Prenatal maternal stress and atopic diseases in the child: a systematic review of observational human studies.

BACKGROUND: A growing number of studies suggest that maternal stress during pregnancy promotes atopic disorders in the offspring. This is the first systematic review to address prenatal maternal stress (PNMS) and the subsequent risk of atopy-related outcomes in the child. METHODS: The review was performed in accordance to the PRISMA criteria. We searched and selected studies in PubMed, Scopus, Embase and PsychINFO until November 2014. RESULTS: Sixteen (with 25 analyses) of 426 identified articles met the review criteria. Five main PNMS exposures (negative life events, anxiety/depression, bereavement, distress and job strain) and five main atopic outcomes (asthma, wheeze, atopic dermatitis, allergic rhinitis and IgE) were assessed across the studies. Overall, 21 of the 25 analyses suggested a positive association between PNMS and atopic outcomes. Of the 11 exposure-response analyses reported, six found statistically significant trends. CONCLUSION: This systematic review suggests a relationship between maternal stress during pregnancy and atopic disorders in the child. However, the existing studies are of diverse quality. The wide definitions of often self-reported stress exposures imply a substantial risk for information bias and false-positive results. Research comparing objective and subjective measures of PNMS exposure as well as objective measures for atopic outcome is needed.

Ambient and at-the-ear occupational noise exposure and serum lipid levels.

OBJECTIVES: Occupational and residential noise exposure has been related to increased risk of cardiovascular disease. Alteration of serum lipid levels has been proposed as a possible causal pathway. The objective of this study was to investigate the relation between ambient and at-the-ear occupational noise exposure and serum levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides when accounting for well-established predictors of lipid levels. METHODS: This cross-sectional study included 424 industrial workers and 84 financial workers to obtain contrast in noise exposure levels. They provided a serum sample and wore portable dosimeters that every 5-s recorded ambient noise exposure levels during a 24-h period. We extracted measurements obtained during work and calculated the full-shift mean ambient noise level. For 331 workers who kept a diary on the use of a hearing protection device (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the mean full-shift noise exposure level at the ear. RESULTS: Mean ambient noise level was 79.9 dB (A) [range 55.0-98.9] and the mean estimated level at the ear 77.8 dB (A) [range 55.0-94.2]. Ambient and at-the-ear noise levels were strongly associated with increasing levels of triglycerides, cholesterol-HDL ratio, and decreasing levels of HDL-cholesterol, but only in unadjusted analyses that did not account for HPD use and other risk factors. CONCLUSION: No associations between ambient or at-the-ear occupational noise exposure and serum lipid levels were observed. This indicates that a causal pathway between occupational and residential noise exposure and cardiovascular disease does not include alteration of lipid levels.

Individual and work-unit measures of psychological demands and decision latitude and the use of antihypertensive medication.

PURPOSE: To analyse whether psychological demands and decision latitude measured on individual and work-unit level were related to prescription of antihypertensive medication. METHODS: A total of 3,421 women and 897 men within 388 small work units completed a questionnaire concerning psychological working conditions according to the job strain model. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were less influenced by reporting bias. Dispensed antihypertensive medication prescriptions were identified in The Danish National Prescription Registry. Odds ratios (OR) comparing the highest and lowest third of the population at individual and work-unit level, respectively, were estimated by multilevel logistic regression adjusted for confounders. Psychological demands and decision latitude were tested for interaction. Supplementary analyses of 21 months follow-up were conducted. RESULTS: Among women, increasing psychological demands at individual (adjusted OR 1.54; 95 % CI 1.02-2.33) and work-unit level (adjusted OR 1.41; 95 % CI 1.04-1.90) was significantly associated with purchase of antihypertensive medication. No significant association was found for decision latitude. Follow-up results supported an association with psychological demands but they were not significant. All results for men showed no association. Psychological demands and decision latitude did not interact. CONCLUSION: High psychological work demands were associated with the purchase of prescribed antihypertensive medication among women. This effect was present on both the work-unit and the individual level. Among men there were no associations. The lack of interaction between psychological demands and decision latitude did not support the job strain model.

Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team.

OBJECTIVE: To examine the relationship between sperm chromatin defects, evaluated by the flow cytometric (FCM) sperm chromatin structure assay (SCSA), and the probability of a pregnancy in a menstrual cycle (fecundability). DESIGN: Follow-up study. SETTING: The Section of Toxicology and Biomedical Sciences, ENEA Casaccia, Rome, Italy, and the Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark. PATIENT(S): Two hundred fifteen Danish first pregnancy planners with no previous knowledge of their fertility capability. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen samples were collected at enrollment to measure semen volume, sperm concentration, motility, and morphology (by microscopy), as well as chromatin susceptibility to in situ, acid-induced partial denaturation by the FCM SCSA. Time to pregnancy was evaluated during a 2-year follow-up period. Demographic, medical, reproductive, occupational, and lifestyle data were collected by questionnaire. Fecundability was correlated with SCSA-derived parameters. RESULT(S): Fecundability declines as a function of the percentage of sperm with abnormal chromatin and becomes small when aberrant cells are >40%. CONCLUSION(S): Optimal sperm chromatin packaging seems necessary for full expression of the male fertility potential. The SCSA emerged as a predictor of the probability to conceive in this population-based study.

Menstrual cycle pattern and fertility: a prospective follow-up study of pregnancy and early embryonal loss in 295 couples who were planning their first pregnancy.

OBJECTIVE: To characterize how the menstrual cycle pattern relates to fertility regardless of potential biases caused by inappropriate coital timing during the menstrual cycle or early embryonal loss. DESIGN: Prospective follow-up study. SETTING: Healthy couples recruited throughout Denmark. PATIENT(S): Two hundred ninety-five couples who were planning their first pregnancy were followed up from the discontinuation of birth control until a pregnancy was recognized within six menstrual cycles. Early embryonal losses were detected by changes in urinary hCG levels. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The probability of pregnancy occurring within one menstrual cycle (fecundity). RESULT(S): In women who had a cycle length that differed by >10 days from the usual cycle length, fecundity was approximately 25% that of women who had no variation (odds ratio 0.25, 95% confidence interval 0.09-0.68). When the combined effect of cycle variation and cycle length was assessed, cycle variation was a persistent strong predictor of fecundity. CONCLUSION(S): The mechanisms of the present findings probably are female functional disturbances in ovulation, conception, implantation, or sustained pregnancy, linked with variable menstrual cycle length. Thus, identification of medical and environmental causes of abnormal menstrual cycle patterns may provide clues to the causes of infertility. Moreover, the menstrual cycle pattern also should be taken into consideration in the clinical decision-making process.

Distress and reduced fertility: a follow-up study of first-pregnancy planners.

OBJECTIVE: To assess the effect of psychological distress on time to first pregnancy. DESIGN: A follow-up study of time to pregnancy with prospective data on distress, with controlling for potential confounding variables. SETTING: Two university hospitals. PATIENT(S): Danish couples (n = 430) who were planning their first pregnancy and had no previous reproductive experience were followed for six menstrual cycles. Psychological distress was measured in each menstrual cycle by the General Health Questionnaire. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A clinically recognized pregnancy or a biochemical pregnancy detected in urine samples from each period of vaginal bleeding. RESULT(S): For cycles with the highest distress score (General Health Questionnaire score >80th percentile), the probability of conception per cycle was 12.8%, compared with 16.5% in other cycles (adjusted odds ratio [OR] 0.6; 95% confidence interval [CI] 0.4-1.0). The effect of distress was found almost exclusively among women with long menstrual cycles (OR 0.1; 95% CI 0.01-0.4 and OR 0.9; 95% CI 0.5-1.4 for women with cycles of > or =35 and <35 days, respectively). An increased incidence of early embryonal loss was also found among highly distressed women with long cycles, but was based on a small number of observations. CONCLUSION(S): Psychological distress may be a risk factor for reduced fertility in women with long menstrual cycles.

