Serum levels and gestational curve of adiponectin and leptin during adolescent pregnancy.

OBJECTIVE: This study aimed to develop a curve of weekly serum levels of adiponectin and leptin among pregnant adolescents. In addition, pregestational body mass index and weight gain were assessed and correlated with the serum concentration of these molecules. METHODS: This was a prospective cohort study, including only pregnant adolescents with eutrophic pre-gestational body mass index who were weekly followed during the evolution of gestation. The serum concentrations of adipokines were determined using commercial ELISA kits and were correlated to pre-gestational body mass index and pregnancy weight gain. A total of 157 pregnant women participated in this study. RESULTS: Adiponectin levels showed a significant decrease among the trimesters (p=0.0004). However, we did not observe significant differences among its levels when compared weekly, neither of which was between adiponectin concentration and pre-gestational body mass index or weight gain (p=0.36 and p=0.10, respectively). In contrast, we detected a significant increase in weekly serum leptin levels (p<0.0001), positively correlated to both pre-gestational body mass index and weight gain (p=0.003 and p=0.0007, respectively). CONCLUSION: These adipokines present a different profile throughout adolescent pregnancy.

Serum levels and gestational curve of adiponectin and leptin during adolescent pregnancy

SUMMARY OBJECTIVE: This study aimed to develop a curve of weekly serum levels of adiponectin and leptin among pregnant adolescents. In addition, pregestational body mass index and weight gain were assessed and correlated with the serum concentration of these molecules. METHODS: This was a prospective cohort study, including only pregnant adolescents with eutrophic pre-gestational body mass index who were weekly followed during the evolution of gestation. The serum concentrations of adipokines were determined using commercial ELISA kits and were correlated to pre-gestational body mass index and pregnancy weight gain. A total of 157 pregnant women participated in this study. RESULTS: Adiponectin levels showed a significant decrease among the trimesters (p=0.0004). However, we did not observe significant differences among its levels when compared weekly, neither of which was between adiponectin concentration and pre-gestational body mass index or weight gain (p=0.36 and p=0.10, respectively). In contrast, we detected a significant increase in weekly serum leptin levels (p<0.0001), positively correlated to both pre-gestational body mass index and weight gain (p=0.003 and p=0.0007, respectively). CONCLUSION: These adipokines present a different profile throughout adolescent pregnancy.

Impaired Treg and NK cells profile in overweight women with gestational diabetes mellitus.

PROBLEM: Maternal obesity is frequently associated with gestational diabetes mellitus (GDM), and immunological mechanisms seem to be involved in the physiopathology of these conditions. The aim of this study was to characterize the profile of immune cells in peripheral blood of overweight women with GDM. METHOD OF STUDY: This case-control study included 27 glucose-tolerant (controls) and 31 GDM overweight pregnant women. Flow cytometry was used to assess the number of regulatory T cells (Treg) and natural killer (NK) cells in the peripheral blood. In addition, the expression of IL-10, TGF-B, and TNF-A in Treg and expression of IFN-G, TNF-A, granzyme, and perforin in NK cells were analyzed. RESULTS: GDM patients had significantly lower frequency of TCD4+ CD25bright and TCD4+ CD25+ FOXP3high cells, higher production of TNF-A by Treg cells and higher percentage of NKCD16+ 56dim cells than the controls. CONCLUSION: The association between obesity and GDM is a condition where it is observed impaired Treg and NK cells profile, findings that seem to be related with the development of IR and inflammation.

Cervical cerclage placement decreases local levels of proinflammatory cytokines in patients with cervical insufficiency.

BACKGROUND: Cervical insufficiency is characterized by premature, progressive dilation and shortening of the cervix during pregnancy. If left unattended, this can lead to the prolapse and rupture of the amniotic membrane, which usually results in midtrimester pregnancy loss or preterm birth. Previous studies have shown that proinflammatory cytokines such as interleukin-1ß, interleukin-6, interleukin-8, and tumor necrosis factor alpha are up-regulated in normal parturition but are also associated with preterm birth. Studies evaluating such markers in patients with cervical insufficiency have evaluated only their diagnostic potential. Even fewer studies have studied them within the context of cerclage surgery. OBJECTIVES(S): The objective of the study was to evaluate the impact of local and systemic inflammatory markers on the pathogenesis of cervical insufficiency and the effect of cerclage surgery on the local immune microenvironment of women with cervical insufficiency. STUDY DESIGN: We recruited 28 pregnant women (12-20 weeks' gestation) diagnosed with insufficiency and referred for cerclage surgery and 19 gestational age-matched normal pregnant women as controls. Serum and cervicovaginal fluid samples were collected before and after cerclage surgery and during a routine checkup for normal women and analyzed using a targeted 13-plex proinflammatory cytokine assay. RESULTS: Before surgery, patients with cervical insufficiency had higher levels of interleukin-1ß, interleukin-6, interleukin-12, monocyte chemoattractant protein-1 and tumor necrosis factor alpha in cervicovaginal fluid compared to controls, but after surgery, these differences disappeared. No differences were found in serum of insufficiency versus control women. In patients with insufficiency, the levels of interleukin-1ß, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and interferon gamma in cervicovaginal fluid declined significantly after cerclage compared with before intervention, but these changes were not detected in serum. CONCLUSION: Compared with normal women, patients with cervical insufficiency have elevated levels of proinflammatory cytokines in cervicovaginal fluid but not in serum, suggesting a dysregulation of the local immune environment. Cerclage intervention led to a significant decline in these proinflammatory cytokines, suggesting that cerclage may help reduce local inflammation in cervical insufficiency.

