Associations of combined polymorphisms of the platelet membrane glycoproteins Ia and IIIa and the platelet-endothelial cell adhesion molecule-1 and P-Selectin genes with IVF implantation failures.

The aim of the study was to investigate the combined impact of the genetic heterogeneity of the glycoproteins Ia (GpIa) and IIIa (GpIIIa) and the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes on IVF embryo transfer implantation failures (IVF-ET failures). Sixty nulligravida women with previous IVF-ET failures and 60 fertile controls were genotyped for the GpIa-C807T, GpIIIa-PlA1/PA2, PECAM-1-C373G (Leu125Val) and P-Selectin-A37674C (Thr715Pro) polymorphisms by pyrosequencing. Compared with wild-type combined homozygotes, carriers of combinations of risk alleles in two gene loci were at significantly increased risk for IVF-ET failure, whereas carriers of the combination of GpIa-807T, GpIIIa-PlA2 and PECAM-1-373G alleles had OR = 52.50 (95%CI: 4.05-680.95, p < .001). The area under the receiver-operating characteristic curve (AUC) based on the number of polymorphisms and the number of risk alleles per subject was 75.4% (95%CI: 66.7%-82.8%, p < .001) and 72.5% (95%CI: 63.6%-80.3%, p < .001), respectively. The OR per polymorphism and risk allele increase was 4.26 (95%CI: 2.15-8.41, p < .001) and 2.85 (95%CI: 1.71-4.76, p < .001), respectively. The above associations were more robust among younger women. The combined analysis of these polymorphisms revealed strong association of combined carriers with IVF-ET failures especially for younger women and provided a genetic risk score with good diagnostic accuracy in the prediction of IVF-ET failures.

Maternal serum levels of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study.

BACKGROUND: The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), and MMP-9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA). METHODS: Neutrophil gelatinase-associated lipocalin, MMP-9, and MMP-9/NGAL were determined in the first, second, and third trimesters in 33 normal pregnancies, 12 pregnancies complicated by preeclampsia, and 14 pregnancies that delivered a SGA neonate. RESULTS: Median NGAL concentration (ng/mL) in normal pregnancies increased significantly from 12.8 in the first trimester to 25.9 in the second trimester (p = 0,002) and 48.0 (p < 0.0001) in the third trimester. In preeclamptic pregnancies, NGAL was significantly higher, compared with normal pregnancies, in the first (30.9; p = 0.006) and second (44.6; p = 0.015) trimesters. MMP-9 and MMP-9/NGAL complex concentrations in preeclamptic pregnancies did not differ significantly from normal pregnancies in either trimester. Pregnancies with an SGA infant did not have different marker concentrations in either trimester, compared with normal pregnancies. CONCLUSION: Maternal serum NGAL, MMP-9, and MMP-9/NGAL complex concentrations tend to increase during pregnancy in normal and preeclamptic pregnancies. NGAL was significantly elevated in the first and second trimesters, in pregnancies that later developed preeclampsia.

Maternal serum resistin concentrations in gestational diabetes mellitus and normal pregnancies.

AIM: To investigate changes in maternal serum resistin levels during pregnancy and postpartum and clarify their relationship to insulin resistance. METHODS: Thirty normal pregnant women were compared to 30 women diagnosed with gestational diabetes mellitus (GDM). Serum resistin levels were collected at the time of glucose challenge test (26-28 weeks), at 38 gestational weeks and at the third postpartum day and measured with enzyme immunoassay. Correlation of resistin to the homeostatic model assessment-insulin resistance (HOMA-IR) was performed. RESULTS: Maternal serum resistin levels at 38 weeks were significantly higher in pregnant women with GDM compared to the control group (0.28 vs 0.21 ng/mL, P = 0.02) and the same was true for the immediate puerperium (0.25 vs 0.19 ng/mL, P = 0.03). A significant increase in resistin levels was observed in GDM women from 26-28 weeks to 38 weeks (0.21 vs 0.28 ng/mL, P = 0.02), but not in controls. A decrease in serum resistin levels was noted in both the GDM and control groups, at 38 weeks and the immediate postpartum period, but this decrease did not reach statistical significance in either of the two groups. Resistin levels were positively correlated to HOMA-IR at 26-28 weeks of gestation (r = +0.253, P = 0.05). CONCLUSION: GDM is associated with increased resistin serum levels in term pregnancy as well as postpartum. Resistin is positively correlated to HOMA-IR at 26-28 weeks of gestation. A reduction in maternal resistin after delivery indicates a significant placental or fetal contribution in the production of resistin.

