Sándor Valent

Association between subjective feelings of distress, plasma cortisol, anxiety, and depression in pregnant women.

OBJECTIVE Psychosocial stressors are consistently associated with antenatal anxiety and depression, while the impact of cortisol has proved inconsistent. Most studies have focused either on psychological or physiological stress indices. We investigated both subjective and endocrinologic indices of distress in the same subjects. STUDY DESIGN We performed a cross-sectional study in late pregnancy in 79 women to investigate associations between the factors involved in anxiety and depression. Outcome measures were the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale, a Likert-like scale for fear of delivery, a structured interview to assess health and socioeconomic status, and fasting plasma cortisol levels measured in the morning. RESULTS High BDI and STAI scores were associated with high levels of perceived stress and fear of delivery, but not with levels of plasma cortisol typical of the gestation phase. A multiple regression analysis revealed that subjective feelings of distress explained over 50% of the variation in BDI and STAI scores. Plasma cortisol was not a significant predictor of psychometric scores and did not show significant correlation with them in correlation analyses, and subjects with low and high cortisol levels showed similar psychometric scores. CONCLUSION Antenatal depression and anxiety were significantly associated with subjective feelings of distress but not with increased cortisol. This finding may be explained by the blunted cortisol stress responses characteristic of pregnancy. The mechanisms mediating the effects of subjective distress remain obscure: likely candidates include monoamine neurotransmission, and/or stress-induced changes in glucocorticoid receptor expression or distribution.

Nitric oxide and preeclampsia

Preeclampsia is one of the leading causes of obstetric morbidity and mortality. The placenta has a crucial role in the development of preeclampsia. Despite intensive researches the cause of disorder is still unknown. Insufficient NO synthesis may have a key role in pathogenesis. Endothelial NO synthesis (eNOS) is the primary isoenzyme expressed in human placenta, its known disturbances are discussed. Deficiency of substrate (arginine), cofactor (tetrahydrobiopterin, BH4) and calcium can decrease the NO synthesis. Serum levels of free fatty acids (FFA), asymmetric dimethylarginine, reactive oxygen species and glucose may increase in preeclamptic pregnancy. These substances decrease NO production by different ways. The reduced affinity of eNOS to the cofactor BH4 may lead to insufficient NO, but increased superoxide production in preeclamptic placentas. Polymorphisms of eNOS gene (D298E, -786T→C) were associated with preeclamptic complications (not adequately documented). Data suggest that smoking has protective role against preeclampsia. The mechanism is not clear, even the actions of smoking on eNOS are ambivalent. The expression of eNOS is decreased, while the phosphorylation of the activator Ser1177 and also the deactivator Thr495 are increased by cigarette smoke. The oxidative stress directly decreases NO levels. Smoking lowers serum FFA levels, thus the activity of eNOS may be increased. CO produced during smoking mimics the effect of NO and can compensate its absence partially.

[The pathophysiology of preeclampsia in view of the two-stage model].

Preeclampsia is a common and severe disease in pregnancy, a major cause of maternal and fetal morbidity and mortality. The main features of the disease are de novo hypertension after the 20th gestational week and proteinuria, and it is frequently accompanied by edema and other subjective symptoms. The origin of the disease is the placenta, but its sequelae affect multiple organ systems. According to the two-stage model of preeclampsia, the abnormal and hypoperfused placenta (stage 1) releases factors to the bloodstream, which are responsible for the maternal symptoms (stage 2). Oxidative stress, impaired function of nitric-oxide synthase, cellular and humoral immunological factors play an important role in the pathophysiology of the placenta. Endothelial dysfunction is the common denominator of the clinical symptoms. The theory explains the origins of hypertension, proteinuria, edema and other symptoms as well.

Placental gene expression of transforming growth factor beta 1 (TGF-β1) in small for gestational age newborns.

Abstract Objective: The gene expression of transforming growth factor beta-1 (TGF-β1) in human placental samples obtained from pregnancies with small for gestational age fetuses (SGA) was compared to those of normal pregnancies. Methods: In 2011 placental samples from 101 pregnancies with SGA and from 140 normal pregnancies were obtained for analysis of TGF-β1 gene expression. Several clinical parameters were also assessed for correlation between genetic and clinical parameters. Results: There were no significant differences in gene activity of the TGF-β1 gene between the SGA versus normal pregnancy groups (Ln2α: 0.16; p = 0.07). Within the SGA group, no fetal gender-dependent differences were seen in TGF-β1 gene expression (Ln2α: −0.11; p = 0.05). Similarly, no significant differences in gene activity were observed by the degree of severity of SGA as assessed by percentile fetal birth-weight (Ln2α: 0.32; p = 0.06). Conclusion: We found no change in gene expression of TGF-β1 in placental samples obtained from SGA pregnancies versus normal pregnancy suggesting an absence of a direct role of the TGF-β1 gene in the development of SGA. However, the absence of increased gene expression of TGF-β1 in SGA can be conceptualized as a failure to mount a compensatory response in the SGA environment.

Screening of trisomy 21 nowadays. Is maternal age so important

INTRODUCTION Trisomy 21 is the most common chromosomal abnormality, therefore, screening and diagnosis of this disorder is in the centre of attention worldwide. An efficient screening method is the combined test based on maternal age, ultrasound signs, biochemical markers, and a risk ratio can be calculated based on these data. AIM The aim of the authors was to determine the causes of missed prenatal diagnosis of Downs syndrome at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. METHOD A retrospective study was carried out by collecting data from medical records of mothers who had delivered a newborn with Downs syndrome in the Department between 2008 and 2012. Each medical record was analyzed individually. RESULTS In most cases the missed diagnosis of Downs syndrome occurred when the expectant mother failed to attend the first trimester screening or did not take the risk of invasive diagnostic procedures needed for fetal kariotyping. CONCLUSIONS Analysis of fetal DNA circulating in maternal plasma can be a solution for those who refuse invasive fetal diagnostics. This test has high sensitivity and very low false positive rate. It has become available since the end of 2011 in the United States and, since the autumn of 2012, in Hungary, too. The test, however, is not reimbursed by national health insurance.

A 21-es triszómia szűrése napjainkban. Az anyai életkor valóban olyan fontos? [Screening of trisomy 21 nowadays. Is maternal age so important?]

INTRODUCTION Trisomy 21 is the most common chromosomal abnormality, therefore, screening and diagnosis of this disorder is in the centre of attention worldwide. An efficient screening method is the combined test based on maternal age, ultrasound signs, biochemical markers, and a risk ratio can be calculated based on these data. AIM The aim of the authors was to determine the causes of missed prenatal diagnosis of Downs syndrome at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. METHOD A retrospective study was carried out by collecting data from medical records of mothers who had delivered a newborn with Downs syndrome in the Department between 2008 and 2012. Each medical record was analyzed individually. RESULTS In most cases the missed diagnosis of Downs syndrome occurred when the expectant mother failed to attend the first trimester screening or did not take the risk of invasive diagnostic procedures needed for fetal kariotyping. CONCLUSIONS Analysis of fetal DNA circulating in maternal plasma can be a solution for those who refuse invasive fetal diagnostics. This test has high sensitivity and very low false positive rate. It has become available since the end of 2011 in the United States and, since the autumn of 2012, in Hungary, too. The test, however, is not reimbursed by national health insurance.

Ultrasonography in the diagnosis of ovarian and endometrial carcinoma

Transvaginal sonography has become a crucial part of the routine gynecologic examination. It offers now a great help in the diagnosis of almost all gynecological diseases. Transvaginal ultrasound means the first step in the diagnosis of the first two most common gynecological malignancies, and in many cases we are able to set up a diagnosis of its own. The purpose of this article is to emphasize the significant role of transvaginal ultrasonography in the diagnosis of these two dieseases mentioned above, with summarizing the latest developments regarding the capabilities of sonography (Doppler-technique, three-dimensional ultrasonograpy).

High early uterine vascular resistance values increase the risk of adverse pregnancy outcome independently from placental VEGF and VEGFR1 reactivities.

OBJECTIVE From data in the literature, we hypothesized that high vascular resistance values in the uterine arteries at the end of the first trimester would increase adverse pregnancy outcomes and therefore might be accompanied by changes in VEGF/VEGFR1 immunoreactivities. STUDY DESIGN In our university hospital 82 women (Study I n=62 and Study II n=20) were divided into two groups according to their uterine vascular resistance values. Uterine vascular resistance values were measured in the 10-13th weeks of gestation by color-Doppler ultrasonography. Women were divided into low and high vascular resistance groups. In the prospective follow-up study (Study I) the data of the pregnancy outcome were recorded. In cross-sectional study (Study II), VEGF and VEGFR1 immunoreactivities were measured on the tissue samples from women who underwent termination of pregnancy. RESULTS In the high vascular resistance group (PI>2.3), the probability of adverse pregnancy outcome was significantly higher (40.0% vs. 12.8%). No differences in VEGF and VEGFR1 immunoreactivities were observed between groups. In both groups, intense VEGF immunoreactivity was observed in the maternal glandular epithelium and in the decidual cells. Weak reactivity was observed in the villous trophoblast. VEGFR1 immunoreactivity was intense in all regions. CONCLUSIONS Our data suggest that high vascular resistance values in the first trimester are independent from VEGF/VEGFR1 immunoreactivities and markedly increase the probability of adverse pregnancy outcomes. This may be used for early screening of pregnant women in the first trimester.