Effects of SARS-Cov-2 mRNA vaccine on placental histopathology: Comparison of a population of uncomplicated COVID-19 positive pregnant women.

1. INTRODUCTION: This study investigates the impact of SARS-CoV-2 infection on placental histopathology in pregnant women, comparing outcomes between vaccinated and non-vaccinated individuals. Despite known adverse pregnancy outcomes linked to SARS-CoV-2 infection, the specific effects on the placenta remain unclear. Although vaccination has demonstrated a substantial reduction in infection severity, its impact on placental health requires more insight. 2. METHODS: Between March 2021 and July 2022, 387 COVID-19-positive women were admitted for delivery. Of these, 98 with non-severe symptoms were analyzed: 35 vaccinated during pregnancy, and 63 non-vaccinated. Two independent pathologists evaluated all placental specimens. 3. RESULTS: The only differing obstetrical characteristic between groups was the mode of delivery (p 0.047), lacking clinical implications. Over 85% of placentas exhibited microscopic abnormalities, predominantly maternal vascular supply disorders (vaccinated 89.1%; unvaccinated 85.5%). Comparing vaccinated and unvaccinated groups revealed statistically significant differences, notably in increased focal perivillous fibrin deposits (IFPFD) [17.1% vs. 33.3% (p 0.04)] and avascular fibrotic villi (AFV) [0% vs. 11.1% (p 0.04)]. Binomial logistic regression confirmed the vaccine's protective role against IFPFD (aOR 0.36; 95%CI 013-0.99) and AVF (aOR 0.06, 95% CI 0.003-0.98). A sub-analysis in vaccinated women showed a positive correlation between the timing of the first dose and IFPFD presence (p 0.018). 4. DISCUSSION: The lower incidence of maternal and fetal vascular malperfusion placental features in vaccinated women, coupled with the timing correlation, supports the vaccine's protective effect on placental tissue in COVID-19-infected pregnant patients. Notably, no side effects were reported post-vaccination, emphasizing the vaccine's safety and advocating for its secure administration in pregnant populations.

Pravastatin for severe preeclampsia with growth restriction: Placental findings and infant follow-up.

OBJECTIVE: Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading cause of premature delivery worldwide. As well as intrauterine growth restriction (IUGR), PE is associated with pathogenic evidence of placental malperfusion and ischemia. Recent literature has highlighted the potential of pravastatin in the prevention and treatment of these conditions. Aim of this study is to describe perinatal outcomes and placental histopathological findings in a small series of pregnant women with severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow up of these babies is provided. STUDY DESIGN: Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6 gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate treatment with Pravastatin 40 mg a day. Treated women were compared with controls identified with similar data in terms of gestational age at diagnosis, clinical maternal data, Doppler severity findings. Neonates were followed up for two years. RESULTS: The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the group of women treated with pravastatin, maximum transaminase, creatinine levels were lower than in controls, where the minimum platelet count was higher. Placenta examination did not reveal any significant differences in placental histopathological findings. No significant differences were observed in the investigated perinatal data, as well as in infant follow-up, although an increased prenatal weight gain was found in treated pregnancies in comparison to controls. CONCLUSIONS: Our data did not allow us to find significant differences in pregnancy outcome and infant follow-up, as well as in placental histological picture in preeclamptic patients when pravastatin is administered in the late second trimester. However, we suggest its possible role in stabilizing the disease, increasing the prenatal weight gain and prolonging the duration of pregnancy, thus preventing the progression to a more severe maternal disease.

SARS-CoV-2 Infection in Pregnancy: Clinical Signs, Placental Pathology, and Neonatal Outcome-Implications for Clinical Care.

