Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia,and their relation with severity of disease

Abstract

Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants.

Methods: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version.

Results: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p?<?0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p?<?0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age.

Conclusions: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.     

Assessment of maternal–fetal status of some essential trace elements in pregnant women in late gestation: relationship with birth weight and placental weight

Objective: The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal–maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population.

Methods: Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry.

Results: The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2?μg/l, respectively, in maternal venous blood in the pregnant women (n?=?39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p?>?0.05) in the mother–child pairs studied. However, neonatal weight correlated negatively (p?<?0.05) with umbilical venous Cu level. Placental weight correlated positively (p?<?0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood.

Conclusions: Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.     

Lower circulation levels and activity of α-1 Antitrypsin in pregnant women with severe preeclampsia

Objective: α-1 antitrypsin (AAT) is an anti-protease, anti-inflammatory and tissue-protective molecule. Normal circulating levels are <3.5?mg/dl and rise during pregnancy. Although AAT deficiency is associated with several pregnancy and placental disorders, little is known regarding AAT levels and preeclampsia. Since unopposed inflammation might contribute to preeclampsia, we studied whether preeclampsia is associated with lower than normal levels and activity of AAT. Methods: In a prospective case-control study, we compared maternal serum AAT activity and levels between patients with severe preeclampsia (n = 23) and without preeclampsia (n = 18). Results: AAT levels were 1.91?±?0.08-fold lower in the preeclampsia group compared to healthy group (3.854?±?0.26 vs. 7.397?±?0.34?mg/ml; p < 0.001), and correlated with protease inhibitory capacity (46.56?±?2.08% vs. 67.08?±?1.74%; p < 0.001). Conclusions: Our findings show association between lower AAT levels and severe preeclampsia during pregnancy. Further studies are required to identify the mechanism behind the association, and the possibility of safe AAT augmentation for individuals with insufficient circulating AAT.     

Association study of IL-10 and IFN-γ gene polymorphisms in Iranian women with preeclampsia

Preeclampsia (PE) is one of the most serious disorders of human pregnancy and Th1/Th2 imbalance may play a role in its etiology. Considering that cytokine production is under genetic control, in this study we have investigated IFN-γ + 874 (T/A) and three bi-allelic IL-10 promoter polymorphisms in a total of 134 preeclamptic women compared to 164 healthy women. It was shown that the IL-10 −1082 G allele frequency increases significantly in patients compared to the control group (P = 0.045). No significant differences were found in any other genotype or allele frequencies of IL-10 and IFN-γ genes between the two groups. In addition, the frequencies of three common IL-10 haplotypes (GCC, ACC, ATA) did not show any significant difference between the study groups. Since the presence of G nucleotide at position −1082 of IL-10 gene is associated with reduced cytokine production, therefore, the higher frequency of IL-10 −1082 G allele in preeclamptic patients compared to controls may be considered as a genetic susceptibility factor for the development of PE.     

Alteration in IFN-γ and CCL2 serum levels at first trimester of pregnancy contribute to development of preeclampsia and fetal growth restriction

ObjectivePregnancy is a unique challenge for the immune system. Any disturbance in the immune system in the first trimester could result in further pregnancy complications. In this regard, the current study aimed to investigate the association between serum levels of a group of cytokines in the first trimester of pregnancy with the onset of preeclampsia (PE) and fetal growth restriction (FGR).Materials and methodsSerum samples were collected from 550 pregnant women at their 11th - 13th weeks of pregnancy and followed up to delivery. Out of all cases, 15 women complicated with preeclampsia and 15 ones diagnosed with FGR were included in the study. The serum levels of IFN-γ, CCL2, IL-10, IL-35 and IL-27 were checked in the collected sera of mentioned patients and compared to 60 women with normal pregnancy outcomes.ResultsIn the preeclampsia group, the mean level of IFN-γ was significantly higher (p < 0.001) while the CCL2 serum level was significantly lower (p < 0.003) as compared to control group. There was no significant difference between the preeclampsia group and controls regarding other cytokines. In the FGR group, the mean serum level of IFN-γ was significantly higher compared to the healthy pregnancy group (p < 0.001) but other cytokines showed no significant differences. In the FGR group, a significant positive correlation was found between IL-10 level and neonates' weight (p < 0.05).ConclusionBased on the results of the present study, an elevated level of IFN-γ and a reduced level of CCL2 at the first trimester of pregnancy could lead to complications such as PE and/or FGR.     

