TY - JOUR A1 - Alter, Markus L. A1 - Kretschmer, Axel A1 - Von Websky, Karoline A1 - Tsuprykov, Oleg A1 - Reichetzeder, Christoph A1 - Simon, Alexandra A1 - Stasch, Johannes-Peter A1 - Hocher, Berthold T1 - Early urinary and plasma biomarkers for experimental diabetic Nephropathy JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: As the prevalence of diabetes rises, its complications such as diabetic nephropathy affect an increaseing number of patients. Consequently, the need for biomarkers in rodent models which reflect the stage and course of diabetic nephropathy is high. This article focuses on Heart-type fatty acid binding protein (H-FABP), osteopontin (OPN), nephrin, and Neutrophil gelatinase-associated lipocalin (NGAL) in urine, and kidney injury molecule (KIM)-1, clusterin, and tissue inhibitior of metalloproteinases (TIMP) 1 in plasma in uni-nephrectomized rats with streptocotozin-induced type 1 diabetes mellitus, a common animal model to explore renal impairment in the setting of diabetes mellitus. Methods: 23 male Wistar rats were uni-nephrectomized and subsequently divided into two study groups. The diabetic group received streptozotocin (STZ) via tail-vein injection, the non-diabetic group received citrate buffer without STZ. Subsequently, blood glucose, body weight, and blood pressure were checked regularly. After 18 weeks, animals were placed in metabolic cages, blood and urine obtained and subsequently organs were harvested after sacrifice. Results: Blood glucose levels were highly increased in diabetic animals throughout the experiment, whereas systolic blood pressure did not differ between the study groups. At study end, classical biomarkers such as urinary albumin and protein and plasma cystatin c were only slightly but not significantly different between groups indicating a very early disease state. In contrast, urinary excretion of H-FABP, OPN, nephrin, and NGAL were highly increased in diabetic animals with a highly significant p-value (p<0.01 each) compared to non-diabetic animals. In plasma, differences were found for calbindin, KIM-1, clusterin, TIMP-1, and OPN. These findings were confirmed by means of the area under the receiver operating characteristic curve (ROC-AUC) analysis. Conclusions: In summary, our study revealed elevated levels of new plasma and urinary biomarkers (urinary osteopontin, urinary nephrin, urinary NGAL, urinary H-FABP, plasma KIM-1, plasma TIMP-1) in uni-nephrectomized diabetic rats, an established rat model of diabetic nephropathy. These biomarkers appeared even before the classical biomarkers of diabetic nephropathy such as albuminuria and urinary protein excretion. The new biomarkers might offer advantage to urinary albumin and plasma cystatin c with respect to early detection. KW - diabetic nephropathy KW - urinary biomarker KW - blood biomarker KW - heart-type fatty acid binding protein KW - osteopontin KW - nephrin KW - neutrophil gelatinase-associated lipocalin KW - kidney injury molecule 1 KW - clusterin KW - tissue inhibitior of metalloproteinases 1 Y1 - 2012 U6 - https://doi.org/10.7754/Clin.Lab.2011.111010 SN - 1433-6510 VL - 58 IS - 7-8 SP - 659 EP - 671 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Alter, Markus L. A1 - Ott, Ina M. A1 - von Websky, Karoline A1 - Tsuprykov, Oleg A1 - Sharkovska, Yuliya A1 - Krause-Relle, Katharina A1 - Raila, Jens A1 - Henze, Andrea A1 - Klein, Thomas A1 - Hocher, Berthold T1 - DPP-4 Inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background: The need for an improved treatment for diabetic nephropathy is greatest in patients who do not adequately respond to angiotensin II receptor blockers (ARBs). This study