Immunohistochemical Expression of Placental Vitamin D Receptors in Pregnancies Complicated by Early and Late-Onset Preeclampsia.

The aim of our study was to determine whether the immunohistochemical expression of placental vitamin D receptors is altered in pregnancies complicated by preeclampsia. Vitamin D receptor expression was immunohistochemically analysed in the placentas of three groups: a control group, and early- and late-onset preeclampsia groups. Total immunohistochemical intensity staining of placentas showed that the control group had a median vitamin D receptor (VDR) expression significantly higher than the placentas of mothers with early- and late-onset preeclampsia. There was no difference among the three groups in a semiquantitative analysis of VDR staining of the stroma only. Vitamin D receptors showed lower median expression in preeclampsia-affected pregnancies, especially early-onset preeclampsia. Therefore, Vitamin D receptor expression may be an important marker for normal placentation and preeclampsia onset.

Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of the late preterm delivery regardless of the membrane status.

OBJECTIVES: To compare the immunohistochemical expression of IL-6 in placental membranes of late preterm delivery in women with histologically proven chorioamnionitis with and without preterm premature rupture of membranes (PPROM). METHODS: Fetal membranes were collected from 60 women who had late preterm delivery with histologic chorioamnionitis with and without PPROM (30 in each group). Immunohistochemistry for IL-6 was performed on formalin fixed and paraffin-embedded sections. The two groups were matched for age, body mass index and parity. SPSS Version 17.0 was used for statistical analysis. RESULTS: There was no difference in immunohistochemical expression of IL-6 in placental membranes of women with histologic chorioamnionitis regardless of the membrane status. CONCLUSIONS: Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of women with late preterm delivery despite the clinical presentation.

Pregnancy After Simultaneous Pancreas-Kidney Transplantation in Treatment of End-Stage Diabetes Mellitus: a Review.

The majority of patients with simultaneous pancreas and kidney transplant (SPKT) required transplantation owing to a long-standing history of insulin-dependent diabetes mellitus (IDDM). The disease causes multiple organ damage, impairs fertility, and affects quality of life. A successful kidney and pancreas transplant can improve health, ameliorate the consequences of pre-existent diabetes, and restore fertility. Good graft function, without any sign of rejection, and stable doses of immunosuppressant drugs are of utmost importance prior to the planned pregnancy. SPKT recipients who become pregnant may be at an increased risk for an adverse outcome and require meticulous multidisciplinary surveillance. We present experiences with SPKT pregnancies, traditional approaches, and recent considerations. In light of complex interactions between new anatomic relations and the impact of developing pregnancy and immunosuppressive medications, special stress is put on the risk of graft rejection, development of pregnancy complications, and potential harmful effects on fetal development. Recent recommendations in management of SPKT recipients who wish to commence pregnancy are presented as well. Key words: transplantation, pregnancy, pancreas, kidney, simultaneous pancreas and kidney transplantation (SPKT).

Maternal body mass index change as a new optimal gestational weight gain predictor in overweight women.

AIM: To investigate the relationship between maternal pre-pregnancy body-mass index (BMI) and neonatal birth weight. METHODS: The observational study included 2906 mothers and their neonates born from 2005 to 2011 at the Department of Gynecology and Obstetrics, Split University Hospital Center. Mothers with singleton term pregnancies who were overweight before pregnancy (BMI 25-29.9 kg/m2) were compared with those with normal pre-pregnancy weight (BMI 18.5-24.9 kg/m2). BMI change was assessed as a predictor of birth weight, categorized as small (SGA), appropriate (AGA), or large for gestational age (LGA). RESULTS: The rate of SGA infants was significantly lower (n=199; 6.8% vs n=1548; 9.2%) and the rate of LGA infants significantly greater among pre-pregnancy overweight mothers compared with normal-weight mothers (n=371; 12.8% vs n=1302; 7.8%; P<0.001 both). Overweight mothers had a significant probability of delivering an SGA neonate when they gained less than 6 kg, as compared with 8 kg among normal-weight mothers. They had a significant probability of delivering an LGA neonate when they gained more than 14 kg, compared with more than 20 kg among normal-weight mothers. BMI change was a more consistent indicator, suggesting that the ranges of 3.0-7.9 kg/m2 in overweight and 2-5.9 kg/m2 in normal-weight women were not associated with a significant increase in the rate of SGA or LGA. CONCLUSION: Maternal height seems to be an important factor in optimal weight gain definition, suggesting that BMI change should be a preferred measure of pregnancy-related weight.

