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BACKGROUND: Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. METHODS: 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9+/-0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. RESULTS: 155 of 719 (21.6 %) children had ASD traits and 59 of 719 (8.2 %) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 µg/L increment in selenium was 0.76 (95 % CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 µg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. CONCLUSIONS: The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.
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Transtorno do Deficit de Atenção com Hiperatividade , Glutationa Peroxidase , Efeitos Tardios da Exposição Pré-Natal , Selênio , Selenoproteína P , Humanos , Selênio/sangue , Selênio/deficiência , Feminino , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Gravidez , Glutationa Peroxidase/sangue , Masculino , Dinamarca/epidemiologia , Pré-Escolar , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Selenoproteína P/sangue , Adulto , Biomarcadores/sangue , Estudos Prospectivos , Transtorno Autístico/sangue , Transtorno Autístico/epidemiologia , Estudos de Coortes , Criança , Zinco/sangue , Zinco/deficiência , Cobre/sangueRESUMO
BACKGROUND: Diet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive. OBJECTIVES: The aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring. METHODS: This study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations. RESULTS: Se and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (â¼20%) mediated by fasting glucose concentrations (P = 0.006). CONCLUSIONS: Low serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.
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Diabetes Gestacional , Resistência à Insulina , Selênio , Feminino , Humanos , Gravidez , Biomarcadores , Glicemia/metabolismo , Estudos de Coortes , Diabetes Gestacional/metabolismo , Insulina , Estudos Prospectivos , Selenoproteína PRESUMO
BACKGROUND: Prenatal cortisol exposure is essential for neurodevelopment. Maternal cortisol levels could be associated with offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). AIM: To investigate associations between maternal 3rd trimester cortisol and offspring traits of ASD and ADHD. MATERIAL AND METHODS: Mother-child pairs were included from the prospective study Odense Child Cohort. Morning serum cortisol and 24-hour urine cortisol/cortisone were collected at gestational week 27-30. Offspring ASD and ADHD traits were assessed at age three and five years using the Child Behavior Checklist. Maternal cortisol measurements and offspring ASD and ADHD traits assessment were available in (n = 1131; 52% boys) mother-child pairs at age three and (n = 717; 54% boys) at five years of age. Maternal 24-hour urine measurement was available in a subset, at offspring three years of age (n = 300) and at five years of age (n = 217). Associations between maternal cortisol (continuous and tertiles) and offspring ASD or ADHD traits were examined in regression models adjusted for offspring sex, maternal age, pre-pregnancy BMI, parity, maternal education level, parental psychiatric disorders, and maternal smoking and stratified for offspring sex. RESULTS: Maternal mean age ( ± SD) was 30 years ( ± 4.4) and median BMI (25%; 75% percentiles) 23.5 kg/m2 (21.3; 26.6). Higher maternal serum cortisol levels were associated with higher prevalence of offspring ASD traits at three years of age in the total study cohort and in boys after stratifying for offspring sex. In the total population, tertiles of serum cortisol showed a significant dose-response relationship to ASD traits in unadjusted and adjusted models (p-values for linear trend, p < 0.01 and p = 0.02, respectively). In offspring at five years, associations between maternal cortisol and offspring ASD traits were non-significant (all p-values > 0.2). Maternal cortisol was not associated with offspring ADHD traits (all p-values > 0.07) in offspring at three and five years. Maternal 24-hour urine cortisol, cortisone, or cortisol/cortisone ratio were not associated with offspring ASD or ADHD traits. CONCLUSION: Higher maternal serum cortisol in 3rd trimester was associated with offspring ASD traits at three years of age in the whole study cohort and in boys, but not in girls. This association was non-significant at five years of age.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Cortisona , Transtornos do Neurodesenvolvimento , Efeitos Tardios da Exposição Pré-Natal , Masculino , Gravidez , Feminino , Humanos , Adulto , Pré-Escolar , Estudos Prospectivos , Hidrocortisona , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologiaRESUMO
