Impact of the COVID-19 Pandemic on Prenatal Care Utilization Among Italian and Immigrant Pregnant Women: A Multicenter Survey.

Objectives: To compare the utilization of prenatal services between immigrant and Italian women during the COVID-19 pandemic. Methods: A cross-sectional survey was conducted at 3 maternity care centers in Italy. Results: We included 1,312 women, 1,198 (91.3%) were Italian and 114 (8.7%) were immigrants. A significantly higher proportion of Italians underwent 8 or more prenatal care visits (64.4% vs. 54.4%, p = 0.03) and more immigrants than Italians attended their appointments at hospital settings (45% vs. 18%, p < 0.001). Regarding prenatal course, Italians were more likely than immigrants to attend a non-hospital setting or an online class (49.6% and 30.2% vs. 34.9% and 11.6%, p = 0.008). A higher influenza vaccine uptake among immigrants compared with Italians was observed (39.5% vs. 19.8%, p < 0.001). Among women not receiving certain prenatal services, immigrants were more likely to state COVID-19 pandemic was the main reason for non-compliance. Conclusion: Immigrant pregnant women were more likely to receive prenatal services at a hospital setting than their Italian counterparts. Among women who did not comply with prenatal services, immigrants were more likely to cite the pandemic as their main reason.

Human Breast Milk: A Source of Potential Probiotic Candidates.

This study focuses on the isolation of lactobacilli/bifidobacteria from human breast milk and their first characterization, in the perspective to find new probiotic candidates to be included in food products. More specifically, breast-milk-isolated strains demonstrated a very good aptitude to adhere to intestinal cells, in comparison with L. rhamnosus GG strain, taken as reference. The same behavior has been found for hydrophobicity/auto-aggregation properties. A remarkable antagonistic activity was detected for these isolates not only against spoilage and pathogenic species of food interest, but also against the principal etiological agents of intestinal infections. Indeed, isolated strains impaired spoilage and pathogenic species growth, as well as biofilm formation by gut pathogens. In addition, breast milk strains were characterized for their antibiotic susceptibility, displaying species-specific and strain-specific susceptibility patterns. Finally, to assess their technological potential, the fermentation kinetics and viability of breast milk strains in pasteurized milk were investigated, also including the study of the volatile molecule profiles. In this regard, all the strains pointed out the release of aroma compounds frequently associated with the sensory quality of several dairy products such as acetic acid, diacetyl, acetoin, acetaldehyde. Data here reported point up the high potential of breast-milk-isolated strains as probiotics.

Targeted management of evolving and established chronic lung disease of prematurity assisted by cardiopulmonary ultrasound: A case report of four patients.

Bronchopulmonary dysplasia (BPD) is one of the most common complications of premature birth. The current definition of BPD is based on the duration of oxygen therapy and/or respiratory support. Among the pitfalls of all the diagnostic definitions, the lack of a proper pathophysiologic classification makes it difficult to choose an appropriate drug strategy for BPD. In this case report, we describe the clinical course of four premature infants, admitted to the neonatal intensive care unit, for whom the use of lung and cardiac ultrasound was an integral part of the diagnostic and therapeutic process. We describe, for the first time to our knowledge, four different cardiopulmonary ultrasound patterns of evolving and established chronic lung disease of prematurity and the consequent therapeutic choices. This approach, if confirmed in prospective studies, may guide the personalized management of infants suffering from evolving and established BPD, optimizing the chances of success of the therapies and at the same time reducing the risk of exposure to inadequate and potentially harmful drugs.

Mode of birth in women with low-lying placenta: protocol for a prospective multicentre 1:3 matched case-control study in Italy (the MODEL-PLACENTA study).