Calculation of optimal gestation weight gain in pre-pregnancy underweight women due to body mass index change in relation to mother's height.

BACKGROUND: Optimal gestational weight gain has not yet been clearly defined and remains one of the most controversial issues in modern perinatology. The role of optimal weight gain during pregnancy is critical, as it has a strong effect on perinatal outcomes. PURPOSE: In this study, gestational body mass index (BMI) change, accounting for maternal height, was investigated as a new criterion for gestational weight gain determination, in the context of fetal growth assessment. We had focused on underweight women only, and aimed to assess whether the Institute of Medicine (IOM) guidelines could be considered acceptable or additional corrections are required in this subgroup of women. METHODS: The study included 1205 pre-pregnancy underweight mothers and their neonates. Only mothers with singleton term pregnancies (37th-42nd week of gestation) with pre-gestational BMI < 18.5 kg/m2 were enrolled. RESULTS: The share of small for gestational age (SGA) infants in the study population was 16.2 %. Our results showed the minimal recommended gestational weight gain of 12-14 kg and BMI change of 4-5 kg/m2 to be associated with a lower prevalence of SGA newborns. Based on our results, the recommended upper limit of gestational mass change could definitely be substantially higher. CONCLUSION: Optimal weight gain in underweight women could be estimated in the very beginning of pregnancy as recommended BMI change, but recalculated in kilograms according to body height, which modulates the numerical calculation of BMI. Our proposal presents a further step forward towards individualized approach for each pregnant woman.

Increased expression of matrix metalloproteinase-1 in uterosacral ligament tissue from women with pelvic organ prolapse.

Mechanical stability of the urogenital tract depends on intact collagen fibers. Because of difficulties in quantitating collagen, some authors have investigated collagen breakdown by measuring matrix metalloproteinases expression. We biopsied 68 post-menopausal women during operation to evaluate matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament biopsies from women with pelvic organ prolapse (POP) (n = 34) and controls with normal pelvic support (n = 34). The controls were matched to the POP group by age, body mass index, parity and duration of postmenopausal state. Immunohistochemistry for MMP-1 was performed on formalin fixed and paraffin embedded sections. Women with POP had a significantly higher MMP-1 expression (p = 0.047) which confirms an association, although not a causal relation, between POP and increased MMP-1 expression.

Expression of matrix metalloproteinase-1 in uterosacral ligaments tissue of women with genital prolapse.

Collagen metabolism is altered in the pelvic organ tissues of women with genital prolapse. The aim of this study was to compare collagen metabolism by measuring matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament tissues of postmenopausal women with and without genital prolapse. Uterosacral ligament tissues were obtained at the time of abdominal or vaginal surgery from twenty-four patients with pelvic organ prolapse (POP) and 21 women who underwent gynecologic surgery for benign indications. The tissue samples were analyzed by immunohistochemistry. There were no differences in age, BMI and parity between two groups. The patients with genital prolapse demonstrated significantly higher occurences of MMP-1 expression compared to controls. These findings indicate that increased MMP-1 expression in uterosacral ligaments is associated with genital prolapse. Our data are consistent with the theory that increased collagen breakdown may play an important role in the onset and development of pelvic organ prolapse (POP).

A Retrospective Study of Discordant Twin Growth in Dichorionic Twin Pregnancies and Risk of Preterm Delivery at Split University Hospital Centre: Three-Year Experience.

The aim was to determine whether discordant twin growth has an impact on preterm birth in dichorionic pregnancies. This retrospective study included dichorionic twin pregnancies in the period from January 1, 2013 to December 31, 2015. The following variables were investigated: maternal age (years), parity, body mass index (kg/m2), week (≤366/7 and ≥37) and mode of delivery (vaginal and cesarean section), birth weight (grams) and Apgar score (≤7, 8-10). Discordant twin growth in dichorionic pregnancies was found to be associated with preterm birth (χ2=4.74; p=0.03) but had no impact on the mode of delivery (χ2=0.119; p=0.73). There was a statistically significant difference in the rate of small for gestational age (SGA) neonates (χ2=16.4556; p=0.000267) and Apgar score (χ2=7.9931; p<0.05) between the study groups. Mode of conception in dichorionic pregnancies was not a risk factor for preterm delivery (χ2=1.417; p=0.23). In conclusion, discordant twin growth in dichorionic pregnancies is a risk factor for preterm delivery and has no impact on the mode of delivery but has an impact on the rate of SGA and Apgar score.

