Food & Fertility Study: study protocol for a Danish multicentre prospective cohort study investigating the association between food intake and semen quality, pregnancy and birth outcomes in infertile women and men.

INTRODUCTION: Worldwide infertility is highly prevalent, and lifestyle factors, such as food intake, could have an essential role in the success of a fertility treatment. The literature is not consistent and adequate for recommendations to the increasing number of women and men of reproductive age who ask for lifestyle guidance. Therefore, the aims of the Food & Fertility Study will be to investigate the possible association between food intake and semen quality in men, and pregnancy and live birth rates in women undergoing intrauterine insemination or assisted reproductive technology treatment. METHODS AND ANALYSIS: The Food & Fertility Study is a multicentre prospective cohort study which plans to enrol a total of 4000 women and men between 2022 and 2024. Data collection will take place in four fertility clinics through a web-based Food Frequency Questionnaire. Data on sperm quality and pregnancy and live birth rates will be obtained from medical records and national registers. ETHICS AND DISSEMINATION: The study is registered with and approved by the Danish Data Protection Agency, the North Denmark Region (j.nr: 2019-055298). Further, a Statement of Work and a Master Collaboration Agreement have been submitted and approved by the regional legal departments (AGR-2019-731-9667). Dissemination of the results will be through national and international conferences, in scientific environments, in the form of lectures to the broader public, and by peer-reviewed publications in international scientific journals. TRIAL REGISTRATION NUMBER: NCT05454046.

Social economic factors and the risk of multiple chemical sensitivity in a Danish population-based cross-sectional study: Danish Study of Functional Disorders (DanFunD).

OBJECTIVES: Multiple chemical sensitivity (MCS) is a rare multisystem and poly-symptomatic disease characterised by a report of various somatic symptoms attributed to inhalation of volatile chemicals in usually harmless doses. The aim was to explore four selected social factors and the risk of MCS in the general Danish population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Disorders was conducted from 2011 to 2015 which included 9656 participants. PARTICIPANTS: A total of 8800 participants were included in analyses after observations with missing data on exposure and/or outcome were excluded. A total of 164 cases fulfilled the questionnaire criteria for MCS. Of the 164 MCS cases, 101 reported no comorbid functional somatic disorder (FSD) and were included in a subgroup analysis. A total of 63 MCS cases fulfilled the criteria for at least one additional FSD, this subgroup was not included in further analysis. The remaining study population without MCS or any FSD were regarded as controls. OUTCOME MEASURES: We used adjusted logistic regression to calculate OR and 95% CIs of MCS and MCS without FSD comorbidities for each social variable separately including education, employment, cohabitation and subjective social status. RESULTS: We found an increased risk of MCS among the unemployed (OR: 2.95, 95% CI: 1.75 to 4.97), and a twofold increased risk of MCS among individuals with low subjective social status (OR: 2.00, 95% CI: 1.08 to 3.70). At the same time, 4 years or more of vocational training were protective of MCS. No significant associations were observed among MCS cases with no comorbid FSD. CONCLUSION: Lower socioeconomic status was found to be associated with a higher risk of having MCS but not with MCS without FSD comorbidities. Due to the cross-sectional design of the study, we cannot determine whether social status is a determinant or a consequence of MCS.

Association between infections and functional somatic disorders: a cross-sectional population-based cohort study.

OBJECTIVES: It has been suggested that infections can trigger functional somatic disorders (FSD). However, current evidence is limited by inconsistent findings in smaller studies conducted in clinical settings within selected populations and short follow-up times. We aimed to test the hypothesis that former infections are associated with FSD using data from nationwide registries and a large population-based cohort study, the Danish Study of Functional Disorders study. DESIGN: FSD cases were identified in a cross-sectional population-based cohort and linked retrospectively to former hospital contacts with infections identified in the Danish National Patient Registry. The associations between FSD and former infections within 17 years were analysed using logistic regressions to calculate ORs and 95% CIs adjusted for age, sex and subjective social status. SETTING: A population-based cohort in Denmark examined between 2011 and 2015. PARTICIPANTS: A total of 9656 men and women aged 18-76 years. MAIN OUTCOME MEASURES: FSD measured by various delimitations, including bodily distress syndrome (BDS), irritable bowel (IB), chronic fatigue (CF), chronic widespread pain (CWP), and multiple chemical sensitivity (MCS). RESULTS: Overall, infections were associated with increased risk of all delimitations of FSD. The associations were more pronounced for multisystemic FSD. The number of prior infections increased the risk in a dose-response manner (p<0.0001). Bacterial but not viral infections were significantly associated with BDS (OR 1.69 (95% CI 1.46 to 1.96)), IB (OR 1.41 (95% CI 1.06 to 1.88)), CWP (OR 1.47 (95% CI 1.13 to 1.90)) and CF (OR 1.62 (95% CI 1.34 to 1.96)), but not MCS. CONCLUSION: Former infections leading to hospital contacts were associated with a higher risk of having FSD. These associations were more pronounced for bacterial than viral infections, and more infections increased the risk in a dose-response manner. These results tend to support the idea that severe infections could play a role in FSD.

Correction: Mother's dietary quality during pregnancy and offspring's dietary quality in adolescence: Follow-up from a national birth cohort study of 19,582 mother-offspring pairs.

[This corrects the article DOI: 10.1371/journal.pmed.1002911.].

Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit.

N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined the NAT2 enzyme-activity by caffeine test. No additional genetic variants were identified in the coding sequence of NAT2, so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel. Studying the enzyme activity by the ratio of the two caffeine metabolites AFMU and 1X in 260 participants showed a high rate of slow phenotypes with intermediate or rapid genotype. These misclassifications were mainly observed in urine samples with pH<3, a deviation from the standard protocol due to the field work character of the study, where immediate pH adjustment to pH=3.5 was not possible. We excluded these samples. For the remaining 143 individuals with pH>3, we observed a moderate level of discrepancies (19 of the 116 individuals with intermediate or rapid genotype status having a slow phenotype). Further investigation showed that drinking coffee and not tea or cola was the most important factor for high levels of both metabolites. The concordance between phenotype and genotype status with regard to slow metabolism supported the recommendation of lower isoniazid doses in individuals with slow genotype status in order to avoid liver injury, a frequent side effect. The phenotypical variation observed for individuals with intermediate or rapid genotype status warrants further research before increased dosing of isoniazid can be recommended.