08.
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.


Assuntos
Exercício Físico/fisiologia , Hiperêmese Gravídica/epidemiologia , Atividades de Lazer , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Hospitalização , Humanos , Noruega/epidemiologia , Gravidez , Fatores de Risco , Autorrelato , Inquéritos e Questionários , Adulto Jovem
15.
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
16.
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
17.
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
18.
BMJ Open ; 9(1): e027941, 2019 01 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.


Assuntos
Intervalo entre Nascimentos , Internacionalidade , Complicações na Gravidez/epidemiologia , Austrália , Estudos de Coortes , Países Desenvolvidos , Feminino , Finlândia , Humanos , Noruega , Gravidez , Projetos de Pesquisa , Estados Unidos
19.
J Allergy Clin Immunol ; 143(6): 2062-2074, 2019 06.
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.


Assuntos
Asma/genética , Ilhas de CpG/genética , Canal de Potássio ERG1/genética , Epigenoma/genética , Subunidade alfa de Receptor de Interleucina-5/genética , Criança , Estudos Transversais , Metilação de DNA , Epigênese Genética , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido
20.
Int J Epidemiol ; 47(6): 1855-1864, 2018 12 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.


Assuntos
Pulmão/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Fumar/efeitos adversos , Adulto , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gravidez , Sistema de Registros , Fatores de Risco , Autorrelato , Espirometria , Reino Unido/epidemiologia , Capacidade Vital
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