Vitamin D3 among neonates born after in vitro fertilization compared with neonates from the general population.

INTRODUCTION: Sufficient levels of vitamin D have been associated with higher chances for both clinical pregnancy and live birth among women undergoing assisted reproductive techniques, whereas low levels of maternal vitamin D have been associated with preeclampsia and late miscarriage. In Denmark, subgroups at risk for low vitamin D levels, including neonates and toddlers, are recommended to use supplementation. The aim was to study the level of vitamin D3 among neonates born after in vitro fertilization compared with neonates from the general population. MATERIAL AND METHODS: In this cohort study a random sample of 1326 neonates representing the general population and 1200 neonates conceived by in vitro fertilization born in Denmark from 1995 to 2002 were identified from registries covering the whole Danish population. Information on use of assisted reproduction was collected from the Danish In Vitro Fertilization register, ICD-10 code: DZ358F. 25-Hydroxyvitamin D was measured from dried blood spots routinely collected by heel prick 48-72 h after birth and corrected according to the hematocrit fraction for capillary blood of neonates. Linear regression analysis was performed, both crude and adjusted, for predefined putative confounders, identified through directed acyclic graphs. RESULTS: Vitamin D3 analysis could be performed from a total of 1105 neonates from the general population and 1072 neonates conceived by in vitro fertilization that were subsequently included in the study. The median vitamin D3 was 24.0 nmol/L (interquartile range [IQR] 14.1-39.3) and 33.0 nmol/L (IQR 21.3-48.8) among neonates from the general population and neonates conceived by in vitro fertilization, respectively. The adjusted mean difference between neonates from the general population and those conceived by in vitro fertilization was 6.1 nmol/L (95% confidence interval 4.1-8.1). CONCLUSIONS: In this study, children born after in vitro fertilization have a higher vitamin D3 than a random sample of neonates in Denmark.

Vitamin D Supplementation and Vitamin D Status during Pregnancy and the Risk of Congenital Anomalies-A Systematic Review and Meta-Analysis.

Maternal dietary factors have been suggested as possible contributing influences for congenital anomalies (CAs). We aimed to assess the association between vitamin D supplementation or vitamin D status (s-25OHD) during pregnancy and CAs in the offspring. A comprehensive literature search was conducted in the three electronic databases: PubMed, Embase, and Cochrane Library. Included studies were critically appraised using appropriate tools (risk of bias 2, ROBINS-I). A protocol was registered in the International Prospective Register of Systematic Reviews (CRD42019127131). A meta-analysis of four randomised controlled trials (RCTs) including 3931 participants showed no effect of vitamin D supplementation on CAs, a relative risk of 0.76 (95% CI 0.45; 1.30), with moderate certainty in the effect estimates by GRADE assessment. Of the nine identified observational studies, six were excluded due to a critical risk of bias in accordance with ROBINS-I. Among the included observational studies, two studies found no association, whereas one case-control study identified an association between s-25OHD < 20 nmol/L and neural tube defects, with an adjusted odds ratio of 2.34 (95% CI: 1.07; 5.07). Interpretation of the results should be cautious given the low prevalence of CAs, RCTs with onset of supplementation after organogenesis, and low-quality observational studies.

Association between intake of marine fat and adiposity development among children ages 2 to 6 y: Substitution analyses from the Healthy Start intervention study.

OBJECTIVES: A few previous studies have described a potential role of Ω-3 long-chain polyunsaturated fatty acids from marine animals in obesity in children, but the results are conflicting. The objectives of this study were to examine if intake of marine fat was related to less gain in body mass index (BMI) and body fat (BF) over a 15-mo period among Danish children age 2 to 6 y, and if potential associations depended on which types of fatty acids were replaced. METHODS: A total of 355 children age 2 to 6 y were included in the study. Weight, height, and BF percentage (BF%) assessed by bioimpedance were measured by trained research personnel. Multivariable linear regression models were used to investigate associations between marine fat intake and changes in BMI or BF% over the subsequent 15 mo. To investigate substitution effects, we constructed regression models that included marine fat and all other energy yielding dietary components, except for the nutrient to be substituted for either all fats or specific subgroups (saturated, monounsaturated, or other polyunsaturated fatty acids). RESULTS: No significant associations were observed between intake of marine fat and development in BMI or BF% in any of the analyses, either with or without specified substitutions. Furthermore, the results were independent on whether intake was expressed in g/d or percentage of energy, and were not modified by age or BMI status. CONCLUSIONS: This study suggests that marine fat intake and fat composition in a diet may have little or no effect on weight and adiposity development among preschool-aged children.

Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project.

