Disrupted Balance of the Oxidant-Antioxidant System in the Pathophysiology of Female Reproduction: Oxidative Stress and Adverse Pregnancy Outcomes.

The significance of oxidative stress in the pathophysiology of male reproductive processes has been closely studied in the last two decades. Recently, it has become clear that oxidative stress can lead to numerous pathological conditions during female reproductive processes as well, contributing to the development of endometriosis, polycystic ovary syndrome and various forms of infertility. During pregnancy, physiological generation of reactive oxygen species (ROS) occurs in association with several developmental processes including oocyte maturation and implantation. An overproduction of ROS can lead to disturbances in fetal development and increases the risk for missed abortion, intrauterine growth restriction, pre-eclampsia, premature delivery and gestational diabetes. Our review focuses on the etiological role of the disrupted oxidant-antioxidant system during human gestation as it relates to adverse pregnancy outcomes.

The role of apoptosis in the complex pathogenesis of the most common obstetrics and gynaecology diseases.

PURPOSE: We aimed to assess the etiological role of apoptotic genes Bcl-2 and Bax in the background of major obstetric and gynaecological diseases. METHODS: Placental tissue samples were collected from 101 pregnancies with intrauterine growth restriction and 104 pregnancies with premature birth with 140 controll samples from term, eutrophic newborns. In addition, gene expression assessment of the genes Bax and Bcl-2 was performed in 101 uterine leiomyoma tissue samples at our disposal with 110 control cases. Gene expression levels were assessed by PCR method. RESULTS: The expression of the Bcl-2 gene was decreased in placental samples with intrauterine growth restriction. Significant overexpression of the proapoptotic Bax gene was detected in samples from premature infants. Antiapoptotic Bcl-2 gene expression was found to be significantly increased in fibroid tissues. CONCLUSION: Apoptosis plays a crucial role in the development of the most common OB/GYN conditions. Decrease in the placental expression of the antiapoptotic gene Bcl-2 may upset the balance of programmed cell death.

Survival and early complications of preterm infants with birthweight less than 500 grams during a 10-year period in Hungary.

BACKGROUND: There are limited data available on the survival and early complications of preterm infants with less than 500 g birthweight. To estimate the outcomes for these infants, it is important for caregivers to be aware of perinatal factors that may affect survival. OBJECTIVES: We assessed the mortality and certain early complications of preterm infants born with less than 500 g in Hungary between 2006 and 2015. METHODS: We reviewed data of 486 infants from the database of the Hungarian Central Statistical Office and in parallel of 407 infants from the "NICU database." The study period was divided into two epochs: 2006-2010 and 2011-2015. RESULTS: The survival was 27.1% in the first epoch and 39.1% in the second epoch, and the incidence of early complications was slightly higher in the second epoch. In the surviving group (first and second epoch combined), gestational age (25.1 vs 23.7 weeks), birthweight (458 vs 447 g) antenatal steroid treatment (66.3% vs 52.3%), surfactant therapy (95.1% vs 84.3%), median Apgar scores (6 vs 3 and 8 vs 5 at 1 and 5 minutes, respectively) and proportion of caesarean delivery (89.3% versus 68.5%) were higher than in the non-surviving group (first and second epoch combined). The proportion of multiple births was lower in the surviving group (15.7% vs 33.4%). CONCLUSIONS: Survival of infants with less than 500 g improved between 2006-2010 and 2011-2015 in Hungary. The slightly higher occurrence of early complications might be associated with improving survival.

Trends in Mortality and Morbidity in Infants Under 500 Grams Birthweight: Observations from Our Neonatal Intensive Care Unit (NICU).

BACKGROUND In our previous study, some changes were presented in obstetric care and we studied the morbidity and mortality trends of infants with <500 grams birth weight. Several neonatal protocol changes occurred during the study period. The aim of this study was to analyze the changes in mortality and morbidity of premature infants in light of changing neonatal protocols. MATERIAL AND METHODS We performed a retrospective study of premature infants with <500 grams birth weight, born at our department between 2006 and 2015. We divided the study period into two 5-year epochs and compared mortality and morbidity rates. We calculated the duration of mechanical ventilation and non-invasive respiratory support, and also investigated the potential impact of the differences in clinical practice. RESULTS The survival rate was 30.8% during first epoch, which was significantly lower than the 70.4% survival rate during second epoch. There was no difference in the rate of complications between the 2 epochs. The total number of ventilator and non-invasive ventilation days was significantly lower in the second epoch. CONCLUSIONS We found significant differences in survival rates but no change in the incidence of morbidities between the 2 epochs. Therefore, although the number of neonates surviving with morbidities has increased, so did the number of those with intact survival. The increased survival of infants born with <500 grams birth weight is not associated with increased rate of morbidities. Protocol changes may have contributed to these findings; however, in a retrospective study it is not possible to separate the impact of individual changes.