Maternal obesity and inflammatory mediators: A controversial association.

The link between maternal obesity and inflammatory mediators is still unclear. Our aim was to summarize the main findings of recently published studies on this topic. We performed a search in Medline for studies published in the last years on obesity, human pregnancy, and inflammatory mediators. We report the findings of 30 studies. The characteristics and number of participants, study design, gestational age at sample collection, and type of sample varied widely. Approximately two-thirds of them investigated more than one mediator, and 50% included participants in only one trimester of pregnancy. The most frequently investigated mediators were leptin, tumour necrosis factor-alpha (TNF-α), and interleukin (IL)-6. Almost all studies reported an association between maternal obesity, leptin, and C-reactive protein (CRP) serum levels but not with IL-1ß and IL-10. The association of IL-6, TNF-α, monocyte chemo-attractant protein-1 (MCP-1), adiponectin, and resistin with maternal obesity is still controversial. To clarify the physiopathological link between maternal obesity and inflammation, more high-quality studies are needed.

Immunoregulatory molecules in patients with gestational diabetes mellitus.

Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case-control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4(+) and CD8(+)), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM patients had a significantly higher frequency of CD4(+)CD69(+) and CD8(+)CD69(+) T cells; only patients with insulin-treated GDM had increased numbers of CD4(+)HLA-DR(+) T cells. We also observed significantly higher percentages of CD4(+)CD28(+)HLA-DR(+), CD3(+)CD4(+)ICOS(+), CD3(+)CD4(+)PD-1(+), CD8(+)CD28(+)CD69(+), CD8(+)CD28(+)HLA-DR(+), CD8(+)CTLA-4(+)HLA-DR(+), and CD3(+)CD8(+)ICOS(+) T cells and lower frequency of CD3(+)CD4(+)CTLA-4(+), CD3(+)CD8(+)CTLA-4(+), and CD8(+)ICOS(+)HLA-DR(+) T cells in GDM patients compared to healthy pregnant women. This first study assessing costimulatory molecules in GDM patients shows that these patients have exacerbated markers of T cell activation along with CTLA-4 deficiency, findings that indicate that the maternal-fetal tolerance is compromised in these patients.

FAS and FAS-L genotype and expression in patients with recurrent pregnancy loss.

We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case-control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules.

Association study of vascular endothelial growth factor and polymorphisms of its gene with ectopic pregnancy.

PROBLEM: In ectopic pregnancy, increased levels of vascular endothelial growth factor are present. The aims of this study were to determine the association between -634C/G, -460T/C, and +936C/T vascular endothelial growth factor (VEGF) polymorphisms and ectopic pregnancy, and to determine whether serum levels of VEGF were affected by genetic factors. METHOD: of study This is a case-control study wherein 74 women with a history of ectopic pregnancy in a tertiary care center were compared to 134 post-menopausal controls with two pregnancies and no ectopic pregnancy for the genotyping of VEGF polymorphisms. For 35 patients with the diagnosis of ectopic pregnancy, serum concentrations of VEGF were obtained before the treatment. Genotyping of VEGF (-634C/G, -460T/C, and +936C/T) polymorphisms was performed by PCR, followed by endonuclease digestion. ELISA was performed to evaluate the VEGF serum levels. RESULTS: The -634C/G, -460T/C, and +936C/T VEGF polymorphisms were not associated with ectopic pregnancy (P = 0.170, P = 0.285, and P = 0.700, respectively). The serum levels of VEGF were not associated with the genotype of -634C/G, -460T/C, and +936C/T VEGF polymorphisms (P = 0.702; P = 0.347, and P = 0.256, respectively). CONCLUSION: There was no association between ectopic pregnancy and -634C/G, -460T/C, and +936C/T VEGF polymorphisms. There was no correlation between VEGF genotype and the expression of VEGF in blood samples.