Recognition of COVID-19 with occupational origin: a comparison between European countries.

OBJECTIVES: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. METHODS: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. RESULTS: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. CONCLUSIONS: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.

Gait and Falls in Benign Paroxysmal Positional Vertigo: A Systematic Review and Meta-analysis.

BACKGROUND AND PURPOSE: Benign paroxysmal positional vertigo (BPPV) is one of the most common vestibular disorders, and is treated effectively with particle repositioning maneuvers (PRM). The aim of this study was to assess the influence of BPPV and treatment effects of PRM on gait, falls, and fear of falling. METHODS: Three databases and the reference lists of included articles were systematically searched for studies comparing gait and/or falls between (1) people with BPPV (pwBPPV) and controls and (2) pre- and posttreatment with PRM. The Joanna Briggs Institute critical appraisal tools were used to assess risk of bias. RESULTS: Twenty of the 25 included studies were suitable for meta-analysis. Quality assessment resulted in 2 studies with high risk of bias, 13 with moderate risk, and 10 with low risk. PwBPPV walked slower and demonstrated more sway during tandem walking compared with controls. PwBPPV also walked slower during head rotations. After PRM, gait velocity during level walking increased significantly, and gait became safer according to gait assessment scales. Impairments during tandem walking and walking with head rotations did not improve. The number of fallers was significantly higher for pwBPPV than for controls. After treatment, the number of falls, number of pwBPPV who fell, and fear of falling decreased. DISCUSSION AND CONCLUSIONS: BPPV increases the odds of falls and negatively impacts spatiotemporal parameters of gait. PRM improves falls, fear of falling, and gait during level walking. Additional rehabilitation might be necessary to improve gait while walking with head movements or tandem walking.Video Abstract available for more insights from the authors (see the Supplemental Digital Content Video, available at: http://links.lww.com/JNPT/A421 ).

Validation of a food-frequency questionnaire to assess methyl-group donor intake in preschoolers.

A good assessment of dietary methyl-group donor intake (folate, choline, betaine, methionine) is needed to investigate the effect of methyl-group donor intake on children's health. The aim is to develop and validate a food-frequency questionnaire (FFQ) to estimate the daily intake of methyl-group donors in preschoolers. For the relative validity and reproducibility of the FFQ, a 7-day estimated dietary record (7d EDR) and repeated measurements 6 weeks apart (n = 77) were used respectively. For the validity (n = 75), a moderate ranking ability was obtained (de-attenuated Pearson correlation = 0.43-0.70; weighted ƙ 0.10-0.40), but the FFQ tends to overestimate the real intake. Cross-classification analysis showed that 38% (choline) and 28% (betaine) of the subjects were misclassified. The FFQ shows a moderate to good reproducibility, intra-class correlation coefficients range between 0.67 (betaine) and 0.76 (choline) with a maximal misclassification of 6.5% for betaine (weighted ƙ 0.37-0.69) (n = 77). CONCLUSION: The FFQ is a tool with a moderate validity and reproducibility to estimate the consumption of dietary methyl-group donors in preschoolers. This tool might be used in future research epidemiological studies including preschoolers. WHAT IS KNOWN: • Poor dietary habits during childhood have been associated with chronic disease in adulthood. • Methyl-group donors are important for DNA methylation, which is the underlying mechanism of disease development. WHAT IS NEW: • For the first time, a food-frequency questionnaire that can assess the intake of methione, folate, choline, and betaine has been developed and validated for the use in preschoolers.

Reproducibility and validity of an FFQ to assess usual intake of methyl-group donors.

