Early vs. standard screening and treatment of gestational diabetes in high-risk women - An attempt to determine relative advantages and disadvantages.

BACKGROUND AND AIMS: Screening for Gestational Diabetes (GDM) is usually recommended between 24 and 28 weeks of pregnancy; however available evidence suggests that GDM may be already present before recommended time for screening, in particular among high-risk women as those with prior GDM or obesity. The purpose of this retrospective study was to evaluate whether early screening (16-18 weeks) and treatment of GDM may improve maternal and fetal outcomes. METHODS AND RESULTS: In 290 women at high-risk for GDM, we analyzed maternal and fetal outcomes, according to early or standard screening and GDM diagnosis time. Early screening was performed by 50% of high-risk women. The prevalence of GDM was 62%. Among those who underwent early screened, GDM was diagnosed at the first evaluation in 42.7%. Women with early diagnosis were more frequently treated with insulin and had a slightly lower HbA1c than women with who were diagnosed late. No differences were observed in the prevalence of Cesarean section, operative delivery, gestational age at the delivery, macrosomia, neonatal weight, Ponderal Index and Large-for-Gestational-Age among women with early or late GDM diagnosis or NGT. However, compared to NGT women, GDM women, irrespective of the time of diagnosis, had a lower gestational weight gain, lower prevalence of macrosomia (3.9% vs. 11.4%), small (1.7% vs. 8.3%) as well as large for gestational age (3.3% vs. 16.7%), but higher prevalence of pre-term delivery (8.9% vs. 2.7%). CONCLUSION: Early vs. standard screening and treatment of GDM in high-risk women is associated with similar short-term maternal-fetal outcomes, although women with an early diagnosis were treated to a greater extent with insulin therapy.

The role of adipokines in the pathogenesis of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and ß-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.

Italian national guidelines for the screening of gestational diabetes: Time for a critical appraisal?

BACKGROUND AND AIM: In 2011, the Italian National Health System guidelines introduced a selective screening for gestational diabetes (GDM) based on risk factors, recommending early evaluation in high risk women. The present study examined to which extent guidelines are applied, and analyzed the effectiveness of GDM diagnosis according to risk profile. METHODS AND RESULTS: We analyzed 1338 pregnant women, consecutively screened for GDM with a 75 g OGTT between January 2013 and December 2015, according to national guidelines. Diagnosis of GDM was based on IADPSG/WHO 2013 criteria. As many as 14.4% of screened women was at high risk, 64% at medium, 21.6% did not have any risk factor. Only 50% of high-risk women were appropriately screened at 16th-18th gestational weeks; 28% of them repeated the OGTT due to NGT. The overall prevalence of GDM was 39.9%, higher in high risk women (67% vs. 40% medium risk vs. 22% low risk; p < 0.0001). An early GDM diagnosis was performed in 40.7% of high-risk women. In low risk women, gestational weight gain at the screening time was independently associated with GDM. CONCLUSIONS: The recommendations for the screening of GDM are still insufficiently implemented, especially for early evaluation in high risk women. Considering the high proportion of early GDM diagnosis, the poor adherence to screening recommendation may result in late diagnosis of GDM. Finally, our finding of a 22% prevalence of GDM among low risk women suggests the need to consider additional risk factors, such as excessive weight gain during pregnancy.

Postpartum screening for type 2 diabetes mellitus in women with gestational diabetes: Is it really performed?