investigated the effect of the novel dipeptidyl peptidase-4 inhibitor linagliptin alone and in combination with the ARB telmisartan on the progression of diabetic nephropathy in diabetic endothelial nitric oxide synthase (eNOS) knockout mice. Methods: Sixty male eNOS knockout C57BL/6J mice were divided into four groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), linagliptin (3 mg/kg), linagliptin + telmisartan (3 mg/kg + 1 mg/kg) and vehicle. Fourteen mice were used as non-diabetic controls. Results: After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were increased and similar in all diabetic groups. Telmisartan alone reduced systolic blood pressure by 5.9 mmHg versus diabetic controls (111.2 +/- 2.3 mmHg vs 117.1 +/- 2.2 mmHg; mean +/- SEM; P = 0.071). Combined treatment significantly reduced albuminuria compared with diabetic controls (71.7 +/- 15.3 mu g/24 h vs 170.8 +/- 34.2 mu g/24 h; P = 0.017), whereas the effects of single treatment with either telmisartan (97.8 +/- 26.4 mu g/24 h) or linagliptin (120.8 +/- 37.7 mu g/24 h) were not statistically significant. DPP-4 inhibition, alone and in combination, led to significantly lower plasma osteopontin levels compared with telmisartan alone. Histological analysis revealed reduced glomerulosclerosis after Linagliptin alone and in combination with telmisartan in comparison to non treated diabetic animals (p < 0.01 and p < 0.05). Kidney malonaldehyde immune-reactivity, a marker of oxidative stress, was significantly lower in animals treated with linagliptin. Conclusions: DPP-4 inhibition on top of ARB treatment significantly reduced urinary albumin excretion and oxidative stress in diabetic eNOS knockout mice. Linagliptin on top of an angiotensin II receptor blocker may offer a new therapeutic approach for patients with diabetic nephropathy. KW - Diabetic nephropathy KW - DPP-4 inhibitor KW - Linagliptin KW - Renin-angiotensin system Y1 - 2012 U6 - https://doi.org/10.1159/000341487 SN - 1420-4096 VL - 36 IS - 1 SP - 119 EP - 130 PB - Karger CY - Basel ER - TY - JOUR A1 - Chen, You-Peng A1 - Li, Jian A1 - Wang, Zi-Neng A1 - Reichetzeder, Christoph A1 - Xu, Hao A1 - Gong, Jian A1 - Chen, Guang-Ji A1 - Pfab, Thiemo A1 - Xiao, Xiao-Min A1 - Hocher, Berthold T1 - Renin angiotensin aldosterone system and glycemia in pregnancy JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: The renin-angiotensin-aldosterone system (RAAS) is involved in the pathogenesis of insulin resistance and type 2 diabetes in the general population. The RAAS is activated during pregnancy. However, it is unknown whether the RAAS contributes to glycemia in pregnant women. Methods: Plasma renin activity (PRA) and plasma aldosterone levels were quantified at delivery in 689 Chinese mothers. An oral glucose tolerance test in fasted women was performed in the second trimester of pregnancy. The diagnosis of gestational diabetes mellitus (GDM) and impaired glucose tolerance during pregnancy were made according to the guidelines of the Chinese Society of Obstetrics. Results: Plasma aldosterone was significantly higher in pregnant women with GDM as compared to those without impairment of glycemic control (normal pregnancies: 0.27 +/- 0.21 ng/mL, GDM: 0.36 +/- 0.30 ng/mL; p<0.05). Regression analyses revealed that PRA was negatively correlated with fasting blood glucose (FBG) (R-2 = 0.03, p = 0.007), whereas plasma aldosterone and aldosterone/PRA ratio were positively correlated with FBG (R-2 = 0.05, p<0.001 and R-2 = 0.03, p = 0.007, respectively). Multivariable regression analysis models considering relevant confounding factors confirmed these findings. Conclusions: This study demonstrated