By utilizing historical changes in Danish legislation related to mandatory vitamin D fortification of margarine, which was implemented in the mid 1930s and abruptly abandoned in June 1985, the studies in the D-tect project investigated the effects of vitamin D on health outcomes in individuals, who during gestation were exposed or unexposed to extra vitamin D from fortified margarine. This paper reviews and narratively summarizes the analytic approaches alongside the results of the societal fortification experiment studies from the D-tect project and addresses the challenges in designing societal experiment studies and evaluating their results. The latter are discussed as lessons learned that may be useful for designers of similar studies, expected to be extensively utilized while researching the health consequences of the COVID-19 pandemic by comparing individuals born before and after the epidemic. In the D-tect project, 16 articles based on the societal fortification experiment were published analyzing 10 different outcomes and using different statistical approaches. Lessons learned included the detail of the analysis of the historical information on the exposure, availability and validity of the outcome data, variety of analytical approaches, and specifics concerning vitamin D effect evaluation, such as consideration of the influence of sunshine or season. In conclusion, the D-tect project clearly demonstrated the cost-effectiveness and research potential of natural- or societal-experiment-based studies.

Systematic Literature Review and Meta-Analysis of the Relationship Between Polyunsaturated and Trans Fatty Acids During Pregnancy and Offspring Weight Development.

Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and trans fatty acids (TFAs) may have an impact on offspring weight development. We conducted a systematic review and meta-analysis according to PRISMA guidelines to evaluate whether levels of these fatty acids during pregnancy influenced offspring weight development. Randomized controlled trials (RCTs) with DHA and/or EPA supplementation or cohort studies, which examined levels of DHA, EPA, or TFAs in maternal or neonatal blood samples and recorded offspring weight, were included. Overall, 27 RCTs and 14 observational studies were identified. The results showed that DHA and/or EPA supplementation doses >650 mg/day resulted in slightly higher birth weight (MD 87.5 g, 95% CI 52.3-122.6, n = 3,831) and combined BMI and BMI z score at 5-10 years (SMD 0.11, 95% CI 0.04-0.18, n = 3,220). These results were rated as moderate quality. Results from the observational studies were generally inconsistent. High TFA levels during pregnancy seemed to be associated with lower birth weight. Finally, this review and meta-analysis supports a relationship between high maternal or neonatal DHA and/or EPA levels and higher offspring birth weight and weight in childhood. More high-quality long-term studies are still needed.

Vitamin D and Calcium Milk Fortification in Pregnant Women with Periodontitis: A Feasibility Trial.

This study aims to assess the acceptability, adherence, and retention of a feasibility trial on milk fortification with calcium and vitamin D (Ca+VitD) and periodontal therapy (PT) among low income Brazilian pregnant women with periodontitis (IMPROVE trial). This 2 × 2 factorial feasibility trial used a mixed-methods evaluation. In total, 69 pregnant women were randomly allocated to four groups: 1. fortified sachet with Ca+VitD and milk plus early PT (throughout gestation); 2. placebo and milk plus early PT; 3. fortified sachet with Ca+VitD and milk plus late PT after childbirth; 4. placebo and milk plus late PT. Data were collected via questionnaires, field notes, participant flow logs, treatment diary, and focal group discussions. Quantitative and qualitative data were analysed using appropriate descriptive statistics and content analysis, respectively. Eligibility rate (12%) was below the target of 15%, but participation (76.1%) and recruitment rate (2 women/week) exceeded the targets. Retention rate (78.6%) was slightly below the target (80%). Adherence to the PT was significantly higher in the early treatment groups (98.8%) compared to the late treatment groups (29%). All women accepted the random allocation, and baseline groups were balanced. There was no report of adverse events. This multi-component intervention is acceptable, well-tolerated, and feasible among low-risk pregnant women in Brazil.

The Role of Vitamin D in the Development of Diabetes Post Gestational Diabetes Mellitus: A Systematic Literature Review.

Women diagnosed with gestational diabetes mellitus (GDM) are more likely to later develop diabetes. Evidence from some previous reviews suggests that low vitamin D status during pregnancy increases the risk of developing GDM, but whether vitamin D during pregnancy also influences the risk of diabetes post GDM is less well studied. Thus, the aim of this systematic literature review was to summarize the current available literature on that topic. This review considered observational studies and randomized controlled trials (RCTs). Five databases were searched. The risk of bias of the included studies was assessed. A total of six studies were included: three observational studies and three RCTs. Findings were inconsistent across the six included studies. However, when considering RCTs only, the findings more strongly suggested that vitamin D supplementation during and after pregnancy did not have an influence on markers of diabetes development or diabetes development post GDM. This systematic review highlights inconsistent findings on the associations between vitamin D supplementation or concentration during and after pregnancy and markers of diabetes development or diabetes development post GDM; and although results from randomized interventional studies more strongly suggested no associations, the conclusion holds a high degree of uncertainty.

