Human Milk Oligosaccharides Reduce Murine Group B Streptococcus Vaginal Colonization with Minimal Impact on the Vaginal Microbiota

During pregnancy, GBS ascension into the uterus can cause fetal infection or preterm birth. In addition, GBS exposure during labor creates a risk of serious disease in the vulnerable newborn and mother postpartum.

Lessons from ten years the prevalence of Congenital Rubella Syndrome (CRS) in young population living in a developing country, Tehran; Iran

Background: A safe and effective rubella vaccine is available and prescribed in IRAN. Objective: This is a survey of CRS cases collected based on WHO criteria one decade after MR vaccination campaign (2003) Methods: This Multi-stage prospective/cross-sectional study was carried out in three stages in 3 educational hospitals in Tehran (Rasoul Aram, Akbar Abadi and Firoozabadi), In the first stage of study between 2011 and 2012 total 186 infants were evaluated and in the second stage of study, total 163 blood samples of infants with suspected INTRA UTERINE INFECTION were compared with a group of healthy matched infants. In the first and second stages, Rubella immunity (IgG&IgM) in cord blood was evaluated by Eliza method. Results: Despite MR vaccination in Iran, after one decade"confirmed CRS" and " compatible CRS" were diagnosed in 5 and 31 from 89 CRS suspected cases. Conclusion: The incidence of "confirmed CRS" in every 100 CRS suspected infants (after campaign) is 5.6 %;and 31 CRS Compatible cases are so important. Without active CRS surveillance, mild infection such as IUGR, hearing loss,heart abnormalities, impaired vision, and mental retardation even in the developed country might be missed. Fetal infection is persistent, which imposes additional costs on the country.Another mass vaccination in women and girls is needed. Also, the anti-rubella IgG testing before pregnancy in women who were not vaccinated; vaccination of women before marriage /pregnancy should be obligatory in order to prevent the CRS.

Fetal Central Nervous System Derived Extracellular Vesicles: Potential for Non-invasive Tracking of Viral Mediated Fetal Brain Injury

Introduction: Extracellular vesicles derived from the fetal central nervous system (FCNSEs) can be purified from maternal serum or plasma using the protein Contactin-2/TAG1that is expressed almost exclusively by developing neurons in the hippocampus, cerebral cortex and cerebellum. We hypothesized that fetal CNSEs could be used to non-invasively detect and quantify viral mediated in-utero brain injury in the first trimester.Materials and Methods: First trimester maternal samples were collected from a human clinical population infected with primary cytomegalovirus (CMV) and a non-human primate model of Zika (ZIKV) infection. In the CMV cohort, a nested case control study was performed comparing pregnancies with and without fetal infection. Cases of fetal infection were further subdivided into those with and without adverse neurologic outcome. ZIKV samples were collected serially following maternal inoculation or saline. All ZIKV cases had histopathologic findings on necropsy. Serum was precipitated with ExoQuick solution and FCEs were isolated with biotinylated anti-Contactin-2/TAG1 antibody-streptavidin matrix immunoabsorption. FCE Synaptopodin (SYNPO) and Neurogranin (NG) protein levels were measured using standard ELISA kits and normalized to the exosome marker CD81.Results: Fetal CNSE SYNPO and NG were significantly reduced in cases of first trimester fetal CMV infection compared to those with infection limited to the mother but could not discriminate between fetal infection with and without adverse neurologic outcome. Following ZIKV inoculation, fetal CNSE SYNPO was reduced by 48 h and significantly reduced by day 4.Discussion: These data are the first to suggest that first trimester non-invasive diagnosis of fetal viral infection is possible. Fetal CNSEs have the potential to augment clinical and pre-clinical studies of perinatal viral infection. Serial sampling may be needed to discriminate between fetuses that are responding to treatment and/or recovering due to innate defenses and those that have ongoing neuronal injury. If confirmed, this technology may advance the paradigm of first trimester prenatal diagnosis and change the calculus for the cost benefit of CMV surveillance programs in pregnancy.