Gestational Diabetes and T-cell (Th1/Th2/Th17/Treg) Immune Profile.

BACKGROUND/AIM: Gestational diabetes mellitus (GDM) is a common pregnancy complication, characterized by insulin resistance and low-grade systemic inflammation with a pro-inflammatory immune system response. Our objective was to study the peripheral Th1, Th2, Th17 and Treg response in GDM compared to normal pregnancy. MATERIALS AND METHODS: Th1, Th2, Th17 and Treg subsets was determined by flow cytometry based on staining for specific intracellular cytokines, as well as C-reactive protein (CRP) and total IgE circulating levels. The health status of all offspring was also assessed 6 months post-delivery. RESULTS: A total of 49 Caucasian adult pregnant women were enrolled into a GDM (n=26) and Control (n=23) group. At the third trimester of pregnancy, the GDM group had a higher proportion of Th2, Th17 and Treg cells compared to control. Contrary to the control group, the GDM group exhibited no significant change in the Th1/Th2/Th17/Treg profile postpartum. Furthermore, higher circulating CRP and total IgE levels were noted in the GDM group compared to controls. At the 6-month post-delivery assessment, 30.8% of the offspring from the GDM group were found to have developed atopic dermatitis, food allergy or allergic proctocolitis compared to none from the control group. CONCLUSION: Compared to an uncomplicated pregnancy, GDM exhibits a significantly different peripheral T-cell profile at the third pregnancy trimester characterized by higher proportion of Th2, Th17 and Treg cells which persist six months post-delivery, while the increased high sensitivity CRP (hsCRP) levels stressed the low-grade inflammatory profile of this disease.

Serum adiponectin during pregnancy and postpartum in women with gestational diabetes and normal controls.

AIMS: To investigate changes in serum adiponectin during pregnancy and postpartum and assess its relationship with insulin resistance as measured by homeostasis model assessment (HOMA-IR). METHODS: Twenty-two normal pregnant women were compared with 22 women diagnosed with gestational diabetes mellitus (GDM). Serum adiponectin levels were measured at the time of the glucose challenge test as well as in the immediate postpartum period and the correlation of adiponectin to HOMA-IR was performed. RESULTS: Adiponectin was significantly lower in women with GDM than in controls during pregnancy (5381 vs. 8449 ng/dl, p = 0.004), as well as postpartum (3278 vs. 6958 ng/ml, p = 0.002). A significant reduction in adiponectin (3278 vs. 5381 ng/ml, p = 0.002) was observed postpartum in GDM women but not in controls. Using a lower cut-off value of 5253 ng/ml, maternal adiponectin could exclude GDM with a sensitivity of 86.4% and a specificity of 59.1% (area under the curve = 0.752, standard error = 0.77, 95% confidence interval 0.601-0.903, p = 0.004). Adiponectin levels during pregnancy were negatively correlated with HOMA-IR (r = -0.375, p = 0.012). CONCLUSION: GDM is associated with decreased serum adiponectin levels both in pregnancy as well as postpartum. Adiponectin is negatively correlated to HOMA-IR. A reduction in maternal adiponectin after delivery indicates a significant placental contribution to adiponectin production.

Pre- and early post-partum adiponectin and interleukin-1beta levels in women with and without gestational diabetes.