BACKGROUND: Synthetic glucocorticoid exposure in late pregnancy may be associated with higher blood pressure in offspring. We hypothesized that endogenous cortisol in pregnancy relates to offspring blood pressure (OBP). OBJECTIVE: To investigate associations between maternal cortisol status in third trimester pregnancy and OBP. METHODS: We included 1317 mother-child pairs from Odense Child Cohort, an observational prospective cohort. Serum (s-) cortisol and 24-hour urine (u-) cortisol and cortisone were assessed in gestational week 28. Offspring systolic blood pressure and diastolic blood pressure were measured at age 3, 18 months, and 3 and 5 years. Associations between maternal cortisol and OBP were examined by mixed effects linear models. RESULTS: All significant associations between maternal cortisol and OBP were negative. In boys in pooled analyses, 1 nmol/L increase in maternal s-cortisol was associated with average decrease in systolic blood pressure (ß=-0.003 mmHg [95% CI, -0.005 to -0.0003]) and diastolic blood pressure (ß=-0.002 mmHg [95% CI, -0.004 to -0.0004]) after adjusting for confounders. At 3 months of age, higher maternal s-cortisol was significantly associated with lower systolic blood pressure (ß=-0.01 mmHg [95% CI, -0.01 to -0.004]) and diastolic blood pressure (ß=-0.010 mmHg [95% CI, -0.012 to -0.011]) in boys after adjusting for confounders, which remained significant after adjusting for potential intermediate factors. CONCLUSIONS: We found temporal sex dimorphic negative associations between maternal s-cortisol levels and OBP, with significant findings in boys. We conclude that physiological maternal cortisol is not a risk factor for higher blood pressure in offspring up to 5 years of age.
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Hipertensão , Hipotensão , Efeitos Tardios da Exposição Pré-Natal , Feminino , Humanos , Masculino , Gravidez , Pressão Sanguínea/fisiologia , Hidrocortisona , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Perfluoroalkyl substances (PFAS) are endocrine disrupting chemicals with elimination half-lives ranging from four to eight years. Experimental studies found PFAS able to interfere with thyroid hormone-binding proteins. During the first 20 weeks of gestation (GW), the fetus is reliant on placental transfer of maternal thyroid hormones, mainly free thyroxine (FT4). However, previous studies investigating associations between exposure to PFAS and thyroid hormone status mainly focused on blood samples from late pregnancy or umbilical cord with mixed findings. OBJECTIVES: To investigate associations between serum-PFAS concentrations and thyroid hormone status in early pregnancy as reflected by FT4 and thyroid-stimulating hormone (TSH). METHODS: In the Odense Child Cohort, a single-center study, we measured maternal pregnancy serum concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA); and FT4 and TSH in 1048 pregnant women at median GW 12 (25th, 75th percentile: 10, 15). Multivariate linear regression models were performed to estimate associations between PFAS exposure and thyroid hormone status. RESULTS: A doubling in PFOS, PFOA, and PFNA concentrations was associated with an increment in FT4 concentration by 1.85% (95% CI: 0.66%, 3.05%), 1.29% (95% CI: 0.21%, 2.39%), and 1.70% (95% CI: 0.48%, 2.94%), respectively, in adjusted analyses. A statistically significant dose-response relationship was observed across exposure quartiles for PFOS, PFOA, and PFNA in the association with FT4. No association was found between concentrations of PFAS and TSH in adjusted analyses. CONCLUSION: Exposure to PFOS, PFOA, and PFNA was associated with higher FT4 concentrations in women during early pregnancy. The potential clinical implications of these findings remain to be clarified.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Criança , Feminino , Humanos , Placenta , Gravidez , Primeiro Trimestre da Gravidez , Hormônios Tireóideos , Tireotropina , TiroxinaRESUMO
CONTEXT: Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, although not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown. OBJECTIVE: To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and to elucidate the potential role of serum-prolactin concentrations in pregnancy. MATERIALS AND METHODS: Pregnant women from the Odense Child Cohort provided blood samples for analysis of 5 major PFAS (n = 1300) and prolactin concentrations (n = 924). They subsequently provided information about the duration of breastfeeding in questionnaires at 3 and 18 months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations. RESULTS: Increased serum concentrations of perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorononanoic acid, and ∑PFAS were associated with a 16% (95% CI: 4%-30%), 14% (95% CI: 2%-26%), 14% (95% CI: 3%-27%), and 20% (95% CI: 6%-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations. CONCLUSIONS: These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences.