INTRAUTERINE FETAL INFECTION - THE REALITIES OF DIAGNOSIS AND TREATMENT

Іntroduction. Intrauterine infection of the fetus is oneof the most important problems in obstetrics. The absenceof adequate treatment leads to a number of complicationsthat develop during pregnancy, childbirth, and postpartumperiod. There are often situations when the consequences ofthe invasion of microorganisms are more important than thepresence of an infectious agent itself.The aim is to analyze the indicators of microcytosis ofthe vagina, cervical canal, the peculiarities of pregnancywith infection of the fetus, and the effectiveness of varioustreatment regimens.Material and methods. 20 healthy women withphysiological course of pregnancy (the control group) and62 pregnant women with signs of fetal infection (the maingroup) were examined using clinical, microbiological,bacteriological, serological methods, statistical analysis,and fetal ultrasound.Results. Depending on the trimester, pregnant womenof the main group were divided into two subgroups: thefirst subgroup - at 18-24 weeks (50 pregnant women), thesecond - at 28-34 weeks (12 pregnant women).The statistical analysis of changes in vaginalmicrocynosis was conducted depending on the term. Thesignificant difference regarding the effect of gram negativediplococci, morphologically similar to gonococcus,Streptococcus agalactiae in the third trimester was found outalong with Ureaplasma urealyticum, Chlamidia trahomatisin the second trimester and Trichomonas vaginalis andMycoplasma hominis regardless of trimester.Ultrasound in the first subgroup revealed a syndromeof fetal growth retardation in 20 % of women, an abnormalamount of amniotic fluid in 24 %, changes in the structureof the placenta in 14 %, enlargement of the pelvic system ofthe kidneys in 52 %, intestinal hyperechogenicity in 60 %,and hepatomegaly in 4 % of cases. In the second subgroup,the abnormal amount of amniotic fluid was found in 16.7 %of pregnant women, changes in the structure of the placentain 83,3 %, and progressive shortening of the cervix in 33.3% of cases.Pregnant women of the main group were offered acourse of specific antibacterial therapy.In case of positive dynamics within three days (reductionof pathological secretions, polyhydramnios and otherultrasound signs of fetal infection), treatment is continued.In case of negative dynamics or no effect within three daysantibacterial agent must be changed. If symptoms reoccur,a repeat course with a new antibacterial agent is prescribed.Conclusions. Disorders of vaginal microcynosis andcervical canal were found in 80.6% of pregnant women,the rest of them were diagnosed with the ultrasound signsof infection of the fetus without changes in vagina andcervical canal.The proposed regimens of antibacterial therapy areeffective in the second trimester of pregnancy, indicatingthe necessity of examination and treatment during thisperiod, and in case of structural changes in the cervix causedby gram-negative diplococci, morphologically similarto gonococcus and Trichomonas vaginalis. Antibacterialtherapy is not effective enough in case of the developmentof placental dysfunction, and the threat of premature birthin the third trimester.

Nonhuman Primate Models of Zika Virus Infection and Disease during Pregnancy

Since the explosive outbreak of Zika virus in Brazil and South/Central America in 2015–2016, the frequency of infections has subsided, but Zika virus remains present in this region as well as other tropical and sub-tropical areas of the globe. The most alarming aspect of Zika virus infection is its association with severe birth defects when infection occurs in pregnant women. Understanding the mechanism of Zika virus pathogenesis, which comprises features unique to Zika virus as well as shared with other teratogenic pathogens, is key to future prophylactic or therapeutic interventions. Nonhuman primate-based research has played a significant role in advancing our knowledge of Zika virus pathogenesis, especially with regard to fetal infection. This review summarizes what we have learned from these models and potential future research directions.

Severe fetal anaemia caused by congenital cytomegalovirus infection

A 22-year-old pregnant woman was referred to our fetal medicine unit due to severe fetal growth restriction at 26 weeks of gestation. An extensive detailed ultrasound revealed signs of bilateral periventricular hyperechogenicity, suggesting fetal infection potentially due to cytomegalovirus (CMV). Doppler ultrasound showed a high peak systolic velocity in the middle cerebral artery. Percutaneous umbilical cord blood sampling confirmed fetal CMV infection and severe fetal anaemia. We present this case to highlight the importance of fetal anaemia, which can be fatal regardless of whether it is associated with generalised oedema or hydrops fetalis.

