Notified occupational mental disorders: associations with health and income.

BACKGROUND: Studies indicate that workers' compensation claim processes may affect patients' health negatively. However, few studies focus on patients with mental health claims, and the claim process varies between countries. AIMS: The aims of this study were to examine whether being notified to the Danish Labour Market Insurance with an occupational mental health condition was associated with changes in visits to the general practitioner (GP), use of medicine and annual income. METHODS: Study participants were 965 patients with a mental disorder examined at a department of occupational medicine. Of these, 669 patients were notified with an occupational mental disorder, 296 were not. Health-related outcomes, including GP visits and prescriptions of psychotropic drugs, were estimated at baseline during the year of medical examination, while annual income was estimated a year before the examination. The follow-up was the year after the year of examination for all outcomes. Outcomes were collected from the Danish National Bureau of Statistics. Analyses were conducted using Poisson regression and conditional logistic regression. RESULTS: All measured outcomes decreased from baseline to follow-up in both groups. These changes were not significantly different depending on notification status at baseline. CONCLUSIONS: This study suggests that being notified with an occupational mental disorder does not significantly affect health-related outcomes. A significant decrease in annual income over time was seen in both groups, the notified and the unnotified group, highlighting the importance of providing support to all employees with a mental disorder.

Is aberrant affective cognition an endophenotype for affective disorders? - A monozygotic twin study.

BACKGROUND: Identification of endophenotypes can improve prevention, detection and development of new treatments. We therefore investigated whether aberrant affective cognition constitutes an endophenotype for affective disorders by being present in monozygotic (MZ) twins with unipolar or bipolar disorder in partial remission (i.e. affected) and their unaffected co-twins (i.e. high-risk) relative to twins with no family history of affective disorder (i.e. low-risk). METHODS: We conducted an assessor blind cross-sectional study from 2014 to 2017 of MZ twins using Danish population-based registers in recruitment. Twins attended one test session involving neurocognitive testing, clinical ratings and questionnaires. Main outcomes were attention to and recognition of emotional facial expressions, the memory of emotional self-referential words, emotion regulation and coping strategies. RESULTS: Participants were 103 affected, 44 high-risk and 36 low-risk MZ twins. Groups were demographically well-balanced and showed comparable non-affective cognitive performance. We observed no aberrant affective cognition in affected and high-risk relative to low-risk twins. However, high-risk twins displayed attentional avoidance of emotional faces (ps ⩽ 0.009) and more use of task-oriented coping strategies (p = 0.01) compared with affected twins. In contrast did affected twins show more emotion-oriented coping than high- and low-risk twins (ps ⩽ 0.004). CONCLUSIONS: Our findings provide no support of aberrant affective cognition as an endophenotype for affective disorders. High-risk twins' attentional avoidance of emotional faces and greater use of task-oriented coping strategies may reflect compensatory mechanisms.

Explained variation in a fully specified model for data-grouped survival data.

An additive hazards model may be used to quantify the effect of genetic and environmental predictors on flowering of sugar beet plants recorded as data-grouped time-to-event data. Estimated predictor effects have an intuitive interpretation rooted in the underlying time dynamics of the flowering process. However, agricultural experiments are often designed using several plots containing a large number of plants that are subsequently being monitored. In this article, we consider an additive hazards model with an additional plot structure induced by latent shared frailty variables. This approach enables us to derive a method to assess the quality of predictors in terms of how much plot variation they explain. We apply the method to a large data set exploring flowering of sugar beet and conclude that the genetic predictor biotype, which has a strong effect, also explains a substantial amount of the plot variation. The method is also applied to a data set from medical research concerning days to virus positivity of serum samples in AIDS patients.

Ambient air pollution triggers wheezing symptoms in infants.