Surveillance of noise exposure in the Danish workplace: a baseline survey.

AIMS: To evaluate an epidemiological approach to a national noise hazard surveillance strategy, and report current exposure levels in the Danish workplace. METHODS: A study base of 840 companies in 10 selected high risk industries in the largest county in Denmark was identified from a national register. Noise exposure was measured among manual workers recruited from a random sample of workplaces in each industry. For reference, financial companies and a sample of residents were investigated according to the same protocol. The A-weighted equivalent sound level (L(Aeq)) for a full shift was measured by portable dosimeters worn by 830 workers employed at 91 workplaces (67% of 136 eligible companies). RESULTS: The epidemiological design proved feasible and established a baseline for future noise surveillance. Substantial resources were needed to motivate workplaces to enlist and the final participation rate was less than optimal (66.9%). The L(Aeq (8)) values in the selected industries were highly elevated (mean 83.7 dB(A) (95% CI 83.3 to 84.1) in comparison with residents and office workers (mean 69.9 dB(A), 95% CI 68.8 to 71.0). Some 50% of the workers were exposed to more than 85 dB(A) and some 20% to more than 90 dB(A) in several industries. CONCLUSION: Noise levels in Danish high risk industries remain high. A substantial proportion of workers are exposed to noise levels above the current threshold limit of 85 dB(A). Ongoing surveillance of noise exposure using full shift dosimetry of workers in random samples of workplaces most at risk to high noise levels may help reinforce preventive measures. Such a programme would benefit from compulsory workplace participation.

Semen quality and sex hormones with reference to metal welding.

Welding may involve hazards to the male reproductive system, but previous studies of semen quality have produced inconsistent results. We studied the effects of welding on markers of semen quality in a Danish nationwide sample of 430 first-time pregnancy planners without earlier reproductive experience. Couples were recruited among members of the union of metal workers and three other trade unions and were followed from termination of birth control until pregnancy for a maximum of six menstrual cycles. The males provided semen samples in each cycle. Median sperm density for welders was 56 x 10(6)/mL (52.5 x 10(6)/mL and 50.0 x 10(6)/mL in two reference groups). No statistically significant differences attributable to welding were found in proportions of morphologically normal sperm, sperm motility assessed by computer-aided sperm analysis, or sex hormones (testosterone, follicle-stimulating hormone, and luteinizing hormone). These negative findings may not apply to populations with high-level exposure to welding fume or to welders exposed to other putative hazards, e.g., heat.

A follow-up study of male exposure to welding and time to pregnancy.

The aim of this study was to estimate whether male welding has an impact on couple fecundability (the probability of conceiving in a menstrual cycle). A sample of Danish couples without previous reproductive experience was recruited nationwide by postal letters to members of the union of metal workers and three other trade unions. Among 430 included couples, 201 males were metal workers and 130 were welders. The couples were followed for a maximum of six menstrual cycles from termination of birth control until a clinical pregnancy was detected. Compared with nonwelding metal workers the fecundability odds ratio (OR) of male exposure to welding was 0.86 (95% confidence interval [CI] 0.58-1.28). An interaction between male smoking and welding was found; within smokers the OR for welding was 0.40 (95% CI 0.17-0.95) and within nonsmokers it was 1.22 (95% CI 0.74-1.99). Previous welding exposure was negatively related to fecundability among smokers (OR 0.84 per year with mild steel welding, OR 0.76 per year with stainless steel welding). No significant results were found when comparing with an external group of nonmetal workers. Decreased fecundability among smoking welders attributable to both current and previous welding exposure is possible, but these findings were the results of subanalyses that were not part of the a priori hypothesis.

Incidence of lymphohematopoietic malignancies among styrene-exposed workers of the reinforced plastics industry.