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Aleitamento Materno/estatística & dados numéricos , Poluentes Ambientais/efeitos adversos , Fluorocarbonos/efeitos adversos , Exposição Materna , Prolactina/sangue , Adulto , Saúde da Criança , Dinamarca , Poluentes Ambientais/sangue , Feminino , Fluorocarbonos/sangue , Humanos , Lactente , Recém-Nascido , Idade Materna , Saúde Materna , Período Pós-Parto , Fatores de Tempo , Adulto JovemRESUMO
AIMS: To examine third trimester fasting venous plasma glucose (FVPG) according to the distribution of a Danish population of pregnant women and identify potential local FVPG thresholds for GDM diagnosis related to risks of adverse pregnancy outcomes. METHODS: In the observational Odense Child Cohort (OCC) study, 1516 women had FVPG measured at 27-28 weeks' gestation and were considered normal by Danish criteria and remained untreated. Maternal FVPG from OCC were standardized according to the local FVPG mean and standard deviation calibrated to data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Associations between maternal FVPG and clinical and anthropometric outcomes were analysed. Potential FVPG cut points were identified. RESULTS: Unadjusted areas under the ROC curve for FVPG to discriminate for large for gestational age (LGA) and hypertensive disorders of pregnancy were 0.61 (95% CI 0.56, 0.67) and 0.57 (95% CI 0.52, 0.63), respectively. The Youden FVPG cut point for LGA was 5.5 mmol/L and 5.0 mmol/L for hypertensive disorders of pregnancy. CONCLUSIONS: This study identified a potential locally appropriate third trimester FVPG cut point between 5.5 and 5.7 mmol/L based on LGA risk in pregnancy. This cut point should be validated prospectively in other Danish cohorts.
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Glicemia/metabolismo , Diabetes Gestacional/diagnóstico , Jejum/sangue , Teste de Tolerância a Glucose/métodos , Adulto , Dinamarca , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez , Resultado da GravidezRESUMO
BACKGROUND: Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive. OBJECTIVE: To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children. METHOD: In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score. RESULTS: BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03). CONCLUSION: Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.
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Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Fenóis/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Compostos Benzidrílicos/urina , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Disruptores Endócrinos/urina , Feminino , Humanos , Masculino , Troca Materno-Fetal , Fenóis/urina , GravidezRESUMO
OBJECTIVE: Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) in normal weight women with PCOS and controls matched for age and BMI. METHODS: From a Nordic cross-sectional base of 2615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI < 25 kg/m2 (512 women with PCOS according to Rotterdam criteria and 281 age and BMI-matched controls). Participants underwent measurement of BP and body composition (BMI, waist-hip ratio), lipid status, and fasting BG. Data were presented as median (quartiles). RESULTS: The median age for women with PCOS were 28 (25, 32) years and median BMI was 22.2 (20.7, 23.4) kg/m2. Systolic BP was 118 (109, 128) mmHg in women with PCOS compared to 110 (105, 120) mmHg in controls and diastolic BP was 74 (67, 81) vs 70 (64, 75) mmHg, both P < 0.001. The prevalence of women with BP ≥ 140/90 mmHg was 11.1% (57/512) in women with PCOS vs 1.8% (5/281) in controls, P < 0.001. In women ≥ 35 years the prevalence of BP ≥ 140/90 mmHg was comparable in women with PCOS and controls (12.7% vs 9.8%, P = 0.6). Using multiple regression analyses, the strongest association with BP was found for age, waist circumference, and total cholesterol in women with PCOS. CONCLUSIONS: Normal weight women with PCOS have higher BP than controls. BP and metabolic screening are relevant also in young normal weight women with PCOS.