INTRODUCTION: The term placenta praevia defines a placenta that lies over the internal os, whereas the term low-lying placenta identifies a placenta that is partially implanted in the lower uterine segment with the inferior placental edge located at 1-20 mm from the internal cervical os (internal-os-distance). The most appropriate mode of birth in women with low-lying placenta is still controversial, with the majority of them undergoing caesarean section. The current project aims to evaluate the rate of vaginal birth and caesarean section in labour due to bleeding by offering a trial of labour to all women with an internal-os-distance >5 mm as assessed by transvaginal sonography in the late third trimester. METHODS AND ANALYSIS: The MODEL-PLACENTA is a prospective, multicentre, 1:3 matched case-control study involving 17 Maternity Units across Lombardy and Emilia-Romagna regions, Italy. The study includes women with a placenta located in the lower uterine segment at the second trimester scan. Women with a normally located placenta will be enrolled as controls. A sample size of 30 women with an internal-os-distance >5 mm at the late third trimester scan is needed at each participating Unit. Since the incidence of low-lying placenta decreases from 2% in the second trimester to 0.4% at the end of pregnancy, 150 women should be recruited at each centre at the second trimester scan. A vaginal birth rate ≥60% in women with an internal-os-distance >5 mm will be considered appropriate to start routinely admitting to labour these women. ETHICS AND DISSEMINATION: Ethical approval for the study was given by the Brianza Ethics Committee (No 3157, 2019). Written informed consent will be obtained from study participants. Results will be disseminated by publication in peer-reviewed journals and presentation in international conferences. TRIAL REGISTRATION NUMBER: NCT04827433 (pre-results stage).

Differences between influenza and pertussis vaccination uptake in pregnancy: a multi-center survey study in Italy.

BACKGROUND: A suboptimal maternal vaccination coverage in 2017-18 has been reported in Italy. The study aims were to (i) assess changes in maternal influenza and tetanus, diphtheria and acellular pertussis vaccination coverage during 2018-19 influenza season compared to the previous season (ii) estimate influenza vaccine coverage among maternal care providers (MCPs) and (iii) explore the characteristics of vaccine delivery to pregnant women. METHODS: We conducted a cross-sectional survey among pregnant women and MCPs about influenza and pertussis immunization during pregnancy. We also collected information regarding prenatal care characteristics and vaccine delivery among four centers in Italy. RESULTS: We recruited 483 pregnant women and 452 MCPs. The influenza and pertussis vaccine uptake among pregnant women for the season 2018-19 was 14.9% and 60.9%, respectively. MCPs' influenza vaccine uptake was 33.6%. Knowing that the flu vaccine was safe for mothers and their infants and being vaccinated in the previous influenza season were associated with higher vaccine uptake. Regarding pertussis, being a housewife was associated to lower vaccine uptake, while knowing the vaccine is effective and safe for mothers and newborns were associated with higher pertussis vaccine uptake. The single most important factor associated to higher coverage of both influenza and pertussis vaccines was receiving a health-care provider's vaccine advice. Most pregnant women (69.4%) stated that they preferred to be vaccinated in their same prenatal care setting. CONCLUSIONS: Receiving a health-care provider's vaccine advice and the availability of vaccines during prenatal care visits might improve vaccination coverage among pregnant women.

Preoperative and postoperative ultrasound assessment of stress urinary incontinence.

INTRODUCTION: The role of ultrasound imaging in urogynecology is not defined. Significant developments in visualization techniques and interpretation of images allowed to study structures of the lower genitourinary tract and pelvic floor. EVIDENCE ACQUISITION: PubMed and Scopus database were searched for publications on the following item: stress urinary incontinence, ultrasound, perineal ultrasound and preoperative and postoperative assessment. EVIDENCE SYNTHESIS: The role of ultrasound in urogynecology could be helpful in diagnosing of urinary incontinence and urethral hypermobility, to document pelvic floor anatomy and to assess anatomic and functional changes before and after surgery. CONCLUSIONS: Ultrasound could be an important step during preoperative and post-operative assessment of patients affected by stress urinary incontinence.

Serum magnesium and calcium levels in infertile women during a cycle of reproductive assistance.

Magnesium (Mg) and calcium (Ca) are essential cations for women's preconception health. It is well known that, in blood, the concentration of ionized form of these two cations is temporally altered during menstrual cycle, suggesting a correlation between sex steroid hormones and serum calcium and magnesium levels. Evidence from literature suggests that in assisted reproductive technology increasing estrogens during ovarian hyperstimulation may also modulate serum magnesium and calcium levels. Therefore, we first examined total serum magnesium and calcium levels during follicular phase in a large population of infertile patients who underwent intrauterine insemination (IUI). The results were compared to a group of fertile women. Successively, we studied the total serum magnesium and calcium concentrations in infertile patients before and after ovarian hyperstimulation for in vitro fertilization (IVF). Results highlight that total serum concentration of magnesium and calcium does not seem altered in infertile women. During stimulation with gonadotropins, the values of the two cations do not change significantly in ovarian-stimulated women. However, we found a downward trend in the total magnesium and calcium levels in relation to the rising estrogens.