OBJECTIVES: The goal of this study was to determine the risk of lymphohematopoietic malignancies for workers exposed to styrene. METHODS: This was a historical cohort study. The observed numbers of newly diagnosed cases of lymphohematopoietic malignancies in the study population were compared with expected numbers based on the national rates. The study took place in the Danish reinforced plastic industry, in which high exposure levels of styrene occur frequently in an environment free of most other suspected carcinogens. Altogether 36,525 male employees of 386 companies producing reinforced plastics and 14,254 nonstyrene exposed employees of similar industries were studied. RESULTS: An insignificantly increased standardized incidence ratio (SIR) of 1.22 [95% confidence interval (95% CI) 0.88-1.65] was found for leukemia among all employees of the reinforced plastics industry. Workers employed in the 1960s (the period with the highest recorded styrene levels) or in companies with the highest exposure probability showed increased SIR values of 1.54 (95% CI 1.04-2.19) and 1.38 (95% CI 0.75-2.32), respectively. Both estimates increased when a 10-year latency period was considered. CONCLUSIONS: An increased risk of leukemia was shown for workers in the early phase of the reinforced plastics industry in Denmark. If this association is not due to chance or confounding, the most likely cause is styrene exposure.

Environmental semen studies--is infertility increased by a decline in sperm count?

The objective of the studies was to evaluate infertility according to sperm count shifts. The distribution of the sperm count of 1024 Danish men (median 56 million/ml) served as reference. The data were transformed with multiplicative or additive models to create alternative distributions with median sperm count values changed by 25-100%. Sperm-count-specific fecundabilities were provided from a follow-up of first-pregnancy planners in a Danish population. The estimated average fecundability of the 1024 Danish men was 16.9% [95% confidence interval (95% CI) 16.7-17.2], and the proportion of cohabiting men with spouses pregnant within 1 year was 86.0% (95% CI 84.1-87.8). Simulations of alternative sperm count distributions indicated that the relationship between sperm count shift and fertility strongly depends on the median level of the sperm count at onset and the type of shift, a dramatic decline from a high level in a multiplicative model indicating a marginal change and a minor decline from a low level in an additive model representing a strong decrease in fertility. In some cases sperm count, therefore, may be an early warning of changes in fertility.

Time to pregnancy among male workers of the reinforced plastics industry in Denmark, Italy and The Netherlands. ASCLEPIOS.

OBJECTIVES: The relationship between occupational styrene exposure and male fecundity was examined. METHODS: Among 1560 Danish, Italian, and Dutch reinforced plastics workers, 220 styrene-exposed workers and 382 unexposed referents who had fathered a child were identified. A total of 768 historical styrene measurements conducted in 1970-1996 in the study companies formed the basis for semiquantitative exposure assessment in combination with measurements of urinary styrene metabolite levels. All the subjects were interviewed about work conditions and other factors potentially related to reduced fecundity. Fecundity was measured as the reported time to pregnancy (number of months a couple needed to conceive their youngest child). RESULTS: A statistically nonsignificantly reduced fecundity was observed for the styrene-exposed workers [fecundity ratio 0.79, 95% confidence interval (95% CI) 0.59-1.05]. But no consistent pattern of a detrimental effect on fecundity was found when time to pregnancy was related to worktasks indicating higher styrene exposure levels or semiquantitative or quantitative measures of styrene exposure. The workers with high exposure showed a fecundity ratio of 1.09 (95% CI 0.69-1.72). CONCLUSIONS: It is unlikely that styrene exposure has a strong effect on male fecundity.

Objectives, designs and populations of the European Asclepios study on occupational hazards to male reproductive capability.

