To construct new Danish growth charts for 0- to 20-year-olds and to compare them with Danish references from 1982 and with World Health Organization (WHO) standards for children aged 0-5 years from 2006, by applying similar inclusion and exclusion criteria.
Anthropometric data from three contemporary Danish population-based studies were combined. References for height were based on healthy Caucasian children born at term. A total of 12,671 height measurements (8055 in boys and 4616 in girls) were included. Reference charts were developed using the generalised additive models for location, scale and shape.
From prepubertal ages, a secular increase in height was observed for both genders. The differences were most pronounced in puberty, and final heights were increased by 1.4 cm in boys and 2.9 cm in girls compared to 1982 references. In boys, but not girls an upward shift in body mass index (BMI) above median levels was found. Reference curves for height were superimposable with standard curves based on the selective WHO criteria. Danish children were longer/taller and heavier and they had larger head circumferences than those reported in the recent multiethnic WHO standards.
We recommend national implementation of these contemporary 2014 Danish references for anthropometric measurements.
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.
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.
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).
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.
A total of 1,215 young Danish men aged 18-28 years were recruited between 2008 and 2012 when they attended a compulsory medical examination to determine their fitness for military service. The participants delivered a semen sample, had a blood sample drawn, and underwent a physical examination. They responded to questionnaires including information on marijuana and recreational drug use during the past 3 months (no use, use once per week or less, or use more than once per week). A total of 45% had smoked marijuana within the last 3 months. Regular marijuana smoking more than once per week was associated with a 28% (95% confidence interval (CI): -48, -1) lower sperm concentration and a 29% (95% CI: -46, -1) lower total sperm count after adjustment for confounders. The combined use of marijuana more than once per week and other recreational drugs reduced the sperm concentration by 52% (95% CI: -68, -27) and total sperm count by 55% (95% CI: -71, -31). Marijuana smokers had higher levels of testosterone within the same range as cigarette smokers. Our findings are of public interest as marijuana use is common and may be contributing to recent reports of poor semen quality.
Comment In: Am J Epidemiol. 2015 Sep 15;182(6):482-426283091
Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries.
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.
Several studies have found an association between sleep duration and morbidity and mortality, but no previous studies have examined the association between sleep disturbances and semen quality. We conducted a cross-sectional study among 953 young Danish men from the general population who were recruited in Copenhagen at the time of determination of fitness for military service between January 2008 and June 2011. All of the men delivered a semen sample, had a blood sample drawn, underwent a physical examination, and answered a questionnaire including information about sleep disturbances. Sleep disturbances were assessed on the basis of a modified 4-item version of the Karolinska Sleep Questionnaire, which includes questions on sleep patterns during the past 4 weeks. Sleep disturbances showed an inverse U-shaped association with sperm concentration, total sperm count, percent motile and percent morphologically normal spermatozoa, and testis size. Men with a high level of sleep disturbance (score >50) had a 29% (95% confidence interval: 2, 48) lower adjusted sperm concentration and 1.6 (95% confidence interval: 0.3, 3.0) percentage points' fewer morphologically normal spermatozoa than men with a sleep score of 11-20. This appears to be the first study to find associations between sleep disturbances and semen quality. In future studies, investigators should attempt to elucidate mechanistic explanations and prospectively assess whether semen quality improves after interventions restoring a normal sleeping pattern.
Comment In: Am J Epidemiol. 2013 May 15;177(10):1038-4123568595
The authors examined the association between semen quality and caffeine intake among 2,554 young Danish men recruited when they were examined to determine their fitness for military service in 2001-2005. The men delivered a semen sample and answered a questionnaire including information about caffeine intake from various sources, from which total caffeine intake was calculated. Moderate caffeine and cola intakes (101-800 mg/day and 14 0.5-L bottles/week) and/or caffeine (>800 mg/day) intake was associated with reduced sperm concentration and total sperm count, although only significant for cola. High-intake cola drinkers had an adjusted sperm concentration and total sperm count of 40 mill/mL (95% confidence interval (CI): 32, 51) and 121 mill (95% CI: 92, 160), respectively, compared with 56 mill/mL (95% CI: 50, 64) and 181 mill (95% CI: 156, 210) in non-cola-drinkers, which could not be attributed to the caffeine they consumed because it was
Comment In: Am J Epidemiol. 2010 Jun 15;171(12):132420507902
Several reports implicated a relation between the trinucleotide (CAG) repeat length in the androgen-receptor gene and male infertility, whereas others failed to find an association. We investigated the CAG repeat length in relation to sperm production and reproductive hormones in 119 infertile men and 110 men with proven fertility. We found no difference in the distribution of CAG repeat lengths between the groups and no association with reproductive parameters. This finding suggests that, within the normal range of 14-33 repeats, there is no biological link between the CAG repeat length and fertility. This lack of association was comfirmed by an analysis of the data from all previously published European studies (in total 674 infertile men and 660 controls).
We describe a new method for identification of confident associations within large clinical data sets. The method is a hybrid of two existing methods; Self-Organizing Maps and Association Mining. We utilize Self-Organizing Maps as the initial step to reduce the search space, and then apply Association Mining in order to find association rules. We demonstrate that this procedure has a number of advantages compared to traditional Association Mining; it allows for handling numerical variables without a priori binning and is able to generate variable groups which act as "hotspots" for statistically significant associations. We showcase the method on infertility-related data from Danish military conscripts. The clinical data we analyzed contained both categorical type questionnaire data and continuous variables generated from biological measurements, including missing values. From this data set, we successfully generated a number of interesting association rules, which relate an observation with a specific consequence and the p-value for that finding. Additionally, we demonstrate that the method can be used on non-clinical data containing chemical-disease associations in order to find associations between different phenotypes, such as prostate cancer and breast cancer.
Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and finally summed di-isononyl phthalate (DiNP) metabolites. All these metabolite levels correlated significantly, indicating that when a participant was highly exposed to one phthalate he was also highly exposed to other phthalates. Several metabolites were also detectable in serum and in seminal plasma, although in much lower levels. Significant correlations between MEP and MiBP levels in serum and urine were observed, showing that serum levels could be used as biomarkers of human exposure. For DEHP and DiNP metabolites, correlations between urine and serum levels were only observed for mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(4-methyl-7-carboxyheptyl) phthalate (MCiOP), indicating that these secondary carboxylated metabolites were better serum markers than primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-iso-nonyl phthalate (MiNP)]. In seminal plasma, only MEP levels correlated significantly to levels in urine and in serum.
Because of wide exposure to phthalates, we investigated whether simultaneous exposure to several phthalates reached levels that might cause adverse antiandrogenic effects. Thirty three healthy young Danish men each delivered three 24-h urine samples during a three months period. The daily intakes of the sum of di-n-butyl and di-iso-butyl phthalate, di(2-ethylhexyl) phthalate, di-iso-nonyl phthalate, and butylbenzyl phthalate were estimated based on urinary excretion of the metabolites. Based on a hazard quotient (HQ) of the individual phthalate (i.e., the ratio between the daily intake and an acceptable level of exposure), a hazard index (HI) for each man was calculated as the sum of HQs for the individual phthalates. All men were exposed to all phthalates during the urine collection periods. Median HIs were all below 1 (i.e., below an acceptable cumulative threshold) ranging from 0.11 to 0.17 over the three different sample collections. Of the 33 men, 2 men had HIs above 1 in one of their three samples, indicating that occasionally the combined exposure to the investigated phthalates reached a level that may not be considered safe. Besides the phthalates investigated here, humans are exposed to numerous other chemicals that also may contribute to a cumulative antiandrogenic exposure.