Mitochondrial DNA content and methylation in fetal cord blood of pregnancies with placental insufficiency.

INTRODUCTION: Intrauterine growth restriction (IUGR) and preeclampsia (PE) are pregnancy disorders characterized by placental insufficiency with oxygen/nutrient restriction and oxidative stress, all influencing mitochondria functionality and number. Moreover, IUGR and PE fetuses are predisposed to diseases later in life, and this might occur through epigenetic alterations. Here we analyze content and methylation of mitochondrial DNA (mtDNA), for the first time in IUGR and PE singleton fetuses, to identify possible alterations in mtDNA levels and/or epigenetic control of mitochondrial loci relevant to replication (D-loop) and functionality (mt-TF/RNR1: protein synthesis, mt-CO1: respiratory chain complex). METHODS: We studied 35 term and 8 preterm control, 31 IUGR, 17 PE/IUGR and 17 PE human singleton pregnancies with elective cesarean delivery. Fetal cord blood was collected and evaluated for biochemical parameters. Extracted DNA was subjected to Real-time PCR to assess mtDNA content and analyzed for D-loop, mt-TF/RNR1 and mt-CO1 methylation by bisulfite conversion and pyrosequencing. RESULTS: mtDNA levels were increased in all pathologic groups compared to controls. Mitochondrial loci showed very low methylation levels in all samples; D-loop methylation was further decreased in the most severe cases and associated to umbilical vein pO2. mt-CO1 methylation levels inversely correlated to mtDNA content. DISCUSSION: Increased mtDNA levels in IUGR, PE/IUGR and PE cord blood may denote a fetal response to placental insufficiency. Hypomethylation of D-loop, mt-TF/RNR1 and mt-CO1 loci confirms their relevance in pregnancy.

Ultrasound in Infertility Setting: Optimal Strategy to Evaluate the Assessment of Tubal Patency.

Tubal patency is a key element in women who are undergoing assisted reproductive techniques (ART), in order to attempt or exclude intrauterine insemination (IUI) cycles. Amongst the different procedures that can be used, without resorting to laparoscopy that remains the gold standard, hystero-salpingo-contrast sonography (HyCoSy) is an acceptable, time-efficient, and well tolerated option; it can be performed with administration of saline and air simultaneously or alternately (air/saline-HyCoSy), or with some other contrast agents, like SonoVue (sulfur hexafluoride microbubbles). In this paper, we describe two different studies: in the first one, our aim is to compare the efficiency of air/saline-HyCoSy with HyCoSy performed with contrast media (SonoVue), considering hysterosalpingography (HSG) and laparoscopy (LPS) as reference tests; in the second one, we estimate the pregnancy rate of a cohort of infertile women selected to undergo IUI cycles after tubal bilateral patency demonstration with air/saline-HyCoSy, to understand if this technique can be used as an efficient screening procedure in a Reproductive Unit.

Heterotopic pregnancy in HIV women.

Heterotopic pregnancy occurs when intrauterine and ectopic pregnancy are concomitant; overall rate rises from 1/30.000 to 1.5/1000 in assisted reproductive technology pregnancies. HIV (human immunodeficiency virus) patients are at increased risk of heterotopic pregnancies due to the greater frequency of assisted reproductive technology and pelvic inflammatory disease. We report the first case of heterotopic pregnancy in HIV woman.

Sex specific adaptations in placental biometry of overweight and obese women.

INTRODUCTION: Placental biometry at birth has been shown to predict chronic disease in later life. We hypothesized that maternal overweight/obesity, a state of low-grade inflammation and risk factor for adverse pregnancy outcome, could negatively influence placental development and that differences would be sex-specific. METHODS: 696 women (537 normal-weight, NW; 112 overweight, OW; 47 obese, OB) with singleton uncomplicated pregnancies were prospectively enrolled at term delivery. Gestational age, maternal (age, height, pre-pregnancy BMI, gestational weight gain -GWG, hemoglobin, hematocrit and glycemia), fetal (weight, length, ponderal index, cranial circumference) and placental (weight, diameters) data were collected. Placental area, thickness and efficiency (fetal/placental weight ratio, F/P) were calculated. RESULTS: GWG was within standard recommendations in OB, while OW exceeded it. Placental weight was significantly higher in OW versus NW, but not in OB, leading to significantly higher placental thickness and lower F/P in this group. In the total population, a significant interaction effect between maternal BMI and fetal sex on placental weight and efficiency was found. Indeed, differences in placental parameters were present only in female offspring. DISCUSSION: In our population of OW and OB uncomplicated pregnancies only OW women, presenting GWG over standard recommendations, had thicker and less efficient placentas. We also reported different placental adaptation depending on fetal sex, with significant changes only in female fetuses. This may be part of a female-specific strategy aiming to ensure survival if another adverse event occurs. Customized counseling according to maternal BMI and fetal sex should be evaluated in clinical care.

