Assigment .Apa seven . All instructions attached.

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Vitamin D and Fracture Risk in Early Childhood: A Case-Control Study

Anisley Longa

PMHNP Post-Master

NGR5674-Population Health, Epidemiology, & Statistical Problems

Professor Diane Gullett, RN, PhD, MSN, MPH

07/09/2023

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SYSTEMATIC REVIEW

Citation: Anderson, L. N., Heong, S. W., & Chen, Y. et al. (2017). Vitamin D and fracture risk in early

childhood: a case-control study. American Journal of Epidemiology, 185(12), 1255– 1262. https://doi.org/10.1093/aje/kww204

Study Design: Case-control Study

Level of Evidence: IV

Clinical Problem: Fractures are common injuries in childhood, with significant implications for a child's health and well-being. Adequate bone health is crucial during early childhood, as this is a period of rapid skeletal growth and development. Vitamin D plays a vital role in maintaining healthy bones and preventing fractures. Therefore, understanding the relationship between vitamin D and fracture risk in early childhood is essential for optimizing pediatric care.

PICO Question: In children aged 1-6 years (P), does adequate vitamin D status (I) compared to inadequate vitamin D status (C) reduce the risk of fractures (O) during early childhood (T)?

Literature Review: Vitamin D is a fat-soluble vitamin that is primarily obtained through sunlight exposure and dietary sources. It plays a crucial role in maintaining calcium and phosphate homeostasis, which are essential for bone mineralization and skeletal health. Inadequate levels of vitamin D can lead to reduced calcium absorption, resulting in weakened bones and an increased risk of fractures. Fracture risk in early childhood is influenced by multiple factors, including genetic predisposition, nutritional status, physical activity levels, and environmental factors. However, vitamin D deficiency has emerged as a significant modifiable risk factor for fractures in this population. Several studies have investigated the association between vitamin D status and fracture risk in early childhood. A systematic review published in 2020 analyzed the findings from 24 studies and found that children with low vitamin D levels were at a higher risk of fractures compared to those with sufficient levels. The review also highlighted that the effect of vitamin D on fracture risk may be more pronounced in certain populations, such as children with chronic diseases or those living in regions with limited sunlight exposure. The evidence suggests that optimizing vitamin D status in early childhood may help reduce the risk of fractures. Healthcare professionals should be vigilant about identifying children at risk of vitamin D deficiency, including those with limited sunlight exposure, darker skin pigmentation, and inadequate dietary intake. .

Introduction/Background Comments/Appraisal Vitamin D deficiency has been associated with an increased risk of fractures in early childhood. Ensuring adequate vitamin D status through appropriate supplementation, dietary intake, and sunlight exposure is crucial for optimizing bone health and reducing fracture risk. Healthcare professionals should be

 Rationale provided for study

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 Significance of study provided

 Current state of science or evidence clearly articulated

 Problem statement or area identified.

 Research purpose clearly stated.

proactive in identifying children at risk and implementing strategies to prevent vitamin D deficiency. Further research is warranted to explore the optimal strategies for vitamin D supplementation in early childhood and evaluate the long-term effects on fracture risk and bone health.

By studying the relationship between vitamin D and fracture risk in early childhood, we can better understand the impact of vitamin D deficiency and develop evidence-based guidelines for screening, supplementation, and preventive strategies. Ultimately, this knowledge can contribute to improved pediatric care, reduced fracture rates, and better long-term bone health outcomes. Fractures are a common childhood injury, with a significant impact on a child's physical health, quality of life, and healthcare costs. Understanding modifiable risk factors, such as vitamin D deficiency, can help in developing preventive strategies to reduce fracture rates.

Studies report a significant association between vitamin D deficiency and an increased risk of fractures in early childhood. Children with lower vitamin D levels have been found to have a higher likelihood of experiencing fractures compared to those with sufficient vitamin D levels. While vitamin D deficiency is considered a significant risk factor for fractures in early childhood, it is important to note that other factors also contribute to fracture risk. These may include genetics, nutritional factors, physical activity levels, and environmental factors. A case-control study can help identify the specific contribution of vitamin D deficiency after controlling for other potential confounding variables.

In a case-control study design, participants with the outcome of interest (cases) and those without the outcome (controls) are compared to assess the association between exposure (vitamin D deficiency) and the risk of the outcome (fractures).

Evaluate the association between serum 25(OH)D concentration and fracture risk among children younger than 6 years of age and evaluate the associations between children’s intake of both vitamin D-fortified cow’s milk and supplements containing vitamin D and fracture risk.