OBJECTIVE: To develop and validate a novel FFQ to assess the daily intake of four methyl-group donors (methionine, choline, betaine and folate). DESIGN: The relative validity of the FFQ was assessed by comparison with 7 d estimated diet records (n 80) and its reproducibility was evaluated by repeated administrations 6 weeks apart (n 92). Paired Student t tests were used to compare group means and de-attenuated intra-class correlations to investigate the ability of the FFQ to rank individuals according to their methyl-group donor intake. De-attenuated intra-class correlation coefficients were calculated between the test and reference method for methionine, choline, betaine, folate and the sum of methyl-group donors. The weighted kappa (κ w) was calculated as a measure of tertile agreement. SETTING: Flanders, Belgium. SUBJECTS: The FFQ was validated among Flemish women of reproductive age (18-35 years). RESULTS: The questionnaire had an acceptable ranking ability (r=0·32-0·68; κ w=0·10-0·35), but overestimated the daily intake of folate (280·6 µg v. 212·0 µg) and betaine (179·1 mg v. 147·0 mg) compared with the 7 d estimated diet record. Cross-classification analysis indicated that 20 % (choline) of the participants were grossly misclassified in the validation study. The correlation between repeated administrations was good (r=0·62-0·83) with a maximal misclassification of 7 % for betaine (κ w=0·44-0·66). CONCLUSIONS: These results indicate that this newly developed FFQ is a reliable instrument with acceptable validity for ranking individuals according to methyl-group donor intake (except for a poor agreement for choline (κ w=0·10) and a fair ranking ability for betaine (r=0·32)) in Flemish women of reproductive age.

Validation of a food-frequency questionnaire assessment of methyl-group donors using estimated diet records and plasma biomarkers: the method of triads.

In this study, the intake of methyl-group donors (methionine, folate, betaine, and choline) among Flemish women of reproductive age (n = 30) assessed by a 7-d estimated diet record (7 d EDR) and food-frequency questionnaire (FFQ) was compared with plasma S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and SAH:SAM ratio. Pearson correlation coefficients were calculated between each of the dietary methods and the validity coefficient was calculated using the method of triads. Correlations were higher between intake assessed by the FFQ and biomarkers than between 7 d EDR and biomarkers. The validity coefficients of the FFQ, when using SAH as a biomarker, were high (0.86 for methionine to 0.94 for folate), when the SAH:SAM ratio was used as a biomarker the validity coefficients ranged from 0.63 to 1.00. These data indicate that the FFQ is a reliable tool to estimate the intake of the methyl-group donors in women of reproductive age.

Effects of exposure to environmental factors on obesity-related growth parameters and leptin (LEP) methylation in children.

The prevalence of childhood obesity is rapidly increasing. Therefore, gaining more information on the role of environmental parameters is key. With overexpression of leptin (encoded by LEP) in obesity, LEP methylation might be altered by environmental exposures. This study aims to assess effects of ambient air pollution and nearby greenness on obesity-related growth and LEP methylation in early childhood. We monitored 120 mother-child pairs from conception until the age of five. Buccal swabs and anthropometric measurements of the children were taken at six months, one year, and five years old. Buccal DNA was extracted to determine LEP methylation levels. Estimates of air pollution and nearby greenness were calculated using high-resolution models. Effects of air pollution and nearby greenness on growth or LEP methylation were investigated using linear mixed effects models. Positive associations were shown for air pollution between conception and age one on impedance in six-month-olds and one-year-olds in the crude model. PM with aerodynamic diameter ≤10 (PM10) and ≤2.5 µm (PM2.5) positively associated with waist-hip-ratio and waist circumference at age five in the fully adjusted model. In early childhood, closest distance to forest negatively, and urban green and forest positively associated with weight-for-length, body mass index, and fat percentage in five-year-olds in the fully adjusted model. No significant associations for noise, and walkability on growth were seen. Negative associations were shown for smaller green clusters and positive associations for greater green clusters on LEP methylation in one-year-olds. For forest distance, walkability, noise, or all green on LEP methylation, no significant associations were found. Evidence is provided that ambient air pollution might have a significant effect on impedance and waist-hip-ratio, suggesting an increased risk of childhood obesity. Based on LEP methylation, greater green clusters might associate with a decreased risk of childhood obesity, while smaller green clusters showed the opposite.

Cross-sectional associations between exposure to per- and polyfluoroalkyl substances and body mass index among European teenagers in the HBM4EU aligned studies.

Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants that may impact youth adiposity patterns. We investigated cross-sectional associations between PFAS and body mass index (BMI) in teenagers/adolescents across nine European countries within the Human Biomonitoring for Europe (HBM4EU) initiative. We used data from 1957 teenagers (12-18 yrs) that were part of the HBM4EU aligned studies, consisting of nine HBM studies (NEBII, Norway; Riksmaten Adolescents 2016-17, Sweden; PCB cohort (follow-up), Slovakia; SLO CRP, Slovenia; CROME, Greece; BEA, Spain; ESTEBAN, France; FLEHS IV, Belgium; GerES V-sub, Germany). Twelve PFAS were measured in blood, whilst weight and height were measured by field nurse/physician or self-reported in questionnaires. We assessed associations between PFAS and age- and sex-adjusted BMI z-scores using linear and logistic regression adjusted for potential confounders. Random-effects meta-analysis and mixed effects models were used to pool studies. We assessed mixture effects using molar sums of exposure biomarkers with toxicological/structural similarities and quantile g-computation. In all studies, the highest concentrations of PFAS were PFOS (medians ranging from 1.34 to 2.79 µg/L). There was a tendency for negative associations with BMI z-scores for all PFAS (except for PFHxS and PFHpS), which was borderline significant for the molar sum of [PFOA and PFNA] and significant for single PFOA [ß-coefficient (95% CI) per interquartile range fold change = -0.06 (-0.17, 0.00) and -0.08 (-0.15, -0.01), respectively]. Mixture assessment indicated similar negative associations of the total mixture of [PFOA, PFNA, PFHxS and PFOS] with BMI z-score, but not all compounds showed associations in the same direction: whilst [PFOA, PFNA and PFOS] were negatively associated, [PFHxS] associated positively with BMI z-score. Our results indicated a tendency for associations of relatively low PFAS concentrations with lower BMI in European teenagers. More prospective research is needed to investigate this potential relationship and its implications for health later in life.

The effect of pre-pregnancy BMI on intention, initiation and duration of breast-feeding.

OBJECTIVE: To determine whether pre-pregnancy BMI influences breast-feeding practice. DESIGN: Retrospective epidemiological study. SETTING: University Hospital Leuven, Catholic University Leuven, Belgium. SUBJECTS: Two hundred women (median age 29 years, interquartile range (IQR) 4; 52 % nulliparae) were grouped into four categories according to pre-pregnancy BMI using WHO cut-offs. RESULTS: The incidence of intention and initiation of breast-feeding was significantly lower in underweight (64 %) and obese women (68 %) compared with normal weight (92 %) and overweight women (80 %). Initiation was also related to parity (OR = 0.582; 95 % CI 0.400, 0.846), but not to gestational weight gain, method of delivery or hypertensive disorders. Fifty-two per cent of underweight, 70 % of normal weight and 56 % of overweight women were exclusively breast-feeding their infant during the first month of life. This incidence was significantly lower in the obese group (34 %; P = 0.030). Only 40 % of all infants were exclusively breast-fed at 3 months of age, with the lowest prevalence among women with obesity (P = 0.0 0 1). The median duration of any breast-feeding in the obese group (1.8 months, IQR 3.4) was significantly shorter than in the underweight (3.0 months, IQR 3.1), normal weight (3.0 months, IQR 2.4) and overweight group (3.0 months, IQR 3.5; P = 0.024). Reasons given for ceasing breast-feeding in the obese group were maternal complications (29 %), insufficient milk supply (23 %), sucking problems (21 %) and work resumption (21 %). CONCLUSIONS: Breast-feeding practice in the total population, but especially among women with obesity, fell short of global WHO recommended standards. Policy initiatives and local interventions should continue to support breast-feeding, but also prevent maternal obesity.

Air pollution and endocrine disruptors induce human microbiome imbalances: A systematic review of recent evidence and possible biological mechanisms.