Introduction: The current COVID-19 pandemic has been associated with high rates of mortality and significant morbidity. Both the risk of infection for pregnant women and the risk of vertical transmission have been evaluated, and the presence of the SARS-CoV-2 virus has been demonstrated both in the placenta and in the amniochorionic membranes. However, the actual effects of this pathogen on pregnancy and on placental morphology are still unclear. Objective: To describe histopathologic findings in the placentas of women with SARS-CoV-2 infection during pregnancy and their correlation with clinical signs and perinatal outcome. Methods: Placental tissues from pregnant women with SARS-CoV-2 infection delivering between March 2020 and February 2021 were analyzed. Results: One hundred six placentas from women with SARS-CoV-2 infection during pregnancy who delivered in Fondazione Policlinico A. Gemelli were examined. Most of them were asymptomatic. All neonates had available test results for SARS-CoV-2 and only one resulted positive. Placental tissues mainly showed signs of maternal vascular malperfusion and of placenta injury in terms of syncytial node increase (96.2%), villar agglutination (77.3%), neointimal hyperplasia (76.4%), excessive fibrin deposition (43.3%), and chorangiosis (35.8%). No significant differences in the frequency of the histopathological lesions were observed according to maternal symptoms. Conclusion: Looking to placental tissues from SARS-CoV-2 positive women at the screening performed close to delivery, placental injuries could be detected without any correlation with fetal and neonatal outcomes. We hypothesize that short latency between SARS-CoV-2 infection and delivery is the main reason for these observations.

Circulating EGFL7 distinguishes between IUGR and PE: an observational case-control study.

Isolated intrauterine growth restriction (IUGR) and preeclampsia (PE) share common placental pathogenesis. Differently from IUGR, PE is a systemic disorder which may also affect liver and brain. Early diagnosis of these conditions may optimize maternal and fetal management. Aim of this study was to assess whether Epidermal Growth Factor-Like domain 7 (EGFL7) dosage in maternal blood discriminates between isolated IUGR and PE. A total of 116 women were enrolled in this case-control study: 12 non-pregnant women, 34 healthy pregnant women, 34 women presenting with isolated IUGR and 36 presenting with PE. Levels of circulating EGFL7 and other known pro- and anti-angiogenic factors were measured by ELISA at different gestational ages (GA). Between 22-25 weeks of gestation, EGFL7 levels in early-onset PE (e-PE) plasma samples were significantly higher than those measured in controls or isolated IUGR samples (69.86 ± 6.17 vs. 19.8 ± 2.5 or 18.8 ± 2.8 µg/ml, respectively). Between 26-34 weeks, EGFL7 levels remained significantly higher in e-PE compared to IUGR. At term, circulating and placental EGFL7 levels were comparable between IUGR and late-onset PE (l-PE). In contrast, circulating levels of PlGF were decreased in both IUGR- and PE- complicated pregnancies, while levels of both sFLT-1 and sENDOGLIN were increased in both conditions. In conclusion, EGFL7 significantly discriminates between isolated IUGR and PE.

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

BACKGROUND: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. METHODS: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. RESULTS: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60' or 120' glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60' or 120' glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score < 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). CONCLUSION: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes.

Perinatal outcome in gestational hypertension: Which role for developing preeclampsia. A population-based cohort study.

OBJECTIVE: To analyze perinatal outcome in singleton pregnancies complicated by gestational hypertension (GH), to investigate the rate of women developing preeclampsia (PE) and to describe maternal features associated with progression to PE. STUDY DESIGN: This is a population-based retrospective cohort-study involving 514 singleton pregnancies with a diagnosis of GH at admission. RESULTS: In pregnancies with GH, a poorer pregnancy outcome in comparison to healthy controls was observed in terms of gestational age at delivery, birthweight and birthweight percentile. The observed overall rate of developing PE was 11.7 %. Of all pregnancies with GH at admission, two different groups were identified based on the diagnosis at delivery: GHPE, i.e. women who developed PE (60/514; 11.7 %), and GHnoPE, i.e. women who did not develop PE (454/514; 88.3 %). In the GHPE group it was observed that the 62 % of the women with diagnosis of GH earlier than 28 weeks developed PE while only 2% developed PE if the diagnosis of GH was performed later than 36 weeks. The observed rate of developing PE was 14.7 % in pharmacologically treated hypertensive women, whereas the diagnosis of PE has been made in only 3% of non-treated women. CONCLUSION: Pregnant women with raised blood pressure are at risk of having a less favourable perinatal outcome. The risk is mainly associated with the progression to PE. Major determinants of the risk of developing PE are the earlier gestational age at diagnosis of GH, the necessity of treatment and the number of anti-hypertensive drugs needed for controlling blood pressure.

Autoimmunity in obstetrics and autoimmune diseases in pregnancy.