that fasting blood glucose in pregnant women is inversely correlated with the PRA, whereas plasma aldosterone showed a highly significant positive correlation with fasting blood glucose during pregnancy. Moreover, plasma aldosterone is significantly higher in pregnant women with GDM as compared to those women with normal glucose tolerance during pregnancy. Although causality cannot be proven in association studies, these data may indicate that the RAAS during pregnancy contributes to the pathogenesis of insulin resistance/new onset of diabetes during pregnancy. KW - Renin-angiotensin-aldosterone system KW - pregnancy KW - fasting blood glucose KW - glycemic control Y1 - 2012 SN - 1433-6510 VL - 58 IS - 5-6 SP - 527 EP - 533 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Chen, You-Peng A1 - Xiao, Xiao-Min A1 - Li, Jian A1 - Reichetzeder, Christoph A1 - Wang, Zi-Neng A1 - Hocher, Berthold T1 - Paternal body mass index (BMI) is associated with offspring intrauterine growth in a gender dependent manner JF - PLoS one N2 - Background: Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. Methods and Results: We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. Conclusions: Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion. Y1 - 2012 U6 - https://doi.org/10.1371/journal.pone.0036329 SN - 1932-6203 VL - 7 IS - 5 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Henze, Andrea A1 - Espe, Katharina M. A1 - Wanner, Christoph A1 - Krane, Vera A1 - Raila, Jens A1 - Hocher, Berthold A1 - Schweigert, Florian J. A1 - Drechsler, Christiane T1 - Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes JF - Diabetes care N2 - OBJECTIVE-BMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients. RESEARCH DESIGN AND METHODS-The TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI >= 23 kg/m(2), albumin concentration >= 3.8 g/dL, and a combination of both. RESULTS-A low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95% CI 1.27-2.14]), patients with BMI >= 23 kg/m(2) (1.70 [1.22-2.37]), albumin >= 3.8 g/dL (1.68 [1.17-2.42]), and the combination of both (1.69 [1.13-2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43-2.24]) and patients with BMI >= 23 kg/m(2) (1.46 [1.09-1.95]). CONCLUSIONS-The current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status. Y1 - 2012 U6 - https://doi.org/10.2337/dc12-0455 SN - 0149-5992 VL - 35 IS - 11 SP - 2365 EP - 2372 PB - American Diabetes Association CY - Alexandria ER - TY - JOUR A1 - Hocher, Berthold A1 - Armbruster, Franz Paul A1 - Stöva, Stanka A1 - Reichetzeder, Christoph A1 - Groen, Hans Jürgen A1 - Lieker, Ina A1 - Khadzhynov, Dmytro A1 - Slowinski, Torsten A1 - Roth, Heinz Jürgen T1 - Measuring Parathyroid Hormone (PTH) in patients with oxidative stress - do we need a fourth generation Parathyroid Hormone assay? JF - PLoS one N2 - Oxidation of PTH at methionine residues results in loss of biological activity. PTH may be oxidized in patients with renal disease. The aim of this study was to develop an assay considering oxidation of PTH. Oxidized hPTH was analyzed by high resolution nano-liquid chromatography coupled to ESI-FTT tandem mass spectrometry (nanoLC-ESI-FT-MS/MS) directly and after proteolytic cleavage. The oxidized hPTH(1-84) sample shows TIC-peaks at 18-20 min and several mass peaks due to mass shifts caused by oxidations. No significant signal for oxidized hPTH(1-84) species after removal of oxidized PTH molecules by a specific column with monoclonal antibodies (MAB) raised against the oxidized hPTH was detectable. By using this column in samples from 18 patients on dialysis we could demonstrate that measured PTH concentrations were substantially lower