Objective
To identify modifiable risk factors for miscarriage and to estimate the preventable proportion of miscarriages that could be attributed to these.
Design
Nationwide observational follow‐up ...study.
Setting
Denmark.
Population
Ninety‐one thousand four hundred and twenty seven pregnancies included in the Danish National Birth Cohort between 1996 and 2002.
Methods
Information on potentially modifiable risk factors before and during pregnancy was collected by means of computer‐assisted telephone interviews and linkage with Danish registers, ensuring almost complete follow‐up of pregnancy outcome. Modifiable risk factors for miscarriage were identified by multiple Cox regression analysis, which provided the background for our estimations of population attributable fractions. In all, 88 373 pregnancies had full information on all covariates and were included in this analysis.
Main outcome measures
Miscarriage before 22 completed weeks of gestation.
Results
The potentially modifiable pre‐pregnant risk factors associated with increased miscarriage risk were: age of 30 years or more at conception, underweight, and obesity. During pregnancy the modifiable risk factors were: alcohol consumption, lifting of >20 kg daily, and night work. We estimated that 25.2% of the miscarriages might be prevented by reduction of all these risk factors to low risk levels. Modification of risk factors acting before and during pregnancy could lead to prevention of 14.7 and 12.5%, respectively, of the miscarriages. Maternal age at conception and alcohol consumption were the most important risk factors.
Conclusions
Miscarriage risk is increased by multiple potentially modifiable risk factors and a considerable proportion of miscarriages may be preventable.
BACKGROUND Cigarette smoking during pregnancy is associated with negative reproductive consequences for male fetuses in adult life such as reduced testicular volume and sperm concentration. The ...present study evaluates the number of germ and somatic cells present in human embryonic first-trimester gonads in relation to maternal smoking. METHODS The study includes 24 human first-trimester testes, aged 37–68 days post-conception, obtained from women undergoing legal termination of pregnancy. A questionnaire was used to obtain information about smoking and drinking habits during pregnancy. Validated stereological methods were used to estimate gonadal cell numbers in histological sections. Results were also evaluated in the context of previously published data on ovaries from our laboratory. RESULTS A significant reduction in the number of germ cells by 55% 95% confidence interval (CI) 74–21% reduction, P = 0.004 and somatic cells by 37% (95% CI 59–3%, P = 0.023) was observed in testes prenatally exposed to maternal cigarette smoking, compared with unexposed. The effect of maternal smoking was dose-dependent being higher in the heavy smokers and remained consistent after adjusting for possible confounders such as alcohol and coffee consumption (P = 0.002). The number of germ cells in embryonic gonads, irrespective of gender, was also significantly reduced by 41% (95% CI 58–19%, P = 0.001) in exposed versus non-exposed embryonic gonads. CONCLUSIONS Prenatal exposure to maternal cigarette smoke reduces the number of germ and somatic cells in embryonic male and female gonads. This effect may have long-term consequences on the future fertility of exposed offspring. These findings may provide one potential cause of the reduced fertility observed during recent years.
Background
The lifetime prevalence of androgenic anabolic steroid abuse is estimated to be around 6% for men, but there is limited knowledge about the side effects of these drugs.
Objective
To ...investigate mortality and morbidity amongst users of androgenic anabolic steroids (AAS).
Methods
In this retrospective matched cohort study, 545 male subjects tested positive for AAS in Danish fitness centres during the period 3 January 2006 to 1 March 2018. Subjects were matched with 5450 male controls. In addition, 644 men who were sanctioned because they refused to submit to a doping test and 6440 controls were included as a replication cohort.
Results
Mortality was three times higher amongst users of AAS than amongst nonuser controls (hazard ratio 3.0, 95% CI 1.3–7.0). The median annual number of hospital contacts was 0.81 in the cohort of AAS users and 0.36 in the control cohort (P < 0.0001). Acne, gynaecomastia and erectile dysfunction affected more than 10% of the androgenic anabolic steroid users, and the prevalence of these disorders was significantly higher than in the control group (P < 0.0001). The results could be replicated in a similar cohort.
Conclusion
Androgenic anabolic steroid users have an increased risk of dying and significantly more hospital admissions than their nonuser peers. Side effects of AAS and their metabolites were highly prevalent. Given the high rate of androgenic anabolic steroid abuse, these side effects are of public health concern.