Autoimmune diseases (AIDs) are associated with strong female preponderance and often present before or during the reproductive years; consequently, pregnancy and breastfeeding are topics of major interest for these patients. AIDs show different responses to pregnancy: some ameliorate, while others remain unchanged, and several AIDs aggravate. The response of the AIDs to the hormonal and immunological alterations of pregnancy reflects the different pathophysiology of each disease. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with multiple autoantibodies, multiorgan involvement, more aggressive therapy, and increased impact on pregnancy outcome. For the management of pregnancy in patients with SLE and/or APS, it is important to individuate the correct risk profile for each woman and timing for treatment. The optimal timing for starting or modulating treatment is at preconception assessment to influence the placentation. In this chapter, we discuss the management of pregnancy in patients with AIDs.

Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia.

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.

Development of a new fetal growth curve from a large sample of Italian population.

BACKGROUND: Intrauterine growth curves are considered an essential instrument in prenatal medicine for an appropriate auxological classification of fetuses and they have a great importance in clinical practice. Nowadays, in Italy a national curve published in 1975, is the most used. It Is based on birth weights of 8458 newborns from physiological pregnancies. The aim of the present study was to develop a modern fetal growth curve based on accurately selection of 35 240 physiological singleton Italian pregnancies with sure gestational age confirmed by ultrasound. METHODS: This is a retrospective analysis of 35,240 pregnancies from "A. Gemelli" University Hospital in Rome and "S. Anna" University Hospital in Turin from January 2001 to December 2006. Non-resident pregnant women or coming from other countries, women with diabetes, hypertensive disorders of pregnancy, multiple pregnancies, fetuses with major malformations and/or chromosomal disorders and stillborn fetuses were excluded. RESULTS: An increasing trend of median neonatal weight, in comparison with the previous Italian National Curve drawn up in 1975, was found. CONCLUSIONS: Combining data from two centers, a new fetal growth curve, in which the 10th and the 90th percentiles are clinically reliable, was performed, in order to have a better tool to evaluate the Italian fetal population. A trend towards an increase of birth weight was observed if compared to previous growth curve drawn up more than 30 years ago.

Is gestational hypertension beneficial in twin pregnancies?

OBJECTIVES: Hypertensive disorders of pregnancy are commonly associated with impaired foetal growth. However, some studies observed that gestational hypertension in twin pregnancy could be beneficial for foetal growth. The aim of this study is to investigate the influence of gestational hypertension on neonatal birth weight among twin pregnancies. STUDY DESIGN: This is a retrospective study about the comparison of 196 hypertensive twin pregnancies to 912 normotensive ones, who gave birth in the teaching hospital "A. Gemelli" in Rome from 1980 to 2006. MAIN OUTCOME MEASURES: Birth weight, inter-twin weight discordance and rate of small for gestational age neonates in the first and second twin. RESULTS: Birth weight, inter-twin weight discordance and rate of small for gestational age neonates were similar between the two groups. In the normotensive group, the discordance >25% was associated with lower gestational age at the delivery (p<0.00001), data not observed in the hypertensive group. The rate of pregnancies with second twin small for gestational age rose while paralleling the degree of the discordance in both groups. CONCLUSION: Gestational hypertension in twin pregnancies, if compared to normotensive ones, is not detrimental for foetal growth.

Use of an intrauterine inflated catheter balloon in massive post-partum hemorrhage: a series of 52 cases.

AIM: Massive post-partum hemorrhage (PPH) is an important cause of maternal death that occurs as a complication of delivery. We report a large case series to evaluate the efficacy of uterine balloon tamponade to treat PPH avoiding hysterectomy. MATERIAL AND METHODS: This prospective study was conducted in two Italian hospitals (from December 2002 to July 2012). Fifty-two patients with PPH not responsive to uterotonics were treated by Rusch balloon. A follow-up was conducted among the study population to assess the subsequent fertility. RESULTS: The most frequent cause of PPH was atony (59.6%), followed by placenta previa (21.2%), placenta accreta (9.6%), and placenta previa and accreta (9.6%). The balloon success rate to control hemorrhage was 75%. From the sample of 52 patients, 13 patients needed additional procedures. In three failure cases, other conservative techniques were used and the overall effectiveness of them was 80.7%. The follow-up group consisted of 31 women. Of these women, 24 women (77.4%) had no further pregnancies, but only one due to sterility. Four of seven patients with subsequent pregnancies made it to term without complications. CONCLUSIONS: The Rusch balloon is effective in controlling non-traumatic PPH in 75% of cases. It is simple to use, readily available and cheap. If necessary, this technique does not exclude other procedures. We suggest that this balloon should be included routinely in the PPH protocol.