Routine screening of abnormal vaginal flora during pregnancy reduces the odds of preterm birth: a systematic review and meta-analysis.

Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18% worldwide. Approximately 30% of preterm deliveries occur as a consequence of fetal or maternal infections. Bacterial vaginosis can increase the risk of ascending infections. However, there is no recommendation or protocol for screening of abnormal vaginal flora. The aim of this systematic review was to investigate the effectiveness of routine screening of abnormal vaginal flora during pregnancy care. We conducted our systematic search in the following databases: MEDLINE via PubMed, Embase, and Cochrane Library. Studies reporting on pregnant women with no symptoms of bacterial vaginosis were included in our analysis if they provided data on the outcome of their pregnancy. The intervention group went through screening of abnormal vaginal flora in addition to routine pregnancy care. Odds ratio (OR) with 95% confidence intervals (CIs) was used as effect size measure. From each study the total number of patients and number of events was extracted in both the intervention and control arm to calculate OR. Altogether we included 13 trials with 143,534 patients. The screening methods were Gram stain, pH screening, pH self-screening and pH screening combined with Gram stain. Regular screening of vaginal flora compared to no screening significantly reduces the odds of preterm birth before 37 weeks (8.98% vs 9.42%; OR 0.71, CI 0.57-0.87), birthweight under 2500 g (6.53% vs 7.24%; OR 0.64, CI 0.50-0.81), preterm birth before 32 weeks (1.35% vs 2.03%; OR 0.51, CI 0.31-0.85) and birthweight under 1000 g (0.86% vs 2.2%; OR 0.33, CI 0.19-0.57). In conclusion, the routine screening of abnormal vaginal flora might prevent preterm birth, extreme preterm birth, low birthweight deliveries and very low birthweight deliveries. Further research is needed to assess the problem more accurately.

Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.

OBJECTIVE: We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. METHODS: During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. RESULTS: There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2α: 0.92; p < 0.06). Within the IUGR group, no fetal gender-dependent differences were seen in placental PIGF gene expression (Ln2α: 0.72; p = 0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2α: -1.49; p < 0.03). CONCLUSION: We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.

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.

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.

Abnormal fetomaternal glucocorticoid metabolism in the background of premature delivery: placental expression patterns of the 11ß-hydroxysteroid dehydrogenase 2 gene.

OBJECTIVE: During pregnancy, 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) is involved in the development of the placental barrier, and its main function is to protect the fetus from the effects of the physiological increase of maternal glucocorticoids. We compared human placental gene expression patterns of 11ß-HSD2 from pregnancies that ended with preterm delivery versus full term pregnancies as controls. STUDY DESIGN: We used real-time PCR to assess the placental gene expression patterns of 11ß-HSD2 in 104 preterm and 140 full term pregnancies (control group) at the time of delivery. RESULTS: In the preterm delivery group, the proportion of smokers was 26.9%, significantly higher than in the control group. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. The 11ß-HSD2 gene was underexpressed in the preterm delivery group compared to normal pregnancy between 28 and 36 gestational weeks, but unchanged between 24 and 28 weeks. There was no fetal gender effect on 11ß-HSD2 gene expression. CONCLUSION: The reduced activity of the 11ß-HSD2 gene seen in the preterm delivery group may impair fetal defences against maternal glucocorticoid exposure. In cases of impending premature delivery, glucocorticoid effects, potentially including postnatal neurological abnormalities and growth restriction, may be worsened by prophylactic steroids given to accelerate fetal lung maturity. The impairment in fetal defences against maternal glucocorticoids due to reduced 11ß-HSD2 enzyme activity appears to begin after gestational week 28.

Gene expression patterns of the Bcl-2 and Bax genes in preterm birth.

OBJECTIVE: The apoptotic genes Bax and Bcl-2 are both involved in the pathogenesis of preterm delivery in conjunction with additional factors. We characterized gene expression patterns of these apoptotic regulatory genes as well as relevant environmental factors. DESIGN: A gene expression study with evaluation of clinical data. SETTING: Semmelweis University, Budapest, Hungary. SAMPLE: Human placental samples from 104 preterm and 140 full-term pregnancies. METHODS: Gene tests were performed using real-time PCR to assess gene expression patterns of Bax and Bcl-2 in human placental samples. Clinical data were collected from our computerized database. MAIN OUTCOME MEASURES: Apoptotic gene expression pattern and clinical information against the background of preterm delivery. RESULTS: In placental samples from preterm delivery pregnancies, expression of the Bcl-2 gene was unchanged, whereas the Bax gene was overexpressed. Placental gene expression of Bax in preterm delivery was dependent on gestational age with gestational weeks 28-32 and 32-36 associated with overexpression, and no overexpression in gestational weeks 24-28. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. CONCLUSIONS: The Bax gene was overexpressed in preterm delivery, whereas expression of the Bcl-2 gene remained unchanged. After the 28(th) gestational week, apoptosis appears to be a key factor in the pathogenesis of preterm delivery.