Objective: Several findings suggest that some patients with depressive or bipolar disorder may be at increased risk of developing dementia. The present study aimed to investigate whether the risk of ...developing dementia increases with the number of affective episodes in patients with depressive disorder and in patients with bipolar disorder. Methods: This was a case register study including all hospital admissions with primary affective disorder in Denmark during 1970–99. The effect of the number of prior episodes leading to admission on the rate of readmission with a diagnosis of dementia following the first discharge after 1985 was estimated. A total of 18 726 patients with depressive disorder and 4248 patients with bipolar disorder were included in the study. Results: The rate of a diagnosis of dementia on readmission was significantly related to the number of prior affective episodes leading to admission. On average, the rate of dementia tended to increase 13% with every episode leading to admission for patients with depressive disorder and 6% with every episode leading to admission for patients with bipolar disorder, when adjusted for differences in age and sex. Conclusion: On average, the risk of dementia seems to increase with the number of episodes in depressive and bipolar affective disorders.
Objective
It is a widely held belief that affective disorders are progressive of nature; however, some recent reviews have questioned this belief. The objective of the present systematic literature ...review was to present evidence for associations between number of affective episodes and (i) the risk of recurrence of episodes, (ii) probability of recovery from episodes, (iii) severity of episodes, (iv) the threshold for developing episodes, and (v) progression of cognitive deficits in unipolar and bipolar disorders.
Method
A systematic review comprising an extensive literature search conducted in Medline, Embase, and PsychInfo up to September 2016 and including cross‐references from identified papers and reviews.
Results
Most of the five areas are superficially investigated and hampered by methodological challenges. Nevertheless, studies with the longest follow‐up periods, using survival analysis methods, taking account of the individual heterogeneity all support a clinical progressive course of illness. Overall, increasing number of affective episodes seems to be associated with (i) increasing risk of recurrence, (ii) increasing duration of episodes, (iii) increasing symptomatic severity of episodes, (iv) decreasing threshold for developing episodes, and (v) increasing risk of developing dementia.
Conclusion
Although the course of illness is heterogeneous, there is evidence for clinical progression of unipolar and bipolar disorders.
Objective To examine the association between leisure time physical exercise during pregnancy and the risk of miscarriage.
Design Prospective study with elements of retrospective data collection.
...Setting Denmark 1996–2002.
Population A total of 92 671 pregnant women enrolled in the Danish National Birth Cohort and interviewed subsequently.
Methods Data on exercise during pregnancy and potential confounders were obtained through computer‐assisted telephone interviews either during pregnancy or after an early miscarriage. Outcome of pregnancy was identified by register linkage. Using Cox regression analysis, we estimated the hazard ratio (HR) of miscarriage according to weekly amount of exercise and the type of exercise. The HR was estimated for <11, 11–14, 15–18, and 19–22 weeks of gestation, respectively.
Main outcome measures Miscarriage, defined as fetal loss before 22 completed weeks of gestation.
Results A stepwise increasing relation was found between amount of exercise and risk of miscarriage, where risk of miscarriage increased by amount of exercise up to HR = 3.7 (95% CI 2.9–4.7) for women who exercised more than 7 hours per week compared with nonexercisers. Particularly ‘high‐impact exercise’ was associated with an increased risk of miscarriage. No association was seen between exercise and risk of miscarriage after 18 weeks of gestation.
Conclusions This study suggests that exercise early in pregnancy is associated with an increased risk of miscarriage. The results should, however, be interpreted cautiously as potential bias arising from retrospective data collection may explain part of the association.
Objective
To investigate whether continued use of non‐aspirin NSAID, low‐dose aspirin, high‐dose aspirin, statins, allopurinol and angiotensin agents decreases the rate of incident depression using ...Danish nationwide population‐based registers.
Methods
All persons in Denmark who purchased the exposure medications of interest between 1995 and 2015 and a random sample of 30% of the Danish population was included in the study. Two different outcome measures were included, (i) a diagnosis of depressive disorder at a psychiatric hospital as in‐patient or out‐patient and (ii) a combined measure of a diagnosis of depression or use of antidepressants.