Risk assessment of intrauterine infection in pregnant women with chronic hepatitis B

Purpose — to develop a method for predicting intrauterine fetal infection in pregnant women with CHB, infected and uninfected HIV, which provides the high accuracy of prognosis, is simple and accessible in practice and is achieved by analyzing multiple risk factors for mother-to-fetus transmission. Materials and methods. The course and consequences of pregnancy were analyzed in 211 women with chronic hepatitis B (CHB), not infected with HIV and in 18 — with CHB infected with HIV. The replicative activity of the virus and the activity of the inflammatory process in the liver were evaluated. We studied the dynamics of indicators depending on the trimester of pregnancy, the degree of immunosuppression caused by HIV. The frequency of risk factors was determined by «case-control» studies, and the frequency of identified risk factors was calculated in the groups of mothers in whom CHB was transmitted to the child and in those in which it did not occur. The degree of influence of individual risk factors was determined by the value of relative risk (RR), determined by their 95% confidence interval (95% CI), the reliability of the results (p) according to the Student's t-test. Differences at p<0.05 were considered probable. Results. It is established that risk factors that contribute to intrauterine infection of the fetus are: maternal — viral load HBV >105 copies/ml in the third trimester, HIV infection, immunosuppression caused by HIV (CD4+ Т-lymphocytes <500 cells/μL), low adherence to antiretroviral therapy, maternal bad habits; fetal — intrauterine growth restriction, fetal distress; obstetric — premature placental abruption, preterm delivery, placental dysfunction, prolonged anhydrous interval, prelabor rupture of membranes. In pregnant women with CHB, each risk factor was assessed in points depending on the RR: those factors whose relative risk was highest — 5 points, those whose score was lower — 4 and 3 points, respectively, and those whose score was the lowest — in 2 points. In order to predict the risk of fetal infection, a working prognostic chart with a score from 2 to 5 was developed. It was found that the risk of HBV infection in women with HIV-negative status is high with a score of 19–34, moderate — at 18–11, low — <10 points. In women with HIV-positive status — high risk of fetal intrauterine infection at a score of 24–46, moderate — at 13–23, low — <12 points. Conclusions. The use of the proposed prognostic map in the practice of medical institutions with a score of total risk factors for each pregnant woman will facilitate early prediction of fetal infection in pregnant women with CHB, taking into account their HIV status, which will allow to diagnose timely congenital infections and provides outpatient observation for these children. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: pregnant women, chronic hepatitis B, co-HIV infection, risk factors for intrauterine infection of the fetus.

Refinement of uterine fragment sampling in experimental studies using small ruminants: from leptospirosis to beyond

Ruminant genital leptospirosis is a particular syndrome, in which leptospires remain lodged in the organs of the reproductive tract causing inflammatory changes and/or embryonic/fetal infection resulting in significant reproductive losses. To collect uterine biopsies from small ruminants, surgeries that are costly and time-consuming, causing injury to the animals, are used. In this article, we describe the technique used of videolaparotomy and we dazzle a satisfactory result, with the collected material and the animal welfare. The animals recovered faster and no antibiotics were needed, improving animal welfare. From the technique of collecting the uterine fragment by videolaparoscopy, it was possible to obtain a biological material of high quality, providing also a shorter handling time for animals, less invasive, lower cost and obtaining the same results as a surgery. This is related to ethical principles, particularly with the third of the 3Rs, Refinement, minimizing potential pain and distress and enhance animal welfare.

Literature Review: Transplacental Transmission of COVID-19 and Its Teratological Aspect

Coronavirus disease 2019 (Covid-19) pandemic affects all populations, including pregnant women. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in pregnancy needs to be a concern because of the risk of transplacental transmission to the fetus and the potential to interfere with fetal development. The objective of this study is to review the transplacental transmission of COVID-19 and the teratological aspects of the event. This article is a literature study. Based on the literature obtained, placental infection, vertical transmission, and fetal infection have been identified in some cases. However, there is still no consistent and enough scientific evidence to show that those condition causes fetal damage or causes congenital anomalies. Virus and host characteristics are thought to explain why SARS-Cov-2 infection has not shown a teratological effect. SARS-CoV-2, similar to severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) infection, does not indicate maternal-fetal transmission. The low-level expression of angiotensin-converting enzyme 2 (ACE2) and S protein priming proteases type II transmembrane serine protease (TMPRSS 2) in the placenta is also considered to be the factor that plays a role in inhibiting the vertical transmission of COVID-19. Adverse outcome of fetal death is more due to pathophysiological conditions of maternal health caused by SARS-CoV-2 infection during gestation.