Different levels of IL-1α, IL-6, TNF-α, NF-κB and PPAR-γ in monocyte cultures exposed by plasma preeclampsia and normotensive pregnancy

ObjectiveTo determine different levels of proinflammatory cytokines IL-1α, IL-6, TNF-α, nuclear NF-κB p50 and PPAR-γ in monocyte cultures exposed to normotensive pregnancy plasma compared with those exposed to preeclamptic plasma.Study designThe study involved primigravidae with preeclampsia (12) and normotensive pregnancy (12) in which their blood plasma was given to monocyte cultures from isolated PBMC of healthy and non-pregnant women. They were divided into 2 groups, the first group was incubated for 24 h and the second one was incubated for 48 h (step 1). The levels of IL-1α, IL-6, TNF-α, and nuclear NF-κB p50 as well as PPAR-γ of both groups were subsequently measured and compared (step 2). Data were analyzed to determine the differences and interaction between both treatment groups using one-way ANOVA.ResultsThere was a significantly different level (p-value <0.05) of IL-1α in monocyte cultures incubated for 24 h compared with those incubated for 48 h, as shown in step 1 of the study. Meanwhile, step 2 of the study found significantly different levels of IL-1α, IL-6, TNF-α, and NF-κB p50 in monocyte cultures exposed to preeclamptic plasma compared with those exposed to normotensive pregnancy, in which the latter showed higher levels. Both groups also showed decreased levels of PPARγ, in which monocyte culture exposed to severe preeclamptic plasma (p value <0.05).ConclusionPreeclamptic plasma significantly increased levels of proinflammatory cytokines IL-1a, IL-6, and TNF-a in monocyte cultures. This condition was consistent with the increasing of NF-κB p50 and decreasing of PPARγ.     

Different maternal serum hCG levels in pregnant women with female and male fetuses: does fetal hypophyseal--adrenal--gonadal axis play a role?

Fetal gender has a significant effect on maternal and cord blood hCG levels, particularly during the last trimester of the pregnancy. However, the reason for this difference is obscure. The aim of the present study was to investigate whether term fetal hypophyseal - adrenal - gonadal axis differs between female and male fetuses thereby causing different hCG levels. The study consisted of 60 women with singleton pregnancies in the third trimester. Thirty-one pregnant women were carrying female fetuses, whereas 29 were carrying male. Human chorionic gonadotropin (hCG), estradiol, progesterone, testosterone, dehydro-epiandrosteron-sulfate (DHEAS), prolactin and growth hormone levels were measured in maternal serum and umbilical cord blood. In female bearing pregnancies maternal and cord blood hCG levels were significantly higher than in male bearing pregnancies (P<0.001). Maternal and cord blood estradiol, progesterone, testosterone, DHEAS, prolactin and growth hormone levels were not significantly different in either fetal gender. When all patients were considered as a group there were no correlations between fetal hCG levels and any of the measured hormones. Term fetal DHEAS, estrogen, progesterone, testosterone, growth hormone and prolactin levels do not contribute to different hCG levels between female and male fetuses. It is possible that fetal hypophyseal-adrenal gonadal axis does not play a central role as the cause of different hCG levels.     

Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia

Background: An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation.

Objective: To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n?=?20), and their controls matched for parity, and maternal and gestational age.

Method: Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay.

Results: Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9?pg/mL, artery and vein, respectively, p?0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0?±?298.4 versus 690.3?±?401.9 mIU/L, artery and vein, respectively, p?<?0.05), and free β-hCG (mean: 33.9?±?4.3 versus 17.2?±?4.0 and 30.1?±?5.2 versus 13.7?±?3.3?ng/mL, artery, and vein respectively, p?<?0.05).

Conclusion: Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.     