Involvement of T lymphocytes in the placentae with villitis of unknown etiology from pregnancies complicated with preeclampsia.

OBJECTIVE: The aim of the study was to compare immunohistochemical expression of different T type lymphocytes in foci of villitis of placentae with villitis of unknown etiology (VUE) without and with preeclampsia (PE). METHODS: Fifty-four placentae were collected from women who had VUE with (N = 27) and without (N = 27) PE. Immunohistochemistry for types of T lymphocytes was performed on formalin fixed and paraffin-embedded sections by use of the CD3, CD4, FOXP3, CD25, CD8 and CD68 antibodies. All data analyses were done by R Development Core Team. RESULTS: There was higher immunohistochemical CD4 positive T lymphocyte count and CD4 positive/CD8 positive ratio in placentae with VUE complicated with PE compared to control group. CONCLUSION: The higher immunohistochemical CD4 positive T lymphocyte count and CD4 positive/CD8 positive ratio in placentae with VUE complicated with PE could point to their role in ethiopathogenesis of PE.

Gestational age--the most important factor of neonatal ponderal index.

Ponderal index (fetal weight in grams X 100 / (fetal length in centimeters)3) (PI) is one of the anthropometric methods used to diagnose impaired fetal growth. Irrespective of the infant's position on the growth-weight-for-gestational age charts, PI is low in malnourished infants and high in obese ones. As fetal growth is affected by ethnicity, geographic location and socioeconomic status, we developed standards for neonatal PI, and assessed the effects of gestational age, sex and maternal parity. Data on 5798 newborns from singleton pregnancies born in the Department of Gynecology and Obstetrics, Split University Hospital, were retrospectively analyzed. Over a 15-month period in 2000/2001, 5596 newborns from 24 to 42 weeks of gestation were born. The other 202 newborns, born from 24 to 34 weeks of gestation in the ten year period, 1990-1999, were added because of the small number of preterm infants; ensuring a minimum of 30 to fill up at least infants in each gestational week. All mothers were of Caucasian origin. Stillbirths and fetuses with congenital malformations were excluded. The 10th, 50th and 90th percentiles, mean values with standard deviation of PI and the 10th, 50th, and 90th percentiles of birth weight and birth length are presented separately at weekly intervals. PI showed linear correlation with gestational age from 24 to 39 weeks, after witch the data plateaued. Sex and parity had no impact on PI in infants born between 24 and 37 weeks. Analysis of variance revealed PI to be significantly higher in female than in male newborns, and in multiparous than in nulliparous infants after 37 weeks of gestation. In conclusion, gestational age is the most important factor of neonatal PI. The effects of sex and parity on PI should only be considered in term neonates.

Uterine artery embolization for the treatment of uterine fibroids.

Uterine artery embolization can be regarded as a less invasive procedure for the treatment of fibroids compared with myomectomy, hysterectomy, and laparoscopic myolysis. The aim of this study was the evaluation of safety and efficacy of uterine artery embolization and of womens' opinion about this treatment. After gynecological examination sixty-nine premenopausal women underwent uterine artery embolization. All procedures but four were technically successful; three women underwent unilateral embolization because of vascular malformation and one of them had an allergic reaction to contrast medium. Of the 69 patients: 58 went home the day after embolization, and 11 within first week. The follow-up examinations after 3, 6 and 12 month showed a significant reduction of uterine and fibroid volume with significant improvement of bleeding. Therefore, according to this report, uterine artery embolization is a successful, minimal invasive treatment of myoma that preserves the uterus and requires shorter hospitalization and recovery times than surgery.

[Does the suture material and technique have an effect on healing of the uterotomy in cesarean section?]. / Utjecu li materijal i tehnika sivanja na cijeljenje uterotomije pri carskome rezu?

The aim of the study is to present the influence of different suturing techniques and different materials (catgut plain, Dexon and Vicryl) on healing of lower transverse uterotomy (in further text uterotomy) in Cesarean section (CS). Uterotomies were sutured by four ways: one row interrupted (group A), one row continuous (group B), two rows interrupted (group C), two rows interrupted and continuous (group D). Uterotomies were classfied according to the material used for suturing into the catgut group, Dexon group and Vicryl group. Between January 1983 and December 2001 out of 7830 CSc 1946 (24.8%) patients had repeat deliveries: 1059 (55.0%) had a vaginal delivery and 887 (45.0%) repeat CS. In the same period out of 1946 deliveries 15 (0.8%) uterine ruptures-dehiscences (URD) were diagnosed. In catgut group out of 302 deliveries 11 (3.6%) URD were registered: nine (7.2%) in group D (N = 125) and two (1.7%) in group C (N = 20). No URD was diagnosed in group A (N = 57). In Dexon group (N = 226) URD were diagnosed regardless of the method of suturing the uterotomy. In Vicryl group out of 1486 deliveries four (0.28%) URD were registered: one (0.16%) in group A (N = 615), one (0.3%) in group B (N = 333), one (0.52%) in group C (N = 190) and one (0.35%) in group D (N = 280). The best uterine scar is the one after using one layer interrupted Vicryl and Dexon suture. The worst healing results were obtained after two-row interrupted and continuous sutures using catgut.