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BACKGROUND: Phthalates are plastic softeners with anti-androgenic properties. Prenatal exposure has led to lower testosterone (T) levels and smaller testicles in adult rats. To our knowledge, no studies have examined associations between prenatal phthalate exposure and sex hormone concentrations in infants. OBJECTIVE: To study associations between phthalate exposure in Danish pregnant women and T, luteinizing hormone (LH), follicle stimulating hormone (FSH), Δ4-androstenedione (adion), 17α-hydroxyprogesterone (17-OHP) dehydroepiandrosterone sulfate (DHEAS) concentrations in their infants (N = 479) during mini-puberty. METHODS: Concentrations of 12 phthalate metabolites from six phthalate diesters were measured in urine samples collected from 2010 to 2012 from 479 pregnant women participating in the Odense Child Cohort at gestational week 28 (range 20.4-30.4). Serum T, LH, FSH, adion, 17-OHP, DHEAS, weight and height were measured approximately three months after expected date of birth. Associations between prenatal phthalate exposure and gonadotropin and androgen metabolite concentrations were estimated in boys and girls separately in adjusted linear regression models. RESULTS: T concentration was lower in boys prenatally exposed to phthalates. Maternal urinary concentrations of summed mono-iso-butyl and mono-n-butyl phthalate (∑MBPi+n) and summed metabolites of di-iso-nonyl phthalate (∑DiNPm) were associated with lower T/LH ratio in male offspring and a dose-response association was found. FSH was 14% (95% CI: 1; 25) lower among male offspring from mothers exposed to ∑DiNPm in the highest compared to the lowest tertile. No association was found for girls. CONCLUSION: Even in these low exposed children, we found a significant decrease in T/LH ratio during mini-puberty in boys prenatally exposed to phthalates, which may suggest impairment of Leydig cells. The children will be followed as they approach adrenarche and pubarche in order to assess if long-term adverse effects persist.
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Ácidos Ftálicos , Animais , Criança , Feminino , Humanos , Hormônio Luteinizante , Masculino , Exposição Materna/efeitos adversos , Ácidos Ftálicos/toxicidade , Gravidez , Puberdade , Ratos , TestosteronaRESUMO
BACKGROUND: Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy. OBJECTIVES: We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy. METHODS: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth (n=613) and at 3 months (n=602) and 18 months (n=503) of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months (n=262) and 18 months (n=198) of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models. RESULTS: PFNA and PFDA were associated with higher BMI SDS [adjusted ß=0.26; 95% confidence interval (CI): 0.03, 0.49 and ß=0.58; 95% CI: -0.03, 1.19, respectively, for 1-ng/mL increases] and ponderal index SDS (ß=0.36; 95% CI: 0.13, 0.59 and ß=1.02; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for 1-ng/mL PFDA, ß=0.40; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (ß=1.06; 95% CI: 0.08, 2.03) (n=83). DISCUSSION: Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. https://doi.org/10.1289/EHP5184.