OBJECTIVE: To investigate maternal serum adiponectin and Interleukin-1beta (IL-1beta) levels during the pre- and post-partum periods in pregnant women with and without gestational diabetes mellitus (GDM). DESIGN: Thirty control pregnant Caucasian women without GDM and thirty body mass index (BMI) and age-matched Caucasian women with GDM examined in the outpatient clinic between the 24th and 26th week of their pregnancy and on the 3rd day postpartum underwent anthropometry and had serum blood taken. Both groups, were monitored by a dietitian and had comparable weight gain during pregnancy. Birth weight was also measured. RESULTS: At the 3rd day postpartum, compared to the 2nd trimester of pregnancy, women with GDM had lower serum adiponectin levels, lower serum IL-1beta levels and lower homeostasis model assessment for insulin resistance (HOMA-IR) values. At the 2nd trimester of pregnancy, women with GDM had lower serum adiponectin levels, higher IL-1beta and higher HOMA-IR values compared to women without GDM. At the 3rd day postpartum, women with GDM had lower serum adiponectin levels, higher IL-1beta and higher HOMA-IR values compared to women without GDM. Second trimester serum adiponectin values of women with GDM correlated negatively with birth weight. CONCLUSIONS: Gestational diabetes is a state of insulin resistance associated with altered levels of proinflammatory cytokines, increased IL-1beta and decreased adiponectin values. Both of these alterations might be attributed to placental pathology in pregnancies with GDM.

Circulating chemoattractants RANTES, negatively related to endogenous androgens, and MCP-1 are differentially suppressed by hormone therapy and raloxifene.

BACKGROUND: The cardinal role of chronic inflammation in the development of atherosclerosis is increasingly being recognized. Estrogens may prevent the evolution of atherosclerosis by suppressing immune response. Furthermore, the conflicting reports on the cardiovascular effects of hormone therapy between observational and clinical trials have triggered interest on the effect of alternative therapies on the cardiovascular system. OBJECTIVE: The aim of this study was to assess the effect of estrogen, estrogen-progestin, tibolone and raloxifene therapy on circulating markers of chemotaxis in healthy postmenopausal women. METHODS: Eighty-eight postmenopausal women aged 44-62 years were randomly allocated to daily: (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and at 3 months. RESULTS: Endogenous testosterone and free androgen index (FAI) correlated negatively, while SHBG correlated positively with serum RANTES (testosterone: r=-0.27, p=0.033; FAI: r=-0.43, p=0.004: SHBG: r=0.34, p=0.026). Serum MCP-1 decreased significantly in the CEE group (baseline 125.3+/-51 pg/ml, 3 months 84.5+/-36.1 pg/ml, p=0.043), while no difference was detected between baseline and post-treatment levels in the other groups. Furthermore, a significant decrease in serum RANTES was observed at the end of 3 months only in the E2/NETA and the raloxifene group (E2/NETA baseline 8690.6+/-3880.0 pg/ml, 3 months 6894.0+/-1720.0 pg/ml, p=0.007; raloxifene baseline 9042.4+/-3765.6 pg/ml, 3 months 6718.1+/-2366.2 pg/ml, p=0.011). CONCLUSION: Endogenous androgens may suppress chemotactic response. Postmenopausal hormone therapy and raloxifene may inhibit the expression of chemoattractant molecules and thus attenuate inflammation. The relevance of these findings in terms of clinically established caridoprotection remains to be clarified.

Successful full-term pregnancy in a woman with Cogan's syndrome: a case report.

Cogan's syndrome (CS) is a chronic inflammatory disorder that most commonly affects young adults. Major clinical features are interstitial keratitis and vestibuloauditory dysfunction. Associations between CS and systemic vasculitis as well as aortitis also exist. The present report is the first case in the literature of pregnancy associated with Cogan syndrome, which posed a therapeutic challenge. There was a relapse of the ocular symptoms only during the first trimester of pregnancy, but the pregnancy was otherwise uneventful. The relevant literature is reviewed both with regard to the relationship of CS to pregnancy and the therapeutic approach in this situation.

Polymorphisms of Platelet Glycoprotein Receptors and Cell Adhesion Molecules in Fetuses with Fetal Growth Restriction and Their Mothers As Detected with Pyrosequencing.

