Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism. In pregnancy, testosterone levels may be higher in women with PCOS compared with controls.
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.
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).
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.
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.
•Prenatal perfluoroalkyl acid (PFAS) exposure increases the risk of hospitalization.•Maternal PFOS concentration was associated with higher risk of any infection.•Maternal PFOS and PFOA increased the ...risk of lower respiratory tract infections.
The immunosuppressive properties of PFASs are widely recognized. Early-life exposure to PFAS has been linked to reduced immune response to childhood vaccinations and increased rates of common infectious diseases, but implications for hospitalizations are unclear.
To investigate the association between maternal serum concentrations of five PFASs during pregnancy and the child’s rate of hospitalization due to common infectious diseases between birth and 4 years of age.
Serum samples from first trimester pregnant women from the Odense Child Cohort (OCC) collected in 2010–2012 were analyzed for concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and three other PFASs. Data on child hospitalizations with an ICD-10 code for infectious disease was obtained from the Danish National Patient Register. The following were identified: upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), gastrointestinal infections (GI), and other infections. The Andersen-Gill Cox proportional hazard model for recurrent events was used to investigate the association between PFAS exposure and hospitalizations. The resulting estimates were hazard ratios (HRs), which express the relative change in the instantaneous risk of hospitalization with a doubling in maternal PFAS concentration.
A total of 1,503 mother–child pairs were included, and 26% of the children were hospitalized at least once for infectious disease. A doubling in maternal PFOS concentration was associated with a 23% increase in the risk of hospitalization due to any infection (HR: 1.23 (95% CI: 1.05, 1.44). There was indication of an interaction between child sex and PFOS (p = 0.07) and PFDA (p = 0.06), although in opposite directions. Further, every doubling of PFOA or PFOS increased the risk of LRTI by 27% (HR: 1.27 (1.01, 1.59)) and 54% (HR: 1.54 (1.11, 2.15)), respectively. Similar tendencies were seen for URTI and the group of other infections. For GIs, the opposite pattern of association was seen as HR’s were consistently below 1 (PFOA, HR: 0.55 (0.32, 0.95)).
We found an association between PFOS and the overall risk of infectious disease, and between PFOS and PFOA exposures and the risk of LRTI’s. These results are in agreement with previous findings from the OCC, in which maternal PFOS and PFOA concentrations were positively associated with the number of days that the children experienced fever, thereby suggesting that PFOS and PFOA may affect the prevalence of both mild and more severe infectious diseases even in a rather low-exposed population.
•PFAS exposure associated with systolic and diastolic blood pressure in pregnancy.•No clear associations between PFAS exposure and PE or GH were found.•Blood pressure increase was small but at a ...population level this may increase hypertension.•This has potential long term health implications for both the mother and the child.
Previous studies of association between exposure to poly- and perfluoroalkyl substances (PFAS) and gestational hypertension (GH) and preeclampsia (PE) have shown conflicting results, but most dichotomized outcome and did not study continuous blood pressure (BP) changes.
To study the association between PFAS exposure in early pregnancy and maternal BP trajectories in pregnancy, gestational hypertension and preeclampsia.
1436 women were enrolled in the Odense Child Cohort in early pregnancy and had a serum sample drawn, from which perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were measured using LC–MS/MS. Repeated BP measurements through pregnancy and information on PE were obtained from hospital files. Adjusted linear mixed models were used to investigate association between PFAS exposure and BP trajectory. Associations between PFAS and PE and GH were assessed by Cox proportional hazards model.
All women had measurable concentrations of PFAS. In all of many comparisons higher PFAS exposure (apart from PFHxS) was associated with higher systolic (SBP) and diastolic (DBP) blood pressures, although not all were significant, which is unlikely to be due to chance. After adjustment, each doubling in PFOS or PFOA exposure was associated with 0.47 mmHg (95% CI: −0.13; 1.08) and 0.36 mmHg (−0.19; 0.92) higher SBP; and 0.58 mmHg (0.13; 1.04) and 0.37 mmHg (−0.05; 0.79) higher DBP. No clear associations between PFAS exposure and PE or GH were found.
The magnitude of the association between PFAS exposure and BP might appear small, statistically non-significant and the possible clinical importance low. However, at a population level this may slightly shift the distribution of BP towards an increased incidence of GH. If BP increases in pregnancy, it may have long-term impact on health not only of the pregnant woman but also of her offspring.
Perfluorinated alkylated substances (PFAS) have been extensively used in consumer products and humans are widely exposed to these persistent compounds. A recent study found no association between ...exposure to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined adverse effect of the more recently introduced PFASs. We therefore conducted a case-control study within a population-based, prospective cohort during 2010-2012. Newly pregnant women residing in the Municipality of Odense, Denmark were invited to enroll in the Odense Child Cohort at their first antenatal visit before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered a miscarriage and 59 had stored serum samples, of which 56 occurred before gestational week 12. They were compared to a random sample (N=336) of delivering women, who had also donated serum samples before week 12. Using a case-control design, 51 of the women suffering a miscarriage were matched on parity and gestational day of serum sampling with 204 delivering women. In a multiple logistic regression with adjustment for age, BMI, parity and gestational age at serum sampling, women with the highest tertile of exposure to perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9-145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane sulfonic acid (PFHxS) was in the same direction, but not statistically significant, while no association was found with PFOA and PFOS. Our findings require confirmation due to the possible public health importance, given that all pregnant women are exposed to these widely used compounds.