[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.

Morbidity and mortality trends in very-very low birth weight premature infants in light of recent changes in obstetric care.

OBJECTIVE: In this study, we describe trends in morbidity and mortality of preterm infants with less than 500mg birth weight in the changing landscape of obstetric and neonatal care. STUDY DESIGN: During a ten year study period between 2006 and 2016 we assessed outcome data for all neonates with less than 500mg birth weight born at our Neonatal Intensive Care Unit. We divided study subjects into two groups based on whether their birth date fell in the first half (2006-2010; n=39) versus the second half (2011-2015; n=27) of the study period comparing clinical outcomes in the two groups. We also assessed several clinical parameters for association with postnatal survival by comparing relative frequencies for each clinical parameter among surviving infants versus mortality cases. RESULTS: Survival rate for preterm neonates with less than 500mg birth weight born between 2006 and 2010 was 30.8%. This survival rate rose to 70.4% in the second half of the study period between 2011 and 2015 (p<0.05). Among surviving babies premature birth was found to be predominantly associated with maternal hypertension or intrauterine growth restriction while in those who died premature birth due to premature rupture of membranes and spontaneous preterm labor were significantly more common. All surviving infants with less than 500mg birth weight were born via cesarean section whereas among those who died cesarean section had been performed in only 80% and vaginal delivery in 20% representing a significant difference between the groups (p<0.05). The majority (90.3%) of surviving infants with less than 500mg birth weight had received surfactant therapy while the proportion of neonates receiving surfactant therapy among mortality cases was significantly lower (65.2%; p<0.05). DISCUSSION: Our findings suggest that among premature neonates with less than 500mg birth weight preterm delivery due to premature rupture of membranes and intrauterine infections represents the worse mortality risk. Steroid prophylaxis and measures to prevent and treat intrauterine infections with appropriate use of antibiotics can markedly improve survival in these cases. In premature neonates with less than 500mg birth weight survival is more favorable after cesarean section compared to vaginal delivery.

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.

Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic Differentiation of Amniotic Fluid Stem Cells.

UNLABELLED: Amniotic fluid stem (AFS) cells represent a major source of donor cells for cartilage repair. Recently, it became clear that mammalian target of rapamycin (mTOR) inhibition has beneficial effects on cartilage homeostasis, but the effect of mTOR on chondrogenic differentiation is still elusive. Therefore, the objectives of this study were to investigate the effects of mammalian target of rapamycin complex 1 (mTORC1) modulation on the expression of SOX9 and on its downstream targets during chondrogenic differentiation of AFS cells. We performed three-dimensional pellet culturing of AFS cells and of in vitro-expanded, human-derived chondrocytes in the presence of chondrogenic factors. Inhibition of mTORC1 by rapamycin or by small interfering RNA-mediated targeting of raptor (gene name, RPTOR) led to increased AKT activation, upregulation of hypoxia inducible factor (HIF) 2A, and an increase in SOX9, COL2A1, and ACAN abundance. Here we show that HIF2A expression is essential for chondrogenic differentiation and that AKT activity regulates HIF2A amounts. Importantly, engraftment of AFS cells in cell pellets composed of human chondrocytes revealed an advantage of raptor knockdown cells compared with control cells in their ability to express SOX9. Our results demonstrate that mTORC1 inhibition leads to AKT activation and an increase in HIF2A expression. Therefore, we suggest that mTORC1 inhibition is a powerful tool for enhancing chondrogenic differentiation of AFS cells and also of in vitro-expanded adult chondrocytes before transplantation. SIGNIFICANCE: Repair of cartilage defects is still an unresolved issue in regenerative medicine. Results of this study showed that inhibition of the mammalian target of rapamycin complex 1 (mTORC1) pathway, by rapamycin or by small interfering RNA-mediated targeting of raptor (gene name, RPTOR), enhanced amniotic fluid stem cell differentiation toward a chondrocytic phenotype and increased their engrafting efficiency into cartilaginous structures. Moreover, freshly isolated and in vitro passaged human chondrocytes also showed redifferentiation upon mTORC1 inhibition during culturing. Therefore, this study revealed that rapamycin could enable a more efficient clinical use of cell-based therapy approaches to treat articular cartilage defects.

[Importance of nerve-sparing surgical technique in the treatment of deep infiltrating endometriosis]. / Az idegkímélo mutéti technika jelentosége a mélyen infiltráló endometriosis sebészetében.

INTRODUCTION: Traditional surgeries performed in cases of deep infiltrating endometriosis lead to impaired quality of life. AIM: To summarize the postoperative outcome and to compare the rate of postoperative complications after different therapeutic approaches applied in deep infiltrating endometriosis. METHOD: The authors analized the articles published between March 31, 2004 and March 31, 2015, in the database http://www.pubmed.org using the following keywords: endometriosis, deep infiltrating, nerve sparing, surgery. RESULTS: Non-nerve sparing surgery resulted in temporary urinary dysfunction in 19.1-38.5% of patients, while it occurred in 0.61-33.3% of patients after nerve-sparing surgery. Non-nerve sparing surgical technique resulted in an average of 121 days of need for self-catheretisation. When nerve-sparing surgeries were performed the duration of self-catheterisation varied between 7 to 39.8 days. After nerve sparing surgeries, permanent bladder dysfunction was not detected in any case. CONCLUSIONS: Because of the successful treatment of the patients symptoms and the lower postoperative complication rate, nerve-sparing surgical technique leads to a significant improvement of the quality of life.

Role of Apoptosis in the Development of Uterine Leiomyoma: Analysis of Expression Patterns of Bcl-2 and Bax in Human Leiomyoma Tissue With Clinical Correlations.

To describe gene expression patterns of the apoptotic regulatory genes Bcl and Bax in human uterine leiomyoma tissue. To investigate the relationship between alterations of gene expression patterns and several relevant clinical parameters. We obtained samples from 101 cases undergoing surgery for uterine leiomyoma for gene expression analysis of the Bcl-2 and Bax genes. Gene expression was quantified using RT-PCR technique. In the leiomyoma group, the Bcl-2 gene was significantly overexpressed compared with the control group although there was no such difference in the gene expression of Bax. Gene activity of Bcl-2 positively correlated with the tumor number in individual uterine leiomyoma cases. Although there was no significant correlation between the length of the cumulative lactation period before the development of uterine leiomyoma and Bcl-2 gene expression in the leiomyoma tissue, we observed a trend for a shorter cumulative lactation period to be associated with overexpression of the Bcl-2 gene. Overexpression of the antiapoptotic Bcl-2 gene appeared to be a factor in the development of uterine leiomyoma, whereas gene activity of the proapoptotic Bax gene did not seem to play a role in the process.

[Epigenetic mechanisms in physiologic and pathologic pregnancies]. / Epigenetikai mechanizmusok élettani és kóros terhességben.

Epigenetic factors are nowadays in the focus of scientific interest in medicine including obstetrics. The environment in utero and early neonatal life may induce a permanent response in the fetus and the newborn leading to enhanced susceptibility to later diseases. There is now growing evidence that the effects of developmental programming may also manifest themselves in the next generations without further suboptimal exposure. The so-called fetal programming may also highlight a tight connection between pathological conditions in pregnancy, environmental factors and the development of chronic diseases in adulthood. Investigation of epigenetic factors may yield new possibilities for the prevention of chronic diseases affecting a significant part of the population.

[Epigenetic background of the most common non-oncologic gynecological diseases]. / A leggyakoribb nem onkológiai eredetu nogyógyászati kórképek epigenetikai háttere.

Epigenetic effects influence the function of genes regulating the main physiological mechanisms. Some of these environmental factors may reduce or inhibit the function of these genes. The environmental effects on gene function may result in a change of the DNA structure leading to non-heritable phenotype changes. Epigenetic factors play an important etiological role in the development of numerous diseases in obstetrics and gynecology. Uterine fibroids probably have a complex etiological background including epigenetic mechanisms. The multifactorial aetiology of endometriosis suggests key roles for immunological and hormonal factors in the development of the diseases. These mechanisms are influenced by epigenetic factors, which may serve as therapeutic targets in the future. The possible in utero origin of polycystic ovary syndrome determines the main directions of research concerning epigenetic factors in the etiological background, with the hope of eventual prevention and/or treatment in the preconceptional period as well as during pregnancy care.

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.

Trends in maternal mortality in Hungary between 1978 and 2010.

