Vaccine hesitancy and knowledge regarding maternal immunization among reproductive age women in central Italy: a cross sectional study.

Background: Vaccination in pregnancy offers protection to the mother and the newborn. In Italy, influenza, pertussis, and COVID-19 vaccinations are recommended in pregnancy, but vaccination coverage is still far from the National Immunization Plan goals. We aimed to assess knowledge and attitude on maternal immunization in two groups of Italian women, in pregnancy and in reproductive age (non pregnant). Methods: A cross sectional study on Italian childbearing age women gathering information on their knowledge on maternal immunization and attitudes to receiving influenza and pertussis vaccines in pregnancy was carried out at the University of Rome Tor Vergata, between September 2019 and February 2020. Logistic and multinomial regressions were chosen as statistical tests for our analysis. Results: 1,031 women participated in the survey by answering the questionnaire. Out of these, 553 (53.6%) women were pregnant, and 478 (46.4%) were in the reproductive age. 37% (204/553) of pregnant women and 41% (198/476) of non pregnant women are aware of the existence of an immunization plan for pregnant women in Italy. The group with age between 20 and 30, for both pregnant women and women in the reproductive age, has a better knowledge of vaccination in pregnancy. Working status is a variable associated with more awareness about vaccination during pregnancy only for pregnant women (OR = 2.34, p < 0.00001). Educational status, trimester of pregnancy and knowledge on the topic are associated with vaccine hesitancy in our multivariate analysis for pregnant women. In the reproductive age group women who had a previous pregnancy are more likely to be hesitant towards vaccination in pregnancy, on the other hand the one with a higher knowledge and educational status are more likely to get vaccinated. Conclusions: The study highlights the persistent vaccine hesitancy among Italian women of reproductive age and pregnant women. Despite healthcare providers being identified as a reliable source of information, their recommendations alone are insufficient to overcome vaccine hesitancy. Factors such as employment status, educational level, pregnancy trimester, and knowledge about vaccinations during pregnancy influence vaccine hesitancy. Tailored educational interventions and communication campaigns targeting these areas can help reduce vaccine hesitancy and promote maternal immunization.

Uterine and placental blood flow indexes and antinuclear autoantibodies in unexplained recurrent pregnancy loss: should they be investigated in pregnancy as correlated potential factors? A retrospective study.

BACKGROUND: The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH. METHODS: 2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women. RESULTS: No differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%. CONCLUSIONS: LMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .

Effect of chorionic villus sampling on placental volume and vascularization in the first trimester of pregnancy.

Objective: To evaluate the effects of chorionic villus sampling (CVS) on placental volume (PV), perfusion, and vasculature in the first trimester of pregnancy.Method: Uterine artery pulsatility index (PI), PV, vascularization index (VI), flow index (FI), and Vascularization Flow Index (VFI) were serially measured in 38 pregnant women who underwent CVS. Thirty-eight women who did not undergo invasive prenatal diagnosis were recruited as controls.Results: CVS was associated with a mild reduction of PI, a reduction of placental VI, FI, and VFI and with an increase in PV detected one week after the procedure. The outcome of pregnancy was similar between women of the two groups.Conclusion: Our findings showed that CVS is associated with mild placental vascular and morphological changes. However, these changes do not seem to be associated with adverse outcome.

Longitudinal Changes of Subpubic Arch Angle throughout Pregnancy.

OBJECTIVE: The objective of this study is to assess whether the subpubic arch angle (SPA) changes throughout pregnancy. MATERIALS AND METHODS: We recruited a group of nulliparous women in the first trimester of pregnancy. Each woman was assessed 3 times throughout pregnancy, once per each trimester, by measuring SPA using a recently described highly reproducible three-dimensional transperineal ultrasound (linear reconstruction with contrast enhancement technique; OmniView-volume contrast imaging). Repeated measures analysis of variance was used to study SPA changes during pregnancy. RESULTS: Overall, 97 women were included in the final analysis. SPA increased progressively and significantly (F = 27.824, p < 0.001) from the first to the second trimester (121.8 ± 8.7 vs. 123.5 ± 8.4°, p = 0.01) and from the second to the third trimester (123.5 ± 8.4 vs. 125.3 ± 8.1°, p = 0.01). CONCLUSION: SPA width increases progressively but slightly during pregnancy. Although this finding is interesting, the extremely small difference detected is unlikely to be clinically significant.