BACKGROUND: There is limited evidence for the role of air pollution in the development and triggering of wheezing symptoms in young children. A study was undertaken to examine the effect of exposure to air pollution on wheezing symptoms in children under the age of 3 years with genetic susceptibility to asthma. METHODS: Daily recordings of symptoms were obtained for 205 children participating in the birth cohort study Copenhagen Prospective Study on Asthma in Children and living in Copenhagen for the first 3 years of life. Daily air pollution levels for particulate matter <10 microm in diameter (PM(10)) and the concentrations of ultrafine particles, nitrogen dioxide (NO(2)), nitrogen oxide (NO(x)) and carbon monoxide (CO) were available from a central background monitoring station in Copenhagen. The association between incident wheezing symptoms and air pollution on the concurrent and previous 4 days was estimated by a logistic regression model (generalised estimating equation) controlling for temperature, season, gender, age, exposure to smoking and paternal history of asthma. RESULTS: Significant positive associations were found between concentrations of PM(10), NO(2), NO(x), CO and wheezing symptoms in infants (aged 0-1 year) with a delay of 3-4 days. Only the traffic-related gases (NO(2), NO(x)) showed significant effects throughout the 3 years of life, albeit attenuating after the age of 1 year. CONCLUSIONS: Air pollution related to traffic is significantly associated with triggering of wheezing symptoms in the first 3 years of life.

Fetal growth between the first and second trimesters and the risk of adverse pregnancy outcome.

OBJECTIVES: To relate growth rate of the biparietal diameter (BPD) between the first and second trimesters to the risk of perinatal death, intrauterine growth restriction (IUGR), macrosomia, preterm/post-term delivery and pre-eclampsia. METHODS: In this retrospective study, we analyzed sonographic BPD measurements at 11-14 and 17-21 weeks from 8215 singleton pregnancies in the Copenhagen First Trimester Study. Growth rate was defined as millimeters of growth per day between the two measurements and was dichotomized into growth rates < 2.5(th) vs. 2.5(th)-97.5(th) centiles, and > 97.5(th) vs. 2.5(th)-97.5(th) centiles. Odds ratios (OR) and 95% CIs for adverse outcome were calculated. RESULTS: Fetuses with growth rates < 2.5(th) centile had an OR of 4.79 (95% CI, 1.43-15.99) for perinatal death and an OR of 2.64 (95% CI, 1.51-4.62) for birth weight < sonographically estimated mean fetal weight (adjusted for gestational age) - 2 SD. Fetuses with growth rates > 97.5(th) centile had an OR of 2.83 (95% CI, 1.58-5.06) for birth weight > mean + 2 SD and an OR of 2.30 (95% CI, 1.15-4.59) for delivery in weeks 34-36. Growth rate showed no association with pre-eclampsia. CONCLUSIONS: There is a significant relationship between the growth rate of BPD from the first to the second trimester and adverse pregnancy outcome. Low growth rates are associated with an increased OR for perinatal death and IUGR, while high growth rates are associated with an increased OR for macrosomia and preterm delivery.

Size distribution and total number concentration of ultrafine and accumulation mode particles and hospital admissions in children and the elderly in Copenhagen, Denmark.

OBJECTIVES: To study the association between short-term exposure to ultrafine particles and morbidity in Copenhagen, Denmark. METHODS: We studied the association between urban background levels of the total number concentration of particles (NC(tot), 6-700 nm in diameter) measured at a single site (15 May 2001 to 31 December 2004) and hospital admissions due to cardiovascular (CVD) and respiratory disease (RD) in the elderly (age >or=65 years), and due to asthma in children (age 5-18 years). We examined these associations in the presence of PM(10), PM(2.5) (particulate matter <10 and 2.5 microm in diameter, respectively) and ambient gasses. We utilised data on size distribution to calculate NC(tot) for four modes with median diameters 12, 23, 57 and 212 nm, and NC(100) (number concentration of particles <100 nm in diameter) and examined their associations with health outcomes. We used a time series Poisson generalised additive model adjusted for overdispersion, season, day of the week, public holidays, school holidays, influenza, pollen and meteorology, with up to 5 days' lagged exposure. RESULTS AND CONCLUSIONS: The adverse health effects of particulate matter on CVD and RD hospital admissions in the elderly were mainly mediated by PM(10) and accumulation mode particles with lack of effects for NC(100). For paediatric asthma, accumulation mode particles, NC(100) and nitrogen oxides (mainly from traffic related sources) were relevant, whereas PM(10) appeared to have little effect. Our results suggest that particle volume/mass from long-range transported air pollution is relevant for CVD and RD admissions in the elderly, and possibly particle numbers from traffic sources for paediatric asthma.

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty: effects of two different treatment regimens with gonadotropin-releasing hormone agonists, without or in combination with an antiandrogen (cyproterone acetate).

Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term treatment with GnRH in combination with an antiandrogen (cyproterone acetate) to block the possible effect of adrenal androgens has not previously been evaluated. We, therefore, studied 40 patients with idiopathic CPP that were treated for 24 months with either GnRH analog (Buserelin) in combination with cyproterone acetate (Androcur; n = 23) or with long acting GnRH analog (Decapeptyl Depot; n = 17). We found that serum IGF-I levels were increased before treatment in both groups (mean +/- SE, 446 +/- 35 and 391 +/- 35 micrograms/L; P < 0.0001, respectively) compared to those in normal age-matched prepubertal children. Similarly, IGFBP-3 levels were significantly elevated (4675 +/- 209 and 4305 +/- 162 micrograms/L, respectively; P < 0.0001) in the two groups. Treatment with GnRH analog in combination with cyproterone acetate significantly decreased height velocity and serum IGF-I and IGFBP-3 levels to normal levels after 2 yr of treatment (P < 0.0001). Serum IGF-I levels remained unchanged during monthly im treatment with long acting GnRH analog, whereas IGFBP-3 levels significantly increased during the first year of this treatment despite unmeasurable estradiol levels. Thus, in both groups, the molar ratio between IGF-I and IGFBP-3 (i.e. free biologically active IGF-I) declined concomitantly with a decrease in growth velocity. Serum levels of IGF-I and IGFBP-3 (expressed as the SD score for bone age), but not those of estradiol, correlated with height velocity before and during treatment (r = 0.34; P < 0.0001 and r = 0.24; P = 0.003, respectively). Six of the patients with a subnormal GH response to clonidine had similar IGF-I and IGFBP-3 serum levels and growth velocity compared to the other 34 girls with CPP and a normal GH response.(ABSTRACT TRUNCATED AT 400 WORDS)

A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth.

The aim of the study was 1) to evaluate the association of maternal serum levels of placental GH and IGF-I with fetal growth, and 2) to establish reference data for placental GH, IGF-I, and IGF-binding protein-3 (IGFBP-3) in normal pregnancies based on longitudinal measurements. A prospective longitudinal study of 89 normal pregnant women was conducted. The women had, on the average, seven blood samples taken and three ultrasound examinations performed. All had normal umbilical artery pulsatility indexes during pregnancy and gave birth to singletons between 37 and 42 wk gestation with birth weights above -2 SD. Placental GH levels were detectable in all samples from as early as 5 wk gestation and increased significantly throughout pregnancy to approximately 37 wk when peak levels of 22 ng/ml (range, 4.64-69.22 ng/ml) were reached. Subsequently, placental GH levels decreased until birth. The change in placental GH during 24.5-37.5 wk gestation was positively associated with fetal growth rate (P = 0.027) and birth weight (P = 0.027). Gestational age at peak placental GH values (P = 0.007) was associated with pregnancy length. A positive association between the change in placental GH and the change in IGF-I levels throughout gestation was found in a multivariate analysis (r(2) = 0.42; P < 0.001). There was no association between placental GH and IGFBP-3 levels. The change in IGF-I throughout gestation (P = 0.039), but not placental GH, was significantly positively associated with placental weight at birth. We found a significant association between placental GH and fetal growth. In addition, we found a highly significant association between the increase in placental GH and the increase in IGF-I. The gestational age at peak placental GH levels was associated with pregnancy length.

Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency.

Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3 determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed, commercially available immunoradiometric assay (Diagnostic Systems Laboratories) to establish valid normative data for this analysis. We studied the diagnostic value of free IGF-I in relation to total IGF-I and IGFBP-3 determinations in adults who were suspected of GHD. A GH provocative test, using oral clonidine, was performed in 108 adult patients who had previously been treated with GH in childhood. In healthy subjects, free IGF-I levels increased during childhood, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of free IGF-I was apparent. We found, unmeasurable free IGF-I values in 34 of the prepubertal children (3.3%). All individuals over 8 yr of age had measurable free IGF-I levels that amounted to approximately 1% of the total IGF-I concentrations. Free IGF-I levels were below--2 SD in 56 of 79 GHD patients (sensitivity, 71%) and above--2 SD in 24 of 29 patients with a normal GH response (specificity, 83%). Multiple linear regression analysis demonstrated that free IGF-I was significantly dependent on peak GH levels, duration of the disease, and number of other pituitary axes affected. We conclude that free IGF-I serum levels increase during childhood with a peak in puberty, whereafter free IGF-I levels return to prepubertal levels. Three percent of healthy prepubertal children had unmeasurable free IGF-I levels using this assay. We found that determination of the free IGF-I serum concentration may predict the outcome of a GH provocative test in adults suspected of GHD, but that a single determination of free IGF-I offered no significant advantage compared to determination of total IGF-I or IGFBP-3 serum levels.