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Adiposidade/fisiologia , Poluentes Ambientais/sangue , Fluorocarbonos/sangue , Exposição Materna/estatística & dados numéricos , Adulto , Ácidos Alcanossulfônicos , Caprilatos , Criança , Estudos de Coortes , Ácidos Decanoicos , Ácidos Graxos , Feminino , Humanos , Lactente , Masculino , Obesidade , Plasma , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Estudos Prospectivos , Ácidos SulfônicosRESUMO
INTRODUCTION: During pregnancy, maternal cortisol levels are increased 3-fold by the third trimester. The enzyme 11ß-hydroxysteroid dehydrogenase (11ß-HSD, isoforms 1 and 2) regulates the balance between cortisol and cortisone levels. Perfluoroalkyl substances (PFAS) have been reported to inhibit 11ß-HSD1 and more potently 11ß-HSD2, which could lead to reduced levels of cortisol and more extensively cortisone. AIM: The aim of this work is to investigate a possible effect of early pregnancy PFAS exposure on late pregnancy activity of 11ß-HSD1 and 11ß-HSD2 assessed by cortisol and cortisone levels in diurnal urine (dU) and blood samples. METHODS: This study is part of the prospective cohort study, Odense Child Cohort (OCC). A total of 1628 pregnant women had serum (S) concentrations of 5 PFAS (perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], perfluorohexane sulfonic acid [PFHxS], perfluorononanoic acid [PFNA], and perfluorodecanoic acid (PFDA)) measured in the first trimester (median gestational week, GW 11). dU cortisol and cortisone (nâ =â 344) and S-cortisol (nâ =â 1048) were measured in the third trimester (median GW 27). RESULTS: In multiple regression analyses, a 2-fold increase in S-PFOS was significantly associated with lower dU-cortisone (ßâ =â -9.1%, Pâ <â .05) and higher dU-cortisol/dU-cortisone (dU-C/C) (ßâ =â 9.3%, Pâ <â .05). In crude models, a doubling in PFOS, PFOA, PFHxS, and PFNA concentrations were associated with a significant increase in S-cortisol; however, these associations became insignificant after adjustment. CONCLUSION: Early pregnancy maternal S-PFAS were inversely associated with late pregnancy dU-cortisone, indicating reduced activity of 11ß-HSD2.
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11-beta-Hidroxiesteroide Desidrogenase Tipo 2/antagonistas & inibidores , Cortisona/sangue , Disruptores Endócrinos/efeitos adversos , Fluorocarbonos/efeitos adversos , Terceiro Trimestre da Gravidez/sangue , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Adulto , Disruptores Endócrinos/sangue , Feminino , Fluorocarbonos/sangue , Humanos , Hidrocortisona/sangue , Gravidez , Primeiro Trimestre da Gravidez/sangue , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Estudos ProspectivosRESUMO
INTRODUCTION: The aim of this study was to compare blood pressure and prevalence of pregnancy-induced hypertension in women with polycystic ovary syndrome and the reference group throughout pregnancy. MATERIAL AND METHODS: This retrospective study was part of the prospective study Odense Child Cohort. Pregnant women were recruited from January 2010 to December 2012. Blood pressure was measured in 200 women with polycystic ovary syndrome and in 2197 in the reference group. Main outcome measures were blood pressure and pregnancy-induced hypertension. Pregnancy-induced hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg occurring after gestational week 20 at two separate visits. Mann-Whitney U test and Chi-square test were used to test differences between women with polycystic ovary syndrome and the reference group. Associations between polycystic ovary syndrome status (PCOS; the reference group) and blood pressure were tested using random mixed-effect linear regression analyses with subjects as random effect to comply with repeated blood pressure measurements. RESULTS: Median blood pressure was comparable in women with polycystic ovary syndrome and the reference group throughout pregnancy: systolic blood pressure 116 (111-123) vs 119 (112-124) (P = .06), diastolic blood pressure 72 (69-77) vs 73 (69-78) (P = .23) and mean arterial pressure 87 (83-93) vs 88 (84-92) (P = .13). In first trimester where systolic blood pressure was lower in polycystic ovary syndrome, median systolic blood pressure was 116 (111-123) vs 119 (112-124) mmHg (P = .04). The prevalence of pregnancy-induced hypertension was similar in polycystic ovary syndrome and the reference group: 17/200 (8.5%) vs 178/1997 (8.9%) (P = .84). Regression analyses showed no significant associations between polycystic ovary syndrome and blood pressure. CONCLUSIONS: Blood pressure and prevalence of pregnancy-induced hypertension were comparable in pregnant women with polycystic ovary syndrome and the reference group.
