Ozdemir Himmetoglu

Role of Oxidative Stress in Intrauterine Growth Restriction

Aims: The objectives of this study were to determine the role of oxidative stress in intrauterine growth restriction (IUGR) and to investigate the possible molecular mechanism(s) leading to oxidant stress in IUGR. Methods: Parameters of the oxidative and antioxidant system were evaluated in maternal plasma, umbilical cord blood, and placental tissue of pregnant women with IUGR fetuses. The same samples were obtained from women with normal pregnancies and were evaluated. Results: The results of this study indicate that while the levels of malondialdehyde (MDA) and xanthine oxidase (XO) were higher in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR when compared to the control group [MDA: 142.8 ± 18.0 vs. 86.4 ± 22.5 nmol/ml, 151.6 ± 25.8 vs. 93.3 ± 7.4 nmol/ml, and 0.72 ± 0.19 vs. 0.42 ± 0.09 nmol/mg protein, respectively (for all p < 0.0005); XO: 1.251 ± 0.674 vs. 0.20 ± 0.019 mIU/ml (p < 0.0005), 1.97 ± 0.73 vs. 0.237 ± 0.143 mIU/ml (p < 0.0005), and 0.023 ± 0.0012 vs. 0.012 ± 0.004 mIU/ml (p < 0.025), respectively], the levels of antioxidant potential were identified to be lower in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR: 63.3 ± 11.9 vs. 198.0 ± 31.9 U/ml (p < 0.0005), 32.6 ± 3.7 vs. 206.5 ± 27.1 U/ml (p < 0.0005), and 0.56 ± 0.23 vs. 1.16 ± 0.29 U/ml (p < 0.0005), respectively. On the other hand, the activities of adenosine deaminase of the IUGR patients were higher than those of the control group in maternal plasma (204.8 ± 103.5 vs. 115.6 ± 31.8 U/l, p < 0.01) and umbilical cord blood samples (584.2 ± 285.2 vs. 147.9 ± 44.8 U/l, p < 0.0005) which may suggest that oxidative stress has a role in IUGR. Moreover, an increased superoxide dismutase activity in maternal plasma (128.2 ± 37.4 vs. 88.8 ± 16.6 U/ml, p < 0.005) and cord blood (162.1 ± 37.0 vs. 116.6 ± 20.7 U/ml, p < 0.005) and an increased glutathione peroxidase activity in maternal plasma (1.83 ± 0.26 vs. 1.47 ± 0.31 IU/ml, p < 0.01) and placental tissue (0.007 ± 0.0015 vs. 0.003 ± 0.0012 IU/ml, p < 0.0005) were detected, while decreased catalase activities in cord blood (23,717 ± 3,538 vs. 16,397 ± 2,771 IU/ml, p < 0.0005) and placental tissue (47.2 ± 17.2 vs. 70.7 ± 11.3 IU/ml, p < 0.005) were identified in IUGR groups. Conclusions: In the light of the results of this study, it can be stated that the oxidative stress increases in patients with IUGR. Providing high-risk patients with an antioxidant may be useful in the prevention or treatment of IUGR, although it is a condition with no certain treatment outcome.

The incidence of congenital malformations in a Turkish population

Objective: To determine the incidence and types of congenital anomalies in a Turkish population. Method: The total number of neonates (9160) born in the Department of Obstetrics and Gynecology, Gazi University Faculty of Medicine during 1988–1995 were studied retrospectively. Newborns with congenital anomaly were identified from their birth registries. The total incidence, types and combined anomalies were determined. Also, the relationship between congenital anomalies and maternal age and/or gender were investigated. For statistical evaluation, Chi‐square test, Yates correction and Fishers exact tests were used where appropriate. Results: The overall congenital anomaly incidence was 1.11% and the NTD incidence was 0.27% in our population. Anencephaly was the second most common NTDs with the ratio of 40%, following the spina bifida cases. There was a significant difference between female and male newborns with ancephalocele (P < 0.05). Urogenital system anomalies were found to be the second most common type of malformation with an incidence of 0.21%. Facial and musculoskeletal system abnormalities were the third and fourth most common malformations. Omphalocele incidence in our population was 5 in 9160 births and gastrochisis was 1 in 9160 births. Conclusion: The overall congenital anomaly incidence in newborns in our population is 1.11%. The most common malformations were CNS and urogenital abnormalities. NTDs incidence was 0.27% in a Turkish population.

The mean platelet volume in gestational diabetes

AbstractObjective: To compare the platelet count and mean platelet volume (MPV) values of pregnancies diagnosed with gestational diabetes with those of healthy pregnancies. Material—method: Between June 2003 and September 2004, 100 healthy pregnancies and 100 pregnancies with gestational diabetes were studied at Gazi University, Department of Obstetrics and Gynecology. Results: While no statistically significant difference was observed in the platelet count between the two groups, the MPV of the gestational diabetes group (9.4 ± 1.6 fl) was evaluated to be significantly higher than the MPV of the healthy pregnancy group (8.3 ± 1.1 fl). Additionally, when linear regression analysis was performed an inverse relationship was observed between platelet number and MPV. Conclusion: There is a need for further research focusing on the platelet function in the observation and treatment of gestational diabetes, which can pose the risk of developing Type 2 diabetes for the mother and has negative consequences for the fetus.

