An Unhealthy Dietary Pattern during Pregnancy is Associated with Neurodevelopmental Disorders in Childhood and Adolescence.

Despite the high prevalence of neurodevelopmental disorders, there are a lack of clinical studies examining the impact of pregnancy diet on child neurodevelopment. This observational clinical study examined the associations between pregnancy dietary patterns and neurodevelopmental diagnoses, as well as their symptoms, in a prospective cohort of 10-year-old children (n=508). Data-driven dietary patterns were derived from self-reported food frequency questionnaires. An Unhealthy dietary pattern in pregnancy (per SD change) was significantly associated with attention deficit hyperactivity disorder (ADHD) OR 1.66 [1.21 - 2.27], p=0.002 and autism diagnosis OR 2.22 [1.33 - 3.74], p=0.002 and associated symptoms p<0.001. Findings for ADHD were validated in two large (n=656, n=348), independent mother-child cohorts via blood metabolome modelling. Objective metabolite scores, assessed at five timepoints in mothers and children in two independent mother-child cohorts, indicated that the strongest association with ADHD was during early-to mid-pregnancy. These results provide evidence for targeted prenatal dietary interventions to prevent neurodevelopmental disorders in children.

No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. METHODS: The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. RESULTS: There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. CONCLUSIONS/INTERPRETATION: Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.

Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis.

INTRODUCTION: Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. METHODS: We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. RESULTS: Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 µIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. CONCLUSIONS: Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.

Determinants of exposure to acrylamide in European children and adults based on urinary biomarkers: results from the "European Human Biomonitoring Initiative" HBM4EU participating studies.

Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (ß coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:ß = - 9.1 µg/g creatinine, 95% CI - 15.8, - 2.4; GAMA: ß = - 3.4 µg/g creatinine, 95% CI - 4.7, - 2.2), living in rural areas (AAMA:ß = - 4.7 µg/g creatinine, 95% CI - 8.6, - 0.8; GAMA:ß = - 1.1 µg/g creatinine, 95% CI - 1.9, - 0.4) and increasing age (AAMA:ß = - 1.9 µg/g creatinine, 95% CI - 2.4, - 1.4; GAMA:ß = - 0.7 µg/g creatinine, 95% CI - 0.8, - 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries.

Time Patterns in Internal Human Exposure Data to Bisphenols, Phthalates, DINCH, Organophosphate Flame Retardants, Cadmium and Polyaromatic Hydrocarbons in Europe.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy - Study design and characteristics of participants.

BACKGROUND: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. METHODS: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. RESULTS: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and <50% of Greek, Cypriot and Icelandic women reported that they had consumed big oily fish. Relevant to non-dietary exposure sources, most participants (>90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. CONCLUSIONS: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.

Postpartum pelvic organ prolapse and pelvic floor muscle training: secondary analysis of a randomized controlled trial of primiparous women.

INTRODUCTION AND HYPOTHESIS: Pelvic floor dysfunction is common after childbirth. We hypothesize that physiotherapist-guided pelvic floor muscle training (PFMT) is effective regarding pelvic organ prolapse (POP) symptoms during the first postpartum year. METHODS: This was a secondary analysis from a randomized controlled trial (RCT), carried out at a physiotherapy clinic, Reykjavik. Participants were eighty-four primiparous women with a singleton delivery. They were screened for eligibility 6-13 weeks postpartum. Women in a training group conducted 12 weekly individual sessions with a physiotherapist within an RCT, starting on average 9 weeks postpartum. Outcomes were assessed after the last session (short term) and at approximately 12 months postpartum (long term). The control group received no instructions after the initial assessment. Main outcome measures were self-evaluated POP symptoms by the Australian Pelvic Floor Questionnaire. RESULTS: Forty-one and 43 women were in the training and control groups, respectively. At recruitment, 17 (42.5%) of the training group and 15 (37%) of the control group reported prolapse symptoms (p = 0.6). Five (13%) from the training group and nine (21%) controls were bothered by the symptoms (p = 0.3). There was a gradual decrease in the number of women with symptoms and no significant short-term (p = 0.08) or long-term (p = 0.6) differences between the groups regarding rates of women with POP symptoms. The difference between groups regarding bother in the short (p = 0.3) or longer term (p = 0.4) was not significant. Repeated-measures analyses using Proc Genmod in SAS did not indicate a significant effect of the intervention over time (p > 0.05). CONCLUSIONS: There was an overall decrease in postpartum symptoms of POP and bother during the first year. Physiotherapist-led PFMT did not change the outcomes. CLINICAL TRIAL REGISTRATION: The trial was registered 30 March 2015 at https://register. CLINICALTRIALS: gov (NCT02682212). Initial participant enrollment was on 16 March 2016 and reported following CONSORT guidelines for randomized controlled trials.

Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014-2021).

As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.

Glyphosate and AMPA in Human Urine of HBM4EU-Aligned Studies: Part B Adults.

Within HBM4EU, human biomonitoring (HBM) studies measuring glyphosate (Gly) and aminomethylphosphonic acid (AMPA) in urine samples from the general adult population were aligned and quality-controlled/assured. Data from four studies (ESB Germany (2015-2020); Swiss HBM4EU study (2020); DIET-HBM Iceland (2019-2020); ESTEBAN France (2014-2016)) were included representing Northern and Western Europe. Overall, median values were below the reported quantification limits (LOQs) (0.05-0.1 µg/L). The 95th percentiles (P95) ranged between 0.24 and 0.37 µg/L urine for Gly and between 0.21 and 0.38 µg/L for AMPA. Lower values were observed in adults compared to children. Indications exist for autonomous sources of AMPA in the environment. As for children, reversed dosimetry calculations based on HBM data in adults did not lead to exceedances of the ADI (proposed acceptable daily intake of EFSA for Gly 0.1 mg/kg bw/day based on histopathological findings in the salivary gland of rats) indicating no human health risks in the studied populations at the moment. However, the controversy on carcinogenicity, potential endocrine effects and the absence of a group ADI for Gly and AMPA induce uncertainty to the risk assessment. Exposure determinant analysis showed few significant associations. More data on specific subgroups, such as those occupationally exposed or living close to agricultural fields or with certain consumption patterns (vegetarian, vegan, organic food, high cereal consumer), are needed to evaluate major exposure sources.

Impact of fibre and red/processed meat intake on treatment outcomes among patients with chronic inflammatory diseases initiating biological therapy: A prospective cohort study.

Background: Biologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies. Objective: To investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID. Methods: In this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14-16 weeks of treatment. Results: Of the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group (N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group (N = 129), but the difference was not statistically significant (OR: 1.48, 0.72-3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35-71.56). Conclusion: Habitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial. Trial registration: (clinicaltrials.gov), identifier [NCT03173144].

Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study): A protocol for an observational longitudinal case-control study.

Recent studies indicate that the interplay between diet, intestinal microbiota composition, and intestinal permeability can impact mental health. More than 10% of children and adolescents in Iceland suffer from mental disorders, and rates of psychotropics use are very high. The aim of this novel observational longitudinal case-control study, "Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study)" is to contribute to the promotion of treatment options for children and adolescents diagnosed with mental disorders through identification of patterns that may affect the symptoms. All children and adolescents, 5-15 years referred to the outpatient clinic of the Child and Adolescent Psychiatry Department at The National University Hospital in Reykjavik, Iceland, for one year (n≈150) will be invited to participate. There are two control groups, i.e., sex-matched children from the same postal area (n≈150) and same parent siblings (full siblings) in the same household close in age +/- 3 years (n<150). A three-day food diary, rating scales for mental health, and multiple questionnaires will be completed. Biosamples (fecal-, urine-, saliva-, blood samples, and buccal swab) will be collected and used for 16S rRNA gene amplicon sequencing of the oral and gut microbiome, measurements of serum factors, quantification of urine metabolites and host genotype, respectively. For longitudinal follow-up, data collection will be repeated after three years in the same groups. Integrative analysis of diet, gut microbiota, intestinal permeability, serum metabolites, and mental health will be conducted applying bioinformatics and systems biology approaches. Extensive population-based data of this quality has not been collected before, with collection repeated in three years' time, contributing to the high scientific value. The MMM-study follows the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) guidelines. Approval has been obtained from the Icelandic National Bioethics Committee, and the study is registered with Clinicaltrials.gov. The study will contribute to an improved understanding of the links between diet, gut microbiota and mental health in children through good quality study design by collecting information on multiple components, and a longitudinal approach. Furthermore, the study creates knowledge on possibilities for targeted and more personalized dietary and lifestyle interventions in subgroups. Trial registration numbers: VSN-19-225 & NCT04330703.

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies.

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.

Improving the Risk Assessment of Pesticides through the Integration of Human Biomonitoring and Food Monitoring Data: A Case Study for Chlorpyrifos.

The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food consumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers' exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer's internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.

Maternal acrylamide exposure during pregnancy and fetal growth: A systematic review and dose-response meta-analysis of epidemiological studies.