Vaginal Dinoprostone Versus Intravenous Oxytocin for Labor Induction in Patients Not Responsive to a First Dose of Dinoprostone: A Randomized Prospective Study.

OBJECTIVE: To evaluate the efficacy of 2 different regimens for labor induction in patients with unfavorable cervix not responsive to a first dose of dinoprostone vaginal insert. METHODS: Between November, 2011 and June, 2014, 338 patients underwent induction of labor. After standard 24 hours treatment, 94 singleton term pregnancies remained with a Bishop score ≤6 and were randomized into 2 different regimens: repeated vaginal dinoprostone (group A, n = 47) or intravenous oxytocin (group B, n = 47). Primary outcome was vaginal delivery, and the secondary outcomes were interval between labor induction and delivery and operative delivery rates. RESULTS: Vaginal deliveries were significantly higher (group A: 26/47 (55.3%) and group B 16/47 (34.0%), P < .05), and cesarean sections were significantly lower (group A 21/47 (44.7%) and group B 31/47 (66%), P < .05) in patients who received a double dose of dinoprostone. The intervals between labor induction and onset of labor and between labor induction and delivery were lower in the group treated with oxytocin. Neonatal outcomes were similar in the 2 groups. CONCLUSION: A second dinoprostone vaginal insert is an effective and safe choice for patients with unfavorable cervix not responsive to a first 24 hours administration of dinoprostone for cervical ripening, and its use is associated with lower cesarean section rates.

Pseudo-mannosylated DC-SIGN ligands as potential adjuvants for HIV vaccines.

The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs). Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19) to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, ß chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated.

A glycomimetic compound inhibits DC-SIGN-mediated HIV infection in cellular and cervical explant models.

OBJECTIVE: Dendritic cell-specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) participates in the initial stages of sexually transmitted HIV-1 infection by recognizing highly mannosylated structures presented in multiple copies on HIV-1 gp120 and promoting virus dissemination. Inhibition of HIV interaction with DC-SIGN thus represents a potential therapeutic approach for viral entry inhibition at the mucosal level. DESIGN: Herein we evaluate the efficacy in inhibiting HIV-1 infection and the potential toxicity of a multimeric glycomimetic DC-SIGN ligand (Dendron 12). METHODS: The ability of Dendron 12 to block HIV-1 infection was assessed in cellular and human cervical explant models. Selectivity of Dendron 12 towards DC-SIGN and langerin was evaluated by surface plasmon resonance studies. ß chemokine production following stimulation with Dendron 12 was also analyzed. Toxicity of the compound was evaluated in cellular and tissue models. RESULTS: Dendron 12 averted HIV-1 trans infection of CD4(+) T lymphocytes in presence of elevated viral loads and prevented HIV-1 infection of human cervical tissues, under conditions mimicking compromised epithelial integrity, by multiple clades of R5 and X4 tropic viruses. Treatment with Dendron 12 did not interfere with the activity of langerin and also significantly elicited the production of the ß chemokines MIP-1α, MIP-1ß and RANTES. CONCLUSION: Dendron 12 thus inhibits HIV-1 infection by competition with binding of HIV to DC-SIGN and stimulation of ß-chemokine production. Dendron 12 represents a promising lead compound for the development of anti-HIV topical microbicides.

Maternal and fetal thrombophilia in intrauterine growth restriction in the presence or absence of maternal hypertensive disease.