The levels of vitamın B12, folate and homocysteine in mothers and their babies with neural tube defects

The aim of the present study was to determine the serum levels of vitamin B₁₂, folate, and homocysteine (Hcy) in mothers and their babies, and to assess the association between these levels and neural tube defect (NTD). The study group included 92 baby-mother pairs, where the babies had NTD, and the control group included 102 pairs, where the babies had no NTD, from May 2012 to May 2015. Plasma vitamin B₁₂, folate, and Hcy levels of the babies and mothers were measured, and compared with each other. NTD was diagnosed in 2.6% of our babies. The vitamin B₁₂ levels in the mothers and the babies in the study group were determined as 166.2?±?63.7?pg/mL and 240.3?±?120.3?pg/mL, and in the control group as 1 9 0?±?80.2?pg/mL and 299.5?±?151.4?pg/mL, respectively. There was a significant difference between the two groups in terms of both the mothers’ and the babies’ vitamin B₁₂ levels (p?=?0.024 and p?=?0.003, respectively). The plasma folate levels of the mothers in the study group (5.2?±?3?ng/mL) were significantly lower than control group (6.4?±?4.3?ng/mL, p?=?0.032).The plasma Hcy level of the mothers in the study group (9.3?±?3.8?μmol/L) was significantly higher than the control group (7?±?3.8?μmol/L, p?<?0.001). High plasma Hcy levels and low plasma folate and vitamin B₁₂ levels are risk factors for NTD. Our results show that the risk for NTD can be decreased by fortification of mothers-to-be, particularly in rural areas with folate and vitamin B₁₂ deficiency, which would lower the plasma Hcy level.     

Cord blood TNF-α and IL-6 levels as diagnostic indicators of brain damage in neonates with non-asphyxia fetal distress

Purpose

We investigated prospectively cord blood TNF-α and IL-6 levels as diagnostic indicators of brain damage in neonates with non-asphyxia fetal distress.

Methods

Eighty neonates delivered by cesarean section from January 2013 to December 2014 were enrolled. Magnetic resonance imaging was conducted to determine brain damage. Neonates were assigned to a healthy control group (n = 30) or, with fetal distress, apportioned to groups with or without brain damage (n = 20 and 30, respectively). After delivery, the umbilical arterial blood of all neonates was harvested. Serum tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) levels were evaluated to investigate a correlation between cord blood TNF-α and IL-6 levels and brain damage caused by non-asphyxia fetal distress.

Results

The TNF-α and IL-6 levels in the cord blood of brain-damaged neonates with fetal distress (75.63 ± 7.68 and 217.95 ± 25.15 pg/mL, respectively) were significantly higher than that of neonates with fetal distress without brain damage (43.67 ± 5.54, 119.08 ± 12.30 pg/mL) or the healthy neonates (42.35 ± 6.63, 128.46 ± 16.15 pg/mL); the latter two groups were comparable for both TNF-α and IL-6. The receiver operating characteristic curve showed that when TNF-α (IL-6) reached 53.23 pg/mL (156.23 pg/mL), the specificity and sensitivity for diagnosis of brain damage was 80.3% (82.5%) and 90.1% (81.5%), respectively.

Conclusion

Monitoring TNF-α and IL-6 levels in umbilical cord blood may assist early diagnosis of brain damage in neonates with non-asphyxia fetal distress.

     

Maternal and umbilical serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-α in normal pregnancies and in pregnancies complicated by preeclampsia

Objectives.?The aim of this study was to investigate the relationship of maternal and umbilical cord interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) serum levels with the existence and severity of preeclampsia. A particular objective was the comparison of normal umbilical serum levels to preeclamptic values.

Materials and Methods.?The study group consisted of 24 patients with third trimester singleton pregnancies complicated by preeclampsia (15 severe and 9 mild preeclampsia). The gestational age-matched 19 healthy pregnant women were compared by study group. Maternal and umbilical serum IL-6, IL-8, and TNF-α were calculated by using enzyme-linked immunosorbent assay.