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Hipertensão Induzida pela Gravidez/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Obesidade Materna/epidemiologia , Gravidez , Técnicas de Reprodução Assistida/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: Fetal programming of the endocrine system may be affected by exposure to perfluoroalkyl substances (PFAAs), as they easily cross the placental barrier. In vitro studies suggest that PFAAs may disrupt steroidogenesis. "Mini puberty" refers to a transient surge in circulating androgens, androgen precursors, and gonadotropins in infant girls and boys within the first postnatal months. We hypothesize that prenatal PFAA exposure may decrease the concentrations of androgens in mini puberty. OBJECTIVES: To investigate associations between maternal serum PFAA concentrations in early pregnancy and serum concentrations of androgens, their precursors, and gonadotropins during mini puberty in infancy. METHODS: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAAs: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured at median gestational week 12 (IQR: 10, 15) in 1628 women. Among these, offspring serum concentrations of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), androstenedione, 17-hydroxyprogesterone (17-OHP), testosterone, luteinizing (LH) and follicle stimulating hormones (FSH) were measured in 373 children (44% girls; 56% boys) at a mean age of 3.9 (±0.9 SD) months. Multivariate linear regression models were performed to estimate associations. RESULTS: A two-fold increase in maternal PFDA concentration was associated with a reduction in DHEA concentration by -19.6% (95% CI: -32.9%, -3.8%) in girls. In girls, also, the androstenedione and DHEAS concentrations were decreased, albeit non-significantly (p < 0.11), with a two-fold increase in maternal PFDA concentration. In boys, no significant association was found between PFAAs and concentrations of androgens, their precursors, and gonadotropins during mini puberty. CONCLUSION: Prenatal PFDA exposure was associated with significantly lower serum DHEA concentrations and possibly also with lower androstenedione and DHEAS concentrations in female infants at mini puberty. The clinical significance of these findings remains to be elucidated.
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Ácidos Alcanossulfônicos , Ácidos Decanoicos , Desidroepiandrosterona , Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Puberdade , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Criança , Ácidos Decanoicos/toxicidade , Desidroepiandrosterona/sangue , Feminino , Fluorocarbonos/toxicidade , Humanos , Lactente , Masculino , Gravidez , Estudos ProspectivosRESUMO
STUDY QUESTION: Are higher testosterone levels during pregnancy in women with polycystic ovary syndrome (PCOS) associated with longer offspring anogenital distance (AGD)? SUMMARY ANSWER: AGD was similar in 3-month-old children born of mothers with PCOS compared to controls. WHAT IS KNOWN ALREADY: AGD is considered a marker of prenatal androgenization. STUDY DESIGN, SIZE, DURATION: Maternal testosterone levels were measured by mass spectrometry at Gestational Week 28 in 1127 women. Maternal diagnosis of PCOS before pregnancy was defined according to Rotterdam criteria. Offspring measures included AGD from anus to posterior fourchette (AGDaf) and clitoris (AGDac) in girls and to scrotum (AGDas) and penis (AGDap) and penile width in boys and body composition (weight and BMI SD scores) at age 3 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was part of the prospective study, Odense Child Cohort (OCC), and included mothers with PCOS (n = 139) and controls (n = 1422). The control population included women with regular menstrual cycles (<35 days) before conception and no signs of androgen excess (hirsutism and/or acne). MAIN RESULTS AND THE ROLE OF CHANCE: AGD measures were comparable in offspring of women with PCOS compared to controls (all P > 0.2) despite significantly higher maternal levels of total testosterone (mean: 2.4 versus 2.0 nmol/l) and free testosterone (mean: 0.005 versus 0.004 nmol/l) in women with PCOS versus controls (both P < 0.001). In women with PCOS, maternal testosterone was an independent positive predictor of offspring AGDas and AGDap in boys. Maternal testosterone levels did not predict AGD in girls born of mothers with PCOS or in boys or girls born of women in the control group. LIMITATIONS, REASONS FOR CAUTION: The diagnosis of PCOS was based on retrospective information and questionnaires during pregnancy. Women participating in OCC were more ethnically homogenous, leaner, more educated and less likely to smoke compared to the background population. Our study findings, therefore, need to be reproduced in prospective study cohorts with PCOS, in more obese study populations and in women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Our finding of the same AGD in girls born of mothers with PCOS compared to controls expands previous results of studies reporting longer AGD in adult women with PCOS. Our results suggest that longer AGD in adult women with PCOS could be the result of increased testosterone levels in puberty, perhaps in combination with weight gain. STUDY FUNDING/COMPETING INTEREST(S): Financial grants for the study were provided by the Danish Foundation for Scientific Innovation and Technology (09-067180), Ronald McDonald Children Foundation, Odense University Hospital, the Region of Southern Denmark, the Municipality of Odense, the Mental Health Service of the Region of Southern Denmark, The Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (2101-08-0058), Odense Patient data Explorative Network, Novo Nordisk Foundation (grant no. NNF15OC00017734), the Danish Council for Independent Research and the Foundation for research collaboration between Rigshospitalet and Odense University Hospital and the Health Foundation (Helsefonden). There is no conflict of interest of any author that could be perceived as prejudicing the impartiality of the research reported.