BACKGROUND: Vascular thrombotic tendency may lead to fetal growth restriction (FGR). Altered platelet function and genetic heterogeneity may play a role in this procedure. We investigated whether maternal or fetal genotypic frequencies of genes polymorphisms for certain platelet receptor and cell adhesion molecules are altered in FGR. MATERIALS AND METHODS: We compared the maternal and fetal genotypic frequencies of single nucleotide polymorphisms (SNPs) in four genes coding for platelet receptors and cell adhesion molecules [integrin alpha subunit 2 (ITGA2)C807T, integrin subunit beta 3(ITGB3) T1565C, platelet cell adhesion protein 1 (PECAM1) CTG-GTG and selectin P(SELP)A/C]. A total of 32 fetuses with fetal growth restriction and their mothers were matched with 18 normal controls. Using maternal venous blood and umbilical cord blood samples, nucleotide sequences were determined from pyrograms. Genotypic frequencies were calculated and analyzed using appropriate tests and logistic regression. RESULTS: There was no statistical difference in the proportion of heterozygotes or homozygotes for any of the genotypic frequencies between FGR and control groups in mothers or fetuses. CONCLUSION: Our study demonstrated no association of maternal or fetal ITGA2 C807T SNP, ITGB3 T1565C SNP, PECAM1 CTG - GTG and SELP A/C polymorphisms with FGR.

Genetic heterogeneity of platelet glycoproteins Ia and IIIa and the risk of spontaneous miscarriages.

OBJECTIVE: The aim of this study was to investigate the association between the genetic heterogeneity of platelet glycoproteins Ia (GpIa-C807T) and IIIa (GpIIIa-PlA1/PlA2) and spontaneous abortions. STUDY DESIGN: Two hundred and twenty two women with a history of unexplained spontaneous miscarriages and no successful pregnancy, and 60 fertile women serving as controls were genotyped for the GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms by pyrosequencing. RESULTS: In comparison with the common alleles homozygotes, GpIa-807T and GpIIIa-PlA2 carriers had an increased risk of fetal loss (OR = 3.36, 95%CI: 1.85-6.11, p < 0.001, and OR = 2.58, 95%CI: 1.30-5.13, p = 0.006, respectively). For subjects who were combined carriers of the GpIa-807T and GpIIIa-PlA2 alleles, the risk increased further (OR = 9.13, 95%CI: 2.99-27.82, p < 0.001). The above ORs were highest for women who were younger than 30 years of age. CONCLUSIONS: The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly their combination are associated with increased risk of spontaneous abortions. The correlations were stronger for younger patients. Our results indicate that GpIa-807T and GpIIIa-PlA2 are susceptibility alleles for fetal loss in the Greek population.

"Reproductive" corticotropin-releasing hormone.

Corticotropin-releasing hormone (CRH), a 41 amino acid peptide, is an important regulatory molecule synthesized by neurons of the parvocellular and magnocellular hypothalamic paraventricular nuclei. It acts as the major physiologic corticotropin (ACTH) secretagogue. The CRH gene is located in humans on chromosome 8. The CRH hormone family has at least four ligands, two receptors (CRH-R1 and CRH-R2), and a binding protein (CRHbp). CRH is the principal regulator of the hypothalamic-pituitary-adrenal axis. Furthermore, CRH has been identified in most female reproductive tissues including the uterus, the placenta, and the ovary. CRH produced in the endometrium may participate in decidualization, implantation, and early maternal tolerance to semiallograft embryo. Placental CRH may participate in the physiology of pregnancy, in late pregnancy complications such as preterm labor and preeclampsia, and also in the onset of parturition. Ovarian CRH is involved in follicular maturation, ovulation, and luteolysis. Increased levels of unbound placental CRH may be responsible for the hypercortisolism of the second half of pregnancy. This hypercortisolism is followed by a transient suppression of hypothalamic CRH secretion in the postpartum period. This may explain the depressive states frequently observed in the postpartum period.