A rich body of literature indicates that environmental factors interact with the human microbiome and influence its composition and functions contributing to the pathogenesis of diseases in distal sites of the body. This systematic review examines the scientific evidence on the effect of environmental toxicants, air pollutants and endocrine disruptors (EDCs), on compositional and diversity of human microbiota. Articles from PubMed, Embase, WoS and Google Scholar where included if they focused on human populations or the SHIME® model, and assessed the effects of air pollutants and EDCs on human microbiome. Non-human studies, not written in English and not displaying original research were excluded. The Newcastle-Ottawa Scale was used to assess the quality of individual studies. Results were extracted and presented in tables. 31 studies were selected, including 24 related to air pollutants, 5 related to EDCs, and 2 related to EDC using the SHIME® model. 19 studies focussed on the respiratory system (19), gut (8), skin (2), vaginal (1) and mammary (1) microbiomes. No sufficient number of studies are available to observe a consistent trend for most of the microbiota, except for streptococcus and veillionellales for which 9 out of 10, and 3 out of 4 studies suggest an increase of abundance with exposure to air pollution. A limitation of the evidence reviewed is the scarcity of existing studies assessing microbiomes from individual systems. Growing evidence suggests that exposure to environmental contaminants could change the diversity and abundance of resident microbiota, e.g. in the upper and lower respiratory, gastrointestinal, and female reproductive system. Microbial dysbiosis might lead to colonization of pathogens and outgrowth of pathobionts facilitating infectious diseases. It also might prime metabolic dysfunctions disrupting the production of beneficial metabolites. Further studies should elucidate the role of environmental pollutants in the development of dysbiosis and dysregulation of microbiota-related immunological processes.

Maternal Vitamin D and Newborn Telomere Length.

Nutrition is important during pregnancy for offspring health. Gestational vitamin D intake may prevent several adverse outcomes and might have an influence on offspring telomere length (TL). In this study, we want to assess the association between maternal vitamin D intake during pregnancy and newborn TL, as reflected by cord blood TL. We studied mother-child pairs enrolled in the Maternal Nutrition and Offspring's Epigenome (MANOE) cohort, Leuven, Belgium. To calculate the dietary vitamin D intake, 108 women were asked to keep track of their diet using the seven-day estimated diet record (EDR) method. TL was assessed in 108 cord blood using a quantitative real-time PCR method. In each trimester of pregnancy, maternal serum 25-hydroxyvitamin D (25-OHD) concentration was measured. We observed a positive association (ß = 0.009, p-value = 0.036) between newborn average relative TL and maternal vitamin D intake (diet + supplement) during the first trimester. In contrast, we found no association between average relative TL of the newborn and mean maternal serum 25-OHD concentrations during pregnancy. To conclude, vitamin D intake (diet + supplements), specifically during the first trimester of pregnancy, is an important factor associated with TL at birth.

The Parental Pesticide and Offspring's Epigenome Study: Towards an Integrated Use of Human Biomonitoring of Exposure and Effect Biomarkers.

In Morocco, due to the lack of education and the presence of a counterfeit market, pesticides constitute a major problem to be addressed by occupational and environmental health agencies. This paper aims to introduce the PaPOE (Parental Pesticides and Offspring Epigenome) prospective study and its goals, to motivate the study rationale and design, and to examine comprehensively whether multi-residue exposure to commonly used pesticides could induce epigenetic alterations through the oxidative stress pathway. The PaPOE project includes a cross-sectional study assessing the occupational exposure among 300 farmworkers in Meknes, and initiates a birth cohort of 1000 pregnant women. Data and biological samples are collected among farmworkers, and throughout pregnancy, and at birth. Oxidative stress biomarkers include Glutathione, Malondialdehyde, and 8-OHdG. Global and gene-specific DNA methylation is assessed. The study began enrollment in 2019 and is ongoing. As of 30 June 2021, 300 farmworkers and 125 pregnant women have enrolled. The results are expected to showcase the importance of biomonitoring for understanding individual risks, and to identify a number of regions where DNA methylation status is altered in the pesticides-exposed population, paving the way for an integrated biomonitoring system in Morocco and Africa to assess environmental exposures and their long-term health consequences.