Intrauterine growth restriction (IUGR) depends on the placental capacity to transfer oxygen and nutrients from the maternal to the fetal circulation. Placental insufficiency may be caused by impairment of the maternal or fetal circulation by a thrombotic event, possibly associated with thrombophilic disorders. The goals of our study were to define the role of maternal/fetal gain-of-function factor V Leiden and prothrombin G20210A mutations in the development of IUGR and to evaluate whether maternal pregnancy-induced hypertensive diseases would modify any such association. This is a case-control study: controls were 259 normal pregnancies, cases were 77 IUGR, 28 with and 49 without preeclampsia (PE) or pregnancy-induced hypertension (PIH). An association was found between IUGR and fetal thrombophilia (OR 2.09 CI 95% 1-4.5). The association was stronger in IUGR without PE and PIH (OR 2.9 CI 95% 1.3-6.6). This suggests a role for the fetal genotype in the development of IUGR.

Epigenetic modulation of the IGF2/H19 imprinted domain in human embryonic and extra-embryonic compartments and its possible role in fetal growth restriction.

Genomic imprinting, resulting in parent-of-origin-dependent gene expression, is mainly achieved by DNA methylation. IGF2 and H19, belonging to the same cluster of imprinted genes and regulated by ICR1, DMR2 and H19 promoter elements, play a major role in fetal/placental growth. Using quantitative approaches, we explored the epigenetic modulation of IGF2/H19 during human development in 60 normal and 66 idiopathic IUGR (Intrauterine Growth Restriction) pregnancies, studying embryonic (cord blood) and extraembryonic (placenta and umbilical cord) tissues. We found ICR1 normal methylation levels ( approximately 50%) and H19 promoter/DMR2 hypomethylation in extra-embryonic tissues. In contrast, in embryonic samples the three loci displayed normal methylation values comparable to those in postnatal blood. This feature is stably maintained throughout gestation and does not vary in IUGR cases. We reported asymmetric allelic expression of H19 and IGF2 as a common feature in pre- and post-natal tissues, independent of H19 promoter and DMR2 methylation levels. In addition, we excluded in IUGR post-transcriptional IGF2 interference possibly related to miRNA 483-3p (IGF2, intron 2) expression defects. Through LINE1 methylation analysis, we observed a methylation gradient with increasing methylation from pre- to post-natal life. The involvement of UPD (Uniparental Disomy) in IUGR aetiology was excluded. Our data indicate that: (1) ICR1 methylation status is a necessary and sufficient condition to drive the imprinting of IGF2 and H19 present in embryonic as well as in extra-embryonic tissues; (2) hypomethylation of H19 promoter and DMR2 does not influence the expression pattern of IGF2 and H19; (3) there is a gradient of global methylation, increasing from extra-embryonic to embryonic and adult tissues. Finally, because of placental hypomethylation, cautions should be exercised in diagnosis of imprinting diseases using chorionic villi.

The role of the placenta in intrauterine growth restriction (IUGR).

Intrauterine growth restriction (IUGR) represents a reduction from the physiological growth rate. Fetal growth depends from the maternal supply of nutrients through the placenta into the umbilical circulation. Consequently, fetal growth restriction is associated with a reduced nutritional placental supply and this can result from a decrease in utero-placental blood flows as well as a reduced placental transport capacity. In IUGR, the placental supply of amino acids is significantly reduced independently from the severity of growth restriction and from the presence of hypoxia. Moreover, maternal-fetal gradients of glucose are increased in severe IUGR fetuses, i. e. those with alterations of umbilical blood flows, and reduced conversion ratios of long chain-polyunsaturated fatty acids (LC-PUFA) from their parent fatty acids have been demonstrated. Mouse and human models suggest that epigenetic regulation of fetal growth may also play a significant role, through placental imprinted genes. This review summarizes the current knowledge about placental role in intrauterine growth restriction.

Angiotensin-converting enzyme and adducin-1 polymorphisms in women with preeclampsia and gestational hypertension.

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the Adducin-1 (ADD1) G460W nonsense single nucleotide polymorphism (SNP) have previously been associated to hypertension, whereas their association with preeclampsia (PE) and gestational hypertension (GH) is still controversial. We genotyped ACE I/D, ADD1 G460W, and ADD1 S586C polymorphisms in 672 unrelated pregnant women: 204 PE (81/204 mild PE), 56 GH, and 412 controls, evaluating both their single and combined effects on these pathologies. The genotype combination of the 3 polymorphisms was not statistically different in cases versus controls, nor were ACE and ADD1 polymorphisms in GH. Nevertheless, the distribution of ACE genotypes was different in PE. This was confirmed in mild PE, whereas no significance was found in severe PE. This could suggest that different factors may lead to mild and severe PE, with ACE polymorphism playing a more important role in the mild form.