Results
A total of 1 576 253 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015. Continued use of low‐dose aspirin, statins, allopurinol and angiotensin agents was associated with a decreased rate of incident depression according to both outcome measures. Continued uses of non‐aspirin NSAIDs as well as high‐dose aspirin were associated with an increased rate of incident depression.
Conclusion
The findings support the potential of agents acting on inflammation and the stress response system in depression as well as the potential of population‐based registers to systematically identify drugs with repurposing potential.
Background Low socioeconomic position is generally associated with increased risk of preterm birth, but it remains unclear whether the inequality depends on the socioeconomic measure used, if the ...associations differ according to the degree of prematurity, and how individual level risk factors mediate the association. Methods The hazard ratios (HR) of preterm birth associated with five different measures of socioeconomic position and three degrees of preterm birth were analysed in a dataset of 75 890 singleton pregnancies (1996–2002) from the Danish National Birth Cohort. This, and the mediating role of selected individual level risk factors (smoking, alcohol consumption, binge drinking, pre-pregnancy body mass index, gestational weight gain) were estimated, using Cox regression analyses. Results Mothers with <10 years of education had an elevated risk of preterm birth compared with mothers with >12 years of education and the association interacted with parity, while income and occupation affected the risk to a lesser degree. The adjusted HR for less educated nulliparous and parous women were 1.22 (95% CI 1.04–1.42) and 1.56 (95% CI 1.31–1.87), respectively, compared with women with >12 years of education. For parous women with <10 years of education inclusion of smoking in the model decreased the HR of preterm birth to 1.43 (95% CI 1.19–1.72). Conclusions Maternal educational level was the strongest predictor of preterm birth among five socioeconomic measures and the gradient did not differ significantly according to the degree of preterm birth. For parous women smoking explained some of the educational gradient but in general the selected risk factors only reduced the relative educational gradient in preterm birth marginally.
Abstract This study investigated the impact of women’s body mass index (BMI) on the outcome after consecutive IVF/intracytoplasmic sperm injection cycles in 487 patients initiating treatment with ...5-year follow-up. The total number of cycles was 1417. In total 103 (21.1%) were overweight (BMI 25–29.9 kg/m2 ) and 59 (12.1%) were obese (BMI ⩾30 kg/m2 ). Number of initiated cycles/woman ( P = 0.01), number of cancelled cycles/woman ( P < 0.01) and the total dose of gonadotrophin used/cycle ( P < 0.01) rose with increasing BMI. A negative linear association between BMI and the number of retrieved oocytes ( B = −0.243, P < 0.001) and an inverse U-shaped relationship between BMI and the number of developed embryos was seen, with less embryos available among underweight and obese women ( P = 0.03). The number with positive serum human chorionic gonadotrophin/cycle decreased significantly with increasing BMI ( P < 0.01). The ongoing pregnancy rate/cycle among the obese women was lower (20.8% versus 28.3% in normal-weight women; P = 0.04). Live-birth rate per cycle was 15.2% versus 21.5%. Multiple logistic regression analysis showed that the only independent predictors of live birth were women’s age ( P = 0.037), women’s BMI ( P = 0.034) and men’s age ( P = 0.040). The purpose of the study was to investigate the impact of women’s body weight on the outcome after repetitive IVF treatments. We included 487 patients initiating IVF treatment at four public IVF clinics in Denmark and all patients were followed for 5 years. The total number of treatment cycles was 1417. In total 103 (21.1%) were overweight (body mass index (BMI) 25–29.9 kg/m2 ) and 59 (12.1%) were obese (BMI ⩾ 30 kg/m2 ). The average number of started treatment cycles per woman, the mean number of cancelled cycles per woman and the total dose of ovarian stimulating hormone used per cycle rose with increasing female BMI. We observed that the higher the women’s BMI was, the lower was the number of oocytes collected during the treatment. Further we found that the number of developed embryos was highest in the normal-weight group, while the underweight and overweight groups developed fewer embryos. The number of positive pregnancy tests per treatment declined with increasing BMI and the rate of clinical pregnancies on ultrasound in week 7 was lower in obese women than among normal-weight women (20.8% versus 28.3%) and live-birth rate per cycle was 15.2% versus 21.5% in obese versus and normal-weight groups, respectively. Outcomes after IVF treatment including pregnancy and live-birth rates were lower in normal-weight versus obese women.
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