when considering oxidized forms of PTH. The relationship between PTH concentrations determined directly and those concentrations measured after removal of the oxidized PTH forms varies substantially. In some patients only 7% of traditionally measured PTH was free of oxidation, whereas in other patients 34% of the traditionally measured PTH was real intact PTH. In conclusion, a huge but not constant proportion of PTH molecules are oxidized in patients requiring dialysis. Since oxidized PTH is biologically inactive, the currently used methods to detect PTH in daily clinical practice may not adequately reflect PTH-related bone and cardiovascular abnormalities in patients on dialysis. Y1 - 2012 U6 - https://doi.org/10.1371/journal.pone.0040242 SN - 1932-6203 VL - 7 IS - 7 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Hocher, Berthold A1 - Groen, Hans Jürgen A1 - Schumann, Claudia A1 - Tsuprykov, Oleg A1 - Seifert, Susanne A1 - Hitzler, Walter E. A1 - Armbruster, Franz Paul T1 - Vitamin D status from dried capillary blood samples JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Given the huge impact of vitamin D deficiency on a broad spectrum of diseases such as rickets, osteoporosis, mineral bone disease-vascular calcification syndrome, infectious diseases, but also several types of cancer and CNS diseases, reliable and simple methods to analyze the vitamin D status are urgently needed. Methods: We developed an easy technique to determine the 25-OH vitamin D status from dried blood samples on filter paper. This allows determination of the 25-OH vitamin D status independently of venous blood taking, since only sampling of capillary blood is required for this new method. We compared the results of vitamin D measurements from venous blood of 96 healthy blood donors with those from capillary blood taken from the same patients at the same time. The capillary blood was dried on filter paper using the D-Vital ID dry-blood collection system. Results: 25-OH vitamin D concentration data from extracted dried capillary blood filters correlated very well with data obtained after direct measurement of venous blood samples of the same blood donor (R: 0.7936; p<0.0001). The correlation was linear over the whole range of 25-OH vitamin D concentrations seen in this study. A Bland-Altman plot revealed good agreement between both tests. Conclusions: The D-Vital ID dry-blood collection system showed an excellent performance as compared to the classical way of 25-OH vitamin D measurement from venous blood. This new technique will facilitate easy and reliable measurement for vitamin D status, in particular, in rural or isolated areas, developing countries, and field studies. KW - 25-OH vitamin D KW - filter paper KW - capillary blood KW - new analysis method Y1 - 2012 U6 - https://doi.org/10.7754/Clin.Lab.2012.120429 SN - 1433-6510 VL - 58 IS - 7-8 SP - 851 EP - 855 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Ikram, M. Arfan A1 - Fornage, Myriam A1 - Smith, Albert V. A1 - Seshadri, Sudha A1 - Schmidt, Reinhold A1 - Debette, Stephanie A1 - Vrooman, Henri A. A1 - Sigurdsson, Sigurdur A1 - Ropele, Stefan A1 - Taal, H. Rob A1 - Mook-Kanamori, Dennis O. A1 - Coker, Laura H. A1 - Longstreth, W. T. A1 - Niessen, Wiro J. A1 - DeStefano, Anita L. A1 - Beiser, Alexa A1 - Zijdenbos, Alex P. A1 - Struchalin, Maksim A1 - Jack, Clifford R. A1 - Rivadeneira, Fernando A1 - Uitterlinden, Andre G. A1 - Knopman, David S. A1 - Hartikainen, Anna-Liisa A1 - Pennell, Craig E. A1 - Thiering, Elisabeth A1 - Steegers, Eric A. P. A1 - Hakonarson, Hakon A1 - Heinrich, Joachim A1 - Palmer, Lyle J. A1 - Jarvelin, Marjo-Riitta A1 - McCarthy, Mark I. A1 - Grant, Struan F. A. A1 - St Pourcain, Beate A1 - Timpson, Nicholas J. A1 - Smith, George Davey A1 - Sovio, Ulla A1 - Nalls, Mike A. A1 - Au, Rhoda A1 - Hofman, Albert A1 - Gudnason, Haukur A1 - van der Lugt, Aad A1 - Harris, Tamara B. A1 - Meeks, William M. A1 - Vernooij, Meike W. A1 - van Buchem, Mark A. A1 - Catellier, Diane A1 - Jaddoe, Vincent W. V. A1 - Gudnason, Vilmundur A1 - Windham, B. Gwen A1 - Wolf, Philip A. A1 - van Duijn, Cornelia M. A1 - Mosley, Thomas H. A1 - Schmidt, Helena A1 - Launer, Lenore J. A1 - Breteler, Monique M. B. A1 - DeCarli, Charles A1 - Adair, Linda S. A1 - Ang, Wei A1 - Atalay, Mustafa A1 - vanBeijsterveldt, Toos A1 - Bergen, Nienke A1 - Benke, Kelly A1 - Berry, Diane J. A1 - Coin, Lachlan A1 - Davis, Oliver S. P. A1 - Elliott, Paul A1 - Flexeder, Claudia A1 - Frayling, Tim A1 - Gaillard, Romy A1 - Groen-Blokhuis, Maria A1 - Goh, Liang-Kee A1 - Haworth, Claire M. A. A1 - Hadley, Dexter A1 - Hebebrand, Johannes A1 - Hinney, Anke A1 - Hirschhorn, Joel N. A1 - Holloway, John W. A1 - Holst, Claus A1 - Hottenga, Jouke Jan A1 - Horikoshi, Momoko A1 - Huikari, Ville A1 - Hypponen, Elina A1 - Kilpelainen, Tuomas O. A1 - Kirin, Mirna A1 - Kowgier, Matthew A1 - Lakka, Hanna-Maaria A1 - Lange, Leslie A. A1 - Lawlor, Debbie A. A1 - Lehtimaki, Terho A1 - Lewin, Alex A1 - Lindgren, Cecilia A1 - Lindi, Virpi A1 - Maggi, Reedik A1 - Marsh, Julie A1 - Middeldorp, Christel A1 - Millwood, Iona A1 - Murray, Jeffrey C. A1 - Nivard, Michel A1 - Nohr, Ellen Aagaard A1 - Ntalla, Ioanna A1 - Oken, Emily A1 - Panoutsopoulou, Kalliope A1 - Pararajasingham, Jennifer A1 - Rodriguez, Alina A1 - Salem, Rany M. A1 - Sebert, Sylvain A1 - Siitonen, Niina A1 - Strachan, David P. A1 - Teo, Yik-Ying A1 - Valcarcel, Beatriz A1 - Willemsen, Gonneke A1 - Zeggini, Eleftheria A1 - Boomsma, Dorret I. A1 - Cooper, Cyrus A1 - Gillman, Matthew A1 - Hocher, Berthold A1 - Lakka, Timo A. A1 - Mohlke, Karen L. A1 - Dedoussis, George V. A1 - Ong, Ken K. A1 - Pearson, Ewan R. A1 - Price, Thomas S. A1 - Power, Chris A1 - Raitakari, Olli T. A1 - Saw, Seang-Mei A1 - Scherag, Andre A1 - Simell, Olli A1 - Sorensen, Thorkild I. A. A1 - Wilson, James F. T1 - Common variants at 6q22 and 17q21 are associated with intracranial volume JF - Nature genetics N2 - During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size. Y1 - 2012 U6 - https://doi.org/10.1038/ng.2245 SN - 1061-4036 VL - 44 IS - 5 SP - 539 EP - + PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Li, Jian A1 - Wang, Zi-Neng A1 - Chen, You-Peng A1 - Dong, Yun-Peng A1 - Mao, Xiao-Min A1 - Hocher, Berthold T1 - Association of fetal but not maternal P-glycoprotein C3435T polymorphism with fetal growth and birth weight, a possible risk factor for cardiovascular diseases in later life JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: The multidrug transporter P-glycoprotein (PGP) is expressed in the human placenta. In particular the C3435T ABCB1 polymorphism was associated with altered tissue expression of PGP in the human placenta. However, the potential functional impact of this polymorphism on the offspring is unknown so far. Methods: We analyzed the impact of the ABCB1/C3435T polymorphism on fetal growth in 262 mother/child pairs. Fetal growth was assessed by differential ultrasound examination of the fetal body prior to birth and by measuring birth weight. Results: The maternal ABCB1/C3435T polymorphism showed no trend for an association with birth weight or any ultrasound parameter describing late gestational fetal body shape. Genotyping the newborns, however, demonstrated that newborns carrying two copies of the T allele had a birth weight of 3176.39 g, whereas CT and