Amniotic fluid antiphospholipid antibodies: potential role in antiphospholipid syndrome-independent aberrant implantation process.

BACKGROUND: The direct role of antiphospholipid antibodies (aPL) at maternal-fetal interface has not been fully investigated, especially whether they are involved in physiological and pathological implantation conditions, in an antiphospholipid syndrome (APS)-independent manner. In fact, trophoblast cells and placental endothelial cells at the implantation site express potential aPL targeted-phospholipid antigens (PL Ags); thus, the local production and presence of their specific antibodies, not related to APS (characterized by aPL presence in the peripheral blood), could be a potential marker of aberrant invasion, implantation and fetal-maternal immune tolerance processes. METHODS: Anti-Beta2glycoprotein I (anti-ß2GPI) and anticardiolipin (aCL Ab) antibodies (the most clinically relevant aPL) were detected by immunoenzymatic assay (ELISA), in the amniotic fluid (AF) of 167 women with physiological and complicated common pregnancy conditions, sharing an aberrant implantation process, such as recurrent pregnancy loss (RPL), autoimmune hypothyroidism (ahT) and smoking. All women included in the study were negative to peripheral blood aPL. RESULTS: aCL and anti-ß2GPI antibodies were detectable in all the AF samples. RPL, ahT and smoking patients had higher level of anti-ß2GPI Abs (IgM) compared to women with physiological pregnancies (p < 0.0001). Since IgM cannot cross the placenta, their local production in response to maternal-fetal interface stimuli, could be hypothesized. CONCLUSIONS: The presence of aPL in the AF (not related to APS) could reveal a potential clinical significance at maternal-fetal interface in selected pregnancy complications, in which an aberrant implantation process, and in turn an impaired fetal-maternal immune tolerance cross-talk, could occur.

OLR1 and Loxin Expression in PBMCs of Women with a History of Unexplained Recurrent Miscarriage: A Pilot Study.

AIMS: The aim of this study was to evaluate the expression of OLR1 and its alternative splicing isoform Loxin in unexplained recurrent miscarriage (uRM). METHODS: Sixty-three women of reproductive age were recruited and were divided into four groups: 18 pregnant and 23 non-pregnant women with uRM, and 12 pregnant and 10 non-pregnant women with physiological pregnancies. Complementary DNA derived from peripheral blood mononuclear cells (PBMCs) was analyzed by quantitative real-time PCR to evaluate the expression of OLR1 and Loxin. Oxidized low-density lipoproteins (ox-LDLs) were assayed from serum by a commercially available kit. RESULTS: Pregnant uRM women presented with a higher, though not significant, OLR1/Loxin ratio and a higher ox-LDLs serum level (p ≤ 0.05) compared with pregnant control women. OLR1 and Loxin levels were significantly decreased in non-pregnant uRM women compared with the control (OLR1: 0.00018 vs. 0.00043, p ≤ 0.005; Loxin: 0.00018 vs. 0.00060, p ≤ 0.005, respectively). Loxin expression decreased by about two-thirds (p ≤ 0.005) in pregnant women compared with non-pregnant control women. A higher expression of OLR1 in pregnant women compared with non-pregnant women with uRM (p ≤ 0.05) was observed, but no variation in Loxin expression was observed. CONCLUSIONS: The results of this study show an association of peripheral OLR1 and Loxin expression levels in uRM women, and they suggest the possible existence of an uncontrolled oxidative stress in these women in the first trimester of pregnancy.

Three-hour analysis of non-invasive foetal sex determination: application of Plexor chemistry.