Assuntos
Canal Anal/anatomia & histologia , Pênis/anatomia & histologia , Síndrome do Ovário Policístico/metabolismo , Escroto/anatomia & histologia , Testosterona/metabolismo , Adulto , Índice de Massa Corporal , Peso Corporal , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Idade Materna , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Gravidez , Terceiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/metabolismo , Estudos Prospectivos , Estudos Retrospectivos , Fatores Sexuais , Testosterona/sangue , Vulva/anatomia & histologiaRESUMO
OBJECTIVE: To determine predictors of maternal serum (S) and urinary (U) cortisol and cortisone levels during the third trimester and to examine associations between maternal cortisol status, offspring sex, and maternal polycystic ovary syndrome (PCOS) status. DESIGN: Prospective observational study. SETTING: The study is part of the prospective Odense Child Cohort. PATIENT(S): The study cohort included 1,489 women (with PCOS, n = 145; without PCOS, n = 1,344). INTERVENTION(S): Fasting blood samples, 24-hour urinary samples. MAIN OUTCOME MEASURE(S): Fasting morning S-cortisol and 24-hour U-cortisol/U-cortisone (24-hour U-C/C) were collected at gestational week 28 and measured by liquid chromatography-tandem mass spectrometry. RESULT(S): Maternal S-cortisol levels were significantly higher in women pregnant with girls (n = 702) vs. boys (n = 787): mean (mean - SD; mean + SD) 833 (643; 1,079) vs. 799 (588; 1,083) nmol/L. In multiple regression analyses, maternal S-cortisol was positively associated with female offspring and inversely associated with maternal age and parity. When women were divided according to PCOS status, 24-hour U-cortisone was higher: 467 (334; 652) vs. 415 (286; 604) nmol/24 hours; and 24-hour U-C/C was lower in women with PCOS compared with women without PCOS. CONCLUSION(S): Maternal third trimester S-cortisol levels were positively associated with female offspring. Cortisol metabolism was higher in women with PCOS vs. women without PCOS.
Assuntos
Hidrocortisona/análise , Síndrome do Ovário Policístico/metabolismo , Adulto , Estudos de Coortes , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Recém-Nascido , Modelos Lineares , Masculino , Gravidez , Terceiro Trimestre da Gravidez , Estudos ProspectivosRESUMO
Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism. In pregnancy, testosterone levels may be higher in women with PCOS compared with controls. Aims: To compare total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) levels in third-trimester pregnant women with PCOS and controls and to establish reference ranges for TT, FT, and SHBG in PCOS and controls. Methods: The study was part of the prospective study, Odense Child Cohort. PCOS was diagnosed by questionnaires and/or patient records. Fasting blood samples were collected at gestational week 28 and plasma TT was measured by liquid chromatography-tandem mass spectrometry in women with PCOS (n = 145) and in women without PCOS (controls, n = 1341). Results: Levels of TT (mean, 2.4 vs 2.0 nmol/L) and FT (mean, 0.005 vs 0.004 nmol/L) were higher, whereas SHBG levels (mean, 447 vs 477 nmol/L) were lower in women with PCOS vs controls (all P < 0.001). Reference intervals for TT, FT, and SHBG in women with PCOS and controls were overlapping, and partitioning of reference intervals was an ambiguous decision. In multiple regression analyses, TT and FT levels were positively associated with PCOS status and BMI and inversely associated with age and parity. Offspring sex did not predict maternal TT and FT. Conclusions: TT and FT levels were higher in third-trimester pregnant women with PCOS compared with controls. Separate reference interval for FT in women with PCOS should be considered.