AIMS: This study evaluates the adherence to postpartum type 2 diabetes mellitus (T2DM) screening in women with previous gestational diabetes (GDM) and identifies elements associated with poor attendance. METHODS: We retrospectively collected data from 650 consecutive women with GDM between 2016 and 2018, who should had 75 g-OGTT, 4-12 weeks after delivery. Impaired glucose regulation (IGR) was defined according with ADA criteria. RESULTS: Only 41% of women had postpartum OGTT. Of these, 1.9% received T2DM diagnosis, with IGR prevalence of 18%. After introducing a recommendation letter, adherence to screening increased (47% in 2017 and 43% in 2018 vs. 32% in 2016). Screening procedure was less common in women with: no-family history of T2DM (38% vs. 46%; p < 0.05), age <35 (33% vs. 47%; p < 0.01), lower level of education (32% no-high-school-diploma vs. 35% high-school-diploma vs. 49% university-degree; p < 0.01) and unstable employment (35% vs. 44%; p < 0.05). At multivariate logistic regression analysis, age <35 years (OR 1.61; 95%CI: 1.14-2.28) and lowest educational level (OR 1.64; 95% CI: 1.13-2.37, compared to University degree) were independently associated with non-adherence. CONCLUSION: Only 41% of women had postpartum T2DM screening. Women with lower attendance are those with age <35 years or low educational level. Further strategies are needed to implement postpartum test.

Placental barrier breakage in preeclampsia: ultrastructural evidence.

OBJECTIVE: It is known that the placenta acts as an immunological barrier between the mother and fetal "graft" allowing two antigenically different organisms to tolerate one another. Preeclampsia may be considered as a fetal rejection consequent to severe damage at placental endothelial and syncytiotrophoblast level. In order to verify this placental barrier damage we undertook the present study by electron microscopy. STUDY DESIGN: 14 placentae from preeclaptic women, and the same number of placentae from healthy controls were examined. RESULTS: The results showed that endothelial cells from preeclamptic placentae express various and severe alterations, consisting of swollen and bulbous cytoplasm, degenerated inter-endothelial junctions with consequent crossing of fetal blood cells outside the vessels. CONCLUSIONS: These lesions could be the ultrastructural evidence of the placental barrier breakage leading to rejective reaction we presumed to be basis of preeclampsia.

HLA-DR in couples associated with preeclampsia: background and updating by DNA sequencing.

The placenta acts as an immunological barrier between the mother and the fetal "graft", allowing two antigenically different organisms to tolerate one another. In placentae from preeclamptic women, we have demonstrated, by an ultrastructural assessment and an immunohistochemical study, a placental barrier breakage leading to the mixing of maternal and fetal antigenically different blood. This condition could be responsible for the triggering of a maternal rejection reaction that we presume to be at the basis of the preeclamptic syndrome. Thus, we have investigated the Human Leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with preeclampsia, their partners and in control couples using the serological Terasaki tecnique. The results showed a statistically significant increase of HLA-DR homozygosity and a reduced antigenic variety in the preeclamptic women and their partners with respect to controls. In this update, we have examined the 2nd exon of the human gene, HLA-DRB1, on the short arm of the chromosome 6 using DNA sequence-based typing (S-BT) PCR in 56 preeclamptic couples and 64 control couples. The results have confirmed the significant excess of HLA-DR homozygosity in couples associated with preeclampsia versus controls. From our results, it emerges that HLA-DR homozygosity and the reduced antigenic variety seem to be associated to a major risk for preeclampsia, which further appears to be a "couple's disease".

Immunohistochemical study of placental endothelium in physiologic and gestosis-complicated pregnancies.

In this study we examined the placentae of gestosic patients and controls, with immunoistochemical method and HLA-DR monoclonal antibody, in order to show the role of placental endothelium in gestosic pathology onset. Our results show a marked expression of class II histocompatibility antigens in gestosic placentae with respect to controls. We suppose, in gestosic patients, a role for a particular, genetically determined HLA haplotype which increases disease receptivity.

Gestosis and fetal rejection: immunopathogenetic role of HLA-DR.

In this study we faced the problem of etiopathogenesis of EPH Gestosis, focusing our attention on the role of immunitary aspects in determining its onset. We typed HLA-DR in 20 couples with gestosic patient and in 20 control couples. Blood samples were taken into heparin-treated test tubes, from all the couples and HLA typed through standard lymphotoxicity technique in accordance with Terasaky (1). Our results in couples with a gestosic patient, showed homozygosis in 65% of patients and in 70% of partners; in 35% of cases homozygosis was present in both partners, and these were the most severe cases. It is also worth mentioning that in all the couples with gestosic patient, at least one of the partners resulted homozygotic. Homozygosis would therefore represent a predisposing factor in the etiopathogenesis of gestosis, and pre-conception HLA-DR typing of the couple could prove to be a valid alarm signal for gestosis risk.