Neonatal Vitamin D Status and Risk of Asthma in Childhood: Results from the D-Tect Study.

BACKGROUND: low vitamin D status in pregnancy can influence the offspring's lung function and contribute to childhood asthma development. The objective of this study was to examine the influence of neonatal vitamin D status on the development of asthma among children age 3-9 years in a large population sample. METHOD: in a case-cohort study utilizing a Danish biobank and register data we examined the association between neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentrations and incidence of asthma among children aged 3-9 years. Cases of asthma (n = 911) were randomly selected among all cases of asthma in the Danish National Patient Register from children born between 1992 and 2002. The sub-cohort (n = 1423) was randomly selected among all children born in the same period. We used a weighted Cox proportional hazard model assessing the hazard of first asthma diagnoses by quintiles of 25(OH)D3. RESULTS: the median 25(OH)D3 (interquartile range) for asthma cases was 23 nmol/L (14-35) and the sub-cohort 25 nmol/L (14-40). The hazard ratio for developing asthma between ages 3 and 9 years was lower for children in the fifth quintile of neonatal 25(OH)D3 compared to children in the first quintile, both in the unadjusted (0.61 95% CI: 0.46-0.80) and adjusted (0.55 95% CI: 0.39-0.77) analyses. CONCLUSION: the results from our study suggest that higher neonatal vitamin D concentration may reduce the risk of developing childhood asthma at ages 3-9 years, indicating that neonatal vitamin D status as a proxy of vitamin D status during the prenatal period is important for normal immune- and lung development.

Substitution of sugar-sweetened beverages for other beverages and the risk of developing coronary heart disease: Results from the Harvard Pooling Project of Diet and Coronary Disease.

Sugar-sweetened beverage (SSB) intake is associated with metabolic disorders. The reduction of SSB intake has been promoted to prevent death and disability from chronic diseases. We investigated the association between SSB intake and the risk of coronary events and death, and assessed if substitution of coffee, tea, milk, fruit juice and artificially-sweetened beverages (ASB) for SSBs was associated with a reduced risk of coronary events and death. This was a follow-up study in which data from six studies were pooled and standard observational analyses were performed. Diet intake was assessed at baseline by food-frequency questionnaires. Hazard ratios (HRs) with 95% confidence intervals for the incidence of coronary events and deaths were calculated by Cox proportional hazards regression. The effect of substituting another beverage for SSBs was calculated by taking the difference in the individual effect estimates. During the median 8.2-year follow-up, 4248 coronary events and 1630 coronary deaths were documented among 284,345 individuals. 355 ml daily increase of SSB intake was associated with an increased risk of coronary events (HR: 1.08; 95%CI: 1.02, 1.14) and possibly coronary death (HR: 1.05; 95%CI: 0.96, 1.16). Substitution analyses suggested that replacing SSBs with coffee (HR: 0.93; 95%CI: 0.87, 1.00) or ASB (HR: 0.89; 95%CI: 0.83, 0.97), might be associated with a lower risk of developing coronary events. We found that SSB intake was associated with an increased risk of coronary events and possibly coronary death. Our findings also suggest that replacing SSB's with ASBs or coffee may lower the risk of developing CHD.

Prevalence of self-reported knee symptoms and management strategies among elderly individuals from Frederiksberg municipality: protocol for a prospective and pragmatic Danish cohort study.

INTRODUCTION: The Global Burden of Disease 2010 study ranked osteoarthritis (OA) as a leading cause of years lived with disability. With an ageing population, increasing body weight and sedentary lifestyle, a substantial increase especially in knee OA (KOA) is expected. Management strategies for KOA include non-pharmacological, pharmacological and surgical interventions. Meanwhile, over-the-counter pain medications have been discredited as they are associated with several risks with long-term usage. By consequence, the use of exercise and all sorts of complementary and alternative medicine (CAM) for joint pain has increased. The available self-management strategies are plenty, but there is no overview of their use at a population level and whether they are used along with doctors' prescriptions or replace these. The aim of this study is to estimate the population incidence of developing knee symptoms and analyse the association between (and impact of) the use of self-reported preventive measures and knee symptoms. METHODS AND ANALYSIS: This prospective cohort study pragmatically recruits individuals from the municipality of Frederiksberg, Denmark. All citizens aged 60-69 years old will be contacted annually for 10 years and asked to participate in a web-based survey. The major outcomes are self-reported knee symptoms and their association with use of various management strategies, including use of non-pharmacological treatments and CAM. Secondary outcomes include the influence of treatments on use of healthcare system and surgical procedures. Descriptive and analytic statistics (eg, logistic regression) will be used to provide summaries about the sample and observations made and the associations between self-management and development of knee symptoms. ETHICS AND DISSEMINATION: This study can be implemented without permission from the Health Research Ethics Committee. Permission has been obtained from the Danish Data Protection Agency. Study findings will be disseminated in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT03472300.