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Biomarcadores/sangue , Análise Química do Sangue/normas , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Adulto , Androgênios/sangue , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Terceiro Trimestre da Gravidez , Prognóstico , Valores de Referência , Globulina de Ligação a Hormônio Sexual/análiseRESUMO
BACKGROUND: Insulin resistance is common in polycystic ovary syndrome (PCOS). PCOS may be associated with increased risk of gestational diabetes mellitus (GDM). OBJECTIVES: To (1) review literature regarding PCOS and hyperglycaemia in pregnancy and (2) present original data from Odense Child Cohort (OCC) regarding GDM in PCOS. METHODS: Literature search including original studies from 2000-18. OCC included 2548 pregnant women, 9.5% (nâ¯=â¯241) had PCOS. Fasting plasma glucose was measured in 1519 and 659 oral glucose tolerance tests were performed (with risk factor for GDM, nâ¯=â¯384, without risk factors, nâ¯=â¯275), applying two different GDM criteria. RESULTS: 30 studies were eligible using 12 different sets of diagnostic criteria for GDM. Ten studies included nâ¯>â¯50, control group, assessment of GDM and BMI. Results were not uniform, but supported that higher BMI, higher age, Asian ethnicity, and fertility treatment increased the risk of GDM in PCOS. In OCC, women with PCOS and controls had similar prevalences of GDM independent of different sets of criteria for GDM. CONCLUSION: PCOS may not be an individual risk factor for GDM. Pregnancies in PCOS are characterized by factors known to increase risk of GDM, especially high BMI and fertility treatment.
Assuntos
Diabetes Gestacional/fisiopatologia , Hiperglicemia/complicações , Síndrome do Ovário Policístico/complicações , Complicações na Gravidez/epidemiologia , Dinamarca/epidemiologia , Feminino , Humanos , Resistência à Insulina , Gravidez , Prevalência , Estudos ProspectivosRESUMO
BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent chemicals with suspected endocrine disrupting abilities applied in consumer products. PFASs have potentially modulating effects on glucose homeostasis. Insulin resistance prevails during third trimester of pregnancy, and this challenge of glucose homeostasis may reveal putative effects of PFAS concentrations on glycemic status. OBJECTIVE: To investigate associations between five serum PFASs and glucose-related outcomes in pregnant Danish women based on their risk of gestational diabetes mellitus (GDM). METHODS: In the prospective Odense Child Cohort serum concentrations of five PFASs - perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) - were measured at median gestational week (GW) 11 in pregnant women. An oral glucose tolerance test (OGTT) was performed at GW 28. The statistical analysis was conducted among 158 women with high GDM risk and 160 women with low GDM risk matched by gestational age. Multiple linear regression models were performed to estimate associations between PFAS concentrations and glucose, insulin, C-peptide, homeostatic model of assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-%ß), and insulin sensitivity (Matsuda index) during the 2-h OGTT. RESULTS: In women with high risk for GDM, a two-fold increase in PFHxS concentration was significantly associated with increased fasting glucose, fasting insulin and HOMA-IR after adjusting for age, parity, educational level and pre-pregnancy BMI. Adjusting for the same confounders, a doubling in PFNA concentration was associated with higher fasting insulin and HOMA-%ß. In women with low GDM risk, no associations were found between PFAS concentrations and glucose-related outcomes. CONCLUSION: PFHxS and PFNA concentrations were associated with impaired glycemic status in metabolically vulnerable pregnant women and might further enhance the risk of developing GDM.