Triclosan (TCS) is widely used as an antibacterial agent in consumer products such as hand soap and toothpaste, and human exposure is widespread. TCS is suspected of having endocrine-disrupting ...properties, but few human studies have examined the developmental effects of prenatal TCS exposure.
We prospectively examined associations between prenatal TCS exposure and anthropometric measures at birth and anogenital distance (AGD) at 3 months of age.
Pregnant women from the Odense Child Cohort (n = 514) provided urine samples at approximately gestational week 28 (median 28.7 weeks, range 26.4-34.0), and urinary TCS concentration was measured by isotope dilution TurboFlow-liquid chromatography-tandem mass spectrometry. Multiple linear regression analysis was used to examine associations between prenatal TCS exposure and measures of size at birth (birth weight, length, head and abdominal circumference) and AGD at 3 months of age (median 3.3 months, range 2.3-6.7 months), controlling for potential confounders.
Newborn boys in the highest quartile of prenatal TCS exposure had a 0.7-cm 95% confidence interval (CI): -1.2, -0.1, p = 0.01 smaller head circumference than boys in the lowest quartile. Additionally in boys, inverse associations of borderline statistical significance were observed between prenatal TCS exposure and abdominal circumference at birth and AGD at 3 months of age (p-values < 0.10). Prenatal TCS exposure was not significantly associated with any of the outcomes in girls. However, AGD was measured in fewer girls, and we observed no significant interactions between a child's sex and prenatal TCS exposure in anthropometric measures at birth.
Prenatal TCS exposure was associated with reduced head and abdominal circumference at birth and with reduced AGD at 3 months of age in boys, although the last two findings were statistically nonsignificant. These findings require replication but are compatible with an anti-androgenic effect of prenatal TCS exposure on fetal growth in boys.
Lassen TH, Frederiksen H, Kyhl HB, Swan SH, Main KM, Andersson AM, Lind DV, Husby S, Wohlfahrt-Veje C, Skakkebæk NE, Jensen TK. 2016. Prenatal triclosan exposure and anthropometric measures including anogenital distance in Danish infants. Environ Health Perspect 124:1261-1268; http://dx.doi.org/10.1289/ehp.1409637.
Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced ...anogenital distance (AGD)-the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported.
We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their male infants at 3 months of age (n = 273).
In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4-30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score.
Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose-response patterns, and associations were not statistically significant (p > 0.05).
We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population.
Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM. 2016. Prenatal exposure to phthalates and anogenital distance in male infants from a low-exposed Danish cohort (2010-2012). Environ Health Perspect 124:1107-1113; http://dx.doi.org/10.1289/ehp.1509870.
•Prenatal exposure to MnBP was related to lower testosterone in 3–4 months old boys.•Maternal phthalate exposure was related to lower T/LH ratio in 3–4 months old boys.•Anti-androgenic phthalates may ...affect mini-puberty occurring at 3–4 months of age.
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.
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.
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.
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.
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.
Abstract
Context
Parabens are used as preservatives in consumer products but are suspected of having endocrine-disrupting properties. A recent study reported an association between in utero exposure ...to butyl paraben and overweight in childhood, with a stronger trend in girls.
Objective
We therefore studied the association between parabens in maternal urine in third trimester and fat percentage in children aged 7 years.
Design, Setting, and Participants
We used data from the Odense Child Cohort, a mother-child cohort with enrollment from 2010 to 2012, in which the children are followed. Paraben concentration was assessed in maternal urine at median gestational week 28.7 and body composition measured as total, gynoid, and android fat percentages assessed by dual X-ray absorptiometry in their children at age 7 years.
Main Outcome Measurements
Total, gynoid, and android fat percentages and z-score for body mass index.
Interventions
None.
Results
Paraben exposure was low. In multivariate linear regressions, detection of butylparaben in maternal urine was associated with an increase of 17% 95% confidence intervals (CI) 3.0%, 32% in total body fat percentage and an increase of 23% (95% CI 5.1%, 43%) in android fat percentage in boys, compared to boys whose mother had no detectable butylparaben in urine. No significant associations between in utero exposure to methyl-, ethyl- or propyl parabens and body composition were found, and no significant associations were seen in girls.
Conclusion
Our findings suggest that parabens, which are believed to have low toxicity, may affect obesity development at vulnerable time periods during development.
During pregnancy, maternal cortisol levels are increased 3-fold by the third trimester. The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD, isoforms 1 and 2) regulates the balance between cortisol ...and cortisone levels. Perfluoroalkyl substances (PFAS) have been reported to inhibit 11β-HSD1 and more potently 11β-HSD2, which could lead to reduced levels of cortisol and more extensively cortisone.
The aim of this work is to investigate a possible effect of early pregnancy PFAS exposure on late pregnancy activity of 11β-HSD1 and 11β-HSD2 assessed by cortisol and cortisone levels in diurnal urine (dU) and blood samples.
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 (n = 344) and S-cortisol (n = 1048) were measured in the third trimester (median GW 27).
In multiple regression analyses, a 2-fold increase in S-PFOS was significantly associated with lower dU-cortisone (β = -9.1%, P < .05) and higher dU-cortisol/dU-cortisone (dU-C/C) (β = 9.3%, P < .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.
Early pregnancy maternal S-PFAS were inversely associated with late pregnancy dU-cortisone, indicating reduced activity of 11β-HSD2.
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.
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.
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.
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).
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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