OBJECTIVE: We evaluated the trends of the last decades in maternal mortality in Hungary and compared Hungarian results with those of other European countries. STUDY DESIGN: Cases of maternal death in Hungary during the study period from calendar year 1978 to 2010 were analyzed in a retrospective manner to characterize mortality distribution and to identify potential clinical or demographic predictors. Data in all cases were extracted both from the national Obstetric Registry operated by the National Institute of Gynecology and Obstetrics, from the Hungarian Central Bureau of Statistics and from the National Public Health and Medical Officer Service. Detailed clinical data were obtained based on obligatory reporting by individual clinical institutions. RESULTS: The annual maternal mortality rate (MMR) was 26.7 per 100,000 live births in the period 1978-1987 and declined significantly to 10.9 per 100,000 live births in the period 1997-2010. In the period 1988-1996 (with missing associated clinical and demographic data) the MMR was 16.4 per 100,000 live births. The proportion of delivery-associated causes of death increased significantly between the two study periods from 49.4% to 62.9% (p<0.05). Among obstetric causes of death, the rate of thromboembolism showed a significant increase, while there was a trend toward a decline in rate of maternal deaths attributable to hemorrhagic shock. Among medical causes of death not directly attributable to obstetric complications, the rate of renal and gastrointestinal etiologies declined significantly throughout the study periods. CONCLUSIONS: We observed a marked decline in maternal mortality during the last few decades in Hungary. Recent changes in mortality distribution highlight current characteristics of pregnancy care in Hungary and may help identify strategies for future improvement.

[Prenatal diagnosis of central nervous system malformations]. / A központi idegrendszer fejlodési rendellenességeinek praenatalis diagnosztikája.

The prenatal diagnosis of fetal malformations have been the subject of numerous publications in the literature. This has dramatically increased in the last 15 years, mainly due to the advent of high-resolution ultrasound. In addition adequate guidelines issued by professional organizations have encouraged the universal approach to the imaging of fetal anatomy as well as malformations. One of the most significant groups of the fetal anomalies is the central nervous system malformation. Due to its prevalence and severity the praenatal diagnostics of central nervous system malformations got basic significance. In this review we attempted to summarize the recent informations concerning the prenatal diagnostics of the central nervous system anomalies.

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.

Isolated and ventriculomegaly-associated cases of spina bifida in genetic counseling: focus on fetal pathology.

Cases of spina bifida alone and in association with ventriculomegaly represent important but different malformations according to clinical characteristics. In our study, we analyzed the data on pregancies terminated because of isolated cases (n=307) and ventriculomegaly-associated cases (n=372) of spina bifida. In spina bifida cases in association with hydrocephalus, positive obstetric history was found approximately 1.5 times more frequently than in the isolated ones. The incidence of positive genetic history was nearly two-fold in the latter cases. In isolated cases of spina bifida, associated malformations were more common than in cases of spina bifida and ventriculomegaly together. The most frequent associated malformations were those of the urogenital system (in cases of spina bifida: 11.1%; in cases of SB+V: 9.14%). The risk of recurrence of SB+V is significantly higher than that of isolated SB (8.9% vs. 2.1%). It can be concluded that positive genetic history is more common in cases of isolated spina bifida. Malformations out of the nervous system are more commonly observed in cases of isolated spina bifida. During the prenatal diagnostics of spina bifida, sonography must focus on malformations of the urogenital system.

Gene expression patterns of insulin-like growth factor 2 in human uterine fibroid tissues: a genetic study with clinical correlations.

BACKGROUND/AIMS: We investigated insulin-like growth factor 2 (IGF-2) gene activity in human uterine fibroid tissue. Results of the genetic testing were correlated with clinical data. METHODS: We obtained samples from patients treated for uterine fibroid and from patients undergoing hysterectomy due to other indications (control group). The examined group (with fibroid) contained 101 cases, while the control group was similar with 110 patients. Gene expression values were determined using the standard PCR technique. Clinical data were available from the computer database of the department. RESULTS: IGF-2 gene expression was significantly higher in the fibroid group. There was no correlation between increase in gene activity and the number of tumors. History of previous uterine fibroid did not seem to predict IGF-2 gene activity in the current fibroid tumor tissue. IGF-2 gene expression did not correlate with cumulative duration of lactation following prior pregnancies. CONCLUSION: IGF-2 gene activity is significantly increased in leiomyoma tissue compared to normal myometrium. Familial aggregation of uterine fibroids is not significantly associated with increased IGF-2 gene activity; other genes may have a stronger etiological role. It appears that the genetic factors potentially important in the development of familiar uterine leiomyoma are not related to the IGF-2 gene.

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.