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The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review.
Prono, F, Bernardi, K, Ferri, R, Bruni, O
International journal of molecular sciences. 2022;23(3)
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Vitamin D deficiency or insufficiency is a global epidemic, estimated to affect over one billion people worldwide, including children. The main function of vitamin D is the regulation of bone homeostasis but it is also involved in many other conditions such as cardiovascular disease, cancer, diabetes mellitus and autoimmune disorders. Recent studies show that sufficient levels of vitamin D seem to be necessary to maintain sleep and low vitamin D levels have been associated with shorter sleep duration. This systematic review is the first to assess the association between Vitamin D and sleep disorders in children, 14 articles were included. Vitamin D deficiency in children is associated with decreased sleep duration and poorer sleep efficiency, as well as with delayed bedtimes. Children with reduced vitamin D serum levels have a higher risk of excessive daytime sleepiness (EDS). Since vitamin D levels influence sleep duration, sleep duration can also influence vitamin D serum concentration suggesting a bidirectional relationship. Evidence is scarce and so further high-quality prospective cohort studies and well-designed randomized controlled trials (RCTs) are needed to determine the effect of vitamin D supplementation in children with sleep disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Vitamin D plays an important role in the sleep quality of children. Healthcare practitioners may wish to establish vitamin D status in children presenting with sleep disturbances.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Vitamin D levels have been associated with improved sleep in adults, but few studies have concentrated on the paediatric population. In order to identify if vitamin D plays a role regulating sleep in children and adolescents the paper reviewed studies, which looked at vitamin D in relation to sleep duration and quality of sleep. This included the following sleep disorders: obstructive sleep apnoea (OSA), restless leg syndrome (RLS) and insomnia.
Methods
- A broad systematic review following the PRISMA guidelines and using PubMed and Cochrane databases
- Search identified 748 papers. After exclusions for non-relevance, incorrect age group, or lack of data on sleep, 14 papers were included
- Due to the shortage of papers on this topic none of these papers were excluded, regardless of quality
- The participants in each study varied from 39 to 5289.
Results
The results highlighted:
- Plasma levels of vitamin D affect sleep duration and quality of sleep in children. Data taken from 5 studies
- Vitamin D cord blood levels were correlated to sleep in preschool children. Partly this was due to the mother’s vitamin D level during pregnancy affecting the level of vitamin D available to the foetus. Venous blood vitamin D level was linked to the sleep wake cycle of children. Data taken from 2 studies
- OSA was more likely to develop in children who had low vitamin D levels with a risk of 14.16% compared to a control group of 5.83% (1 study)
- Vitamin D supplementation was found to reduce neuron damage caused by hypoxia (1 study)
- An association exists between parental vitamin D insufficiency and their child’s vitamin D status (1 study). Data taken from 5 studies
- Vitamin D levels in specific diseases, such as coeliac disease (CD) showed a negative correlation with RLS
- For familial Mediterranean fever (FMF) vitamin D deficiency reduced sleep quality (36.5%). Data taken from 2 studies.
Conclusion
Notwithstanding the small number of studies, the review shows vitamin D deficiency, defined as <20 ng/mL, is associated with an increased risk for sleep disorders in children.
Clinical practice applications:
- Due to the role vitamin D plays in sleep in children, establishing vitamin D status may be useful for children presenting with sleep disturbances
- Adequate vitamin D levels during pregnancy are important to establish a vitamin D pool in the foetus
- Vitamin D supplementation is something to rule out in the case of OSA and associated hypoxia, metabolic dysfunction and systemic inflammation in children
- Due to the negative impact poor sleep has on the body, improving sleep quality at a young age could form an important part of preventative health care.
Considerations for future research:
- Additional studies are required to support the conclusion in this study
- Due to the low number of studies, any additional research should be of a high standard and include prospective cohort studies and randomised control trials.
Abstract
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.
