Age-specific reference intervals for routine biochemical parameters in healthy neonates, infants, and young children in Iran.

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age-specific RIs for 7 laboratory biochemical parameters. This cross-sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high-sensitivity C-reactive protein (hs-CRP) were measured using an Alpha classic-AT plus auto-analyser. We determined age-specific RIs using CLSI Ep28-A3 and C28-A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs-CRP, which remained relatively constant throughout the age range. Age-specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations.

Age and sex-specific reference intervals for prooxidant-antioxidant balance, anti-heat-shock protein 27 (anti-hsp27), and routine laboratory tests in the middle-aged adult population.

INTRODUCTION: We aimed to define specific reference intervals (RIs) for 11 biomarkers including inflammatory and oxidative stress biomarkers, liver, and renal function tests in a healthy Iranian adult population for the first time. METHODS: CLSI Ep28-A3 guidelines were then used to calculate accurate age- and sex- as well as body mass index (BMI)-specific RIs. RESULTS: RIs for studied biomarkers showed no significant age and sex-specific differences, except for uric acid, which had higher concentrations in men when compared to women. Additionally, after partitioning the participants based on the BMI with a cutoff point of 25 kg/m2 , only the levels of hs-CRP were positively associated with higher BMI (RI for BMI>25: 0.51-7.85 mg/L and for BMI<25: 0.40-4.46 mg/L). RI for PAB and anti-hsp-27 were reported 4.69-155.36 HK and 0.01-0.70 OD in men and women aged 35-65 years old. CONCLUSION: Partitioning by sex and BMI was only required for uric acid and hs-CRP, respectively, while other biomarkers required no partitioning. These results can be expected to valuably contribute to improve laboratory test result interpretation in adults for improved monitoring of various diseases in the Iranian population.

The relationship between genetic variants associated with primary ovarian insufficiency and lipid profile in women recruited from MASHAD cohort study.

BACKGROUND AND AIM: Primary Ovarian Insufficiency (POI) is defined by the occurrence of menopause before the age of 40 years. It is often associated with cardiovascular disease (CVD). The purpose of this study was to explore the relationship between POI-associated genotypes cardiometabolic disorder risk factors. METHODS: One hundred seventeen women with POI and one hundred eighty-three healthy women without POI were recruited in this study. DNA was extracted and analyzed using ASO-PCR or Tetra ARMS-PCR. Lipid profiles were also assessed. RESULTS: Multivariate logistic regression analysis showed that individuals with GG vs. TT genotype of the rs1046089 SNP were more likely to have a higher serum LDL (p = 0.03) compared to the control group. There was also a significant association between low serum HDL and rs2303369 and rs4806660 SNP genotypes in the POI group. In the POI group, the percentage of those with high total cholesterol was lower in those with a CC genotype compared to those with a TT genotype (p = 0.03). CONCLUSION: Some SNPs reported to be associated with POI appear to be independently associated with dyslipidemia. These results may be helpful to identify subjects with POI who may be susceptible to CVD.

Reference intervals for routine biochemical markers and body mass index: A study based on healthcare center database in northeastern Iran.

Age- and sex-specific reference intervals (RIs) for some biochemical tests may be useful for their interpretation, due to the variations in lifestyle and genetic, or ethnic factors. The aim of this study was to obtain RIs for some routine biochemical markers including a serum lipid profile, fasting blood glucose (FBG), aspartate and alanine aminotransferase (AST and ALT), uric acid, and body mass index (BMI) in subjects who attended primary healthcare centers. The large database of primary healthcare centers uses RIs to report results for children, adolescents, and young and old adults. RIs were obtained by using the indirect method, recommended by the CLSI Ep28-A3 guidelines. RIs for FBG, BMI, and serum lipid profile, including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in people aged 18 to 120 years, were obtained without age/sex segmentation. RIs for serum AST, ALT, and uric acid were obtained without age segmentation, though these RIs were higher in males than females. The RIs for AST, ALT, and uric acid were higher in men, while the RIs for the other variables were similar in both sexes. This is the first study reporting the use of indirect RIs for BMI.

Age- and sex-specific reference intervals for superoxide dismutase enzyme and several minerals in a healthy adult cohort.