Inhibin B as a serum marker of spermatogenesis: correlation to differences in sperm concentration and follicle-stimulating hormone levels. A study of 349 Danish men.

Recent studies have focused on reproductive health of men in the general population. However, semen samples are difficult to obtain within sampling frames that allow comparisons. Blood samples are easier to obtain than ejaculates. Therefore, serum biomarkers of spermatogenesis are of major interest for population studies. FSH has previously been used as a marker of spermatogenesis, although it is also influenced by the hypothalamus. Serum inhibin B was recently suggested as a possible, more direct serum marker of spermatogenesis in men with testicular disorders. In a Danish nationwide collaborative study, we found an unexpected difference in semen concentration between two groups of men recruited from two different centres. We, therefore, analyzed reproductive hormones in blood, including inhibin B, to test whether the observed difference in semen concentration was reflected in the reproductive hormones. From 1992 to 1995, a total of 430 men, 20-35 yr old, who lived with a partner and who had not previously attempted to achieve a pregnancy, were recruited. The couples were enrolled into the study in one of two centres (centre A, n = 231; and centre B, n = 199) when they discontinued birth control. At enrollment, they provided a semen sample (n = 419), and a blood sample was drawn (n = 349). The semen analysis was performed in accordance with the WHO 1992 guidelines, and interlaboratory differences were tested. Inhibin B was measured in an enzyme immunometric assay, which has previously been described. All blood samples were analyzed in the same laboratory. Median sperm concentration and the percentage of morphologically normal spermatozoa were significantly higher among men from centre A (56.0 mill/mL and 42.5%), compared with men from centre B (44.8 mill/mL and 39%). Men from centre B had a significantly higher median FSH (3.42 IU/L) and a lower inhibin B (186 pg/mL) than men from centre A (3.21 IU/L and 209 pg/mL). The differences persisted after control for potentially confounding variables. A significant correlation was found between the cubic root-transformed serum FSH and inhibin B levels (r = -0.61, P < 0.001), between the cubic root-transformed serum FSH and sperm concentration (r = -0.40, P < 0.001), and between the cubic root-transformed inhibin B and sperm concentration (r = 0.38, P < 0.001). The predictive power of detecting sperm counts below 20 mill/mL among men who's inhibin B and FSH both were below 80 pg/mL and above 10 IU/L, respectively, was 100%. The unexpected significant difference in semen concentration between two groups of normal Danish men was probably caused by differences in sampling procedures in the two centres where the men were recruited, rather than geographical differences. However, similar differences in serum levels of inhibin B and FSH between centres were found. These findings suggest that a real difference in spermatogenic potential between the two groups of men existed. We suggest that serum inhibin B, in future population studies on male reproductive health, may serve as a new marker of spermatogenesis, in addition to sperm concentration and serum FSH.

The acid-labile subunit of human ternary insulin-like growth factor binding protein complex in serum: hepatosplanchnic release, diurnal variation, circulating concentrations in healthy subjects, and diagnostic use in patients with growth hormone deficiency.

Circulating insulin-like growth factor-I (IGF-I) is predominantly bound in the trimeric complex comprised of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). Circulating concentrations of IGF-I, IGFBP-3 and ALS are believed to reflect the GH secretory status, but the clinical use of ALS determination is not known. We therefore, determined the: 1) hepatosplanchnic release of ALS by liver vein catheterization (n=30); 2) 24-h diurnal variation of ALS (n=8); 3) normal age-related ranges of circulating ALS (n=1158); 4) diagnostic value of ALS in 108 patients with childhood-onset GH deficiency (GHD). We found: 1) no significant arteriovenous gradient over the liver ofALS, IGF-I, and IGFBP-3; 2) the diurnal variation of ALS was 12% (mean coefficient of variation percent); 3) ALS levels increased throughout childhood with maximal levels in puberty, with a subsequent decrease with age in adults; and 4) ALS levels were below -2 SD in 57 of 79 GHD patients (sensitivity 72%) and above 2 SD in 22 of 29 patients with normal GH response (specificity 76%), which was similar, compared with the diagnostic utility of IGF-I and IGFBP-3. Finally, our findings indicate that hepatic ALS production is not measurable by this approach or, alternatively, that the liver is not the primary source of circulating ALS, IGF-I, or IGFBP-3 in humans. In conclusion, we have provided extensive normal data for a novel ALS assay and found that circulating ALS levels exhibit minor diurnal variation. We suggest that ALS determination may be used in future classification of adults suspected of GHD.