BACKGROUND: Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans. OBJECTIVES: We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the relationship between maternal acrylamide exposure during pregnancy and the risk of being small for gestational age (SGA) and birth weight, birth head circumference and birth length. METHODS: We performed the literature search in PubMed, Scopus, and Web of Science, until June 6th, 2022. Studies carried out in mother-newborn pairs, assessing maternal acrylamide exposure during pregnancy, either via dietary assessments or biomarkers i.e., hemoglobin adducts of acrylamide (AA-Hb) and glycidamide (GA-Hb), and evaluating birth outcomes were included. We employed a random-effects model to assess the pooled effect estimates and their 95% confidence intervals (CI) for the association between acrylamide exposure and birth outcomes. Risk of Bias for Nutrition Observational Studies tool was used for bias assessment. RESULTS: Out of 169 records identified, five original studies were eligible, including 53,870 mother-newborn pairs in total. Means were 21.9 µg/day for estimated dietary acrylamide exposure (3 studies), and 18.4 and 14.9 pmol/g for AA-Hb and GA-Hb, respectively (2 studies). Higher risk of SGA and lower birth weight and head circumference were observed in the highest quartile of AA-Hb [odds ratio (OR): 1.20 (95% CI: 1.08; 1.33); mean difference (MD): -131 g (95% CI: -204; -58) and -0.31 cm (95% CI: -0.58; -0.04), respectively], and GA-Hb [OR: 1.36 (95% CI: 1.13; 1.64), MD: -161 g (95% CI: -271; -52); and MD: -0.38 cm (95% CI: -0.66; -0.10), respectively], whereas a lower birth length was observed only in the highest quartile of GA-Hb (MD: -0.85 cm (95% CI: -1.38; -0.33). Results from the dose-response meta-analysis between increasing maternal acrylamide exposure during pregnancy and birth weight showed no clear evidence of a deviation from linearity. CONCLUSIONS: Overall, our findings strengthen the evidence of an adverse effect of maternal acrylamide exposure during pregnancy on fetal growth. These results encourage to increase preventive actions towards lowering acrylamide exposure in the population.

[Correlation between intake of fish or supplements containing omega-3 fatty acids and early pregnancy plasma concentrations.]

INTRODUCTION: Long-chain polyunsaturated omega-3 fatty acids are considered important for fetal development, but previous studies suggest suboptimal intake in part of pregnant women in Iceland. The study aim was to evaluate intake of food and supplements containing omega-3 fatty acids, among pregnant women in Iceland and correlations to fatty acid composition in plasma. MATERIALS AND METHODS: Subjects were 853 pregnant women attending their 11-14 weeks ultrasound appointment. Information on intake of food and supplements containing long-chain omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) as well as background was obtained by a questionnaire. Blood samples were collected for analysis of plasma fatty acids. Correlation was evaluated using the Spearman correlation. RESULTS: Median intake of lean fish was 1.3 times per week, while fatty fish was consumed once monthly. About 50% of the women took omega-3 containing supplements daily. Higher intake of both fish and omega-3 containing supplements was reflected in higher omega-3 plasma levels (r=0.37 p<0.001). A positive correlation was seen between intake of cod liver oil/capsules (r=0.23, p=0.001), omega-3 oil/capsules (r=0.20, p=0.001) and plasma concentration of omega-3. However, no correlation was seen between intake of a maternal multivitamin containing omega-3 and corresponding plasma concentration (r=0.03, p=0.98). CONCLUSION: Intake of food and supplements containing omega-3 fatty acids was reflected in plasma concentration, except for an Icelandic maternal multivitamin. One third of the women followed the recommendation of eating fish at least twice weekly. About 50% had a daily intake of supplements containing omega-3 fatty acids.

Dietary Acrylamide Exposure and Risk of Site-Specific Cancer: A Systematic Review and Dose-Response Meta-Analysis of Epidemiological Studies.

Diet is a main source of acrylamide exposure to humans. Existing observational data on the relationship between dietary exposure to acrylamide and risk of cancer are inconsistent. We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the association between dietary acrylamide exposure and several site-specific cancer. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases until March 7, 2022. Studies were eligible if they were carried out in non-occupationally exposed adults, assessed dietary acrylamide exposure (µg/day) and reported risk estimates of cancer incidence (all but gynecological cancers). Using a random-effects model, we performed a meta-analysis of site-specific cancer risk comparing the highest vs. lowest category of dietary acrylamide exposure. We also carried out a one-stage dose-response meta-analysis assessing the shape of the association. Out of 1,994 papers screened, 31 were eligible (total of 16 studies), which included 1,151,189 participants in total, out of whom 48,175 developed cancer during the median follow-up period of 14.9 years (range 7.3-33.9). The mean estimated dose of dietary acrylamide across studies was 23 µg/day. Pooled analysis showed no association between the highest vs. lowest dietary acrylamide exposure and each site-specific cancer investigated, with no evidence of thresholds in the dose-response meta-analysis. There were also no associations between dietary acrylamide exposure and the risk of cancers when stratifying by smoking status, except for increased risk of lung cancer in smokers. In conclusion, high dietary acrylamide exposure was not associated with an increased risk of site-specific non-gynecological cancer.

