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.

Newly Diagnosed Celiac Disease and Bone Health in Young Adults: A Systematic Literature Review.

Celiac disease (CD), a gluten-induced autoimmune disease, is associated with low bone mineral density (BMD) among children. Unfortunately, it is often diagnosed in adulthood, which may lead to an increased risk of fragile bones. The aim of this systematic review was to report on BMD status among young adults newly diagnosed with CD, and to examine the effect of a gluten-free diet (GFD), nutritional supplements, such as vitamin D, or antiresorptive medications on BMD recovery. Databases searched were Medline, Embase, and Cochrane Library up to July 2nd, 2020. Both observational studies and clinical trials were considered, if patients were newly diagnosed and between 20 and 35 years of age and reported on BMD. We critically appraised the identified studies using ROBINS-I and summarized the findings narratively. Out of 3991 references, we identified 3 eligible studies: one cross-sectional study and two longitudinal studies. In total, 188 patients were included, and the study population consisted primarily of women with an age range between 29 and 37 years old. Compared to healthy controls, our target population had lower BMD. Moreover, a strict GFD may increase BMD during a follow-up period of up to 5 years. Newly diagnosed CD patients aged 20-35 years are at risk of lower BMD. Therefore, it may be crucial to assess BMD at time of diagnosis in young women. Whether the results can be extrapolated to young men is unknown. While strict GFD may improve BMD over time, there is a lack of robust evidence to demonstrate that nutritional supplements or antiresorptive agents are beneficial in the prevention of fragile bones in this age group.

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.

Efficacy and Safety of Polyunsaturated Fatty Acids Supplementation in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents: A Systematic Review and Meta-Analysis of Clinical Trials.

Based on epidemiological and animal studies, the rationale for using polyunsaturated fatty acids (PUFAs) as a treatment for Attention Deficit Hyperactivity Disorder (ADHD) seems promising. Here, the objective was to systematically identify and critically assess the evidence from clinical trials. The primary outcome was ADHD core symptoms. The secondary outcomes were behavioral difficulties, quality of life, and side effects. We performed a systematic search in Medline, Embase, Cinahl, PsycInfo, and the Cochrane Library up to June 2020. The overall certainty of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified 31 relevant randomized controlled trials including 1755 patients. The results showed no effect on ADHD core symptoms rated by parents (k = 23; SMD: -0.17; 95% CI: -0.32, -0.02) or teachers (k = 10; SMD: -0.06; 95% CI: -0.31, 0.19). There was no effect on behavioral difficulties, rated by parents (k = 7; SMD: -0.02; 95% CI: -0.17, 0.14) or teachers (k = 5; SMD: -0.04; 95% CI: -0.35, 0.26). There was no effect on quality of life (SMD: 0.01; 95% CI: -0.29, 0.31). PUFA did not increase the occurrence of side effects. For now, there seems to be no benefit of PUFA in ADHD treatment; however, the certainty of evidence is questionable, and thus no conclusive guidance can be made. The protocol is registered in PROSPERO ID: CRD42020158453.

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.

Prenatal exposure to vitamin D from fortified margarine and risk of fractures in late childhood: period and cohort results from 222 000 subjects in the D-tect observational study.

Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification programme, we examined the risk of fractures among 10-18-year-old children from proximate birth cohorts born around the date of the termination of the programme. For all subjects born in Denmark during 1983-1988, civil registration numbers were linked to the Danish National Patient Registry for incident and recurrent fractures occurring at ages 10-18 years. Multiplicative Poisson models were used to examine the association between birth cohort and fracture rates. The variation in fracture rates across birth cohorts was analysed by fitting an age-cohort model to the data. We addressed the potential modification of the effect of vitamin D availability by season of birth. The risk of fractures was increased among both girls and boys who were born before the vitamin D fortification terminated in 1985 (rate ratio (RR) exposed v. non-exposed girls: 1·15 (95 % CI 1·11, 1·20); RR exposed v. non-exposed boys: 1·11 (95 % CI 1·07, 1·14). However, these associations no longer persisted after including the period effects. There was no interaction between season of birth and vitamin D availability in relation to fracture risk. The study did not provide evidence that prenatal exposure to extra vitamin D from a mandatory fortification programme of 1·25 µg vitamin D/100 g margarine was sufficient to influence the risk of fractures in late childhood, regardless of season of birth. Replication studies are needed.