Increased Maternal Serum Interleukin-6 Concentrations at 11 to 14 Weeks of Gestation in Low Risk Pregnancies Complicated with Gestational Diabetes Mellitus: Development of a Prediction Model.

The aim of the study was to examine interleukin-6 (IL-6) maternal serum concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit. Study population included 40 GDM cases and 94 controls. Maternal characteristics, first trimester ultrasound markers, biochemical indices, and IL-6 levels were used for our analysis. IL-6 was related to maternal weight among the maternal characteristics, (R(2)=0.0679, p=0.01). IL-6 was increased (p=0.001) in the GDM group (median=2 pg/ml) compared to the control group (median=1.5 pg/ml) even after adjustment for maternal weight. IL-6 was inversely related to birth weight adjusted for gestational age at delivery (r=-0.3382, p<0.001) and glucose levels at oral glucose test. Maternal weight and age were the only predictors of GDM among the maternal characteristics [Detection Rate (DR)=59.4%; for 25% False Positive Rate (FPR); Area Under the Curve (AUC)=0.7291; Model R(2)=0.1096, p<0.001]. IL-6 alone was a significant predictor of GDM (DR=51.3%; for 25% FPR; AUC=0.6731; Model R(2)=0.0616, p<0.001). Combination of maternal characteristics with IL-6 yielded an improved prediction (DR=67.5%; for 25% FPR; AUC=0.7586; Model R(2)=0.1521, p<0.001). IL-6 concentrations are increased at 11-14 weeks in pregnancies with GDM. Combination of maternal characteristics and maternal serum IL-6 levels may provide effective first trimester screening for GDM.

Role of the angiopoietin/Tie system in pregnancy (Review).

Angiopoietin-1 and -2 are endogenous ligands for the vascular endothelium-specific receptor tyrosine kinase Tie-2. The angiopoietin/Tie system plays a critical role in the regulation of endothelial cell survival and vascular maturation and stability. Apart from its well-established role in vascular morphogenesis, emerging data support the involvement of angiopoietins in inflammation and various malignancies. Previous studies have underlined the significance of several angiogenic factors in normal placental development. In addition, angiogenic imbalance is observed in pregnancy complications related to impaired placentation, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). However, there is only limited information available on the role of the angiopoietin/Tie system in the establishment of a competent feto-maternal vascular system. In this review, we present the current knowledge regarding the role of angiopoietins in normal pregnancy and pregnancy complications.

Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie-2 is altered in pregnancies complicated by preeclampsia.

OBJECTIVE: To investigate the placental expression of angiopoietin (Ang)-1, Ang-2 and their receptor, Tie-2, in preeclampsia (PE) with or without intrauterine growth restriction (IUGR). METHODS: Case-control study including placentas from 28 PE pregnancies, 30 PE-IUGR pregnancies and 40 controls. The expression status of the genes was evaluated by quantitative real-time PCR. RESULTS: In both PE and PE-IUGR groups, compared to the control group, there was significantly higher expression of Ang-2 (p < 0.001) and Tie-2 (p = 0.008) and lower expression of Ang-1 (p = 0.001). The magnitude of the difference was similar for Ang-1 for both groups, whereas the magnitude of the differences was higher for Ang-2 and Tie-2 in PE-IUGR group compared to controls. Ang-2 and Tie-2 were correlated in both PE (r = 0.8602, p < 0.001) and PE-IUGR (r = 0.6342, p < 0.001) groups. In PE-IUGR group, Ang-1 was associated to Ang-2 (r = 0.3458, p = 0.0452) and Tie-2 (r = 0.4448, p = 0.0084). Log10Ang-1 but not Ang-2 was gestational age dependent (R2 = 0.40, p < 0.001). After conversion in Multiples of the Median (MoM) log10 MoM Ang-1 was reduced in the PE group (mean = -0.8181, p < 0.001) and the PE-IUGR group (mean = -1.2583, p < 0.001) compared to control group (mean = -0.0924). DISCUSSION: We have demonstrated increased placental expression of Ang-2 and Tie-2 along with lower expression levels of Ang-1 in pregnancies with PE and PE-IUGR. CONCLUSION: The angiopoietin axis seems to be disrupted in PE pregnancies. Whether the results of this study represent the angiogenic imbalance observed in PE pregnancies or they are part of the pathophysiology of this condition has to be further investigated.

Dialkyl phosphates in amniotic fluid as a biomarker of fetal exposure to organophosphates in Crete, Greece; association with fetal growth.

The aim of this study was to evaluate fetal exposure to organophosphate pesticides (OPs) by measuring their non-specific dialkyl-phosphate metabolites (DAPs) in amniotic fluid (AF), and to examine the potential association between prenatal exposure and fetal growth. AF samples were collected from 415 women during the second gestational trimester. The determined OPs metabolites were DMP, DMTP, DEP, DETP, and DEDTP. DAPs were extracted by liquid-solid extraction, derivatized and analyzed by gas chromatography-mass spectrometry. 97.8% of AF samples were positive for at least one DAP. DAPs levels did not differ between urban and rural areas. Macrosomic neonates have significantly higher sum levels of DMPs (p=0.043), which exerted a linear positive association with birth-weight centile (b=4.43, p=0.016). Conclusively, as DAPs are detectable in AF they may be used as a potential biomarker of fetal exposure to OPs. Sum levels of DMPs appear to be associated with birth weight independently of other covariates.

