Classification of stillbirths is an ongoing dilemma

Aim: To compare different classification systems in a cohort of stillbirths undergoing a comprehensive workup; to establish whether a particular classification system is most suitable and useful in determining cause of death, purporting the lowest percentage of unexplained death. Methods: Cases of stillbirth at gestational age 22–41 weeks occurring at the Department of Gynecology and Obstetrics of Foggia University during a 4 year period were collected. The World Health Organization (WHO) diagnosis of stillbirth was used. All the data collection was based on the recommendations of an Italian diagnostic workup for stillbirth. Two expert obstetricians reviewed all cases and classified causes according to five classification systems. Results: Relevant Condition at Death (ReCoDe) and Causes Of Death and Associated Conditions (CODAC) classification systems performed best in retaining information. The ReCoDe system provided the lowest rate of unexplained stillbirth (14%) compared to de Galan-Roosen (16%), CODAC (16%), Tulip (18%), Wigglesworth (62%). Conclusion: Classification of stillbirth is influenced by the multiplicity of possible causes and factors related to fetal death. Fetal autopsy, placental histology and cytogenetic analysis are strongly recommended to have a complete diagnostic evaluation. Commonly employed classification systems performed differently in our experience, the most satisfactory being the ReCoDe. Given the rate of “unexplained” cases, none can be considered optimal and further efforts are necessary to work out a clinically useful system

Can endometrial arylsulfatase A activity predict the onset of endometrial polyps over the years?

PURPOSE: To assess if arylsulfatase A activity (ASA) and sulfatide (SL) concentration in the human endometrium can be predictive of the development of endometrial polyps over the years, since ASA activity reflects the endometrial sensitivity to hormones. METHODS: ASA activity and SL concentration were determined by biochemical procedures on endometrial samples collected between 1990 and 1994 in non-menopausal women. These women underwent a new endometrial sampling following the clinical indication some years after the first endometrial sampling. The histological assessment of the second endometrial specimens found four patients with normal endometrial pattern and 10 patients with one or more endometrial polyps. ASA activity/years elapsed and SL concentration/years elapsed were compared using two tailed Mann-Whitney test for unpaired data between patients with normal pattern and patients with endometrial polyps. RESULTS: Median ASA activities were 2.62 (normal pattern) versus 1.85 (endometrial polyps) nmol hydrolized substrate/min. Median activity/years elapsed is higher in patients with second endometrial sample presenting normal pattern (p=0.006) and median SL concentration/years elapsed does not differ significantly among groups, even if median SL concentration seems to be higher in patients who subsequently developed polyps (1031 µg/g of fresh tissue versus 341,5 µg/g of fresh tissue). CONCLUSIONS: ASA activity can predict the onset of endometrial polyps over the years. OBJETIVO: Avaliar se a atividade da arilsulfatase A (ASA) e a concentração de sulfatida (SL) no endométrio humano pode ser preditivo em relação ao desenvolvimento de pólipos endometriais ao longo dos anos, posto que atividade da ASA reflete a sensibilidade do endométrio aos hormônios. MÉTODOS: A atividade da ASA, assim como a concentração de SL, foi determinada por meio de procedimentos bioquímicos em amostras de endométrio coletadas entre 1990 e 1994, em mulheres que não se encontravam na menopausa. Essas mulheres foram submetidas a uma nova amostragem endometrial após indicação clínica alguns anos depois da primeira amostragem endometrial. A avaliação histológica dos segundos espécimes endometriais permitiu identificar quatro pacientes com padrão endometrial normal e 10 com um ou mais pólipos endometriais. A atividade da ASA/anos depois e a concentração de SL/anos depois foram comparadas, utilizando o teste bilateral U de Mann-Whitney para dados não pareados entre as pacientes com padrão normal e as pacientes com pólipos endometriais. RESULTADOS: A ativitade da ASA foi 2,62 (padrão normal) em comparação com 1,85 (endometrial pólipos) de substrato hidrolisado/min. A atividade da ASA/anos depois é maior em pacientes com segunda amostra endometrial a apresentarem um padrão normal (p=0,006), e a concentração mediana de SL/anos depois não difere de forma significativa entre os grupos, apesar de a concentração mediana de SL parecer maior em pacientes que posteriormente desenvolveram pólipos (1031 µg/g de tecido fresco em comparação com 341,5 µg/g de tecido fresco). CONCLUSÕES: A atividade da ASA pode prever a aparição de pólipos endometriais ao longo dos anos

Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients

Mosaic Trisomy 16 Confined to Placenta: Pregnancy Outcome and Postnatal Follow up

The mother was a 29-year-old Caucasian healthy woman gravida 1, para 0 and she was referred to prenatal diagnosis to S..

Detection of Antibodies to Human Herpesvirus 8 (HHV-8) among Women of Child-Bearing Age in the Apulia Region (South-Eastern Italy):

In this study the authors investigated the presence of serum antibodies to Human Herpesvirus 8 (HHV-8) in a group of women of child-bearing age in the Apulia region (South Eastern Italy). A seroprevalence of 16.8% was observed, increasing, although non significantly, with the age of the women (10.6% in women between 19 and 25 years, 25.3% in women aging more than 35 years). The presence of antibodies to Hepatitis C Virus (HCV) was significantly associated to the detection of antibodies to HHV-8. Possible mother-to-child transmission of HHV-8 as well as the outcome of fetuses or children born to HHV-8 positive mothers are still a matter of debate. This study, showing the wide diffusion of HHV-8 infection in healthy women of child-bearing age in our geographical area, highlights the urgency of studies aimed to better clarify these relevant topics

Prenatal predictors of adverse perinatal outcome in congenital cytomegalovirus infection: a retrospective multicenter study

Objectives To identify predictors of adverse perinatal outcome in congenital cytomegalovirus (CMV) infection. Methods In a multicenter study fetuses with congenital CMV infection diagnosed by PCR on amniotic fluid and normal prenatal imaging at the time of diagnosis were included. Primary outcome was the occurrence of structural anomalies at follow-up ultrasound or prenatal magnetic resonance imaging (MRI). Secondary outcomes were the occurrence of anomalies detected exclusively postnatally and the rate of symptomatic infection. Results One hundred and four fetuses with congenital CMV were included in the study. Anomalies were detected at follow-up ultrasound or MRI in 18.3% (19/104) cases. Additional anomalies were found after birth in 11.9% (10/84) of cases and 15.5% (13/85) of newborns showed clinical symptoms related to CMV infection. There was no difference in either maternal age (p=0.3), trimester (p=0.4) of infection and prenatal therapy (p=0.4) between fetuses with or whiteout anomalies at follow-up. Conversely, median viral load in the amniotic fluid was higher in fetuses with additional anomalies at follow-up (p=0.02) compared to those without. At multivariate logistic regression analysis, high viral load in the amniotic fluid, defined as >= 100,000 copies/mL was the only independent predictor for the occurrence of anomalies detected exclusively at follow-up ultrasound assessment or MRI, with an OR of 3.12. Conclusions Viral load in the amniotic fluid is a strong predictor of adverse perinatal outcome in congenital CMV infection. The results of this study emphasize the importance of adequate follow up even in case of negative neurosonography to better predict postnatal adverse outcomes of infected newborns, especially in amniotic fluid high viral load

Vaginal Lactoferrin Modulates PGE 2

Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n = 57) or treated with LF 4 hours before amniocentesis (n = 54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p < 0.01, p < 0.005, and p < 0.001, resp.). Conversely, active MMP-2 (p < 0.0001) and MMP-2/TIMP-2 molar ratio (p < 0.001) were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563

Influence of hCG on inducible nitric oxide synthase gene expression in ram testicular arteries

Background. Experimental evidence suggests a relationship between the vasodilatory effect of hCG and the NOS system in the testis. The influence of hCG administration on testicular vascular NOS gene expression has not been fully investigated. Objective: This study aimed to evaluate the presence of the nitric oxide syntheses gene in ram testicular arteries and the influence of hCG administration on its expression. Materials and methods: Both testicular arteries of sixteen rams were extracted before and after i.v. administration of 5000 IU of hCG or placebo. The expression of the iNOS gene was investigated by real time PCR. Data were analyzed by means of Wilcoxon and Mann-Whitney tests. A p value of &lt; 0.05 was considered statistically significant. Results: PCR revealed the presence of iNOS mRNA in all basal samples but the expression of the iNOS gene was significantly reduced in all arteries obtained 24 h after the administration of either hCG or placebo. A significant reduction in the expression of iNOS gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups. On the other hand hCG stimulation did not significantly influence iNOS expression following its administration compared to a placebo. Conclusion: Ram testicular arteries express the iNOS gene but hCG stimulation did not significantly influence iNOS expression. A significant reduction in the expression of this gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups, suggesting that iNOS expression on the testicular artery could be influenced by the spermatic vessel ligation of the controlateral testis

The clinical impact of the first-trimester nuchal translucency between the 95th-99th percentiles

Objectives: To evaluate the clinical significance of nuchal translucency (NT) between the 95th-99th percentile in terms of typical and atypical chromosomal abnormalities (ACAs), associated fetal congenital defects and postnatal outcome. Methods: A retrospective cohort study of fetuses with NT between the 95th-99th percentile. Data regarding the rate of associated fetal defects, genetic abnormalities and postnatal outcome were collected. Results: A total of 306 cases of fetuses with an NT between the 95th-99th percentiles were included. The overall rate of genetic abnormalities was 12.1% (37/306). Chromosomal abnormalities were found in 10.1% (31/306) of cases and 2% were ACA (6/306). Within this group, two were pathogenic Copy Number Variants (CNVs) and four were single gene disorders. The overall rate of fetal congenital defects was 13.7% (42/306). All ACAs were found in fetuses with congenital defects. Postnatally, a new diagnosis of a single gene disorder was made in 0.85% of cases (2/236). Conclusions: The presence of an NT between the 95th-99th percentiles carries a 10-fold increased risk of fetal defects, representing an indication for referral for a detailed fetal anatomy evaluation. The risk of ACA is mainly related to the presence of fetal defects, irrespective of the combined test risk

Serum IgG antibodies from pregnant women reacting to mimotopes of simian virus 40 large T antigen, the viral oncoprotein

Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected from pregnant and non-pregnant women, with the same mean age. Women were in the range of 15-48 years old. Samples were assayed by an indirect ELISA employing specific SV40 LT mimotopes as antigens, whereas functional analysis was performed by neutralization of the viral infectivity in cell cultures. As a control, sera were analyzed for Ab against BK polyomavirus (BKPyV), which is a human polyomavirus homologous to SV40. Statistical analyses employed chi-square with Yates' correction, and Student's t tests. Indirect ELISAs indicated that pregnant women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non-pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were detected with a prevalence of 80% in pregnant women and with a prevalence of 78% in non-pregnant women. These data indicate that SV40 infects at a low prevalence pregnant women. We may speculate that SV40, or a close human polyomavirus still undetected, could be transmitted from mother to fetus