INTRODUCTION: The aim of this study was to establish RIs for clinically important markers including superoxide dismutase (SOD), serum copper, zinc, calcium, magnesium, and phosphate in a cohort of healthy Iranian adults. MATERIALS: A subsample from MASHAD cohort study was used to assess serum SOD, copper, zinc, calcium, magnesium and phosphate. Serum SOD was measured according to its inhibitory potential of pyrogallol oxidation. Micro- and macro-minerals were measured using flame atomic absorption spectrometry and a BT3000 autoanalyzer, respectively. Sex- and age-specific RIs were then calculated based on CLSI Ep28-A3 guidelines. RESULTS: Reference value distributions for studied parameters did not demonstrate any age-specific differences that were statistically significant. In addition, sex partitioning was not required for all parameters, apart from serum magnesium, which showed a wider range in females (0.81-1.26 mg/dl) compared with males (0.82-1.23 mg/dl). CONCLUSION: The RIs established in this study can be expected to improve mineral assessment and clinical decision-making in the Iranian adult population.

Association between dietary inflammatory index and risk of cardiovascular disease in the Mashhad stroke and heart atherosclerotic disorder study population.

The dietary inflammatory index (DII) is a novel way of describing diet that has been studied in relation to various health conditions, including cardiovascular disease (CVD) in several populations. We aimed to investigate the association between DII and CVD events among a representative population sample in northeastern Iran. This prospective cohort study was a subsample of 4,672 adults aged 35-65 years, and recruited as part of Mashhad stroke and heart atherosclerotic disorder cohort study population. The DII was computed at baseline according to a 65-item validated food frequency questionnaire. Cox regression was used to determine the association of DII with incident CVD. One hundred twenty-four participants developed CVD (including 24 cases of myocardial infarction [MI], 34 cases of stable angina [SA], and 66 cases of unstable angina [UA]). After adjusting for potential confounding factors, a hazard ratios of 1.06 (95% confidence interval: 0.70-1.60), 1.36 (95% confidence interval: 0.52-3.52), 1.33 (95% confidence interval: 0.60-2.94), and 0.86 (95% confidence interval: 0.48-1.53) were found for total CVD, MI, SA, and UA events, respectively, among the participants with proinflammatory diet (DII ≥ 0) versus those with anti-inflammatory diet (DII < 0). There was no statistically significant association between the DII and total CVD, MI, SA, or UA in this population of middle-aged Iranian men and women.

Association between Dietary Inflammatory Index (DII®) and depression and anxiety in the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) Study population.

BACKGROUND: Systemic inflammation is emerging as an important factor in the etiology of psychiatric disorders such as depression and anxiety. Therefore, the inflammatory potential of the diet may also be an etiological factor for these conditions, and this may be estimated by calculating the dietary inflammatory index (DII®) score. We aimed to investigate the association between DII score and incidence of depression and anxiety among a representative sample in northeastern Iran. METHODS: This cross-sectional study undertook in a sub-sample of 7083 adults aged 35 to 65 years recruited as part of Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study population, and after excluding subjects with incomplete data. All participants completed the Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI-II), and a validated 65-item food frequency questionnaire (FFQ). Logistic regression was used to evaluate the association between DII score and depression/anxiety score. RESULTS: Of the study participants, 37.1% (n = 2631) were found to have mild to severe depression, and 50.5% (n = 3580) were affected by mild to severe anxiety. After adjusting for confounding factors, in women, the third (OR: 1.41, 95% CI: 1.06-1.88, p-values< 0.05) and fourth quartiles (OR: 1.37, 95% CI: 1.03-1.83, p-values< 0.05) of DII score were associated with increased risk of a high depression score compared to the first quartile of DII score. CONCLUSION: There was a significant association between DII score and severe depression among women but not men in this Iranian population. In order to confirm the association between DII food score, depression, and anxiety, further research is required in different populations, and perhaps an intervention study.

Dyslipidemia and cardiovascular disease risk among the MASHAD study population.

INTRODUCTION: Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran. MATERIAL AND METHODS: This prospective cohort study comprised a population of 8698 men and women aged 35-65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence. RESULTS: After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19-2; P-value< 0.01; HR: 1.53; 95% CI: 1.18-1.98; P < 0.01; HR: 1.57; 95% CI: 1.27-2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12-6.57; P-value< 0.05). CONCLUSION: In the present study, TC baseline level was significantly associated with the risk of MI among men.

Dietary Inflammatory Index is associated with Healthy Eating Index, Alternative Healthy Eating Index, and dietary patterns among Iranian adults.

BACKGROUND: Recent investigations have evaluated the effect of the inflammatory potential of diet in several populations by calculating the Dietary Inflammatory Index (DII) score. We aimed to evaluate the association of the DII with the Healthy Eating Index (HEI), the Alternative Healthy Eating Index (AHEI), and dietary pattern (DP) among healthy Iranian adults. METHODS: A cross-sectional study was conducted among 4365 middle-aged adults. Major DPs and DII score were identified using a validated semi-quantitative food frequency questionnaire (FFQ). Poisson regression was used to evaluate the association of DPs, HEI, and AHEI across tertiles of DII. RESULTS: After adjustment for confounding variables, a low HEI (HEI < 55) and AHEI (AHEI < 56.5) were more prevalent among the participants in the highest tertile of DII compared to the first tertile (PR: 1.13, P-value <.05; PR: 1.10, P-value <.05; respectively). Adherence to a balanced healthy dietary pattern was significantly lower in subjects with a diet that was more pro-inflammatory compared to those with anti-inflammatory diet (PR: 0.85, P-value P < .01). No significant association was found between the DII and a western DP. High levels of HDL and hip and waist circumference were observed in the highest tertile of DII, and high levels of dietary intake of protein and fiber, minerals, fasting blood glucose, and monounsaturated fat were reported in the lowest tertile of DII. CONCLUSION: The highest tertile of the DII (a pro-inflammatory diet) was associated with a lower HEI, AHEI, and lower adherence to balanced DP in a representative sample of adults in Iran.

Pediatric reference intervals for hematology parameters in healthy infants and young children in Iran.

INTRODUCTION: Defining accurate age- and sex-specific reference intervals (RIs) for hematology parameters, especially for the pediatric population, is important for making an appropriate clinical diagnosis. To address gaps, we established age-specific RIs for 11 hematologic parameters in Iranian children younger than 30 months for the first time. METHODS: Fresh whole blood samples collected from a total of 344 participants (males: 158 and females: 186) ages 3 days to 30 months, with a mean age of 12.91 ± 7.15 months, were recruited from healthcare centers in Mashhad, Iran. Hematologic parameters, including complete blood count (CBC), were analyzed on the Sysmex auto-analyzer system (KX-21 N). RIs were calculated with 90% confidence intervals using the direct method based on CLSI Ep28-A3 and C28-A3 guidelines. RESULTS: None of the CBC parameters required sex partitioning. Of 11 CBC parameters, six required age partitions of 3 days-<4 months, 4-<10, 10-<15, and 4-<30 months. Five parameters (i.e., white blood cell count, mean corpuscular hemoglobin concentration, mean platelet volume, red cell distribution width, and platelet distribution width) did not demonstrate age-specific changes. RIs of red blood cell count and hematocrit, as well as hemoglobin, increased with age, while mean corpuscular volume, mean corpuscular hemoglobin, and platelet count, decreased with age. CONCLUSION: In this study, we established RIs for 11 hematology parameters in young children. Age partitioning was required for six parameters demonstrating marked changes during the early period of growth and development and necessitating the use of pediatric-specific reference standards.

Evaluation of ABO blood group in subjects with CVD risk factors in a population sample from northeastern Iran.

BACKGROUND AND AIMS: The ABO blood group system is a genetic polymorphism which can affect the clearance of von Willebrand factor. We aimed to assess the levels of newer biomarkers of cardiovascular disease (CVD) risk; pro-oxidant-antioxidant balance (PAB), high sensitivity C-reactive protein (hs-CRP) and anti-heat-shock protein27 (anti-Hsp27) antibody titers in subjects with various blood groups (A, B, AB and O) and with or without traditional CVD risk factors. METHODS: The cross-sectional study comprised 6910 subjects. Antigen-antibody agglutination was evaluated by the slide test method for identification of ABO blood groups. RESULTS: Among three markers, only Serum anti-Hsp27 titers significantly differed between the four blood groups and showed the highest and lowest values in AB and O blood groups (0.26 ± 0.22 and 0.23 ± 0.18 OD, respectively; P < 0.05). Serum anti-Hsp27 was higher in individuals with an AB blood group with metabolic syndrome (MetS), dyslipidemia, hypertension (HTN) and obesity and it was lower in subjects with O blood group; though, two other biomarkers, serum PAB and hs-CRP, were not significantly different between the ABO blood groups. However, they were not different among blood groups in participants with or without diabetes mellitus (DM) (P > 0.05). CONCLUSION: Individuals with an AB blood group and high levels of anti-Hsp27 antibody titers may be predisposed to CVDs that can be mediated through the traditional CVD risk factors among middle-aged subjects from northeastern Iran. The fact that differences in anti Hsp27 are only found in the subgroup with other risk factors suggest that the difference between ABO blood groups is a consequence rather than a cause.