 Design Comments/Appraisal  Research question

clearly defined and focused

 Cases clearly

What is the association between vitamin D deficiency and the risk of fractures in early childhood?

Yes, based on the patient´s age, type of fracture, and clinical

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defined?  What is the case

definition?

 Were cases incident or prevalent?

 How were cases selected?

 What proportion of eligible cases were included in study?

 Controls clearly defined?

 Were controls adequate?

 How were controls selected? Selection procedure clearly defined?

 Were controls independent of exposure?

 What proportion of controls were included in study?

 How were exposures ascertained?

 Exposure was clear, specific, and measurable. How was exposure measured?

confirmation. Children were eligible if they were less than 6 years of age with a bone fracture in a lower extremity or upper extremity where the fractures were confirmed radiographically.

The cases are incidents based on the patients who develop the outcome of interest (fractures) during the study period. These cases are compared to a control group to assess the association between vitamin D levels and fracture risk in early childhood.

Cases were recruited from the pediatric fracture clinic at the Hospital for Sick Children in Toronto from May 2009 to April 2013.

82.7 % (206/249 eligible cases) because they were determined to have 25(OH)D measured.

Controls were recruited and selected for the study by matching them 2:1 to cases on season of blood draw, age, sex, and height. For cases for whom 2 controls could not be matched, 1 matched control was used

Controls were obtained from TARGet Kids! primary health-care practice-based research network.

Controls were chosen based on criteria that are unrelated to the exposure being studied (in this case, vitamin D levels).

79.76% (343/430 control cases.

Based on the criteria of fractures, the level of vitamin D in serum, and the patient´s consumption of sources of vitamin D.

The primary exposure, total serum 25(OH)D concentration, measured from blood samples collected at the fracture clinic for the cases and during well-child primary health-care visits for controls. Serum samples for both cases and controls were batch- analyzed for total 25(OH)D using liquid chromatography–

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 What was the potential for exposure misclassification?

 Was exposure determination similar for cases and controls?

 Sample recruitment and selection was appropriate?

 Study variables clearly identified? How were study variables measured?

 Level of significance established

 Data management and analysis plan clearly described

tandem mass spectrometry. Measurement of vitamin D levels, difficulty accurately recalling their past vitamin D levels, possibility of proxy reporting bias if parents or caregivers are not able to accurately recall or report the child's exposure.

The authors mentioned that the laboratory methods were similar for both cases and controls, ensuring that the exposure determination was comparable between the two groups.

Sample size was calculated for the primary outcome, assuming a mean 25(OH)D concentration, standard deviation, using a simple 2-tailed t test with a type I error probability of 0.05. A sample size of 250 cases and a minimum of 250 controls would have 80% power to detect a small difference. Only 125 cases and 125 controls would be required to detect a larger difference in 25(OH)D.

Using the blood sample collection, laboratory methods, and the analysis of 25(OH)D levels.

Statistical significance was defined as P < 0.05, and all tests were 2-sided. Odds ratios and 95% confidence intervals were obtained from conditional logistic regression.

The authors collected relevant information through questionnaires and medical records. They collected data on demographic factors, potential confounders, and vitamin D levels measured from blood samples. The data management process, including data cleaning, quality control, and handling of missing data, is not explicitly mentioned in the article.

Results/Findings Comments/Appraisal  How comparable were the cases and

controls?

 Were potential confounders equally distributed between cases and

To ensure comparability between cases and controls, the authors used matching criteria. Controls were individually matched to cases based on age, sex, and place of residence. This matching process helped to ensure that the control group was similar to the cases in terms of these key characteristics.

Yes, based on those confounding factors related to age, sex, and geographical location.

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controls?

 Were potential confounders adjusted for? How were the confounders adjusted for?

 Sample size appropriate based on power analysis?

 What was the strength of association between the exposure and outcome?

 How accurate was the estimate of association between the exposure and outcome (confidence intervals or p- values)?

No, the potential confounders were not adjusted. This means a limitation for the generalizability of the findings to populations outside the specific matched criteria. All multivariable models included potential confounders identified a priori: skin type, standardized waist circumference, history of fracture, outdoor free play time, income based on postal code, birth weight, and soda intake.

Yes. Only 125 cases and 125 controls would be required to detect a larger difference in 25(OH)D based on 95% of significance, but with 80% power. A larger sample size may have revealed more statistically significant associations.