High rate of allergies among women with endometriosis.

Women with endometriosis frequently suffer from autoimmune inflammatory diseases, allergies and asthma. This study was conducted to examine whether the prevalence of allergies is higher in patients with endometriosis than in the control group, and to show potential correlation with endometriosis stages. We evaluated the medical files of 501 women with laparoscopically-diagnosed endometriosis and 188 women without endometriosis enrolled in Yale University Hospital. Main outcome measures used were allergy on medications, complaints of sinus or perennial allergic rhinitis, asthma, family history of allergic disease, and correlation with stages of endometriosis. Our results indicated that the overall risk of women with endometriosis and positive history of allergies was 4.28 (95% CI, 2.9-6.3) (p < 0.001). Significant excesses were identified for medications, sinus allergic rhinitis, and asthma; also, women with endometriosis were significantly more likely to report a positive family history of allergies. Overall, our study indicated a link between endometriosis and increased risk of allergic autoimmune disorders that should further be explored.

Three-dimensional ultrasound and three-dimensional power Doppler improve the preoperative evaluation of complex benign ovarian lesions.

PURPOSE OF INVESTIGATION: To evaluate the diagnostic accuracy of three-dimensional ultrasound (3D-US) and three-dimensional power-Doppler (3DPD-US) as adjuncts to conventional B-mode-US in evaluation of complex benign ovarian lesions. METHODS: Transvaginal B-mode-US, 3D-US and 3DPD-US were performed in 29 patients with unilateral ovarian lesion. Patients were classified as low or high risk for malignancy according to a standardized scoring system composed of ten morphological and vascular parameters. Preoperative scores were matched to the histological results and the diagnostic performance of the scoring system was calculated. RESULTS: Seven out of the 16 cases of endometriomas (44%) were graded as low risk masses according to B-mode-US, while the addition of 3D-US and 3DPD-US increased the accuracy to 56% and 94%, respectively. All dermoid cysts were classified as high risk cases by B-mode-US, but 3D-US and 3DPD-US correctly classified 14% and 57% of cases, respectively. The use of B-mode-US, 3D-US and 3DPD-US correctly classified all four cystadenomas. Only the use of 3DPD-US correctly classified one out of two hemorrhagic corpus luteum cases, whereas the other imaging modalities characterized these lesions as high risk. The overall diagnostic accuracy increased from 38%, 48%, ana 83% with the application of B-mode-US alone, or combined with 3D-US and 3DPD-US, respectively. CONCLUSION: Conventional ultrasound supplemented with 3D-US and 3DPD-US and the evaluation of findings according to a specific scoring system can facilitate the preoperative classification of complex benign ovarian lesions.

Maternal serum insulin-like growth factor-binding protein-3 (IGFBP-3) at 11-13 weeks in preeclampsia.

The objective of this study was to determine if the maternal serum concentration of insulin-like growth factor-binding protein-3 (IGFBP-3) at 11-13 week's gestation is altered in pregnancies that subsequently develop preeclampsia (PE). Maternal serum concentration of IGFBP-3, pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (PI) were measured in 60 cases that developed PE, including 20 that developed early-PE requiring delivery before 34 weeks, and compared with 120 unaffected controls. In the unaffected pregnancies, the median multiple of the normal median (MoM) values of serum IGFBP-3, PAPP-A and uterine artery PI were 1.0 MoM. In late-PE, but not in early-PE, serum IGFBP-3 was significantly increased (1.16 and 1.06 MoM, respectively), whereas in early-PE, but not in late-PE, uterine artery PI was increased (1.41 and 1.11 MoM, respectively) and serum PAPP-A was decreased (0.53 and 0.87 MoM, respectively). In the PE group, there was no significant association between IGFBP-3 and either uterine artery PI (P=0.775) or maternal serum PAPP-A (P=0.275). First-trimester serum IGFBP-3 is increased in pregnancies that subsequently develop late-PE in a mechanism that is unrelated to impaired placentation, as reflected in uterine artery PI and serum PAPP-A.

Medical treatments for endometriosis.

Despite the extensive research, endometriosis remains an enigmatic disease as up to now there is no consensus regarding the exact underlying mechanisms which could explain its development and progress. A local environment enriched in estrogens, progesterone resistance, local inflammatory response and multiple other molecular alterations appear to be pivotal events in the establishment and development of ectopic tissue. In the light of the evidence produced by molecular pathology research, in vivo and in vitro studies, modifications in current treatment options are anticipated. Current management of endometriosis is based on pharmacologic treatment and surgical intervention. In particular, combined oral contraceptives, danazol, gonadotropin-releasing hormone (GnRH) analogues and progestins have been extensively used in clinical practice. Novel agents that will hopefully improve the therapeutic potential include aromatase inhibitors, immunomodulators, anti-inflammatory agents, steroids receptor modulators and GnRH antagonists. It is still early for enthusiasm as there is limited knowledge about their short- and long-term side effects, their optimal administration route, their selectivity towards their target genes and the duration of treatment. Although there is a continual report of novel findings, the application of them in clinical practice is a long-lasting procedure requiring longitudinal clinical trials so as to achieve a balance between efficacy and safety.

Endometriosis-associated Lyme disease.

The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases.