Perfluorinated chemicals (PFCs) have been widely used and have emerged as important food contaminants. A recent study on pregnant women suggested that PFC exposure was associated with a longer time ...to pregnancy (TTP). We examined the association between serum concentrations of PFCs in females and TTP in 222 Danish first-time pregnancy planners during the years 1992–1995.
METHODS
The couples were enrolled in the study when discontinuing birth control and followed for six menstrual cycles or until a clinically recognized pregnancy occurred. Fecundability ratio (FR) was calculated using discrete-time survival models. In addition, odds ratio (OR) for TTP >6 cycles was calculated.
RESULTS
OR for TTP >6 cycles for those with PFC concentrations above the median were 0.96 95% confidence interval (CI): 0.54–1.64 for perfluorooctane sulfonic acid (PFOS), the major PFC, compared with those below the median. FRs for those with PFOS concentrations above the median were 1.05 (95% CI: 0.74–1.48) compared with those below the median. Other PFCs showed the same lack of association with TTP. The results were not affected by adjustment for covariates. PFOS and perfluorooctanoic acid concentrations were similar to those observed in a previous Danish study.
CONCLUSIONS
These findings suggest that exposure to PFCs affects TTP only to a small extent, if at all.
Due to their extensive usage, organophosphorus flame retardants (OPFRs) have been detected in humans and in the environment. Human are exposed to OPFRs via inhalation of indoor air, dust uptake or ...dietary uptake through contaminated food and drinking water. Only recently, few studies addressing dietary exposure to OPFRs were published. In this study, we used human biomonitoring (HBM) data of OPFRs to estimate how much the dietary intake may contribute to the total exposure. We estimated by reverse dosimetry, the daily intake of tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for children using HBM data from studies with sampling sites in Belgium, Denmark, France, Germany, Slovenia and Slovakia. For estimating the dietary exposure, a deterministic approach was chosen. The occurrence data of selected food categories were used from a published Belgium food basket study. Since the occurrence data were left-censored, the Lower bound (LB)-Upper bound (UB) approach was used. The estimated daily intake (EDI) calculated on the basis of urine metabolite concentrations ranged from 0.03 to 0.18 µg/kg bw/d for TDCIPP, from 0.05 to 0.17 µg/kg bw/d for TCIPP and from 0.02 to 0.2 µg/kg bw/d for TCEP. Based on national food consumption data and occurrence data, the estimated dietary intake for TDCIPP ranged from 0.005 to 0.09 µg/kg bw/d, for TCIPP ranged from 0.037 to 0.2 µg/kg bw/d and for TCEP ranged from 0.007 to 0.018 µg/kg bw/d (summarized for all countries). The estimated dietary intake of TDCIPP contributes 11-173% to the EDI, depending on country and LB-UB scenario. The estimated dietary uptake of TCIPP was in all calculations, except in Belgium and France, above 100%. In the case of TCEP, it is assumed that the dietary intake ranges from 6 to 57%. The EDI and the estimated dietary intake contribute less than 3% to the reference dose (RfD). Therefore, the estimated exposure to OPFRs indicates a minimal health risk based on the current knowledge of available exposure, kinetic and toxicity data. We were able to show that the dietary exposure can have an impact on the general exposure based on our underlying exposure scenarios.
Between 1996 and 1999, the authors invited all young men from five European countries who were undergoing compulsory medical examination for possible military service to participate in a study on ...male reproductive health. The participation rate was 19% in two cities in Denmark (n = 889), 17% in Oslo, Norway (n = 221), 13% in Turku, Finland (n = 313), 14% in Kaunas, Lithuania (n = 157), and 19% in Tartu, Estonia (n = 190). Each man provided a semen sample, was examined by a physician, and, in collaboration with his mother, completed a questionnaire about general and reproductive health, current smoking habits, and exposure to smoking in utero. After adjustment for confounding factors, men exposed to smoking in utero had a reduction in sperm concentration of 20.1% (95% confidence interval (CI): 6.8, 33.5) and a reduction in total sperm count of 24.5% (95% CI: 9.5, 39.5) in comparison with unexposed men. Percentages of motile and morphologically normal sperm cells were 1.85 (95% CI: 0.46, 3.23) and 0.64 (95% CI: –0.02, 1.30) percentage points lower, respectively, among men exposed in utero, and exposed men had a 1.15-ml (95% CI: 0.66, 1.64) smaller testis size. The associations were present when data from the study centers were analyzed separately (though not in Lithuania, where only 1% of mothers smoked during pregnancy), although the strength of the association varied. Maternal smoking may have long-term implications for the reproductive health of the offspring. This is another good reason to advise pregnant women to avoid smoking.
Vaginal candidiasis is frequent among pregnant women and it is treated with anti-fungal medication (conazoles). Conazoles have anti-androgenic properties and prenatal exposure in rodents is ...associated with a shorter (less masculine) anogenital distance (AGD) in male offspring. To our knowledge this has never been studied in humans.
In the Odense Child Cohort pregnant women residing in Odense municipality, Denmark, were recruited at gestational age 8-16 weeks between 2010 and 2012. Of the eligible 2421 mother-child pairs, 812 mother-son pairs were included. Questionnaire data on medicine use were collected in first and third trimester and physical examination at age 3 month was performed. Ano-scrotal distance; measured from the centre of anus to the posterior base of scrotum (AGDas). Ano-cephalad distance; measured from the centre of anus to the cephalad insertion of the penis (AGDap) and penile width; measured at the base of the penis.
Eighty seven women had used antifungal medicine during pregnancy. Maternal use of oral fluconazole (n = 4) was associated with a 6.4 mm shorter AGDas (95% CI: -11.9;-0.9) in the male offspring. Use of antifungal vaginal tablets (n = 21), was associated with a non-significantly shorter AGDas (-1.9 mm; 95% CI: -4.3; 0.5) whereas exposure to vaginal cream (n = 23) was not associated to AGDas. Use of antifungal medicine in the window of genital development between 8 and 14 weeks of gestation was associated with a larger reduction in AGDas than exposure outside this window. Antifungal medicine intake was not associated with AGDap and penil width.
Our preliminary findings prompted us to hypothesize that maternal use of conazole antifungal medication during pregnancy may affect the masculinization of male offspring. If confirmed, pregnant women should be advised to use antifungal medicine with caution.
The knowledge of the effects of organophosphate flame retardants on children’s neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to ...organophosphate flame retardants and children’s neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children’s urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = −1.30; 95%CI = −2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = −0.98; 95%CI = −2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = −1.42; 95% CI = −2.70; −0.06; p-value = 0.04) and no clear association with DPHP (β = −1.09; 95% CI = −2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was −0.49 (95%CI = −1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was −0.35 (95%CI = −1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.
Objective Calculating the free testosterone level has gained increasing interest and different indirect algorithms have been suggested. The objective was to compare free androgen index (FAI), free ...testosterone estimated using the linear binding model (Vermeulen: cFTV) and the binding framework accounting for allosterically coupled SHBG monomers (Zakharov: cFTZ) in relation to cardiometabolic conditions. Design A prospective cohort study including 5350 men, aged 30–70 years, participating in population-based surveys (MONICA I–III and Inter99) from 1982 to 2001 and followed until December 2012 with baseline and follow-up information on cardiometabolic parameters and vital status. Results Using age-standardized hormone levels, FAI was higher among men with baseline cardiometabolic conditions, whereas cFTV and cFTZ levels were lower compared to men without these conditions as also seen for total testosterone. Men in highest quartiles of cFTV or cFTZ had lower risk of developing type 2 diabetes (cFTV: HR = 0.74 (0.49–1.10), cFTZ: HR = 0.59 (0.39–0.91)) than men in lowest quartile. In contrast, men with highest levels of FAI had a 74% (1.17–2.59) increased risk of developing type 2 diabetes compared to men in lowest quartile. Conclusion The association of estimated free testosterone and the studied outcomes differ depending on algorithm used. cFTV and cFTZ showed similar associations to baseline and long-term cardiometabolic parameters. In contrast, an empiric ratio, FAI, showed opposite associations to several of the examined parameters and may reflect limited clinical utility.
Semen analysis is part of the routine assessment of infertile couples. WHO defines a sperm concentration above 20×10
6 per mL seminal fluid as normal. We studied the association between semen quality ...and the probability of conception in a single menstrual cycle in Danish couples with no previous reproductive experience.
In 1992–94, we invited 52 255 trades-union members aged 20–35 years, who lived with a partner and had no children to take part in the study; 430 couples agreed. The couples discontinued use of contraception, and were followed up for six menstrual cycles or until a pregnancy was verified within this period. Each man was asked to provide a semen sample at enrolment (which was analysed without freezing). Women kept a daily record of vaginal bleeding and sexual activity. The association between semen quality and likelihood of pregnancy was assessed by logistic regression, adjusted for sexual activity and female factors associated with low fertility.
There were 256 (59·5%) pregnancies among the 430 couples: 165 (65·0%) among those with a sperm concentration of 40×10
6/mL or more and 84 (51·2%) among those with lower sperm concentrations. The probability of conception increased with increasing sperm concentration up to 40×10
6/mL, but any higher sperm density was not associated with additional likelihood of pregnancy. The proportion of sperm with normal morphology was strongly related to likelihood of pregnancy independently of sperm concentration. Semen volume and motility were of limited value in pregnancy prediction.