Endothelin 1 and leptin in the pathophysiology of intrauterine growth restriction

Objectives: To evaluate the relationship of endothelin 1 (ET‐1) and leptin concentrations in women and newborns following a pregnancy complicated with intrauterine growth restriction (IUGR). Methods: Twenty‐five women with a pregnancy complicated with IUGR at 19 different gestational ages were matched with women with uncomplicated pregnancies. Blood samples from the umbilical artery and maternal peripheral venous circulation were collected at delivery, and ET‐1 and leptin levels were determined from the blood samples. Data relating to obstetric complications (e.g., pregnancy‐induced hypertension), delivery (e.g. mode, birth weight, signs of intrapartum fetal distress, and Apgar scores) were also recorded. Results: Mean maternal ET‐1 (13.4±6.2–9.9±2.9 pmol/l) and mean fetal ET‐1 (14.5±4.2–11.7±3.1 pmol/l) concentrations were significantly higher when women had experienced pregnancies complicated with IUGR than when they had had normal pregnancies. Mean fetal leptin concentration was significantly lower in the study group (6.8±2.2 ng/ml) than in the control group (10.6±3.6 ng/ml (P<0.05). However, fetal leptin per kilogram of fetal weight was not significantly different in the study group (3.16±1.18 ng/ml) than in the control group (3.23±0.96 ng/ml) (P>0.05, paired t‐test). However, a statistically significant correlation was observed between fetal leptin concentrations per kilogram of fetal weight and fetal endothelin concentrations in pregnancies complicated with IUGR (r=0.546; P<0.05). Conclusions: These results suggest the intertwined roles of ET‐1 and leptin in the pathophysiology of IUGR. Further studies concerning interaction between these peptides in different pregnancy conditions may provide important information about the actions of ET‐1 and leptin on fetal growth.

The effect of maternal anemia and iron deficiency on fetal erythropoiesis: comparison between serum erythropoietin, hemoglobin and ferritin levels in mothers and newborns.

Objective: Maternal and fetal serum erythropoietin levels were correlated with hemoglobin, mean corpuscular volume and serum ferritin in a group of anemic pregnant women to evaluate the effect of maternal anemia on fetal erythropoiesis. Methods: Serum erythropoietin, ferritin, hemoglobin and mean corpuscular volume were investigated in 33 pregnant women with anemia, 11 women with normal hematological parameters and in their newborns. Results: Maternal serum erythropoietin concentration (mean ± SEM) was significantly higher in the anemic group (145.2 ± 42.9 mU/ml) as compared to the control group (37.3 ± 7.6 mU/ml) (p < 0.05). In newborns, all parameters were comparable in both groups except cord serum erythropoietin concentration (mean ± SEM) which was significantly higher in newborns born to anemic women (43.9 ± 5.3 mU/ml) than controls (29.4 ± 3.7 mU/ml) (p < 0.05). In the anemic group, maternal serum erythropoietin was inversely correlated to maternal hemoglobin (r = -0.375, p = 0.03), maternal hemoglobin was inversely correlated to cord serum erythropoietin (r = -0.552, p = 0.001) and maternal ferritin was correlated to fetal ferritin (r = 0.521, p = 0.002). Conclusion: Although cord hemoglobin and mean corpuscular volume were not affected by maternal anemia, increased cord serum erythropoietin levels related to low maternal hemoglobin levels suggest an induced fetal erythropoiesis in maternal anemia.

Effect of different degrees of glucose intolerance on maternal and perinatal outcomes

Objective. To evaluate the effect of markedly elevated 50-g glucose loading test (GLT) (≥200 mg/dL) and equivocal 100-g GLT (one abnormal value) results on maternal and perinatal outcomes. Methods. Retrospective analysis of 2029 singleton pregnancies screened for gestational diabetes mellitus (GDM). Maternal and perinatal outcomes in five different groups with different degrees of glucose intolerance were compared. First group consisted of patients with normal 50-g test, second group was formed by patients with abnormal 50-g glucose test but a normal 100-g test. Third group included patients with one abnormal value after 100-g test. Patients in the fourth group were diagnosed to have GDM after an abnormal 100-g test. Patients in the fifth group had a value ≥200 mg/dL after 50-g test and were diagnosed to have GDM. Results. Macrosomia and large for gestational age incidence were highest in the group with one elevated glucose tolerance test (GTT) value. Hospitalisation rates, hypoglycemia, hyperbilirubinemia and polycythemia were more common in neonates born to mothers with one elevated GTT value and to mothers with a GLT > 200 mg/dL. Conclusion. Adverse maternal and perinatal outcomes in patients with one elevated GTT value and in patients with a GLT value > 200 mg/dL warrant close glucose monitoring and treatment in these groups even in the absence of a diagnostic abnormal GTT.