PROBE Study: A Sentinel Surveillance System to Monitor Exposure of Belgian Employees to Hazardous Chemicals: A Feasibility Study.

OBJECTIVE: To test the feasibility of collecting reliable and representative data on exposure of Belgian employees to a selection of hazardous chemicals by using a sentinel surveillance method. METHOD: In PROBE (Hazardous chemical Products Register for Occupational use in Belgium), 47 occupational physicians were recruited as a sentinel network. Employees answered a web-based survey assessing their past week exposure to 22 chemicals. RESULTS: 47% employees were exposed to at least one chemical. The most frequently reported exposures was to diesel exhaust (14%). The exposed employees were mostly older men, with most exposed during production and manufacturing, and working in smaller companies. For diesel exhaust, wood dust, and crystalline silica, 54%, 32%, and 20% of the exposed employees, did not use collective/personal protective equipment. CONCLUSION: Sentinel surveillance is a feasible method for obtaining high-quality data on the exposure of Belgian employees to hazardous chemicals.

Methodological approaches to compile and validate a food composition database for methyl-group carriers in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

A standardised methodology was used to compile and validate a methyl-group carrier database (MGDB) including folate, choline, betaine and methionine, for use in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Compilation was performed by following structured guidelines to match the EPIC dietary intake data to food items from four food composition databases, according to their assigned priority of use. To assess relative validity, calculated dietary folate intakes were compared between the MGDB and the EPIC nutrient database (ENDB), used as the reference database. Folate intakes based on the MGDB and those generated using the ENDB showed good agreement (weighted κ = 0.63) and were strongly correlated (r = 0.81). This MGDB can be used for investigating potential associations between methyl-group carrier intakes and risk or prognosis of cancer and other diseases in the EPIC study population.

The Influence of the Duration of Breastfeeding on the Infant's Metabolic Epigenome.

Nutrition in the postnatal period is associated with metabolic programming. One of the presumed underlying mechanisms involves epigenetic modifications (e.g., DNA methylation). Breastfeeding has an unknown impact on DNA methylation at a young age. Within the Maternal Nutrition and Offspring's Epigenome (MANOE) study, we assessed the effect of breastfeeding duration on infant growth and buccal methylation in obesity-related genes (n = 101). A significant difference was found between infant growth and buccal RXRA and LEP methylation at 12 months of breastfeeding. For RXRA CpG2 methylation, a positive association was found with duration of breastfeeding (slope = 0.217; 95% confidence interval (CI) 1.03, 0.330; p < 0.001). For RXRA CpG3 and CpG, mean methylation levels were significantly lower when children were breastfed for 4-6 months compared to non-breastfed children (only CpG3), and those breastfed for 7-9 months, 10-12 months, or 1-3 months. On the other hand, higher LEP CpG3 methylation was observed when mothers breastfed 7-9 months (6.1%) as compared to breastfeeding for 1-3 months (4.3%; p = 0.007) and 10-12 months (4.6%; p = 0.04). In addition, we observed that infant weight was significantly lower when children were breastfed for 10-12 months. Breastfeeding duration was associated with epigenetic variations in RXRA and LEP at 12 months and with infant biometry/growth. Our results support the hypothesis that breastfeeding could induce epigenetic changes in infants.

Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants.