CC newborns had a birth weight of 3345.04 g (p = 0.022). Adjusting for gestational age at delivery, child's gender, maternal BM1, maternal age and body weight at delivery confirmed this finding (p = 0.009). Considering gestational day of late ultrasound examination, gestational age at delivery, child's gender, maternal BMI, maternal age and maternal body weight at delivery, the fetal ABCB1/C3435T genotype revealed likewise a significant negative correlation with abdominal diameter and abdominal circumference (R-2 = 0.538, p = 0.010 and R-2 = 0.534, p = 0.005, respectively). Conclusions: Low birth weight may be a risk factor for cardiovascular diseases in later life. The fetal ABCB1/C3435T gene polymorphism may contribute to this risk. Since PGP controls transport of various biological agents, we suggest that PGP is involved in the transport of biological agents to the fetus that are important for normal fetal growth. Y1 - 2012 U6 - https://doi.org/10.7754/Clin.Lab.2012.110920 SN - 1433-6510 VL - 58 IS - 9-10 SP - 1085 EP - 1089 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Li, Jian A1 - Wang, Zi-Neng A1 - Chen, You-Peng A1 - Dong, Yun-Peng A1 - Shuai, Han-Lin A1 - Xiao, Xiao-Min A1 - Reichetzeder, Christoph A1 - Hocher, Berthold T1 - Late gestational maternal serum cortisol is inversely associated with fetal brain growth JF - Neuroscience & biobehavioral reviews : official journal of the International Behavioral Neuroscience Society N2 - To analyze the association between fetal brain growth and late gestational blood serum cortisol in normal pregnancy.Blood total cortisol was quantified at delivery in 432 Chinese mother/child pairs. Key inclusion criteria of the cohort were: no structural anomalies of the newborn, singleton pregnancy, no alcohol abuse, no drug abuse or history of smoking no hypertensive disorders and no impairment of glucose tolerance and no use of steroid medication during pregnancy. Differential ultrasound examination of the fetal body was done in early (gestational day 89.95 +/- 7.31), middle (gestational day 160.17 16.12) and late pregnancy (gestational day 268.89 +/- 12.42). Newborn's cortisol was not correlated with any of the ultrasound measurements during pregnancy nor with birth weight. Multivariable regression analysis, considering timing of the ultrasound examination, the child's sex, maternal BMI, maternal age, maternal body weight at delivery, the timing of cortisol measurement and maternal uterine contraction states, revealed that maternal serum total cortisol was significantly negative correlated with ultrasound parameters describing the fetal brain: late biparietal diameter (R-2 =0.512, p =0.009), late head circumference (R-2 = 0.498, p= 0.001), middle biparietal diameter (R-2= 0.819, p = 0.013), middle cerebellum transverse diameter R-2 = 0.76, p= 0.014) and early biparietal diameter(R-2 = 0.819, p = 0.013). The same analysis revealed that birth weight as well as ultrasound parameters such as abdominal circumference and femur length were not correlated to maternal cortisol levels. In conclusion, our study demonstrates that maternal cortisol secretion within physiological ranges may be inversely correlated to fetal brain growth but not to birth weight. It remains to be demonstrated whether maternal cortisol secretion negatively influencing fetal brain growth translates to adverse neurological outcomes in later life. KW - Brain development KW - Fetal programming KW - Cortisol Maternal cortisol KW - Head circumference KW - Biparietal diameter Y1 - 2012 U6 - https://doi.org/10.1016/j.neubiorev.2011.12.006 SN - 0149-7634 VL - 36 IS - 3 SP - 1085 EP - 1092 PB - Elsevier CY - Oxford ER -