[Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction]. / A legjelentosebb angiogeneticus gének méhlepényi expressziójának változásai a méhen belüli növekedési visszamaradás hátterében.

Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

Placental gene expression of transforming growth factor beta 1 (TGF-ß1) in small for gestational age newborns.

OBJECTIVE: The gene expression of transforming growth factor beta-1 (TGF-ß1) 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-ß1 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-ß1 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-ß1 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-ß1 in placental samples obtained from SGA pregnancies versus normal pregnancy suggesting an absence of a direct role of the TGF-ß1 gene in the development of SGA. However, the absence of increased gene expression of TGF-ß1 in SGA can be conceptualized as a failure to mount a compensatory response in the SGA environment.

Placental gene expression patterns of endoglin (CD105) in intrauterine growth restriction.

OBJECTIVE: In this study, we describe placental gene expression patterns of endoglin in pregnancies with intrauterine growth restriction (IUGR) compared to normal pregnancies. METHODS: Placental samples were obtained from 101 pregnancies with IUGR using 140 normal pregnancy cases as control. Gene expression patterns and protein levels of the endoglin were compared between the two groups. For the gene expression analysis real-time PCR was applied, while for the estimation of placental protein level we performed Western analysis. RESULTS: The placental endoglin gene was significantly overexpressed in the IUGR group versus the control group (Ln2(α): 1.69). The placental endoglin protein level proved to be significantly higher in case of IUGR (endoglin/ß-actin ratio: 13.8 ± 2.3) versus the control cases (5.3 ± 1.1). The placental gene expression as well as the protein levels of endoglin showed no significant difference between female and male newborns. Concerning the placental gene expression and protein level, no significant difference was justified between the more (0-5 percentile) and less (5-10 percentile) severe cases of IUGR. CONCLUSION: Increased placental gene expression of endoglin may result in vascular dysfunction leading to chronic fetal hypoxia, which may induce VEGF-A to stimulate angiogenesis. This can be explained as feed back response to restore fetal placental circulation.

Placental gene expression patterns of epidermal growth factor in intrauterine growth restriction.

OBJECTIVE: In this study, we compared human placental gene expression patterns of epidermal growth factor (EGF) in pregnancies with intrauterine growth restriction (IUGR) vs. normal pregnancies as control. STUDY DESIGN: Gene expression of EGF was determined from human placental samples collected from all pregnancies presenting with IUGR at our institution during the study period January 1, 2010-January 1, 2011. Multiple clinical variables were also assessed including maternal age, gestational weight gain, increase of BMI during pregnancy and fetal gender. RESULTS: A total of 241 samples were obtained (101 in the IUGR pregnancy group, 140 in the normal pregnancy group). EGF was found to be underexpressed in the IUGR group compared to normal pregnancy (Ln2(α): -1.54; p<0.04). Within the IUGR group no fetal gender-dependent difference was seen in EGF gene expression (Ln2(α): 0.44; p<0.06). Similarly, no significant difference in EGF expression was noted in cases with more vs. less severe forms of IUGR (Ln2(α): -0.08; p=0.05). IUGR pregnancies were significantly more common in the maternal age group 35-44 years compared to other age groups. Gestational weight gain and gestational BMI increase were significantly lower in IUGR pregnancies compared to controls. CONCLUSIONS: Placental expression of EGF was found to be reduced in IUGR pregnancies vs. normal pregnancies. This may partly explain the smaller placental size and placental dysfunction commonly seen with IUGR. An increased incidence of IUGR was observed with maternal age exceeding 35 years. The probability of IUGR correlated with lower gestational weight gain and lower BMI increase during pregnancy.

Gene expression patterns of vascular endothelial growth factor (VEGF-A) in human placenta from pregnancies with intrauterine growth restriction.

OBJECTIVE: In this study, we describe changes in gene expression pattern of vascular endothelial growth factor (VEGF)-A in human placenta obtained from pregnancies with intrauterine growth restriction using placenta from normal pregnancies as control. METHODS: We compared gene expression of VEGF-A in placental samples from Intrauterine growth restriction (IUGR) pregnancies versus placenta obtained from normal pregnancies. Among potential confounders, important clinical informations were also analyzed. RESULTS: In the IUGR group, the VEGF-A gene was overexpressed compared to the normal pregnancy group (Ln 2(α)ß-actin: 1.32; Ln 2(α)GADPH: 1.56). There was no correlation between the degree of growth restriction and VEGF-A gene expression (Ln 2(α)(0-5)percentile: 0.58; Ln 2(α)(5-10)percentile: 0.64). Within the IUGR group, there was a trend toward a positive correlation between placental VEGF-A gene activity and gestational age at delivery (Ln 2(α)< 33 weeks: 1.09; Ln 2(α)33-37 weeks: 1.27; Ln 2(α)> 37 weeks: 1.35). CONCLUSIONS: Our findings suggest that the increase in placental expression of the VEGF-A gene and the resultant stimulation of angiogenesis are a response to hypoxic environment developing in the placental tissue in IUGR. Thus, it appears to be a secondary event rather than a primary factor in the development of IUGR There is a trend toward a positive correlation between gestational age and placental VEGF-A gene activity.