Results.?Significantly increased maternal and umbilical serum levels of IL-6, IL-8, and TNF-α were found in preeclamptic patient group in comparison with the control group. Maternal serum IL-8 and TNF-α concentration were significantly higher in patients with severe preeclampsia than in mild preeclampsia. Increased umbilical serum levels of IL-6 and IL-8 were found in severe preeclampsia than in mild preeclampsia. There were significantly higher levels of maternal serum IL-8 and TNF-α in patients with preeclampsia with IUGR than in patients with preeclampsia with normal fetal growth.

Conclusion.?Our findings suggest that increased concentrations of IL-6, IL-8, and TNF-α in the maternal and umbilical serum play a significant role in pathogenesis of preeclampsia. Alterations in maternal and umbilical serum levels of IL-6, IL-8, and TNF-α may also play role in preeclampsia complicated by intrauterine growth retardation. These associations may offer insight into the etiology and pathogenesis of preeclampsia.     

Levels of oestrogen receptor,progesterone receptor and αB-crystallin in eutopic endometrium in relation to pregnancy in women with endometriosis

Endometriosis affects fertility in many women and may partly be due to decreased endometrial receptivity. Several mechanisms have been suggested, notably, progesterone resistance for which a number of candidate biomarkers have been suggested. Here we demonstrate aberrant levels of steroid hormone receptors and the small heat shock protein αB-crystallin in eutopic endometrial epithelium from 38 women with peritoneal endometriosis diagnosed during investigation for secondary infertility. Spontaneous pregnancies within 1 year after medical and surgical treatment for endometriosis were recorded and semi-quantitative immunohistochemistry data compared between women with endometriosis who did or did not become pregnant and healthy controls.

Stronger immunostaining for ER-α was detected in luminal and glandular endometrial epithelium from women with endometriosis who did not become pregnant during the post-treatment observation period versus endometriosis patients who became pregnant and controls. Staining levels of PR and PR-B were lower in patients without subsequent pregnancies than in the two other groups. Endometrial levels of αB-crystallin in endometriosis patients similar to those in controls were strongly correlated with the chance of becoming pregnant, whereas higher or lower levels were not.     

Evaluation of maternal serum hypoxia inducible factor-1α, progranulin and syndecan-1 levels in pregnancies with early- and late-onset preeclampsia

Objective: To determine the serum levels of HIF-1 α, progranulin, and syndecan-1 in preeclampsia (PE) and normal pregnancy, and to compare whether these markers demonstrate any difference between early-onset PE (EO-PE) and late-onset PE (LO-PE).

Methods: This cross-sectional study was conducted on 27 women with EO-PE, 27 women with LO-PE, and 26 healthy normotensive pregnant controls matched for gestational age. Maternal levels of serum HIF-1 α, progranulin, and syndecan-1 were measured with the use of an enzyme-linked immunosorbent assay kit.

Results: Statistical analysis revealed significant differences between the control and the PE groups in progranulin (p?p?<.001) levels. There were no significant differences in the serum HIF-1 α levels between these groups (p=?.069). When PE patients were evaluated by considering subgroups; statistical analysis revealed significant inter-group differences in all biomarkers. Serum progranulin levels were significantly higher in LO-PE compared with the other two groups (EO-PE versus LO-PE and LO-PE versus controls p?=?.000). Control group presented significantly higher syndecan-1 levels, than EO and LO-PE (p?p=?.000).

Conclusions: Serum progranulin may have potential to be used as a biomarker for the differentiation of EO-PE and LO-PE. The co-operative action between HIF-1 α and progranulin might play a key role in the pathogenesis of LO-PE. The predominant feature of LO-PE seems to be an inflammatory process, whereas in EO-PE placentation problem seems to be the main pathology.     

Are plasma levels of visfatin and retinol-binding protein 4 (RBP4) associated with body mass,metabolic and hormonal disturbances in women with polycystic ovary syndrome?

Objective

To analyze potential interactions of visfatin and retinol-binding protein 4 (RBP4) levels with body mass, metabolic, and hormonal status in normal weight and obese women with PCOS.