Lower Intake of Saturated Fatty Acids Is Associated with Improved Lipid Profile in a 6-Year-Old Nationally Representative Population.

To strengthen the organization of new national dietary surveys and interventions in childhood, our aim was to study macronutrient intake and blood lipid profile at 6 years of age by comparing results from two earlier population-based cohorts. Subjects were n = 131 and n = 162 in the years 2001−2002 and 2011−2012, respectively. Three-day weighed food records were used to estimate diet and calculate nutrient intake. Total cholesterol, HDL-cholesterol and triacylglycerol were measured in serum and LDL-cholesterol was calculated. The average intake of saturated fatty acids (SFA) and trans FA was lower in 2011−2012 than 2001−2002 (13.3E% vs. 14.7E%, p < 0.001, and 0.8E% vs. 1.4E%, p < 0.001, respectively), replaced by a higher intake of unsaturated fatty acids. Total cholesterol and LDL-cholesterol were significantly lower in 2011−2012 than 2001−2002 (4.6 vs. 4.4 mmol/L, p = 0.003 and 2.8 vs. 2.5 mmol/L, p < 0.001, respectively). In a multiple linear regression model, one E% increase in SFA intake was related to a 0.03 mmol/L increase in LDL cholesterol (p = 0.04). A lower intake of saturated and trans fatty acids, replaced by unsaturated fatty acids, may have contributed to an improved lipid profile in a healthy 6-year-old population. Biological data for analysis of blood lipids are important in national dietary surveys in healthy children to monitor important health outcomes of interventions.

Growth Rate in Childhood and Adolescence and the Risk of Breast and Prostate Cancer: A Population-Based Study.

Growth rate is regulated by hormonal pathways that might affect early cancer development. We explored the association between rate of growth in height from ages 8 to 13 years (childhood) and from age 13 to attainment of adult height (adolescence), as measured at study entry, and the risk of breast or prostate cancer. Participants were 2,037 Icelanders born during 1915-1935, who took part in the Reykjavik Study, established in 1967. Height measurements were obtained from school records and at study entry. We used multivariable Cox regression models to calculate hazard ratios with 95% confidence intervals of breast and prostate cancer by rates of growth in tertiles. During a mean follow-up of 66 years (women) and 64 years (men), 117 women were diagnosed with breast cancer and 118 men with prostate cancer (45 with advanced disease). Women in the highest growth-rate tertile in adolescence had a higher risk of breast cancer (hazard ratio = 2.4, 95% confidence interval: 1.3, 4.3) compared with women in the lowest tertile. A suggestive inverse association was observed for highest adolescent growth rate in men and advanced prostate cancer: hazard ratio = 0.4, 95% confidence interval: 0.2, 1.0. Rapid growth, particularly in adolescence may affect cancer risk later in life.

Serum 25-Hydroxy-Vitamin D Status and Incident Hip Fractures in Elderly Adults: Looking Beyond Bone Mineral Density.

Observational studies have consistently reported a higher risk of fractures among those with low levels of serum 25-hydroxyvitamin D (25(OH)D). Emerging evidence suggests that low serum 25(OH)D levels may increase the rate of falls through impaired physical function. Examine to what extent baseline measures of volumetric bone mineral density (vBMD), absolute bone mineral content (BMC), and markers of physical function may explain incident hip fractures in older adults with different serum levels of 25(OH)D. A prospective study of 4309 subjects (≥66 years) recruited between 2002 and 2006 into the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study. Hip fractures occurring until the end of 2012 were extracted from hospital records. Prevalence of serum 25(OH)D deficiency (<30 nmol/L), inadequacy (30-<50 nmol/L), and sufficiency (≥50 nmol/L) was 6%, 23%, and 71% for males; and 11%, 28%, and 53% for females, respectively. Female participants had ~30% lower absolute BMC compared to males. Serum 25(OH)D concentrations were positively associated with vBMD and BMC of the femoral neck and markers of physical function, including leg strength and balance. Those who had deficient compared to sufficient status at baseline had a higher age-adjusted risk of incidence hipfractures with hazard ratios (HRs) of 3.1 (95% confidence interval [CI], 1.9-5.2) and 1.8 (95% CI, 1.3-2.5) among males and females, respectively. When adjusting for vBMD and measures of physical function, the association was attenuated and became nonsignificant for males (1.3; 95% CI, 0.6-2.5) but remained significant for females (1.7; 95% CI, 1.1-2.4). Deficient compared to sufficient serum 25(OH)D status was associated with a higher risk of incident hip fractures. This association was explained by poorer vBMD and physical function for males but to a lesser extent for females. Lower absolute BMC among females due to smaller bone volume may account for these sex-specific differences. © 2021 American Society for Bone and Mineral Research (ASBMR).