The regulation of apoptosis in intrauterine growth restriction: a study of Bcl-2 and Bax gene expression in human placenta.

OBJECTIVE: In this study, we assessed Bcl-2 and Bax gene expression patterns in human placental samples from intrauterine growth restriction (IUGR) pregnancies using normal pregnancy as control. METHODS: We compared Bcl-2 and Bax gene expression in placental samples from all IUGR pregnancies treated in our clinic between 1 January 2010-1 January 2011 vs. 140 normal pregnancy samples from the same study period. We also assessed clinical parameters such as maternal age, gestational weight gain, gestational body mass index (BMI) change, and maternal birth weight. RESULTS: In IUGR, the Bcl-2 gene was underexpressed compared to normal pregnancy. There was no difference in the Bax gene activity in the two groups. The degree of growth restriction within the IUGR group did not correlate with Bcl-2 or Bax gene activity. CONCLUSIONS: Our study revealed that it is the reduced inhibitory activity of the Bcl-2 gene rather than an enhanced stimulatory activity of the Bax gene in the background of the increased apoptosis observed in IUGR. IUGR appears to be more common with maternal age around 20 years and above 35 years. Gestational weight gain and gestational BMI change also predict the risk for IUGR.

Etiology, prenatal diagnostics and outcome of ventriculomegaly in 230 cases.

OBJECTIVE: The aim of this study was to review and summarize the information regarding the etiology, diagnostics and outcome of ventriculomegaly. METHODS: The study included 230 cases of ventriculomegaly examined between 1979 and 2000. The main diagnostic criterion for ventriculomegaly was the transverse diameter of the ventricular atrium at the level of the glomus of the chorioid plexus measuring >10 mm, irrespective of gestational age. RESULTS: Gender distribution (male:female ratio: 0.98) coincided with that of the general population. In 32% of the cases (72/230), the history was positive; 6% (12/230) had a positive genetic history, while 26% (60/230) were associated with pathological obstetric events. The incidence rate of ventriculomegaly in the patients' history was found to be 2.61% (6/230). In nearly 60% of the cases included in this study, ventriculomegaly was diagnosed before the 24th week of pregnancy. Fresh fetal infection confirmed by Toxoplasma PCR real-time examination was diagnosed only in cases of severe ventriculomegaly. Based on the measurement of the diameter of the atrium of the lateral ventricle, severe and mild ventriculomegaly was diagnosed in 142/230 (61.7%) and 88/230 cases (38.3%), respectively. Termination of pregnancy was significantly more frequent in cases of severe than of mild ventriculomegaly (92 vs. 66%). CONCLUSIONS: The importance of positive obstetric and/or genetic history should be emphasized as it is in direct relationship with the increased incidence of this malformation. Regarding the practice of ultrasonography, mild ventriculomegaly (transverse diameter of the lateral ventricle <15 mm) has a much better prognosis than the severe form (transverse diameter of the lateral ventricle >15 mm) of the malformation. Based on the ultrasonographic diagnosis of ventriculomegaly, TORCH serological examination is also recommended since treating toxoplasmosis by medication may have a promising prognosis for the pregnancy. In cases of isolated ventriculomegaly alone, intrauterine karyotyping is not necessarily indicated, but in cases where ventriculomegaly is associated with other genetic disorders karyotyping should definitely be performed. Since ventriculomegaly is not incompatible with postnatal life by itself, the decision about the fate of the pregnancy is largely dependent on the presence of other organic disorders.

[Common malformations in fetopathologic investigations between 1995 and 2006. Accuracy of ultrasonography confirmed by post mortem investigations]. / Gyakoribb fejlodési rendellenességek a fetopatológiai vizsgálatok anyagában 1995-2006 között. Az ultrahang-diagnosztika hatékonysága a post mortem vizsgálatok tükrében.

