Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid.

BACKGROUND: Diagnosing cobalamin deficiency is critical, given the high prevalence of cobalamin deficiency particularly in developing countries. Measuring serum cobalamin levels is of limited diagnostic sensitivity, in other words its specificity and sensitivity are low. The present study investigated the changes in the levels of metabolic markers - plasma homocysteine, plasma methylmalonic acid (MMA) and urinary MMA - of cobalamin metabolism. METHODS: Plasma cobalamin and serum folic acid were studied in 206 pregnant women over the last four prenatal weeks. Plasma cobalamin, folic acid, homocysteine, MMA from umbilical cord blood and urinary MMA in newborns were studied. RESULTS: Plasma cobalamin values were low in 66% of the mothers. There was a positive correlation between maternal and neonatal plasma cobalamin values (r = 0.72, p < 0.001). B12 was strongly inversely associated with plasma MMA, urine MMA and plasma homocysteine. To predict cobalamin deficiency, sensitivities of plasma MMA, urinary MMA and homocysteine were 96.4%, 95.6% and 88.2%, respectively. And positive predictive values (PPV) were 96.2%, 96.9% and 86% for plasma MMA, urinary MMA and plasma homocysteine levels, respectively. CONCLUSION: Plasma MMA and urinary MMA B12 are the most robust markers of cobalamin deficiency. As a non-invasive method, urinary MMA is a sensitive method in demonstrating cobalamin deficiency in the newborn.

Neonatal hyperbilirubinemia in a Turkish cohort: association of vitamin B12.

BACKGROUND: Deficiency of vitamin B12 (VitB12) causes failure of erytrocyte maturation leading to cell lysis. Red blood cell lysis causes excess heme production that ends with hyperbilirubinemia. In this study, we aimed to evaluate the role of VitB12 in neonatal hyperbilirubinemia (NNH) with prolonged jaundice and to compare patients with control group who did not develop hyperbilirubinemia. METHODS: A total of 20 patients (M/F = 13/7) with jaundice and 20 healthy controls (M/F = 11/9) were included in the study. RESULTS: The mean indirect bilirubin level of patient group was 9.91 ± 1.90 mg/dL (6.71 - 15.2 mg/dL) and control group was 3.18 ± 1.24 mg/dL (1.16 - 4.96 mg/dL). The mean VitB12 level of patient group was 119.9 ± 43.9 ng/L (42.35 - 178 ng/L) and the control group was 286.17 ± 97.43 ng/L (207.90 - 624.10 ng/L). There was a statistically significant difference in terms of VitB12 level (< 0.001) between the study groups. CONCLUSION: To our knowledge, this study is the first study showing that low VitB12 level has been observed as a risk factor in NNH for the first time in the literature. We suggest that prophylactic use of VitB12 by pregnant women so will greatly benefit to prevent VitB12 deficiency and its complications in the first years of life such as NNH.

Severe vitamin D deficiency among pregnant women and their newborns in Turkey.

OBJECTIVES: Vitamin D deficiency is an important health problem in pregnant women and their infants in sunny countries. Low socio-economic status (LSES), covered dressing style, pregnancies in winter season and having dark skin are the major risk factors for vitamin D deficiency. The present study evaluated serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations in pregnant women and in their newborns and determined the risk factors in LSES cities in Turkey. METHODS: Ninety-seven pregnant women and their newborns were included in the study between December 2012 and February 2013. All of the pregnant women had irregular follow-up or had received no antenatal care, were pregnant during summer, had presented to the hospital after 37 weeks of gestation (WG) and had received no vitamin D supplementation. A detailed history was obtained, which included mothers' age, number of births and dressing sytle. Maternal and cord blood samples were taken to measure 25(OH)D3 levels. RESULTS: All of the pregnant women were predominantly LSES, had covered dressing style and none of them had received vit D3 supplementation during pregnancy. The mean serum 25(OH)D3 level and mean cord blood level of of 97 mothers were 4.97 ± 3.27 ng/ml and 4.29 ± 2.44 ng/ml, respectively. There was a strong positive correlation between maternal serum and umbilical cord 25(OH)D3 levels (r: 0.735, p < 0.05). Ninety-five mothers had serum 25(OH)D3 below 20 ng/ml and all cord blood serum 25(OH)D3 levels were below 20 ng/ml. Level of 25(OH)D3 was not correlated with mother age, WG or newborn weight. Serum 25(OH)D3 concentrations in primigravida and multigravida were 3.71 ± 1.88 and 5.2 ± 3.4 ng/ml, respectively, with a significant difference between them (p < 0.05). CONCLUSION: Severe vitamin D deficiency is common in reproductive women and their newborns in LSES cities of Turkey. Covered dressing style, not receiving any vitamin D supplementation and primigravida women are at greatest risk. Vitamin D supplementation campaigns which should cover pregnant women and the newborn to prevent maternal and perinatal vitamin D deficiency should be implemented especially in risk areas.

Mitochondrial DNA polymorphisms associated with longevity in the Turkish population.

The accumulation of mutations in mitochondrial DNA is a widely recognized mechanism for aging and age related diseases. However, studies indicate that some mutations could be beneficial to longevity by slowing down the function of the electron transport chain, reducing free radical production. In this study, we re-sequenced the entire mitochondrial DNA from 50 individuals and examined aging-related variations in the Turkish population. We evaluated sequence data by comparing whole SNP frequencies, individual SNP frequencies, the effect of SNPs, SNP accumulation in certain mtDNA regions and haplotype profiles between elderly and control groups. The frequency of total mitochondrial SNPs was significantly higher in nonagenarians than controls (p=0.0094). Furthermore, non-coding, synonymous and tRNA mutations were more prevalent in the 90+ group compared to controls (p=0.0001, p<0.001, p=0.0096, respectively). A73G and C152T polymorphisms were significantly associated with longevity in the Turkish population (p=0.0086 and p=0.004, respectively). Additionally, C150T was specific to the 90+ group, but the difference failed to reach statistical significance (p=0.053). We also detected a novel transversion in the ATPase6 gene (C8899A) that was negatively associated with longevity (p=0.0016). Examining the distribution of SNPs among genes and functionally associated gene regions revealed a significant accumulation of mutations in the D-loop region and genes encoding Complex I subunits (ND1-6) (p<0.0001, p=0.0302, respectively). Moreover, there was an increase in the non-synonymous mutation frequency of Complex I genes in aged subjects (p<0.0001). Haplotype H was also significantly increased in the control group (p=0.0405). Overall, our findings support a role for mitochondrial genome variations and the functionality of oxidative phosphorylation in longevity. In this report, we sequenced the whole mtDNA of the Turkish population for the first time.