Androgen levels in the third trimester of pregnancy in patients with preeclampsia.

OBJECTIVE(S): To investigate if testosterone levels are higher in patients with preeclampsia compared to normotensive pregnant patients. STUDY DESIGN: The levels of serum total and free testosterone, dehydroepiandrosterone sulfate, androstenedione and sex hormone binding globulin were estimated in 28 patients during the third trimester of pregnancy with established preeclampsia and 25 normotensive women. RESULTS: No statistically significant differences were noted between the two groups regarding the maternal age, gestational age, body mass index (BMI) haematocrit and neonatal sex. The mean+/-S.D. total testosterone and free testosterone levels were significantly higher (p < 0.01) in the group with preeclapsia compared to the control group. The values of DHEA-S, androstenedione and sex hormone binding globulin were lower in the group with preeclampsia but the difference did not reach statistical significance. CONCLUSION(S): The levels of total and free testosterone appear to be higher in patients with preeclampsia compared to normotensive pregnant women during the third trimester of pregnancy. This difference could indicate an involvement of testosterone in the pathophysiology of preeclampsia and stimulates research in the potential role of anti-androgens in the management of preeclampsia.

The clinical significance of Doppler findings in fetal middle cerebral artery during labor.

OBJECTIVES: (1) To investigate fetal intracranial circulation, relative to peripheral blood flow, during labor with abnormal cardiotocographic (CTG) patterns, using three non-invasive methods. (2) To determine the utility of monitoring middle cerebral artery (MCA) Doppler during labor. INTERVENTIONS: Fetuses were assessed using simultaneous CTG, pulse oximetry, and Doppler ultrasonography of both the MCA and umbilical artery (UA) to measure the pulsatility index (PI), resistance index (RI), and flow velocity integral (FVI). STUDY DESIGN: During labor 20 term fetuses with abnormal CTG patterns and oxygen saturation values >30%, and 24 term fetuses with abnormal CTG patterns and oxygen saturation values <30% were studied, and peripartum outcomes were compared. The groups were comparable with regard to maternal age and parity. Results were evaluated using the Student's t-test and Fisher exact test. RESULTS: MCA Doppler showed significantly lower PI and RI, and higher FVI in the presence of reduced oxygen saturation. Differences in fetal outcomes between the two groups correlated with MCA Doppler findings. CONCLUSIONS: In experienced hands, Doppler screening of fetal middle cerebral artery waveforms during labor can be useful in the evaluation of intrapartum hypoxia in complicated pregnancies.

Continuous versus cyclic use of oral contraceptives after surgery for symptomatic endometriosis: a prospective cohort study.

OBJECTIVE: To evaluate the efficacy of continuous oral contraceptive (OC) use versus the usual cyclic fashion in the recurrence of endometriosis-related symptoms after surgery. DESIGN: Prospective cohort trial involving patients in two tertiary care units. SETTING: Academic institution in collaboration with a private hospital. PATIENT(S): 356 patients underwent surgical treatment by laparoscopy for symptomatic endometriosis. INTERVENTION(S): After surgical treatment for endometriosis, patients offered 6-month course of cyclic OC (including a 7-day pill-free period) or continuous OC. MAIN OUTCOME MEASURE(S): Recurrence rate of endometriosis-related symptoms and endometriomas after fertility-sparing surgery. RESULT(S): Out of 356 patients, 167 were placed on the usual cyclic OC course and 85 on continuous OC for a minimum of 6 months. The continuous OC group experienced a statistically significant reduction in recurrence rates for endometrioma, dysmenorrhea, and non-menstrual pelvic pain as compared with the cyclic OC group. There was no reduction in the recurrence of dyspareunia between the two groups. CONCLUSION(S): After surgical treatment of endometriosis, the use of both cyclic and continuous OC improves pain symptoms when compared with preoperative scores. Continuous OC appears to be associated with a reduced recurrence rate for dysmenorrhea, non-menstrual pelvic pain, and endometrioma but not for dyspareunia as compared with cyclic OC.

Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers for the prediction of preeclampsia but not for small for gestational age neonates: a longitudinal study.

OBJECTIVE: To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia. STUDY DESIGN: In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy. RESULTS: In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p=0.035) and in the 3rd trimester (202; 109-284) (p=0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p=0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%. CONCLUSIONS: Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia.

Placental growth factor (PlGF): a key to optimizing fetal growth.

The needs of the uterus and the fetus for the provision of nutrients and oxygen, supplied by the blood flow, are understandably extremely high, with the circulatory system playing the most important role in this action. Abnormal vascular growth and transformation that create a high vessel resistance network have been associated with various pregnancy pathologies, including miscarriage, small for gestational age (SGA) fetuses with or without preeclampsia and intrauterine growth restriction (IUGR). Placental growth factor (PlGF) has a major role in vasculogenesis and angiogenesis in human placenta. Low concentrations of PlGF and high concentrations of its inhibitor-soluble Fms-like tyrosine kinase-1 (sFlt-1) are linked with impaired angiogenesis and placental development, leading to the above pregnancy complications. The activity of vascular endothelial growth factor (VEGF), which is the most potent of all angiogenic mediators, is partly modulated by PlGF. Although the mechanisms via which PlGF exerts its various effects are still under investigation, we herein discuss the known actions exerted by this major mediator together with its results on fetal growth.

Association of adiponectin and placental growth factor in amniotic fluid with second trimester fetal growth.

BACKGROUND: We investigated the associations between second trimester amniotic fluid (AF) levels of human adiponectin and placental growth factor (PLGF) in small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) fetuses. MATERIALS AND METHODS: Adiponectin and PLGF levels were determined by enzyme immunoassay in AF of 21 SGA, 13 LGA and 44 AGA fetuses between 15-22 weeks of gestation, derived from pregnant women who underwent amniocentesis. RESULTS: Adiponectin and PLGF levels were detectable in AF. Median (25th-75th percentile) adiponectin levels were 16.1 (10.9-32.3) ng/ml in SGA, 19.5 (15.1-30.9) ng/ml in AGA, and 18.2 (14.7-30.8) ng/ml in LGA fetuses. Median (25th-75th percentile) PLGF levels were 24.2 (19.9-34.9) pg/nl in SGA, 26.4 (20.9-33.8) pg/ml in AGA and 33.5 (21.8-40.4) pg/ml in LGA fetuses. The differences were not statistically significant. Nevertheless, indication of differentiation of levels existed when SGA and LGA fetuses in the extremes of distribution were considered. Specifically, very severely SGA fetuses (≤2.5th percentile) tended to have high levels of adiponectin and reduced levels of PLGF in AF. CONCLUSION: This is the first study presenting adiponectin and PLGF concentrations in early second trimester amniotic fluid in AGA, SGA and LGA fetuses. The altered concentrations of adiponectin and PLGF in very severely SGA fetuses possibly result from the growth-promoting effect of these factors through the metabolic route and the vascular integrity of the placenta, respectively.

Maternal circulating osteoprotegerin and soluble RANKL in pre-eclamptic women.