The main objective of the Asclepios program was to examine occupational risk factors for the male reproductive system. The program focused on occupational exposure to fungicides (farmers, greenhouse workers, and vineyard workers), styrene (laminators in the reinforced plastics industry) and inorganic lead (battery workers, foundry workers, and lead smelters). Questionnaire studies of time to pregnancy were combined with longitudinal and cross-sectional studies of semen quality. The 8 data-collecting centers addressed 6553 male workers and contributed time-to-pregnancy values on the 3077 most recent pregnancies. Data collection was by interview or self-collection. The average response rate across all exposures and centers was 69.8%. The Asclepios project is the first international multicenter research project on environmental risks to male reproductive function. A protocol for epidemiologic research on occupational risk factors to the male reproductive system was developed, and links between epidemiologic and experimental units were established. The majority, but not all, of the studies was completed within the given time frame.

Clonal chromosome aberrations in myeloid leukemia after styrene exposure.

OBJECTIVES: The purpose of the study was to determine the risk of myeloid leukemia subclassified according to clonal chromosome aberrations in styrene-exposed workers. METHODS: A nested case-referent study was carried out on 19 myeloid leukemia patients, of which 12 showed clonal chromosome aberrations, and 57 referents ascertained within the Danish reinforced plastics industry and similar industries with no styrene exposure. RESULTS: A 2.5-fold increased risk for myeloid leukemia with clonal chromosome aberrations (95% confidence interval 0.2-25.0) was found among workers of companies with styrene exposure. CONCLUSIONS: The results suggest that styrene may cause leukemia through a clastogenic effect. But similar findings could also have been found if the exposure was associated with a specific subtype of leukemia prone to develop the chromosome aberrations in question. Due to the few observations and the lack of detailed exposure data, additional studies are needed to corroborate or refute the present suggestive findings.

Male-mediated spontaneous abortion among spouses of stainless steel welders.

OBJECTIVES: Male-mediated spontaneous abortion has never been documented for humans. The welding of stainless steel is associated with the pulmonary absorption of hexavalent chromium, which has genotoxic effects on germ cells in rodents. Clinical and early subclinical spontaneous abortions were examined among spouses of stainless-steel welders. METHODS: A cohort of first-pregnancy planners was recruited from members of the union of metal workers and 3 other trade unions. The cohort was followed for 6 menstrual cycles from the cessation of contraceptive use. Altogether, 280 pregnancies were conceived, of which 35 were detected by human chorionic gonadotrophic hormone analysis and did not survive to a clinically recognized pregnancy. Information on exposure was collected prospectively in relation to the outcome and was available for all cycles resulting in a pregnancy. Information on pregnancy outcome was collected for all 245 clinically recognized pregnancies. RESULTS: Increased risk of spontaneous abortion was found for pregnancies with exposure to paternal stainless-steel welding (adjusted relative risk 3.5, 95% confidence interval 1.3-9.1). The results were consistent in analyses of both biochemically and clinically recognized abortions. There was no increased risk for spontaneous abortion in pregnancies with paternal exposure to the welding of metals other than stainless steel. CONCLUSIONS: Male welding of stainless steel was associated with an increased risk of spontaneous abortion in spouses. A mutagenic effect of hexavalent chromium has been found previously in both somatic and germ cells, and the findings could be due to mutations in the male genome.

Job strain and time to pregnancy.

OBJECTIVES: The association between fertility and job strain defined as high job demands and low job control has not previously been studied. A follow-up study was conducted with prospective collection of information on job strain among women, achievement of pregnancy, and potential confounding variables. METHODS: A total of 297 Danish couples without previous reproductive experience was followed for a maximum of 6 menstrual cycles from termination of birth control until pregnancy. Job demand and job control were measured by a questionnaire developed by Karasek and his co-workers. RESULTS: The odds ratio and 95% confidence interval (95% CI) for conception per menstrual cycle for women with high job strain was 0.9 (95% CI 0.5-1.5) when compared with that of women in low-strain jobs. Only in secondary analyses restricted to couples with no suspected competitive causes of reduced fertility was a statistically significant reduced odds found for women with high-strain jobs compared with all other jobs. CONCLUSIONS: The main finding of this study did not corroborate a hypothesis of a substantial detrimental effect of job strain on fecundability.

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.