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Effects of Vitamin D Supplementation During Pregnancy on Birth Size: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Maugeri, A, Barchitta, M, Blanco, I, Agodi, A
Nutrients. 2019;11(2)
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Vitamin D deficiency may affect mother and neonatal outcomes, increasing the risk of pregnancy complications, preterm birth, low birth weight (LBW), small for gestational age (SGA), and poor offspring health. This systematic review and meta-analysis evaluates the effects of oral vitamin D supplementation during pregnancy on foetal growth and incidence of LBW and SGA births. 13 randomised controlled trials (RCTs), published between 1980 and 2016, were included in the meta-analysis, including in total 2016 newborns (1184 from mothers in the intervention groups and 832 from controls). Dosages ranged from 200-4000 IU for daily intakes and 35000 IU to 600000 IU for single or intermittent administration. Whilst there was no evidence for publication bias (e.g. an over-reporting of positive outcomes), overall, the quality of the reviewed studies varied from very low (head circumference) to moderate (birth weight, birth length, LBW, and SGA). All studies evaluating the effect of vitamin D supplementation on blood 25-hydroxyvitamin D (OHD) levels showed that intervention significantly increased 25-OHD concentration in both mothers and infants. The meta-analysis showed that vitamin D supplementation significantly increased birth weight and length, independent of dosage and whether vitamin D was administered daily or in single/intermittent high dosages. Head circumference was increased in a non-dose dependent way with daily but not with single/intermittent vitamin D supplementation. Effects on all three parameters were seen when vitamin D was supplemented alone, but not in combination with other nutrients. Both, risk of LBW and SGA, were also significantly reduced with vitamin D supplementation.
Abstract
During pregnancy, vitamin D supplementation may be a feasible strategy to help prevent low birthweight (LBW) and small for gestational age (SGA) births. However, evidence from randomized controlled trials (RCTs) is inconclusive, probably due to heterogeneity in study design and type of intervention. A systematic literature search in the PubMed-Medline, EMBASE, and Cochrane Central Register of Controlled Trials databases was carried out to evaluate the effects of oral vitamin D supplementation during pregnancy on birthweight, birth length, head circumference, LBW, and SGA. The fixed-effects or random-effects models were used to calculate mean difference (MD), risk ratio (RR), and 95% Confidence Interval (CI). On a total of 13 RCTs, maternal vitamin D supplementation had a positive effect on birthweight (12 RCTs; MD = 103.17 g, 95% CI 62.29⁻144.04 g), length (6 RCTs; MD = 0.22 cm, 95% CI 0.11⁻0.33 cm), and head circumference (6 RCTs; MD:0.19 cm, 95% CI 0.13⁻0.24 cm). In line with these findings, we also demonstrated that maternal vitamin D supplementation reduced the risk of LBW (3 RCTs; RR = 0.40, 95% CI 0.22⁻0.74) and SGA (5 RCTS; RR = 0.69, 95% CI 0.51⁻0.92). The present systematic review and meta-analysis confirmed the well-established effect of maternal vitamin D supplementation on birth size. However, further research is required to better define risks and benefits associated with such interventions and the potential implications for public health.
3.
Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.
Martineau, AR, Jolliffe, DA, Hooper, RL, Greenberg, L, Aloia, JF, Bergman, P, Dubnov-Raz, G, Esposito, S, Ganmaa, D, Ginde, AA, et al
BMJ (Clinical research ed.). 2017;356:i6583
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Acute respiratory tract infections are responsible for more than 2.5 million deaths worldwide. Previous studies report consistent associations between low vitamin D levels and an increased risk of acute respiratory tract infection. Vitamin D may protect against respiratory pathogens of viral and bacterial origin, due to antimicrobial and other mechanisms. This paper is a systematic review and meta-analysis of 25 randomised double-blind placebo controlled trials of vitamin D supplementation for the prevention of acute respiratory tract infection. The trials were conducted in 14 countries in 4 continents and included a total of 11,321 participants of both sexes, aged 0-95 years. The follow-up durations ranged from seven weeks to 1.5 years. All studies administered vitamin D3 orally, using either daily or weekly doses or bolus doses 1-3 months apart, or combined daily and bolus doses. Individual participant data were obtained from 96.6% of participants. The majority of studies that were included in the analyses were considered to be of a high quality, with a low risk of bias. The analyses showed that vitamin D supplementation reduced the risk of acute respiratory tract infections among all participants. The strongest positive effects were seen in those with baseline vitamin D levels less than 25 nmol/l, when compared to those with levels higher than 25 nmol/l, although benefits were also seen in the latter. Furthermore, daily or weekly vitamin D supplementation, without additional bolus doses were shown to protect against acute respiratory tract infections, while regimens with large bolus doses did not. The authors concluded that people who are very deficient in vitamin D are most likely to benefit from daily or weekly vitamin D supplementation, without additional bolus doses, in the prevention of acute respiratory tract infections. They call for the introduction of public health measures, such as food fortification, to improve vitamin D status, particularly in settings where vitamin D deficiency is common.
Abstract
Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.