Exposure to Vitamin D Fortification Policy in Prenatal Life and the Risk of Childhood Asthma: Results From the D-Tect Study.

Prenatal vitamin D insufficiency may be associated with an increased risk of developing childhood asthma. Results from epidemiological studies are conflicting and limited by short follow-up and small sample sizes. The objective of this study was to examine if children born to women exposed to the margarine fortification policy with a small dose of extra vitamin D during pregnancy had a reduced risk of developing asthma until age 9 years, compared to children born to unexposed women. The termination of a Danish mandatory vitamin D fortification policy constituted the basis for the study design. We compared the risk of inpatient asthma diagnoses in all Danish children born two years before (n = 106,347, exposed) and two years after (n = 115,900, unexposed) the termination of the policy. The children were followed in the register from 0-9 years of age. Data were analyzed using Cox proportional hazards regression. The Hazard Ratio for the first inpatient asthma admission among exposed versus unexposed children was 0.96 (95%CI: 0.90-1.04). When stratifying by sex and age, 0-3 years old boys exposed to vitamin D fortification showed a lower asthma risk compared to unexposed boys (HR 0.78, 95%CI: 0.67-0.92). Prenatal exposure to margarine fortification policy with extra vitamin D did not affect the overall risk of developing asthma among children aged 0-9 years but seemed to reduce the risk among 0-3 years old boys. Taking aside study design limitations, this could be explained by different sensitivity to vitamin D from different sex-related asthma phenotypes in children with early onset, and sex differences in lung development or immune responses.

Duration of exclusive breastfeeding may be related to eating behaviour and dietary intake in obesity prone normal weight young children.

Infants who are breastfed are introduced to a variety of flavours from the maternal milk, and thus the transition from maternal milk to complementary foods may be easier for these children. The aim of this study was to investigate if duration of exclusive breastfeeding was associated with pickiness or dietary intake of vegetables, fruit, starchy foods or sugar sweetened beverages among obesity prone normal weight children aged 2-6 years. This cohort study was based on data from the Healthy Start primary intervention study, the Danish Medical Birth registry and the Danish Health Visitor's Child Health Database. Infant feeding was registered by health nurses while home-visiting the mother and child up to four times within the first year. Information on eating behaviour and diet intake at age 2-6 years was obtained by parents. Crude and adjusted logistic and general linear regression models were used to investigate associations. A total of 236 children had complete information on all variables. Data showed lower odds of picky eating behaviour when exclusively breastfed until age 4-5 months compared to exclusively breastfed for 0-1 months (OR = 0.35, 95CI = 0.16;0.76, p = 0.008). In the crude analysis only, exclusively breastfed until age 6-10 months was associated with a higher daily intake of vegetables (p = 0.04). This study suggests that exclusive breastfeeding duration seems to influence pickiness and may contribute to facilitate the consumption of more vegetables in later childhood in obesity prone normal weight children.

Extra vitamin D from fortification and the risk of preeclampsia: The D-tect Study.

The objective of the study was to examine if exposure to extra vitamin D from food fortification was associated with a decrease in the risk of preeclampsia. The study was based on a natural experiment exploring the effect of the abolition of the Danish mandatory vitamin D fortification of margarine in 1985. The effect of the extra vitamin D (1.25µg vitamin D/100 g margarine) was examined by comparing preeclampsia risk in women who have been exposed or unexposed to extra vitamin D from the fortified margarine during pregnancy, and who gave birth in the period from June 1983 to August 1988. The Danish National Patient Registry allowed the identification of pregnancies complicated by preeclampsia. The study included 73,237 women who gave birth during 1983-1988. We found no association between exposure to vitamin D fortification during pregnancy and the risk of any of the pregnancy related hypertensive disorders, including preeclampsia: Odds ratios (OR, 95%) for all hypertensive pregnancy related disorders among exposed vs. unexposed women was (OR 1.04, 95%CI: 0.98,1.10). In conclusion, the extra vitamin D from the mandatory vitamin D fortification did not influence the risk of preeclampsia.