UNLABELLED: Fetopathologic investigations are of great importance since they are aimed at assessing the risks of a malformation to recur in a mother's future pregnancy. AIMS: The authors wished to assess and analyse the accuracy of ultrasonography based on the results of fetopathologic investigations in view of malformations of higher prevalence. STUDY DESIGN: The authors have processed the details of 683 cases affecting the nervous, cardiovascular, urinary and skeletal systems, and the abdominal/thoracic walls detected at our department in the period of 1995-2006. RESULTS: No significant differences could be justified as far as the major statistical parameters of maternal and gestational ages at the time of the diagnosis were concerned. There were one or another positive detail in the history in a quarter of malformations affecting the central nervous, cardiovascular and skeletal systems and in one sixth of the cases with disorders of the urinary tract as well as the abdominal/thoracic wall. Urinary tract and cardiovascular malformations were far more common among male fetuses, while moderate female dominance could be observed in malformations of the central nervous system and of the abdominal/thoracic wall. In the four investigated groups of malformations, the proportion of sonographic diagnoses completely coinciding with the post mortem results was found to be approximately or more than 70%, but it was found to be much lower (38%) in urinary malformations. Based on the full sample, the cumulative proportion of coinciding sonographic and fetopathologic diagnoses were more than 63%, while completely incorrect ultrasonographic diagnoses amounted to 18%. CONCLUSIONS: (Even multiple) sonographic investigations are to be performed in a genetic centre if urinary tract malformation with subsequent oligohydramnion is detected. Since the associability of omphalocele and chromosome aberrations has been an established fact, and because some of the cases with omphalocele have been diagnosed as gastroschisis, it may be advisable to perform chromosome investigations in ultrasonographically diagnosed cases of gastroschisis. In cases of VSD, echocardiography should be performed in high-risk pregnancies even if ultrasonography cannot reveal any changes in the patients.

[Assessment of serum interleukin-6 with a rapid test. The diagnosis of neonatal sepsis can be established or ruled out]. / Szérum-interleukin-6-meghatározás gyorsteszt segítségével. Az újszülöttkori szepszis korai diagnózisa, kizárása.

INTRODUCTION: The mortality rate from sepsis is high and the risk of sepsis increases in prematurity in proportion to the decrease in birth weight. MATERIAL AND METHOD: The authors report the assessment of serum interleukin-6 levels in 12 term, at-risk newborn infants after birth and 60 VLBW neonates after detection of non-specific signs of infection or sepsis, treated in NICU at the Semmelweis University, 1st Department of Obstetrics and Gynecology in 2005-2006. The serum IL-6 level with a rapid test (Milenia Quickline IL-6 and PicoScan system) was investigated. The simultaneous assessment of C-reactive protein levels was analysed as well. RESULTS: The assessment of serum interleukin-6 and CRP levels for the early diagnosis of sepsis can be established or ruled out. The sensitivity of serum IL-6 level assessment was 100%. There were no false negative cases. The positive predictive value was 93%. There was a significant difference between the sepsis and infection group of VLBW infants in the serum Il-6 levels ( p = 0.048), and between the infection and non-infection groups in the interleukin-6 levels ( p < 0.005). CONCLUSIONS: In comparing the diagnostic value of IL-6 measurement in VLBW infants with signs of infection to the diagnostic methods currently in use, results showed that a combination of early assessment of IL-6 and CRP seems to increase diagnostic accuracy in attempting to differentiate between septic and nonseptic patients. Such increased accuracy will decrease neonatal morbidity as well as the financial cost of treatment.

Risk of recurrence in major central nervous system malformations between 1976 and 2005.

OBJECTIVE: The goal of the current publication is to review isolated central nervous system malformations (CSMs) using a database in excess of 75 000 cases, with special regard to the risk of recurrence of these malformations alone or in combination. METHODS: In the period between 1 January 1976 and 31 December 2005, among the 75 320 documented cases, consultations were requested due to earlier isolated CSMs in the patients' histories in 3030 cases (4.2%). Processing the data we only considered disorders of genetic origin, and that was why we excluded the cases due to intrauterine infection. Monogenically inherited malformations were also excluded from the analysis. The diagnosis of the malformations was based on the prenatal diagnosis of ultrasonography as well as the findings of the foetopathological examination. RESULTS: In 65% of the cases, the couples sought counselling because of malformation in a previous pregnancy. In these cases, the risk of recurrence was thought to be 5.2%, while in the case of two affected children this figure stood at 21.9%. Analysing the values for the risk of recurrence in 5-year periods, neural tube defects (NTDs) (particularly anencephaly and spina bifida) showed a detectable decrease, which could be attributed to a growing use of folic acid supplementation around the time of conception and during pregnancy. CONCLUSION: There is a clear decrease of risk of recurrence of NTDs, while in the case of the other CSMs in this study, there is no noteworthy chronological change in their risk of recurrence.