Male reproductive health and environmental xenoestrogens.

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

Semen quality among Danish and Finnish men attempting to conceive. The Danish First Pregnancy Planner Study Team.

OBJECTIVE: To assess differences in semen quality between similar populations from Denmark and Finland. DESIGN: Comparison of semen quality between 221 Finnish men (of whom 115 had no proven fertility) and 411 Danish men with no proven fertility in two follow-up studies among normal couples trying to conceive. METHODS: In Finland male partners of couples without experienced infertility attempting to conceive were recruited through advertisements in local newspapers from 1984 to 1986. From 1992 to 1995 Danish men who lived with a partner and who had not attempted to achieve a pregnancy previously were recruited through their union when they discontinued birth control. All semen analyses were performed in accordance with the World Health Organization guidelines. RESULTS: Median sperm concentration, total sperm count and the percentage of morphologically normal spermatozoa were significantly higher among the Finnish men without proven fertility (104.0 million/ml, 304.0 million and 58% respectively) compared with the Danish men (53.0 million/ml, 140.8 million, and 41% respectively). Sperm concentration was 105.7% (95% confidence interval (CI) 58.1%-167.6%) and total sperm count was 127.4% (95% CI 71.4%-201.6%) higher among Finnish men without proven fertility than among Danish men after control for confounders. CONCLUSIONS: Some, but hardly all, of the observed difference in semen quality may be explained by differences in recruitment procedures, selection of the men and by methodological differences in semen analysis between the two countries. Also a birth cohort effect may explain some of the differences between countries as the Finnish men were recruited 11 years before the Danish men. Therefore, follow-up studies with identical recruitment and selection of men from the two countries are needed.

Declining human fertility?

PIP: This article comments on the conclusion reached by Akre et al. in their study on human fertility. Akre et al. concluded that subfertility (measured as a waiting time to pregnancy of 1 year) decreased from 1983 to 1993 in Sweden and that the decline followed a birth cohort pattern. In addition, they speculated that the decrease in subfertility during the 1980s is mainly due to the eradication of gonorrhea. However, the data they presented does not seem to justify their conclusion. The researchers did not study the consequences of truncation of the waiting-time distribution in 1993 and 1983, the association between smoking and infertility, and declining semen quality in order to further support their conclusion.^ieng

The epidemiology of febrile malaria episodes in an area of unstable and seasonal transmission.

This study investigated the epidemiology of uncomplicated falciparum malaria in an area of unstable and seasonal transmission in eastern Sudan. About 90% of malaria morbidity in this region occurs in the months of September to November, and very few malaria cases occur during the intensely arid Sudanese dry season and during years of drought. The malaria situation in the study site, the village of Daraweesh, was analysed during 3 consecutive malaria seasons in 1993-95 during which the 457 inhabitants suffered at total of 436 episodes of falciparum malaria. Using an Andersen-Gill proportional hazard model for recurrent events stratified by family, we have calculated the relative hazard for clinical malaria episodes by age, sex, haemoglobin genotype, blood type and infection in the previous season. The malaria risk was significantly lower in individuals aged 20-88 years than in the 5-19 years age-group. The relative protection due to adulthood varied between seasons (relative risk, RR, 0x34 to 0x67). Serological data were not consistent with the hypothesis that the age difference in incidence was due to differences in exposure. During the 1993 season the malaria incidence in males was lower than in females (RR = 0x75), during the 1994 season the incidences were comparable, whereas males had an increased risk of malaria in 1995 (RR = 1x87). The relative risk in individuals carrying the haemoglobin AS genotype compared to homozygous AA individuals was 0x57.

The influence of climate on development of winter depression.