Gene expression patterns of the 11ß-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: the role of impaired feto-maternal glucocorticoid metabolism.

OBJECTIVE: To assess 11-ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) gene expression patterns in human placental samples from intrauterine growth restriction (IUGR) pregnancies using normal pregnancy as control. STUDY DESIGN: We compared 11-ß-HSD2 gene expression in placental samples from all IUGR pregnancies treated in our clinic between January 1, 2010 and January 1, 2011 vs. 140 normal pregnancy samples from the same study period. Clinical characteristics were also assessed and compared between the IUGR and normal pregnancy groups. RESULTS: Mean gestational weight gain in the IUGR group was significantly lower than in the control group. Similarly, change in body mass index (BMI) was lower. Impending intrauterine fetal asphyxia was significantly more common in the IUGR group. The 11ß-HSD2 gene was underexpressed compared to controls, but this underexpression was only observed after the 33rd gestational week. Within the IUGR group, in cases of impending intrauterine fetal asphyxia the 11ß-HSD2 gene was underexpressed compared to both impending asphyxia in non-IUGR cases, or IUGR without impending asphyxia. CONCLUSION: Low gestational weight gain appears to predict IUGR. The 11ß-HSD2 gene in IUGR is underexpressed and may result in an impaired placental barrier, decreasing protection against maternal glucocorticoids, which are thought to be prominent in fetal programming. Maternal glucocorticoid exposure resulting from an impaired placental barrier may increase the risk for cardiovascular and metobolic disorders later in adult life. In IUGR, before the 33rd gestational week, the expression of the 11ß-HSD2 gene remains physiological. The underexpression of this gene after the 33rd week in impending intrauterine fetal asphyxia in IUGR points to an increased sensitivity to hypoxia when impending asphyxia is present in the late phase of IUGR pregnancies.

Gene expression patterns of insulin-like growth factor 1, 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in human placenta from preterm deliveries: influence of additional factors.

OBJECTIVE: To compare patterns of human placental gene expression of IGF from pregnancies that ended with preterm delivery vs. full term pregnancies as controls. STUDY DESIGN: Real-time PCR was used to assess gene expression of IGF in human placental samples from 104 preterm and 140 full term pregnancies. RESULTS: In the preterm delivery group, the proportion of smokers was significantly higher than in the control group. A history of preterm delivery was more common in the preterm delivery group compared to the control group. In the preterm delivery group, placental samples showed an underexpression of the IGF-1 gene compared to controls. In cases of male fetal gender an overexpression of both the IGF-2 and the IGFBP-3 genes was observed. CONCLUSION: Among environmental factors influencing preterm delivery, smoking was the most significant in our study. In the majority of cases, preterm delivery was induced by intrauterine infection leading to a decreased activity of the IGF system. This mechanism may also play a role in the development of neurological sequelae and in decreased tolerance to fetal distress. The overexpression of the IGF-2 gene observed in the placenta with male fetal gender can be explained by its physiological role in the development of the male phenotype.

Gene expression patterns of insulin-like growth factor 1, insulin-like growth factor 2 and insulin-like growth factor binding protein 3 in human placenta from pregnancies with intrauterine growth restriction.

INTRODUCTION: In this study, we compared insulin-like growth factor (IGF)-gene expression patterns and characteristics of glucose and insulin metabolism in human placenta from pregnancies with or without intrauterine growth restriction (IUGR). MATERIALS AND METHODS: We compared 101 human placentas from intrauterine growth restriction pregnancies to those of 140 normal pregnancies treated at our department in a one-year period. We have also assessed the serum glucose and insulin levels of the IUGR and control groups. Several possible predicting factors of IUGR were also investigated. RESULTS: Risk for IUGR was suggested by gestational weight gain and gestational increase in maternal body mass index (BMI) as well as maternal birthweight. In pregnancies without IUGR, umbilical cord glucose and insulin levels were significantly higher than in pregnancies with IUGR. In placentas from pregnancies with IUGR an overexpression of the IGF-2 and the insulin-like growth factor binding protein (IGFBP)-3 genes was found. In placentas from pregnancies with male fetal gender we found a significant overexpression of the IGF-2 gene. DISCUSSION: Gestational weight gain and BMI increase seem to predict the development of IUGR. Insulin and carbohydrate metabolism are also impaired in IUGR fetuses. In the placentas from pregnancies with IUGR, IGF-2 is overexpressed reflecting its physiological role in optimizing energy distribution in a low-energy environment.