Study design

Body composition was determined by bioimpedance in 83 women (44 obese) diagnosed with PCOS and in 67 women (36 obese) without PCOS. In addition, serum glucose, lipids, androgens, FSH, LH, SHBG, insulin, visfatin, and RBP4 were measured in a fasting state and the free androgen index (FAI) was calculated, as was insulin resistance using the HOMA-IR assessment.

Results

Plasma RBP4 levels were significantly higher in women of normal weight compared to obese subjects when both were diagnosed with PCOS (14.1 ± 4.6 vs.10.9 ± 4.5 ng/mL, p < 0.001); while in non-PCOS subjects the opposite was found (10.8 ± 4.5 vs. 18.4 ± 11.6 ng/mL, p < 0.01; respectively). Plasma visfatin levels were similar in PCOS and non-PCOS subjects. In non-PCOS subjects, positive correlations between RBP4 level and anthropometric parameters were observed. In PCOS, RBP4 levels inversely correlated with serum insulin levels and HOMA-IR values. No correlation was found between plasma visfatin levels and anthropometric parameters in all study groups. Similarly, no correlation was found in PCOS and non-PCOS subgroups. Additionally, there was an inverse correlation between RBP4 and LH concentrations and LH/FSH ratio in all study subjects.

Conclusions

Plasma visfatin level is not a useful biomarker of insulin resistance and hyperandrogenism. RBP4 level reflects visceral body fat content in non-PCOS women. Decreasing RBP4 release along with increasing insulin resistance and hormonal disturbances may be a compensatory mechanism preventing deterioration in obese PCOS.     

A systematic review of concepts related to women’s empowerment in the perinatal period and their associations with perinatal depressive symptoms and premature birth

Background

The perinatal period, which we here define as pregnancy and the first year postpartum, is a time in women’s lives that involves significant physiological and psychosocial change and adjustment, including changes in their social status and decision-making power. Supporting women’s empowerment at this particular time in their lives may be an attractive opportunity to create benefits for maternal and infant health outcomes such as reductions in perinatal depressive symptoms and premature birth rates. Thus, we here systematically review and critically discuss the literature that investigates the effects of empowerment, empowerment-related concepts and empowerment interventions on reductions in perinatal depressive symptoms, preterm birth (PTB), and low birthweight (LBW).

Methods

For this systematic review, we conducted a literature search in PsychInfo, PubMed, and CINAHL without setting limits for date of publication, language, study design, or maternal age. The search resulted in 27 articles reporting on 25 independent studies including a total of 17,795 women.

Results

The majority of studies found that, for the most part, measures of empowerment and interventions supporting empowerment are associated with reduced perinatal depressive symptoms and PTB/LBW rates. However, findings are equivocal and a small portion of studies found no significant association between empowerment-related concepts and perinatal depressive symptoms and PTB or LBW.

Conclusion

This small body of work suggests, for the most part, that empowerment-related concepts may be protective for perinatal depressive symptoms and PTB/LBW. We recommend that future theory-driven and integrative work should include an assessment of different facets of empowerment, obtain direct measures of empowerment, and address the relevance of important confounders, including for example, ethnicity and socioeconomic status.

     

Serum TNF-α, IL-6, lupus anticoagulant and anticardiolipin antibody in women with and without a past history of recurrent miscarriage

Objective The aim of the this study was to investigate Lupus Anticoagulan (LA), Anticardiolipin Antibody (ACA), Tumor Necrosis Factor- (TNF-) and Interleukin-6 (IL-6) serum levels in 40 pregnant and 20 nonpregnant.Materials and methods The women were divided into three groups. The first group consisted of 20 pregnant women of less than 20 gestational weeks and a past history of habitual abortion . The second group consisted of 20 non pregnant patients with a past history of habitual abortion. The third group consisted of 20 healthy non pregnant women. RESULT: LA was found in only one patient in the Group 2. ACA Ig G positivity were found 1 patient in the Group 1, 3 patients Group 2 and 1 patient in Group 3. Mean ACA IgG was highest in the Group 2. High serum TNF- levels were found in the 12 (60%), 6(30%) and 2 (10%) women in the Groups 1, 2, and 3, respectively. Significant difference were found for TNF- among the groups (P<0.05). The highest level of TNF- was found in the Group 1 and the lowest in the Group 3. There were statistically significant differences for IL-6 among the three groups (P>0.05).Conclusion We propose that cytokines especially TNF- was found to be related to the pregnancy loss.     