OBJECTIVE: To evaluate alterations in the concentrations of osteoprotegerin (OPG), RANKL and the OPG/RANKL ratio in pre-eclamptic women during the puerperium. STUDY DESIGN: This cross-sectional study was performed in the maternity ward of Aretaieio Hospital in Athens, Greece. Fifteen pregnant women with severe pre-eclampsia and 15 matched controls with premature rupture of the membranes were recruited. Fasting blood samples were obtained antepartum, immediately after diagnosing pre-eclampsia (median: 32nd gestational week), and during the 3rd-6th day postpartum, to estimate levels of circulating OPG and RANKL as well as the OPG/RANKL ratio. The anthropometric parameters evaluated included body mass index and blood pressure. RESULTS: Mean circulating OPG levels decreased significantly in both groups in the postpartum period (controls: 43.7 ± 19.1 ng/ml vs 22.9 ± 9.1 ng/ml, p = 0.008; pre-eclamptic group: 72.3 ± 49.9 vs 49.7 ± 40.9 ng/ml, p = 0.002). The antepartum OPG/RANKL ratio was elevated in hypertensive pregnancies (2.41 ± 1.72) compared to normotensive pregnancies (1.45 ± 0.63), but the difference did not reach statistical significance (p = 0.1). The OPG/RANKL ratio decreased in the control group (0.76 ± 0.30, NS) following delivery, while it remained unchanged in the pre-eclamptic women (1.63 ± 1.40, p = 0.13). Consequently, the postpartum OPG/RANKL ratio was significantly higher in the pre-eclamptic women compared to control women (1.63 ± 1.40 vs 0.76 ± 0.30, p = 0.01). Levels of RANKL demonstrated no significant alterations during puerperium in both cases. CONCLUSION: Pregnancies complicated with pre-eclampsia exhibit higher OPG levels and OPG/RANKL ratios, compared to control pregnancies, which might be compatible with lower bone turnover. The significance of this finding with respect to bone metabolism remains to be elucidated in larger studies.

Antepartum and postpartum maternal plasma levels of E-selectin and VE-cadherin in preeclampsia, gestational proteinuria and gestational hypertension.

OBJECTIVE: To investigate the alterations of maternal antepartum and postpartum plasma levels of sE-selectin and VE-cadherin in normotensive pregnant women, women with preeclampsia (PE), gestational hypertension (GH), and gestational proteinuria (GP). METHODS: A total of 37 pregnant women were included in the present study; 12 with PE, 10 with GH, 5 with GP, and 10 controls. sE-selectin and VE-cadherin levels were assessed in maternal plasma at three periods; before delivery, 3-6 days after delivery, and 12-14 weeks postpartum. RESULTS: Women with severe preeclampsia (SPE) and GP had significantly higher plasma sE-selectin levels as compared to controls in all three periods of sampling. In the GH group, sE-selectin levels did not differ from controls. During the study, even after 12 weeks postpartum, the plasma sE-selectin levels remained unchanged in all preeclamptic groups (PE, GH, and GP). There was no difference in VE-cadherin levels between women with preeclampsia (PE, GH, and GP) and normal pregnancies. CONCLUSIONS: We found no changes in VE-cadherin levels in preeclamptic groups. Increased antepartum and postpartum levels of sE-selectin in women with SPE and GP suggest that endothelial dysfunction may be one of the key processes in the pathogenesis of PE and the underlying mechanism, as well, that links PE with cardiovascular disease in later life. GP, also, appears to be a mild variant of PE.

Antepartum and postpartum serum heme oxygenase-1 levels in preeclamptic and normotensive pregnant women.

AIM: To determine antepartum and postpartum serum heme oxygenase-1 (HO-1) levels in pre-eclamptic (PE) and normotensive pregnant women and to investigate the relationship between HO-1 levels and severity of PE. PATIENTS AND METHODS: Ten normotensive women were compared to 9 women with mild PE and 12 women with severe PE. Serum HO-1 levels were measured at 30-34 gestational weeks and 12-14 weeks postpartum. RESULTS: The severe PE group had significantly higher serum HO-1 levels antepartum compared to the mild PE and normotensive groups (5.50 ± 1.54 vs. 3.04 ± 0.72 ng/ml, p=0.0003, and 5.50 ± 1.54 vs. 3.12 ± 1.57 ng/ml, p=0.002, respectively). Serum HO-1 levels decreased significantly postpartum in the normotensive group only (3.12 ± 1.57 vs. 2.00 ± 0.97 ng/ml, p=0.0005). In the severe PE group, HO-1 levels antepartum were positively correlated to mean blood pressure (r=+0.79, p=0.004). CONCLUSION: Severe PE is associated with elevated serum HO-1 levels both antepartum and postpartum, suggesting a key role of chronic oxidative stress in the pathogenesis of PE and the endothelial dysfunction of these patients later in their life.