Fetopathological investigations after induced abortions performed in mid-term gemini pregnancies.

Multiple pregnancies present a special obstetric condition whose importance has increased due to the spread of assisted reproductive techniques. We have processed the fetopathological data of 43 abortions induced in mid-term gemini pregnancies, owing to malformations affecting one or both fetuses. 67.4% of the gemini pregnancies were conceived naturally and 32.6% by assisted reproduction techniques. The most commonly occurring malformations affected the fetuses' cardiovascular and central nervous systems. Positive histories could be detected in 23% of the cases. The male-to-female ratio was found to be 1.14. In the majority of the cases with central nervous system malformation, fetus "A" was affected (85.7%). In 29.4% of the cases, monochorionic placentation was established. Ultrasonography and fetopatological findings yielded perfectly matching results in 78.9% of the cases. The incidence of fetal malformations is probably not higher among fetuses conceived by assisted reproduction techniques compared to the ones conceived naturally. Fetal central nervous system malformations usually affect fetus "A". Based on the results of the fetopathological examinations, ultrasonography is a reliable method in the diagnostics of malformations affecting twin fetuses. Fetal echocardiography is indicated simply because of the pregnancy being a multiple one.

Successful operative management of an intact second trimester abdominal pregnancy with additional preoperative selective catheter embolization and postoperative methotrexate therapy.

BACKGROUND: Abdominal pregnancy is a rare condition that may lead to severe complications. CASE REPORT: The authors report the case of a 17-week intact abdominal pregnancy diagnosed in the course of an investigation of lower abdominal pain. Ultrasonography and MR examination revealed an intact abdominal pregnancy. Subsequent angiography was performed to occlude the supportive artery of the pregnancy by selective embolization. The pregnancy was terminated safely by laparotomy a day later. The placenta was left in the abdominal cavity because of the high risk of massive and often uncontrollable bleeding, and treatment with methotrexate was applied postoperatively. CONCLUSIONS: Preoperative embolization and the postoperative methotrexate therapy facilitate the safe surgical treatment of abdominal pregnancy.

Non-syndromic malformations of the central nervous system in twin pregnancies: diagnostic and other clinical features of importance.

OBJECTIVE: The incidence of central nervous system malformations is higher among twins. Our aim was to summarize information about these malformations in twin pregnancies. STUDY DESIGN: Based on a sample originating from the biggest genetic centre in Hungary between January 1990 and December 2008, we examined the data of 42 twin pregnancies associated with non-syndromic malformations of the central nervous system. RESULTS: The involvement of monozygotic fetuses and dizygotic ones of the same gender was found to be 62.5%. Usually only one of the fetuses was affected (57.1%), while the other one was healthy. The male-to-female ratio was 0.75. Identical and fraternal twins were found in 68.4% and 31.6% of the cases, respectively. In the pregnancies of our study the malformation was diagnosed before the 24th gestational week in 90% of the cases. Polyhydramnios (54.8%) was the most commonly associated non-central nervous system malformation. CONCLUSION: Our findings suggest that, in addition to placentation and gestational age, the position of the affected fetus with relation to the uterine orifice is of great importance in determining whether selective abortion is an option in deciding about the outcome of pregnancies affected by craniospinal malformation.

Current concepts in the genetic diagnostics of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology. HLA-DRB1 and PTPN22 1858T gene variants are risk factors of RA, clinical manifestations and rate of progression of joint destruction in this autoimmune disease. Currently, several immunopathogenetic models of other genes (CTLA4, MIF, PADI4 and SLC22A4) are under debate. The clinical influence of some of the gene polymorphisms associated with RA and the principles of pharmacogenetics applied to different therapies, such as classical disease-modifying anti-rheumatic drugs and new biological agents. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient's genetic profile.

[Successful laparoscopic management of a non-communicating rudimentary horn pregnancy]. / Nem kommunikáló rudimenter szarvban kialakult terhesség sikeres eltávolítása laparoszkópia útján.

Pregnancy in a rudimentary horn is a rare entity with the most significant risk of life-threatening intraabdominal bleeding caused by rupture. With the use of vaginal ultrasonography, an early diagnosis can be made before symptoms occur. Management consists of laparoscopic resection of the rudimentary horn with the pregnancy and the ipsilateral tube. Authors present a case of a 9-week pregnancy successfully treated with laparoscopic resection.