Expression of lipoxin A4, TNFα and IL-1β in maternal peripheral blood,umbilical cord blood and placenta,and their significance in pre-eclampsia

Objective: The purpose of this study was to investigate the expression of lipoxin A₄, TNFα and IL-1β in maternal peripheral blood, umbilical cord blood and placenta, and to assess their significance in pre-eclampsia. Methods: Ninty pregnant women were divided into three groups: a mild PE group (n?=?30), a severe PE group (n?=?30) and a control group (n?=?30). We measured serum levels of lipoxin A₄, TNFα and IL-1β using ELISA. Expression levels of lipoxin receptor (FPR2/ALX) mRNA were compared using quantitative RT-PCR. Results: Mean circulating levels of lipoxin A₄, TNFα and IL-1β in the PE groups were significantly increased compared with matched women in the control group. The ratios of lipoxin A₄/TNFα and of lipoxin A₄/IL-1β in the PE groups were significantly decreased compared with matched women in the control group. No lipoxin A₄ was detected in umbilical cord blood. There was a significant increase in FPR2/ALX mRNA expression in placenta obtained from the PE groups. Conclusions: The level of lipoxin A₄ in maternal peripheral blood may correlate with the expression of FPR2/ALX in placenta. Lipoxin A₄ increased to a lesser degree than either TNFα or IL-1β with progression of PE. This may be one of the reasons why oxidative stress and endothelial dysfunction in severe preeclamptic patients are much more serious that in cases of less severe preeclampsia. Moreover, lipoxin A₄ does not have any effect on the fetus through the placenta. We conclude that supplementing with lipoxin A₄ to ensure adequate levels may be a novel method for the treatment of pre-eclampsia without any effects on the fetus.     

Association of Maternal Serum CRP,IL-6, TNF-α, Homocysteine,Folic Acid and Vitamin B12 Levels with the Severity of Preeclampsia and Fetal Birth Weight

Objective: To assess the levels and clinical significance of high sensitive(hs)-CRP (C‐reactive protein), IL-6(interleukin-6), TNF-α(tumor necrosis factor-α), homocysteine, folic acid and vitamin B12 in normotensive healthy pregnant women, mild and severe preeclamptic patients, and to evaluate the correlations between these markers and the severity of preeclampsia and fetal birth weight. Study design: Using a cross-sectional study design, hs-CRP, IL-6, TNF-α, homocysteine and vitamin B12 were measured in the third trimester of pregnancy from normotensive healthy women with uncomplicated pregnancies (n = 62), mild (n = 61) and severe (n = 60) preeclamptic patients. Results: There were statistically significant differences between three groups for hs-CRP (p = 0.012), TNF- α (p = 0.046), IL-6 (p = 0.015), homocysteine (p < 0.001) and fetal birth weight (p < 0.001). Fetal birth weights in mild (2477 ± 746) and severe (2435 ± 768) preeclamptic patients were significantly lower than controls (3485 ± 365) (p < 0.001). No significant difference was found between the three groups for folic acid (p = 0.066) and vitamin B12 (p = 0.286). Bonferroni adjusted multiple comparison test showed that the statistical differences with respect to TNF-α, IL-6 and homocysteine were mainly created by control and severe preeclampsia groups. Hs-CRP levels still remained higher in severe preeclampsia patients than mild preeclampsia and normotensive patients except for overweight patients in the previous two groups after Bonferroni post hoc adjustment test. Conclusion: Elevated maternal serum levels of hs-CRP, TNF- α, IL-6 and homocysteine in preeclamptic women correlate with fetal birth weight in the early third trimester.     

Metformin 2,500 mg/day in the treatment of obese women with polycystic ovary syndrome and its effect on weight, hormones, and lipid profile

Purpose  

The objective of this study was to assess the efficacy and safety of metformin at the dosage of 2,500 mg/day in the treatment of obese women with PCOS and also to evaluate its effect on weight, hormones, and lipid profile.