Immunohistochemical expression of RECK protein in placental membranes of the preterm delivery with and without chorioamnionitis.

OBJECTIVE: To compare the immunohistochemical expression of RECK protein in placental membranes of late preterm delivery in women with and without histologically proven chorioamnionitis. STUDY DESIGN: Fetal membranes were collected from women who had late preterm delivery with (n=8) and without (n=9) histologic chorioamnionitis. Immunohistochemistry for RECK protein was performed on formalin fixed and paraffin-embedded sections. The two groups were matched for age, body mass index and parity. SPSS Version 13.0 was used for statistical analysis. RESULTS: There was weaker immunohistochemical expression of RECK protein in placental membranes of women with histologic chorioamnionitis compared to control subjects (P=0.0498). CONCLUSIONS: Chorioamnionitis has an impact on immunohistochemical expression of RECK protein in placental membranes in late preterm delivery.

Maternal pre-pregnancy underweight and fetal growth in relation to institute of medicine recommendations for gestational weight gain.

PURPOSE: Maternal nutritional status is one of the most important factors of fetal growth and development. Consequently, the currently increasing prevalence of underweight women worldwide has come in the focus of interest of perinatal medicine. The aim of the study was to assess the effect of low pre-pregnancy body mass index (BMI) on fetal growth. MATERIALS AND METHODS: Data on 4678 pregnant women and their neonates were retrospectively analyzed. Pre-pregnancy BMI of study women was categorized according to the WHO standards. Fetal growth was assessed by birth weight and birth length, birth weight for gestational age, and ponderal index. RESULTS: Study group included 351 (7.6%) women with pregestational BMI<18.5kg/m(2), while all women with pregestational BMI 18.5-25kg/m(2) (n=3688; 78.8%) served as a control group. The mean birth weight and birth length of neonates born to underweight mothers were by 167g and 0.8cm lower in comparison with the neonates born to mothers of normal nutritional status, respectively (P<0.001 both). The prevalence of small for gestational age (SGA) births was twofold that found in the control group of mothers of normal nutritional status (9.7% vs. 4.9%; P<0.001). The inappropriately low gestational weight gain additionally increased the rate of SGA infants in the group of mothers with low pre-pregnancy BMI (21.4% vs. 10.4%; P=0.02). Pre-pregnancy BMI category did not influence neonatal growth symmetry. CONCLUSION: Low maternal pregestational BMI is associated with fetal growth assessment. Improvement of the maternal nutritional status before pregnancy can increase the likelihood of perinatal outcome.

Is there difference in perinatal outcome of singleton and twin pregnancies after assisted conception: two-year experience.

The aim of the study was to compare perinatal outcome of singleton and twin pregnancies conceived after assisted reproductive technologies (ART). This retrospective study included singleton and twin pregnancies conceived after ART in the period from January 1, 2007 until December 31, 2008. The study variables were maternal age (years), parity, body mass index (BMI; kg/m2), week (< or =36 (6/7) and > or = 37) and mode of delivery (vaginal and cesarean section), birth weight (grams) and APGAR score (< or = 7; 8-10). During the study period, there were 195 pregnancies after ART that fulfilled inclusion criteria. We found no between-group difference in parity (chi2 = 0.0133; P = 0.9081), but such difference was found in mean age (t = 2.0486; P = 0.0419) and BMI (chi2 = 31.038; P = 0.001). A statistically significant difference was recorded in preterm delivery rate (chi2 = 25.539; P = 0.001), average duration of pregnancy (t = 12.8591; P = 0.001), average birth weight (t = 10.5446; P = 0.001) and mode of delivery (chi2 = 13,691; P = 0.001). A statistically significant difference was found in low birth weight babies (chi2 = 102.02; P = 0.001) and APGAR score (chi2 = 19.96; P = 0.001), but there was no difference in the prevalence of small for gestational age babies (chi2 = 0.90629; P = 0.635). In conclusion, this study indicated the perinatal outcome after ART to be considerably poorer in twins than in singletons.