BACKGROUND: Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring's Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ). Before and during pregnancy, we evaluated maternal methyl-group donor intake through diet and supplementation (folic acid) in relation to gene-specific (IGF2 DMR, DNMT1, LEP, RXRA) buccal epithelial cell DNA methylation in 6 months old infants (n = 114) via pyrosequencing. In the early postnatal period, we determined the effect of maternal choline intake during lactation (in mothers who breast-fed for at least 3 months) on gene-specific buccal DNA methylation (n = 65). RESULTS: Maternal dietary and supplemental intake of methyl-group donors (folate, betaine, folic acid), only in the periconception period, was associated with buccal cell DNA methylation in genes related to growth (IGF2 DMR), metabolism (RXRA), and appetite control (LEP). A negative association was found between maternal folate and folic acid intake before pregnancy and infant LEP (slope = -1.233, 95% CI -2.342; -0.125, p = 0.0298) and IGF2 DMR methylation (slope = -0.706, 95% CI -1.242; -0.107, p = 0.0101), respectively. Positive associations were observed for maternal betaine (slope = 0.875, 95% CI 0.118; 1.633, p = 0.0241) and folate (slope = 0.685, 95% CI 0.245; 1.125, p = 0.0027) intake before pregnancy and RXRA methylation. Buccal DNMT1 methylation in the infant was negatively associated with maternal methyl-group donor intake in the first and second trimester of pregnancy and negatively in the third trimester. We found no clear association between maternal choline intake during lactation and buccal infant DNA methylation. CONCLUSIONS: This study suggests that maternal dietary and supplemental intake of methyl-group donors, especially in the periconception period, can influence infant's buccal DNA methylation in genes related to metabolism, growth, appetite regulation, and maintenance of DNA methylation reactions.

Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation.

Maternal nutrition is critically involved in the development and health of the fetus. We evaluated maternal methyl-group donor intake through diet (methionine, betaine, choline, folate) and supplementation (folic acid) before and during pregnancy in relation to global DNA methylation and hydroxymethylation and gene specific (IGF2 DMR, DNMT1, LEP, RXRA) cord blood methylation. A total of 115 mother-infant pairs were enrolled in the MAternal Nutrition and Offspring's Epigenome (MANOE) study. The intake of methyl-group donors was assessed using a food-frequency questionnaire. LC-MS/MS and pyrosequencing were used to measure global and gene specific methylation, respectively. Dietary intake of methyl-groups before and during pregnancy was associated with changes in LEP, DNMT1, and RXRA cord blood methylation. Statistically significant higher cord blood LEP methylation was observed when mothers started folic acid supplementation more than 6 months before conception compared with 3-6 months before conception (34.6 ± 6.3% vs. 30.1 ± 3.6%, P = 0.011, LEP CpG1) or no folic acid used before conception (16.2 ± 4.4% vs. 13.9 ± 3%, P = 0.036 for LEP CpG3 and 24.5 ± 3.5% vs. 22.2 ± 3.5%, P = 0.045 for LEP mean CpG). Taking folic acid supplements during the entire pregnancy resulted in statistically significantly higher cord blood RXRA methylation as compared with stopping supplementation in the second trimester (12.3 ± 1.9% vs. 11.1 ± 2%, P = 0.008 for RXRA mean CpG). To conclude, long-term folic acid use before and during pregnancy was associated with higher LEP and RXRA cord blood methylation, respectively. To date, pregnant women are advised to take a folic acid supplement of 400 µg/day from 4 weeks before until 12 weeks of pregnancy. Our results suggest significant epigenetic modifications when taking a folic acid supplement beyond the current advice.

Maternal Methyl-Group Donor Intake and Global DNA (Hydroxy)Methylation before and during Pregnancy.

It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxyl)methylation. Pregnancy methylation profiling and its link with methyl-group intake in a healthy population could enhance our understanding of the development of pregnancy related disorders. One hundred forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring's Epigenome) study. Thiry-four women were enrolled before pregnancy and 116 during the first trimester of pregnancy. Global DNA (hydroxy)methylation in blood using LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and choline) using a food-frequency questionnaire were estimated pre-pregnancy, during each trimester, and at delivery. Global DNA (hydroxy)methylation levels were highest pre-pregnancy and at weeks 18-22 of pregnancy. We observed a positive relation between folic acid and global DNA methylation (p = 0.04) and hydroxymethylation (p = 0.04). A high intake of methionine pre-pregnancy and in the first trimester showed lower (hydroxy)methylation percentage in weeks 11-13 and weeks 18-22, respectively. Choline and betaine intake in the first weeks was negatively associated with hydroxymethylation. Women with a high intake of these three methyl groups in the second and third trimester showed higher hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time trend in DNA (hydroxy)methylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy.