Reini W. Bretveld

Web-based Questionnaires: The Future in Epidemiology?

The traditional epidemiologic modes of data collection, including paper-and-pencil questionnaires and interviews, have several limitations, such as decreasing response rates over the last decades and high costs in large study populations. The use of Web-based questionnaires may be an attractive alternative but is still scarce in epidemiologic research because of major concerns about selective nonresponse and reliability of the data obtained. The authors discuss advantages and disadvantages of Web-based questionnaires and current developments in this area. In addition, they focus on some practical issues and safety concerns involved in the application of Web-based questionnaires in epidemiologic research. They conclude that many problems related to the use of Web-based questionnaires have been solved or will most likely be solved in the near future and that this mode of data collection offers serious benefits. However, questionnaire design issues may have a major impact on response and completion rates and on reliability of the data. Theoretically, Web-based questionnaires could be considered an alternative or complementary mode in the range of epidemiologic methods of data collection. Practice and comparisons with the traditional survey techniques should reveal whether they can fulfill their expectations.

Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings.

The impact of pesticides on male fertility

Purpose of review Observations in several Western countries point toward a decline in semen quality which may be associated with exposure to environmental endocrine disruptors such as several frequently used pesticides. The scarce literature on the effects of pesticides on male fertility will be reviewed with a focus on semen quality and time-to-pregnancy. Recent findings The majority of studies published since 2000 reported some effects of pesticide exposure on semen quality or time-to-pregnancy. The results are not consistent, however, with some studies showing reduced sperm concentrations and others showing low percentages of morphologically normal and/or motile sperm. In time-to-pregnancy studies, reduced male fertility measured as prolonged time-to-pregnancy related to pesticide exposure was observed for first pregnancies only. Some of the inconsistencies may be explained by heterogeneity in populations, pesticide exposure, and study design. Summary Despite this heterogeneity, the conclusion can be drawn that pesticide exposure may affect spermatogenesis leading to poor semen quality and reduced male fertility. More research is needed to unravel the pathophysiological mechanisms and the role of endocrine disruption.

Time-to-pregnancy among male greenhouse workers.

Objectives: Fertility problems are an increasing public health issue in industrialised countries. Exposure to exogenous agents with endocrine disrupting properties, such as some pesticides, are potential risk factors for subfertility. The aim of this study was to determine whether time-to-pregnancy (TTP) is prolonged in male greenhouse workers exposed to pesticides in comparison with a non-exposed reference group. Methods: Data were collected through self-administrated questionnaires with detailed questions on TTP, as well as on lifestyle (for example, smoking habits, coffee and alcohol consumption), work tasks, and occupational exposures of the men and their partners in the six months before conception of the most recent pregnancy. TTP was compared between male greenhouse workers (n = 694) and a non-exposed reference group (n = 613) by means of discrete proportional hazards regression analysis. Results: The crude analyses did not show a decreased overall fecundability among greenhouse workers compared to the non-exposed reference group. However, when fecundability was assessed for primigravidous couples, duogravidous couples, and multigravidous couples separately, greenhouse workers were found to be less fecund when trying to conceive their first pregnancy (FR = 0.65; 95% CI 0.46 to 0.92), which is also the most valid analysis in which pregnancy planning issues were avoided. Among couples who already experienced one or more pregnancies, no association was seen between pesticide exposure and TTP after adjustment for confounders. Conclusion: A prolonged time-to-pregnancy was observed in male greenhouse workers exposed to pesticides before conception of their first pregnancy.

Comparing the effectiveness of interventions to improve ventilation behavior in primary schools

UNLABELLED Poor air quality in schools has been associated with adverse health effects. Indoor air quality can be improved by increasing ventilation. The objective of this study was to compare the effectiveness of different interventions to improve ventilation behavior in primary schools. We used indoor CO(2) concentrations as an indicator. In 81 classes of 20 Dutch primary schools, we applied three different interventions: (i) a class-specific ventilation advice; (ii) the advice combined with a CO(2) warning device and (iii) the advice combined with a teaching package. The effectiveness of the interventions was tested directly after intervention and 6 weeks after intervention by measuring the CO(2) concentrations and comparison with a control group (iv). Before intervention, the CO(2) concentration exceeded 1000 ppm for 64% of the school day. The class-specific ventilation advice without further support appeared an ineffective tool to improve ventilation behavior. The advice in combination with a CO(2) warning device or the teaching package proved effective tools and resulted in lower indoor CO(2) concentrations when compared with the control group. Ventilation was significantly improved, but CO(2) concentrations still exceeded 1000 ppm for more than 40% of the school day. Hence, until ventilation facilities are upgraded, the CO(2) warning device and the teaching package are useful low-cost tools. PRACTICAL IMPLICATIONS To improve ventilation behavior and indoor air quality in schools, CO(2) warning device and teaching package combined with a class-specific ventilation advice, are effective tools, while giving the ventilation advice solely, is not effective. Although ventilation is significantly improved through behavioral change, the ventilation rate is still insufficient to maintain good air quality during the full school day. Therefore, the improvement of the ventilation facilities is recommended. Hence, until ventilation facilities in schools are upgraded, the CO(2) warning device and the teaching package are useful low-cost tools to improve current indoor air quality.

Rationale and Design of the PRegnancy and Infant DEvelopment (PRIDE) Study

Background To optimise the health of pregnant women and their children by evidence-based primary and secondary prevention, more scientific knowledge is needed. To overcome the methodological limitations of many studies on pregnancy and child health, which often use a retrospective design, we established the PRIDE (PRegnancy and Infant DEvelopment) Study. Methods and Results The PRIDE Study is a large prospective cohort study that aims at including 150 000–200 000 women in early pregnancy to study a broad range of research questions pertaining to pregnancy complications, maternal and child health, and adverse developmental effects in offspring. Women are invited to participate by their prenatal care provider before or at their first prenatal care visit and are asked to fill out web-based questionnaires in gestational weeks 8–10, 17, and 34, as well as biannually throughout childhood. In addition, a food frequency questionnaire and a paternal questionnaire are administered and medical records are consulted. Multiple validation studies will be conducted and paper-and-pencil questionnaires are available for women who cannot or do not want to participate through the Internet. For subgroups of participants, blood and saliva samples for genetic and biochemical analyses are being collected. The pilot phase, which started in July 2011, showed a response rate of 47%. Recruitment will eventually cover all of the Netherlands. Conclusions We expect that this study, which will be the largest birth cohort in the world so far, will provide new insights in the aetiology of disorders and diseases that originate in pregnancy. The PRIDE Study is open for collaboration.

Estrogenic and androgenic activities in total plasma measured with reporter-gene bioassays: Relevant exposure measures for endocrine disruptors in epidemiologic studies?

Measurements of estrogenic and androgenic activities in total plasma with Chemically Activated LUciferase gene eXpression (CALUX®) bioassays could provide biologically relevant measures for exposure to endocrine disruptors in epidemiologic studies. The objective of this study was to explore the effects of a variety of sources of potential endocrine disruptors on estrogenic and androgenic activities in total plasma measured by CALUX®. Plasma samples and interview data on sources of potential endocrine disruptors were collected from 108 men with different exposures profiles. CALUX® measurements (BioDetection Services) involved human U2-OS cell lines controlled by the estrogen receptor alpha and the androgen receptor. Mean differences (beta) in 17β-estradiol equivalents (EEQs) and dihydrotestosterone equivalents (AEQs) between exposure groups were estimated using general linear models. Mean plasma AEQs and EEQs were 9.1×10(-1)ng/ml and 12.0pg/ml, respectively. Elevated AEQs were found in smokers (beta 1.9 (95%CI 0.1-3.6)×10(-1)ng/ml) and heavy drinkers (1.4 (0.2-3.1)×10(-1)ng/ml), and in men occupationally exposed to disinfectants (1.6 (0.3-3.5)×10(-1)ng/ml) or welding/soldering fumes (1.4 (-0.2-2.9)×10(-1)ng/ml). Occupational exposure to pesticides, disinfectants, and exhaust fumes seemed to be associated with increased plasma EEQs: 1.5 (-0.2-3.2)pg/ml, 2.1 (0.2-3.9)pg/ml, and 2.9 (0.6-5.2)pg/ml, respectively. Moderate to high plasma dioxin levels, measured in a subgroup by the dioxin-responsive CALUX®, were accompanied by a 20% increase in AEQs. This is the first study in which CALUX® was used to assess hormone activities in total plasma. Although the results are not yet readily interpretable, they indicate that these measurements can be valuable for epidemiologic studies on endocrine disruptors and give direction for further research.

Exposure profiles of pesticides among greenhouse workers: Implications for epidemiological studies

The aim of this study was to assess exposure to pesticides for a longitudinal epidemiological study on adverse reproduction effects among greenhouse workers. Detailed information on pesticide use among greenhouse workers was obtained on a monthly basis through self-administered questionnaires and subsequent workplace surveys. Questionnaires were filled in for a whole year. Dermal exposure rankings were developed for each task using the observational method Dermal Exposure Assessment Method (DREAM). Exposure scores were calculated for each worker for each month during the year, taking into account frequency, duration and exposure intensity for each task. A total number of 116 different active ingredients were used in the population, whereas a mean number of 15 active ingredients were applied per greenhouse. DREAM observations provided insight into the exposure intensity of 12 application techniques and three mixing and loading activities. Relatively high DREAM scores were obtained for scattering, fogging, dusting, and mixing and loading of powders. Observations with DREAM indicated that application with a horizontal ground-boom, motor driven boom, and bulb shower resulted in low dermal exposure. Exposure scores showed substantial variation between workers and over the year. It can be concluded that exposure variation between- and within greenhouses is very large, both in terms of chemical composition and exposure intensity. This may be a significant contributor to the inconsistent results of studies evaluating health effects of pesticide exposure.

Reporting on the modes of data collection

In her Comment (Oct 30, p 1448), Seema Kang discusses Case Reports in The Lancet according to specialty interest and mentions that “more than one specialty might be involved in managing a case”. She comments on the absence of contributions from general practice, but makes no comment on the contribution of other specialities such as radiology and pathology. Many patients require multidisciplinary inves ti gation or management. For example, in the diagnosis of breast disease, the triple approach of clinical examination, radiology, and pathology is recommended. Over the past 2 years (November, 2008, to October, 2010) histo pathology had an important role in the diagnosis in 36 Case Reports in The Lancet. A histopathologist was an author in 20. In the other 16 there was no apparent recognition of histo pathology in terms of authorship or acknowledgment, although it had an essential role in ten and was contributory in six. Reporting on the modes of data collection