Cell-mediated immunity in the course of cervical ectropion.

In the present study we evaluated cellular immunitary response in course of asymptomatic ectropion. Biopsies of the injured and healthy zones of the exocervix were carried out. All biopsies were examined by an immuno-histo-chemical method (Avidin-Biotin Complex, ABC) with monoclonal antibodies, in order to phenotype T lymphocytic subpopulations, in particular T helper lymphocytes (CD4), T suppressor lymphocytes (CD8) and Langerhans cells (CD1), which are basic elements of the monocytic-macrophagic series. Our preliminary findings showed a reduction of CD4, CD8 and CD1 lymphocytic subpopulations in ectropion zones, while these subpopulations are normally present in healthy zones of the exocervix. These findings support the hypothesis that, in ectropion, as in HPV infections and in CIN, a localized immuno-deficiency may appear and depress immuno-surveillance and cell-mediated response. In conclusion, it may be supposed that ectropion represents a non-stable lesion, which therefore needs suitable therapeutic intervention.

[Topical therapy with placental polydeoxyribonucleotide in cervical ectopy and ectropion]. / Terapia topica con polidesossiribonucleotide placentare nella ectopia e nell'ectropion cervicali.

Twenty outpatients, aged 18-45 yrs, with cervical ectropion have been treated with vaginal suppositories of PDRN (a placental derivate). The drug has been given randomly in two preparations of 5 g and 10 g, however both containing the same amount of the active component (5 mg). The results show the effectiveness of the eutrophic and antiphlogistic action of both preparations, with a remarkable reduction of the leukorrhea. The patients preferred the vaginal suppositories of 5g both for the greater maniability and for the smaller vaginal discharge after the administration. The reduction of the excipients in the new vaginal tablets, besides improving the compliance of patients, brings about a longer contact of the drug with the vaginal walls, hence a better bioavailability of the active principle.

[Clinico-morphological changes in ectropion after treatment with polydeoxyribonucleotide (PDRN)]. / Modificazioni clinico-morfologiche dell'ectropion dopo trattamento con polidesossiribonucleotide (PDRN).

Thirty patients in fertile age affected by ectropion were treated with Polydeoxyribonucleotide (PDRN) (*) vaginal suppositories for 24 days. No other local or general therapy was allowed. The following parameters were evaluated: local symptomatology, tolerability and compliance, vaginal cytology, colposcopic examination, bioptic sampling of affected area prior to and after treatment, and local immune response. The results show the efficacy of PDRN. In fact, after the treatment: reduction of subjective symptomatology with decrease of average score for each symptom; excellent or good tolerability and acceptability; reduced inflammation; increased iodine-dark areas; reestablishment of normal balance in T- and B-lymphocytic populations have been found.

Increased HLA-DR homozygosity associated with pre-eclampsia.

It is generally accepted that maternal recognition of paternally derived fetal antigens occurs during normal pregnancy and may be beneficial for implantation and maintenance of gestation. Thus, we have investigated the human leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with pre-eclampsia, their partners and in control couples. The HLA-DR antigens were tested in 70 pre-eclamptic primigravidae women and their partners and 70 healthy control couples using the serological Terasaki technique. Our results did not show any particular HLA-DR antigen to be correlated with pre-eclampsia, but a statistically significant increase of only one identifiable HLA-DR antigen, which was presumed to express homozygosity at the HLA-DR locus, in the pre-eclamptic women and their partners: 67.1 versus 7. 9% in the control couples (P < 0.000001). The analysis of HLA-DR compatibility between pre-eclamptic women and their partners showed a statistically highly significant increase of the female-to-male compatibility (P = 0.0003) and a lower but significant male-to-female compatibility in comparison with controls (P = 0.014). From our results, it emerges that HLA-DR homozygosity and reduced antigenic disparity seem to be associated to a major risk for pre-eclampsia, which consequently appears to be a 'couple's disease'.