Maternal and fetal plasma endothelin levels in intrauterine growth restriction: relation to umbilical artery Doppler flow velocimetry.

Abstract The objective of this study was to examine maternal and fetal endothelin-1 (ET-1) in pregnancies complicated with intrauterine growth restriction (IUGR) and to correlate these data with umbilical artery Doppler flow velocity waveforms (FVW). Higher mean maternal (13.8±6,4 vs 9.2±3,4 pmol/L, p < 0.05 ) and fetal (18.5±9.6 vs 11.7±6.9 pmol/L, p < 0.05) ET-1 levels were found in pregnancies complicated with IUGR than in controls. Fetal ET-1 level was related to birth weight percentile for gestational week. Maternal and fetal ET-1 concentrations were not related to umbilical artery Doppler flow S/D ratio, PI and RI. Maternal or fetal ET- 1 concentrations were also not related to umbilical artery pH, PO2 and PCO2. Pregnancy-induced hypertenXsion was significantly associated with an elevated fetal and maternal ET-1 concentration. In conclusion, increased production and secretion of ET-1 may play a role in the pathophysiology of idiopathic IUGR. Over-production of ET-1 in IUGR is not associated with increased placental resistance as reflected in abnormal umbilical artery Doppler FVW.

Zinc and Homocysteine Levels in Polycystic Ovarian Syndrome Patients with Insulin Resistance

In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

Transvaginal color Doppler ultrasonography for prediction of pre-cancerous endometrial lesions

Objective: To determine whether measurements of blood flow in endometrial and uterine vessels by transvaginal color Doppler ultrasonography was valuable in the diagnosis of a neoplastic endometrial pathology (hyperplasia and carcinoma) in women with abnormal bleeding. Methods: This is a prospective study and included 105 post‐menopausal women and 33 pre‐menopausal women with abnormal uterine bleeding. All subjects underwent transvaginal color Doppler ultrasonography. We investigated whether obtained results were correlated with histopathological findings. Results: There was no significant difference in the mean±S.D. RI of the left and the right uterine arteries, intramyometrial arteries and endometrial arteries between patients with neoplastic and non‐neoplastic endometrium on histopathological examination. Dopplers velocity waveforms of small endometrial blood vessels could be detected in 9% of the women with non‐neoplastic endometrium and in 42% of the women with neoplastic endometrium (P<0.05). The mean±S.D. of the endometrial thickness was significantly higher in the women with neoplastic endometrium than that of the women with non‐neoplastic endometrium (16.6±6.1 mm vs. 9.5±4.7 mm, P<0.05). Conclusion: Dopplers velocity waveforms of uterine vessels coupled with transvaginal ultrasonography are not valuable enough to replace histopathological examination in the diagnosis of a neoplastic endometrial pathology. However, it may be helpful in cases in which invasive techniques are difficult to perform and in the differentiation of a certain group of patients at little risk of endometrial carcinoma.

Urogenital symptoms of postmenopausal women in Turkey.

Objective: The objective of this study was to collect data on the prevalence and risk factors of urogenital symptoms in postmenopausal women in Turkey. Design: The study was performed with the participation of 510 postmenopausal women who presented to previously defined clinics for reasons other than urogenital complaints. Women completed a questionnaire including questions about their demographic properties and their urogenital symptoms. Data were analyzed by SPSS 10.0. The chi-square test was the statistical test of choice. Results: The mean age of participants was 58.64 ± 8.14 years. The mean age of menopause was 47.21 ± 4.36 years. Urinary frequency was found to be the most common postmenopausal urogenital symptom (16.5%), followed by stress incontinence (10.4%), dyspareunia (10%), and vaginal dryness (9.6%). Risk factors investigated were found not to affect the prevalence of the vaginal symptoms in postmenopausal women. Dysuria was found to be more common in women with diabetes mellitus (P = 0.022) and in women who had given birth to more children (P = 0.018). Stress incontinence was more common in those 60 years of age or older (P = 0.03), in those who had been in the postmenopausal period for more than 20 years (P = 0.01), and in those who had more than three pregnancies (P = 0.047) or who had given birth to more than three children (P = 0.011). Diabetes mellitus (P = 0.001) and use of hormone therapy (P = 0.001) significantly increased the prevalence of urinary frequency. Conclusions: Urogenital symptoms observed in our population were found to be fewer than reported previously. Symptoms that appear in the postmenopausal period may be related to several factors such as age, number of births, time elapsed since menopause, presence of diabetes mellitus, and use of hormone therapy, but this topic requires further study.