Estrogen replacement therapy improves pulmonary function in postmenopausal women with genital prolapse.

OBJECTIVE: This study examined the impact of estrogen replacement therapy with spirometry on pulmonary function in surgically castrated (salpingo-oophorectomy) postmenopausal women with genital prolapse. METHODS: The study included 60 postmenopausal women with pelvic organ prolapse. The study received institutional Ethics Committee approval, and all subjects signed an informed consent. Women were randomly divided into two groups of 30 subjects: Group 1 (n=30) was administered estrogen replacement with 1 mg of stradiol hemihydrate (1 mg/day) orally for 6 months, and group 2 (n=30) was not taking estrogen. Both groups were matched by age, height, body mass index, parity, and duration of postmenopause. All subjects were evaluated with spirometry initially and after 6 months. For statistical analysis, descriptive and analytical methods were used, based on data type and distribution. The mean and standard deviations were used as measures of central tendency and variability. Categorical data were expressed as absolute and relative numbers (percentage). The t-test for independent samples (for comparison of groups) and t-test for dependent samples (for comparison of serial measurements in the same patients) were used. The analysis was performed using R software ( www.r-project.org ), with the level of significance set at p<0.05. RESULTS: Analysis of spirometry parameters showed statistically significant differences between the estrogen users and the nonusers groups. CONCLUSION: The most important study result was the significantly improved lung respiratory function in postmenopausal women with genital prolapse after 6 months of taking estrogen, confirming that hormone replacement therapy should be recommended to postmenopausal women. The findings of our study suggest the need for further research into the effect of estrogen on pulmonary function.

Difference in expression of collagen type I and matrix metalloproteinase-1 in uterosacral ligaments of women with and without pelvic organ prolapse.

OBJECTIVE: To compare the expression of collagen type I and matrix metalloproteinase-1 (MMP-1) in uterosacral ligament biopsies from women with and without pelvic organ prolapse (POP). STUDY DESIGN: Uterosacral ligament biopsies were obtained from women with POP (n=46) and control subjects (n=49). Immunohistochemistry for collagen type I and MMP-1 was performed on formalin-fixed and paraffin-embedded sections. The two groups were matched for age, body mass index, parity and postmenopausal status. Statistical Package for the Social Sciences Version 13.0 was used for statistical analysis. RESULTS: The expression of collagen type I (p=0.034) and MMP-1 (p=0.038) differed between women with POP and control subjects. There was increased expression of MMP-1 and decreased expression of collagen type 1 in uterosacral ligaments of women with POP compared with control subjects. CONCLUSIONS: This difference indicates a possible relationship between POP and the immunohistochemical expression of collagen type I and MMP-1 in uterosacral ligaments.

Matrix metalloproteinases-1, -2 expression in uterosacral ligaments from women with pelvic organ prolapse.

OBJECTIVE: This study investigated matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-2 (MMP-2) immunohistochemical expression in uterosacral ligament biopsies from women with pelvic organ prolapse (POP), and controls with normal pelvic support. DESIGN: Prospective observational experimental study. SETTING: A tertiary Urogynecology Unit and Institute of Pathology, University Hospital Split, Croatia. POPULATION: Women referred for hysterectomy for prolapse or benign gynecological disease. METHODS: Eighty postmenopausal women were included in the study after Ethical Committee approval and informed consent. During surgery, uterosacral ligament biopsies were obtained from patients with POP (n=40) and women without evidence of pelvic floor weakening (n=40). Immunohistochemistry for MMP-1 and MMP-2 was performed on formaline fixed and paraffin embedded sections. Statistical evaluations were made by Student t-test or chi(2) test. MAIN OUTCOME MEASURES: Immunohistochemical expression of MMP-1 and MMP-2 in the uterosacral ligaments of women with and without genital prolapse. RESULTS: Forty women with POP and 40 controls without POP were included. The controls were matched to the women with POP in age, body mass index, parity and duration of postmenopausis. A significant increase in MMP-1 immunohistochemical expression was seen in uterosacral ligament tissue from women with POP (P=0.029). In contrast, there was no difference in immunohistochemical expression of MMP-2 between women with POP and those without (P=0.899). CONCLUSION: These data suggest that MMP-1 may be marker of collagen degradation. Increased MMP-1 immunohistochemical expression in uterosacral ligaments is associated with urogenital prolapse.