season of birth, neonatal vitamin d status
TRANSCRIPT
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Season of birth, neonatal vitamin D status, and cardiovascular disease risk at 35 y of age: a cohort study from Sweden
Tornhammar P, Ueda P, Hult M, Simila H, Eyles D, Norman M. Season of birth, neonatal vitamin D status, and cardiovascular disease risk at 35 y of age: a cohort study from Sweden. Am J Clin Nutr [Internet]. 2014 [cited 2015 Oct 1];99(3):472-80. doi: 10.3945/ajcn.113.072520
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A REVIEW OF THE LITERATURE• Vitamin D status may be associated with a higher risk of cardiovascular disease, impaired glucose tolerance and metabolic syndrome• Vitamin D status during the gestational period may influence future cardiovascular and metabolic health in their offspring• Indian study• United Kingdom study• Why is this study important?
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BACKGROUND OF STUDY• Longitudinal cohort study- level 2 evidence• Objective: “to assess the link between season of birth, neonatal 25-hydroxyvitamin D³ [25(OH)D³] status and adult cardiovascular disease risk”• Hypothesis: low neonatal Vitamin D status, due to birth at the end of the winter would be associated with risk of cardiovascular disease and poor metabolic profile in adulthood•Dependent Variable(s): •Neonatal vitamin D status•Adult cardiovascular disease risk: • aortic stiffness, blood pressure, BMI, glucose tolerance, blood lipids, inflammation (C-reactive protein)
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CRITICAL ANALYSIS•Multiple dependent variables….what’s missing?• New research- no study has ever examined early-life vitamin D status and cardiovascular disease risk beyond childhood
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SAMPLE SIZE• 284 subjects (from a pool of 1305 subjects)• Chosen from Swedish Phenylketonuria (PKU) register in order in which they were listed• 35 years of age: born Feb. 9th- Mar 7th 1975; or Sept 14-29th 1975• born in Stockholm region• no sample size calculation
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CRITICAL ANALYSIS• No sample size calculation – red flag! •Weakens external validity• Examined a specific population- Swedish PKU register• Born Feb. 9th- Mar 7th 1975; or Sept 14-29th 1975• Did not disclose why these dates were chosen• No randomization- weakens internal validity• Chosen in order in which they were listed reduces bias
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STUDY DESIGN• Winter group: February 9-March 7, 1975 = 138 subjects; summer group: September 14-29 = 146 subjects• Subjects examined between July 5-August 30, 2010•Collected the following data: origin of parents; level of education, smoking, previously diagnose diabetes or hypertension, current medications, hours of physical activity/wk, weekly fish consumption, and family history of diabetes•Day of examination instructions•Collected data (measurements of dependent variables)
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STUDY DESIGN• Blood spots stored for 37 years• Conducted a pilot study to assess feasibility of study• Compared samples from 1980 and 2010 • Reduction in 25(OH)D³ samples from 1980 compared to 2010 samples• 1980: 28.1 ± 11.4 2010: 58.6 ± 26.2 •25(OH)D³ was therefore not analyzed based on clinical cut-offs, but as a continuous variable
• Investigators blinded to season of birth, 25(OH)D³ measurement and clinical examination
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CRITICAL ANALYSIS• Number of subjects in each group are similar• Collected data on several confounding factors• Confounding factors controlled for, but…• Degradation of vitamin D in dried blood spot samples proposes challenges of true concentrations•Also possibility of lower Vitamin D status in individuals in general in 1975
• Blinding of investigators reduces bias
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STATISTICAL TESTS• Means and (±SDs) for normally distributed continuous variables• Geometric means and 95% CI for variables with skewed distribution• Proportions (%) for categorical variables•ORs and 95% CIs used to assess relationship between neonatal 25(OH)D³ concentration and risk of prehypertension/ hypertension, overweight, obesity and impaired fasting glucose/diabetes
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CRITICAL ANALYSIS• Statistical tests described are appropriate for what they are measuring • Use of geometric means is questionable- why not a log transformation?• Disclosed the reason they did not adjust for multiple comparisons
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RESULTS• Cohort characteristics: reported significant differences in maternal age at delivery between groups
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RESULTS- SEASON OF BIRTH• Neonatal 25(OH)D³ concentrations significantly lower in winter group than summer group
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RESULTS- NEONATAL 25(OH)D³
• Neonatal 25(OH)D³ concentration was significantly associated with weight, fasting insulin, cholesterol (women) and triglycerides. Once controlled for BMI, significance no longer existed• Reported a significant interaction between sex and neonatal 25(OH)D³ against adult height, BMI, serum cholesterol and HDL cholesterol. •Height and HDL increased at a higher rate per 1-nmol/L increase in neonatal 25(OH)D³ concentration in men•BMI and cholesterol increased at a higher rate per 1-nmol/L increase in neonatal 25(OH)D³ concentration in women
• Higher neonatal 25(OH)D³ concentration was associated with a higher adult BMI in women but not in men
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• Reported in results and again in the discussion of the significant p-values. However the odds ratio suggest it is possible there is almost no association
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STUDY LIMITATIONS Reported Limitations•Lack of data on body composition at follow-up, birth weight, and maternal characteristics, including BMI and vitamin D supplementation•Subjects not at a high cardiovascular disease risk age•Potential degradation of dried blood spots prevented stratification by clinically relevant cut-offs•Timing and place of study•Outcomes not detected due to sample size•Possibility those who chose to participate are more health conscious
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FUTURE RESEARCH• Determine a sample size that would suggest clinically relevant results• Account for maternal vitamin D supplementation• Review the literature and justify choosing one cardiovascular disease risk factor as an outcome variable•Possibly triglycerides due to results of this study?
• Conduct the study when subjects are at an older age in which cardiovascular disease risk is more prevalent