126 patients suffering from winter depression participated in the study. Every second week patients completed the 13 item Beck Depression Inventory (BDI) in the period September to May in the years 1991 to 1994. Local weather data from this period were obtained from the Meteorological Institute, Copenhagen. No significant correlation was found between score on BDI and cloud cover, rainfall or atmospheric pressure. A significant correlation was found between score on BDI and minutes of sunshine, global radiation, length of daylight and temperature. This is in accordance with the theory, that lack of light is a contributing factor for development of winter depression.

Caffeine intake and fecundability: a follow-up study among 430 Danish couples planning their first pregnancy.

Fecundability has been defined as the ability to achieve a recognized pregnancy. Several studies on caffeine and fecundability have been conducted but have been inconclusive. This may be explained partly by lack of stratification by smoking. Furthermore, few researchers have tried to separate the effect of caffeine from different sources (coffee, tea, cola, and chocolate). Clearly, the relationship between caffeine and fecundability needs further research, given the high prevalence of caffeine intake among women of childbearing age. We examined the independent and combined effects of smoking and caffeine intake from different sources on the probability of conception. From 1992 to 1995, a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old, lived with a partner, and had no previous reproductive experience. At enrollment and in six cycles of follow-up, both partners filled out a questionnaire on different factors including smoking habits and their intake of coffee, tea, chocolate, cola beverages, and chocolate bars. In all, 1596 cycles and 423 couples were included in the analyses. The cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle (pregnant or not pregnant) in a Cox discrete model calculating the fecundability odds-ratio (FR). Compared to nonsmoking women with caffeine intake less than 300 mg/d, nonsmoking women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [95% confidence interval (CI) 0.60-1.31], whereas women with a higher caffeine intake had a FR = 0.63 (95% CI 0.25-1.60) after adjusting for female body mass index and alcohol intake, diseases of the female reproductive organs, semen quality, and duration of menstrual cycle. No dose-response relationship was found among smokers. Among males, the same decline in point estimates of the FR was present. Smoking women whose only source of caffeine was coffee (>300 mg/d) had a reduced fecundability odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between caffeine and smoking is biologically plausible, and the lack of effect among smokers may be due to faster metabolism of caffeine. Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake.

PIP: The independent and combined effects of smoking and caffeine intake from different sources on fecundability were assessed in a national survey of 423 Danish couples. Couples were recruited to the study in 1992-95 through a mailing to 52,255 female trade union members seeking women who were 20-35 years old, lived with a partner, had no previous pregnancies, and intended to discontinue contraception in order to become pregnant. A total of 1596 cycles were included in the 6-month study and the cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome (pregnant, not pregnant) in a Cox discrete model. Compared with nonsmoking women with a caffeine intake less than 300 mg/day, nonsmoking women who consumed 300-700 mg/day of caffeine had a fecundability odds ratio (FR) of 0.88 (95% confidence interval (CI), 0.60-1.31), while those with a higher consumption had an FR of 0.63 (95% CI, 0.25-1.60), after adjustments for body mass index, alcohol intake, diseases of the female reproductive organs, semen quality, and duration of the menstrual cycle. No such dose-response relationship was detected among smokers. The same decline in point estimates of the FR was present was males. Smoking women whose only source of caffeine was coffee (over 300 mg/day) had a reduced FR (0.34; 95% CI, 0.12-0.98). The lack of adverse effect among smokers may be due to faster metabolism and clearance of caffeine. Overall, these findings indicate that nonsmoking women who wish to achieve pregnancy should consider reducing their caffeine intake.

Year of birth and sperm count in 10 Danish occupational studies.

OBJECTIVES: Several reports indicate a secular decline of human sperm counts. It is still not known if these findings are artifacts related to shortcomings in the data and applied methodologies. Even less is known about possible mechanisms, but it has been proposed that potential changes may be related to disruption of the hormonal regulation of testicular development in prenatal life. The objective of this study was to examine whether sperm count was related to year of birth. METHODS: An analysis was made of the sperm count of 1196 men participating in 10 cross-sectional occupational sperm studies in 3 regions of Denmark from 1986 through 1995. RESULTS: The median sperm concentration was 63 million per milliliter for men born in 1937-1949 and 52 million per milliliter for men born in 1970 or later, and the median total sperm was 206 million and 117 million, respectively. The inverse relationship between sperm concentration and year of birth was statistically significant even after adjustment for duration of sexual abstinence, season of the year, and study population. However, bias because of differential participation related to age and fertility or lack of comparability across the populations cannot be ruled out. CONCLUSIONS: The apparent decline of sperm count with increasing year of birth is compatible with the hypothesis of a common risk factor for male reproductive health operating in prenatal life or early childhood, but the evidence is circumstantial. Age-related selection bias is an alternative and perhaps not a less likely explanation.

Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy.

OBJECTIVE: To examine the effect of alcohol consumption on the probability of conception. DESIGN: A follow up study over six menstrual cycles or until a clinically recognised pregnancy occurred after discontinuation of contraception. SUBJECTS: 430 Danish couples aged 20-35 years trying to conceive for the first time. MAIN OUTCOME MEASURES: Clinically recognised pregnancy. Fecundability odds ratio: odds of conception among exposed couples divided by odds among those not exposed. RESULTS: In the six cycles of follow up 64% (179) of women with a weekly alcohol intake of less than five drinks and 55% (75) of women with a higher intake conceived. After adjustment for cycle number, smoking in either partner or smoking exposure in utero, centre of enrolment, diseases in female reproductive organs, woman's body mass index, sperm concentration, and duration of menstrual cycle, the odds ratio decreased with increasing alcohol intake from 0.61 (95% confidence interval 0.40 to 0.93) among women consuming 1-5 drinks a week to 0.34 (0.22 to 0.52) among women consuming more than 10 drinks a week (P=0.03 for trend) compared with women with no alcohol intake. Among men no dose-response association was found after control for confounders including women's alcohol intake. CONCLUSION: A woman's alcohol intake is associated with decreased fecundability even among women with a weekly alcohol intake corresponding to five or fewer drinks. This finding needs further corroboration, but it seems reasonable to encourage women to avoid intake of alcohol when they are trying to become pregnant.

PIP: The effect of alcohol consumption on the probability of conception was investigated in a prospective study of 430 Danish couples seeking to achieve pregnancy for the first time. Couples were recruited through a national mailing to trade union members and followed for six menstrual cycles after contraception discontinuation or until a clinically recognized pregnancy occurred. Mean weekly alcohol intake was 4.0 drinks among women and 9.5 drinks among their male partners; 73 women (17%) abstained from alcohol drinking throughout the six cycles. During the study period, 179 (64%) of the 280 women with an average weekly alcohol intake of less than five drinks and 75 (55%) of the 136 women with a higher intake conceived. Among male partners, these rates were 67% and 58%, respectively. After adjustment for cycle number, smoking, enrollment center, diseases of the reproductive system, body mass index, sperm concentration, and menstrual cycle duration, the odds ratio decreased with increasing alcohol consumption from 0.61 (95% confidence interval, 0.40-0.93) among women who consumed 1-5 drinks a week to 0.55 (95% CI, 0.36-0.85) among those reporting 6-10 drinks a week to 0.34 (95% CI, 0.22-0.52) among women consuming 11-15 drinks a week compared with women with no alcohol intake. No dose-response relationship was found in male partners after adjustment for the same confounders. Although these findings require further corroboration, they suggest that even moderate alcohol consumption has a significant adverse effect on fecundability.

[Body proportions of Danish children. Curves for sitting height ratio, subischial length and arm span]. / Kropsproportioner hos danske børn. Kurver for siddehøjde, siddehøjderatio, subiskial benloengde og armspoend.

No previous Danish growth charts have been published for sitting height, subischial leg length, armspan or the ratio of sitting height to stature. These growth charts are useful in the evaluation of dysproportional growth retardation. Foreign standards have previously been used. However, due to population-specific differences and "the secular trend", the construction of Danish growth charts was found to be appropriate. We examined 1977 children (927 boys and 1050 girls) from the Copenhagen area, aged six to 20 years. Height, sitting height and armspan were measured. Growth charts were constructed using local linear regression and smoothing of residuals. We found sitting height values in Danish children to be comparable to English and Norwegian children. Sitting height values were lower than values of Dutch children, but higher than values of Swiss and Swedish children. The extremities of Danish children were 3-4 cm longer than the extremities of English children, but Dutch children had 2-3 cm longer armspan than the Danish boys and girls. Growth charts for sitting height, sitting height ratio, subischial leg length and armspan are presented. These charts should be useful when evaluating dysproportionality in growth retarded children and when assessing the effect of growth modulating therapy in children.