Our study suggests that the current WHO guidelines for normal semen quality should be used with caution. Some men with sperm counts above the lower limit of the normal range defined by WHO may in fact be subfertile.
Purpose The etiology of hypospadias is poorly understood. Exposure to pesticides has been considered a risk factor, although findings are inconsistent. Diet constitutes a significant exposure route ...for pesticides, and pesticide residues are more frequently reported in conventional than organic food products. We examined the association between organic dietary choice during pregnancy and presence of hypospadias in the offspring. Materials and Methods Mothers of 306 boys operated on for hypospadias were frequency matched for geography and child birth year to 306 mothers of healthy boys in a case-control study. Telephone interviews were conducted regarding demographic and lifestyle factors, including intake and organic choice of selected food items (milk, dairy products, egg, fruit, vegetables and meat). Logistic regression models were constructed for dietary variables, and odds ratios were calculated controlling for maternal age, body mass index and alcohol consumption. Results Overall organic choice of food items during pregnancy was not associated with hypospadias in the offspring. However, frequent current consumption of high fat dairy products (milk, butter) while rarely or never choosing the organic alternative to these products during pregnancy was associated with increased odds of hypospadias (adjusted OR 2.18, 95% CI 1.09–4.36). Conclusions This large case-control study of boys operated on for hypospadias suggests an association between hypospadias in the offspring and the mother not choosing the organic alternative, and having a high current intake of nonorganic butter and cheese. This finding could be due to chemical contamination of high fat dairy products. However, general lifestyle and health behavior related to choosing organic alternatives may also explain the finding.
Background
Studies have reported associations between psychological stress and semen quality, but most have been performed on selected populations using different stress measures. Thus, it is ...uncertain which stress scale best quantifies the effects of stress on testicular function.
Objective
To study the association between three different measures of stress and testicular function in young men.
Material and Methods
In total, 1362 men (median age 19 years) delivered semen and blood samples. They also answered a questionnaire including information from three stress scales: Stress Symptoms, Stressful Life Events and Perceived Stress. Various statistical analyses for associations between stress and testicular function (semen quality and reproductive hormones) were performed.
Results
Perceived Stress was negatively associated with sperm concentration, total count and motility and positively associated with serum FSH. Men with the highest scores (>30 points) had 38% (95% CI 3‐84%) lower sperm concentration, 42% (95% CI 5‐91%) lower total count and 22% (95% CI 2‐32%) lower proportion of motile spermatozoa than men with the lowest scores (0‐10 points). For the stress symptoms score, men with highest scores (>95th percentile vs. lower) had lower sperm concentration, total sperm count, motility and serum Inhibin‐B/FSH‐ratio. Although men with highest stress levels were characterized by an unhealthier lifestyle, adjusting for lifestyle factors did not attenuate results suggesting that the associations between stress and testicular function were not mediated by lifestyle. Stressful Life Events were not associated with testicular function.
Discussion and Conclusion
The linear association between Perceived Stress and semen parameters and lack of dose‐response association for the other two stress scales indicated that perceived stress was the most sensitive marker of stress affecting semen quality in young men. The lack of associations between Stressful Life Events and testis function confirmed that the perception of stressful events rather than the stressful event per se matters.
Abstract
Background
Adequate thyroid function during pregnancy is essential for optimal fetal growth. Gestational exposure to perfluoroalkyl substances (PFAS) can negatively affect birth size and ...disrupt maternal and neonatal thyroid function, although the interrelationship is unclear.
Objective
We aimed to quantify the associations between maternal serum–PFAS concentrations and birth weight, birth length, and cranial circumference. We also aimed to estimate associations between PFAS and thyroid hormone (TH) concentrations, thereby elucidating whether THs potentially mediate the associations between PFAS concentrations and birth size.
Methods
We studied a population-based prospective cohort of 172 mother-singleton pairs from the Faroe Islands. Twelve PFAS were measured in maternal serum obtained at 34 weeks of gestation. THs were measured in maternal and cord serum. Associations between PFAS concentrations and birth size and TH concentrations were estimated using multivariable linear regressions. Sex-stratified analyses along with a mediation analysis were performed to estimate potential mediating effects of THs in the association between PFAS and birth outcomes.
Results
Several PFASs were negatively associated with birth weight, length, and head circumference, and a general positive association between maternal serum–PFASs and cord serum–thyroid-stimulating hormone (TSH; also known as thyrotropin) was found. For instance, a doubling in perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) was associated with a 53% (95% CI, 18%-99%) and 40% (95% CI, 8%-81%) increases in TSH concentrations, respectively. There was little evidence of sexually dimorphic associations. Overall, THs were not found to mediate associations between PFASs and birth size.
Conclusion
In this study, several PFASs were negatively associated with birth size and increased THs; however, this did not explain lower birth weight among children exposed to PFAS.
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