Based on the statistical comparison, it has been found a statistically significant association between low vitamin D levels and increased fracture risk in early childhood. The odds ratios reported in the study indicate the magnitude of the association.

They used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) as a measure of the association between vitamin D levels and fracture risk.

Bias/Confounders Comments/Appraisal  What was the potential for recall bias?

What research strategies were used to reduce recall bias?

 Did the researcher identify all potentially critical confounders?

Potential recall bias is acknowledged as a concern since case-control studies often rely on self-reported or recalled information about exposures. Several research strategies were employed such as standardized questionnaires to collect data from both cases and controls, close proximity of case ascertainment, and blinding of case-control status.

The authors mentioned adjusting for potential confounding variables in the statistical analysis. Specifically, the analysis models included adjustments for age, sex, body mass

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 What was the potential for selection bias and information bias?

index (BMI), and physical activity. These variables were likely considered based on their potential association with both vitamin D levels and fracture risk. Selection bias may be a concern if the selection of cases or controls was not representative of the underlying population, but residual biases may still exist and can impact the validity of the study findings.

Implications of Findings/Results Comments/Appraisal  What is the potential application of

findings to practice?   Were all the clinically important

outcomes considered?

 How do the study findings fit within the existing state of science and available evidence and practice?

 Were the recommendations supported by the study findings?

The study suggests that low vitamin D levels may be associated with an increased risk of fractures in early childhood. Healthcare professionals may consider incorporating routine screening and monitoring of vitamin D levels in young children to identify those at risk for fractures.

The findings suggest that maintaining adequate vitamin D levels in early childhood may be important for reducing fracture risk. Healthcare providers could consider recommending vitamin D supplementation to children who are at risk of vitamin D deficiency or have low vitamin D levels to potentially decrease their fracture risk.

The study provides valuable insights into the relationship between vitamin D and fracture risk in early childhood. It may encourage further research in this area to explore additional factors influencing the association, such as the optimal vitamin D levels for fracture prevention, the potential benefits of specific dosages of vitamin D supplementation, and the long-term effects of maintaining adequate vitamin D levels during early childhood.

Strengths Comments/Appraisal  What are the major strengths of the

study design? Some major strengths of the study design include: - case-control design allows for efficient

data collection by comparing cases to

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 What are the major weaknesses of the study design?

controls by examining potential risk factors.

- large sample size provides sufficient statistical power to detect meaningful associations between vitamin D levels and fracture risk.

- well-defined cases and controls. - standardized measurement approach

enhances the validity and reliability of the exposure assessment.

Some major weakness of the study design include: - retrospective case-control design, which

relies on the recall of past exposure information.

- potential for selection bias in the case and control selection process.

- limit the generalizability of the findings to other populations or geographic regions.

- lack of temporal relationship. - potential confounding factors. - Vitamin D levels were measured using a

single blood sample, which may not capture long-term variations in vitamin D status.

Limitations Comments/Appraisal  What are the major limitations of the

overall study design?

 What are the major limitations of the sampling method?

The major limitations of study design are based on the retrospective design, the selection bias, the issues with generalizability, and causality, the potential confounding factors, and the simple unit of measure of vitamin D levels.

There may be a risk of selection bias if the cases and controls are not representative of the target population. In this study, recall bias may be a limitation if parents or caregivers of cases and controls have differing recall of vitamin D intake or other relevant factors. The sampling method may be limited if there is a delay between the occurrence of fractures and the assessment of vitamin D exposure.

Measurement methods used to assess vitamin

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 What are the major limitations of the measurement methods?

 What are the major limitations of the data management and analysis methods?

D levels or other relevant variables may have inherent measurement error. This error could arise from factors such as imprecise laboratory techniques, inaccuracies in self- reported data, or inter-observer variability. The study may be limited by the availability and quality of data for the variables being measured.

Missing data can be a limitation in the study. Inadequate control of confounding variables may affect the estimated association between vitamin D and fracture risk. Different statistical methods may yield different results or have different assumptions, which can affect the interpretation of the findings.

Ethical/Legal Comments/Appraisal  Did the research consider human

subjects' protection?

 How were the human subjects’ rights protected?

 Any ethical concerns identified?

 Any potential conflicts of interest identified?

 Any legal concerns identified?

Ethical approval for the study was obtained from the Research Ethics Board at the Hospital for Sick Children and St. Michael’s Hospital, and consent was obtained from the parents of all participating children.

The study does not provide information about participants’ rights protection.

There are not ethical concerns identified.

The authors do not declare any conflict of interest.

There are not any legal concerns identified.