BACKGROUND: The knowledge of the individual genetic "status" in the prenatal era is particularly relevant in the case of positive family history for genetic diseases, in advanced maternal age and in the general screening for foetal abnormalities. In this context, here, we report an innovative molecular assay which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and fast detection of the foetal sex. The study involved 132 pregnant women in their first 3 months of pregnancy, who agreed to give a blood sample. All the collected samples were immediately subjected to the separation of the plasma, which was utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which is able to simultaneously identify, quantify and discriminate the autosomal DNA from the sex-linked DNA. RESULTS: Overall, the Plexor-HY assay demonstrated to be sensitive and specific for the determination of low-template DNA, such as the cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the samples, identifying 70 males and 62 females. As the foetal sex can be provided in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay represents a very fast, safe and non-invasive prenatal method. CONCLUSIONS: The possibility of determining the foetal sex in the early prenatal life consents the application of our assay as a helpful screening test for subjects and families at risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may be of great help even for the specialist, who might promptly advise the patients concerning the foetal risk of inheriting sex-linked disorders and the clinical utility of performing an invasive prenatal diagnosis.

A new case of prenatally diagnosed pentasomy x: review of the literature.

Pentasomy X is a rare chromosomal abnormality probably due to a nondisjunction during the meiosis. Only four cases prenatally diagnosed were described until now. Our case is the fifth one prenatally diagnosed at 20 weeks of gestational age in a 39-years-old woman. She underwent invasive prenatal diagnosis for her advanced maternal age without any other known risk factor. Amniocentesis performed at 17 weeks showed a female 49, XXXXX karyotype. The ultrasonographic examination revealed nonspecific signs of a mild early fetal growth retardation and no significant increased nuchal fold. The fetal autopsy and the X-ray excluded major malformations. Prenatal diagnosis is often difficult due to the lack of indicative ultrasonographic findings and the rarity of described cases. The influence of the mother's age on the occurrence of penta-X syndrome has not been determined. Considering the lack of correlation between advanced maternal age and increased risk for pentasomy X, as well as the absence of typical echographic signs, evaluation of the inclusion of a noninvasive prenatal test (NIPT) that expands clinical coverage to include the X and Y chromosomes in routine prenatal diagnosis should be considered as well as three-dimensional ultrasound to detect any helpful indicative prognostic signs.

Transabdominal coelocentesis as early source of fetal DNA for chromosomal and molecular diagnosis.

This study reports a comparative analysis between results of transabdominal coelocentesis and traditional invasive procedure in order to assess the usefulness of coelocentesis as a source of fetal DNA for molecular and chromosomal analysis. A number of 28 women were included in the study. A successful sampling of coelomic fluid was obtained in 25 women by transabdominal procedure. A positive amplification of DNA with QF-PCR techniques was obtained in 90% of cases, while 10% of cases failed to reveal interpretable results. Although all samples were cultured, the growth rate was not sufficient to determine karyotypes within 2 weeks. Five samples were selected to be analyzed by array-based comparative genomic hybridization (a-CGH) but the interpretation of these results was difficult and ambiguous. Our results suggest that transabdominal coelocentesis is suitable for the detection of single DNA variation and for QF-PCR analysis, while further experiments are needed to develop optimized protocols for traditional karyotyping and array-analysis.

Recurrent miscarriage and cervical human papillomavirus infection.

PROBLEM: To investigate the possible relationship between human papillomavirus (HPV) infection and recurrent miscarriage (RM). METHODS: In this retrospective case-control study, 49 women with unexplained RM (Group 1 - cases) and 475 women without any miscarriage and with at least one pregnancy at term (Group 2 - controls) were checked for cervical HPV infection through Hybrid Capture(®) II (HC 2) or polymerase chain reaction (PCR). RESULTS: HPV+ DNA tests were detected in 13 (26.53%) RM women and in 294 (61.89%) control women (P < 0.001). The prevalence rate in HPV+DNA tests was significantly different in the 30-39 years age range. No differences between groups were detected in HPV types, nor in the cytological and histological findings. CONCLUSION: Women with RM have a lower prevalence of HPV+DNA tests than controls. This suggests that immune reactivity potentially leading to RM could be in some way protective against genital HPV infection.