Fetal Infection Research Articles

Congenital syphilis confirmed by PCR as a result of treatment failure for syphilis in pregnancy. Case report

Introduction: Congenital syphilis is a major public health problem, and early diagnosis and treatment are necessary to prevent it. Penicillin G benzathine is the treatment of choice in pregnant women; however, it may fail to prevent fetal infection, as in the present case. Case presentation: Male newborn, son of an HIV negative mother with gestational syphilis (venereal disease research laboratory (VDRL) 1:4 dilution, positive treponemal test) diagnosed at week 21 of gestation and treated with three doses of 2 400 000 IU of penicillin G benzathine. At delivery, the mother presented VDRL 1:1 dilution. The newborn was diagnosed with congenital syphilis due to VDRL 1:4 dilution, positive treponemal test, elevated aspartate aminotransferases, hyposthenuria, proteinuria, hematuria, and leukocyturia that resolved after treatment with crystalline penicillin for 10 days. The molecular testing in blood showed a high treponemal load. The VDRL test at 3 months was non-reactive. Conclusions: Preventing congenital syphilis with the recommended treatment for gestational syphilis may fail. Moreover, diagnosing this condition in an asymptomatic newborn is difficult. Therefore, clinical and serological tests are recommended to confirm whether maternal treatment was effective in the fetus.

Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study

PurposeEvaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20+0 weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection.MethodsA retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results.ResultsA total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19+3 (13+0–31+4) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20+0 weeks of gestation.ConclusionIUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.

Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues.

Japanese encephalitis virus (JEV) is the emerging and geographically expanding flavivirus and the major causative agent of encephalitis in humans in Asia. There are risks of JEV introduction into the Americas given a large population of amplifying hosts—pigs and wild boars, and insect vectors—Culex mosquitoes. There are emerging concerns about vector-free ways of flavivirus transmission, for example sexual and transplacental Zika virus transmissions, which may change flavivirus epidemiology and expand the geographical range to territories with no insect vectors. It is unknown whether JEV has tropism in the female lower reproductive tract and the potential for sexual transmission in humans. While clinical outcomes of transplacental JEV infection are described in humans and pigs, cellular targets and tissue tropism in the upper reproductive tract are also unknown. Here, we studied JEV infection phenotypes and host transcriptional responses in human reproductive epithelial cells. We found that JEV caused persistent infection and cytopathology in the vaginal epithelium, endometrial epithelium, and trophoblast. Human vaginal epithelial cells infected with JEV had altered transcriptional responses associated with inflammation and disruption of epithelial barrier function. Also, using pigs—the native amplifying host for JEV, we confirmed JEV tropism in the female lower and upper reproductive tracts. We discovered that JEV persists in the vaginal mucosa for at least 28 days and pigs shed the virus in vaginal secretions. We also found JEV persistence in the endometrium and placenta with transplacental and fetal infections. Altogether, we discovered that JEV targets the vaginal epithelium and has the potential for sexual transmission in humans. We also contributed to a better understanding of JEV pathogenesis during transplacental infection. Further studies are needed to better understand the interactions of JEV with reproductive tissues, how persistent infection affects female reproductive functions, and the risks for non-vector transmission.

Faktor-Faktor yang Berhubungan dengan Terjadinya Ketuban Pecah Dini (KPD) di Rumah Sakit Muhammadiyah Palembang Tahun 2021

WHO said cases of premature rupture of membranes ± 5-10% of the total births. PROM in preterm cases is 1% and term pregnancies are 22% of the total pregnancies. Premature rupture of membranes is the rupture of the membranes before the time of delivery that occurs at the end of pregnancy or before. Factors causing PROM are divided into general factors, heredity factors, and obstetric factors. This study aims to determine the relationship between fetal position abnormalities, multiple pregnancies, parity and infection with premature rupture of membranes at Palembang Muhammadiyah Hospital in 2021. Analytical survey research with a Cross Sectional approach. All mothers giving birth at term who were treated at the Palembang Muhammadiyah Hospital in January-May 2021, totaling 965 were used as the population and a sample of 91 mothers were taken using simple random sampling technique. The primary data used was then analyzed by univariate and bivariate analysis by chi square test. The results showed that there was a relationship between fetal position abnormalities (Pvalue = 0.031), multiple pregnancy (Pvalue = 0.001), parity (Pvalue = 0.031) and infection (Pvalue = 0.018) with premature rupture of membranes at Muhammadiyah Hospital Palembang in 2021. It is expected from the results of the study. This can be an illustration for the hospital to further improve health services, especially dealing with the incidence of premature rupture of membranes.

Reactivation and Foetal Infection in Pregnant Heifers Infected with Neospora caninum Live Tachyzoites at Prepubertal Age.

Neospora caninum is recognised for causing cattle abortion, provoking severe economic losses in the livestock industry worldwide. The aim of the present study was to evaluate the reactivation and foetal infection in pregnant heifers inoculated with live N. caninum tachyzoites before puberty. A total of 15 30-month-old pregnant heifers were allocated into four groups: animals inoculated with live tachyzoites of NC-Argentina LP1 isolate before puberty and challenged with live tachyzoites of NC-1 strain at 210 days of gestation (DG) (Group A); animals mock inoculated before puberty and challenged with NC-1 strain at 210 DG (Group B), animals inoculated before puberty but not subsequently challenged (Group C); and noninfected and nonchallenged animals (Group D). The results of this study showed that 100% of animals infected before puberty (Groups A and C) suffered reactivation of the infection at the seventh month of gestation. In addition, in three and two calves from Groups A and C, respectively, congenital infection was confirmed. Interestingly, we provide evidence that the use of live N. caninum tachyzoites in young animals as a strategy to induce protection is neither safe nor effective.

Ultrasound Findings of Fetal Infections: Current Knowledge

Infectious diseases during pregnancy are still a major cause of fetal mortality and morbidity worldwide. The most common teratogenic pathogens are cytomegalovirus (CMV), varicella-zoster virus (VZV), rubeovirus, parvovirus B19, herpes simplex virus (HSV), Toxoplasma gondii, Treponema pallidum and the emergent Zika virus (ZIKV). Ultrasound findings include cerebral anomalies, orbital defects, micrognathia, cardiac defects, hepatosplenomegaly, liver calcifications, abdominal anomalies, skin and limb anomalies, edema, placental and amniotic fluid anomalies and altered Doppler analyses. The classification of ultrasound markers of congenital infections by anatomical region is reported to guide differential diagnosis and prenatal care.

Public Health Surveillance and Reporting for Human Toxoplasmosis - Six States, 2021.

Toxoplasmosis is caused by infection with the zoonotic parasite Toxoplasma gondii. Although disease tends to be mild (e.g., self-limiting influenza-like symptoms) or asymptomatic in immunocompetent persons, toxoplasmosis is more severe in immunocompromised persons, who can develop potentially fatal encephalopathy (1). In addition, primary infections acquired during pregnancy might result in a range of adverse outcomes, including fetal ocular infection, cranial and neurologic deformities, stillbirth, and miscarriage (1,2). An estimated 11% of the U.S. population aged ≥6 years are seropositive for toxoplasmosis, based on analysis of sera collected through the National Health and Nutrition Examination Survey during 2011-2014 (3). Toxoplasmosis is not a nationally notifiable disease in the United States, and currently no national public health surveillance data are available; however, it is reportable in eight states. To better understand how surveillance data are collected and used, reviews of state-level toxoplasmosis surveillance were conducted during June-July 2021 using semistructured interviews with health officials in six states (Arkansas, Kentucky, Minnesota, Nebraska, Pennsylvania, and Wisconsin) where toxoplasmosis is currently reportable. Why or when toxoplasmosis became reportable could not be determined, and many of the states had limited capacity to respond to reported cases. Case definitions varied considerably in terms of clinical description, laboratory criteria, and case classification (i.e., confirmed, probable, or suspect), limiting disease estimates and comparisons among states. Implementation of a standardized case definition would help ensure that cases are counted consistently, enabling better use of surveillance data to characterize disease. Identifying newly acquired cases is challenging because most acute cases among immunocompetent persons (including pregnant women) are asymptomatic, disease among immunocompromised persons is likely reactivation of latent disease, and congenital infections might not manifest until later in life.

Investigation of Campylobacter fetus in breeding bulls of private farms in Bangladesh.

Bovine genital campylobacteriosis (BGC) is a venereal disease caused by Campylobacter fetus that has a negative impact on animal reproduction. The bull is considered to be a symptomless carrier that spreads the disease agent to breeding cows, causing infertility and sporadic abortion. The study aims to estimate the prevalence, identify risk factors of Campylobacter fetus (C. fetus) infection and antimicrobial resistance pattern of the C. fetus isolates. A cross-sectional survey was conducted in Mymensingh district of Bangladesh. Bull smegma samples (single sample from each bull) were collected from 300 bulls from four farms and tested via culture, biochemical identification and finally 16S rRNA and cdtA gene-based molecular assays (PCR) for herd and animal-level prevalence estimation. Herd- and animal-level data on risk factors were collected from the farmers using a pretested questionnaire and analysed by univariable and multivariable logistic regression models with a p value of <0.05 was taken statistically significant for both analyses. Among the surveyed farms, 75% (95% CI: 19.4%-99.4%) were confirmed to have bulls infected with Campylobacter fetus at herd level. However, animal-level occurrence of C. fetus was estimated to be 8.7% (26/300) (95% CI: 5.7%-12.4%). Natural service increases the odds of campylobacteriosis 38.18 times (95% CI: 13.89-104.94) in comparison to artificial insemination for C. fetus infection in bulls. Significantly, half of the isolates (50%, n = 13) were identified to be multidrug resistant (MDR) for three to five antimicrobial agents. This study highlights the need to develop official guidelines for C. fetus control and prevention in Bangladesh including mandatory artificial insemination in reproductive cows and heifers, routine screening of breeding bulls for C. fetus free status.

Enhancement of Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts Under Low-Glucose Stress Conditions.

Rubella virus (RuV) infections in pregnant women, especially first-trimester infections, can lead to congenital rubella syndrome (CRS). However, the mechanisms of fetal RuV infection are not completely understood, and it is not observed in every pregnant woman infected with RuV. As gestational diabetes mellitus is a risk factor for congenital viral infections, we investigated the possible roles of hypoglycemia-related endoplasmic reticulum (ER) stress as a key factor for vertical RuV infection using immortalized human first-trimester trophoblasts. Low-glucose stress was induced prior to RuV infection by culturing HTR-8/SVneo and Swan.71 cells in low-glucose (LG) medium for 24 h or high-glucose medium for 6 h and then LG medium for an additional 18 h. Clinically isolated RuV was inoculated at a multiplicity of infection of 5 to 10. The intracellular localization of the RuV capsid protein was investigated 24 to 48 h post-infection (pi) with flow cytometry (FCM) analysis and fluorescence microscopy. Viral progeny production was monitored by FCM analysis. Increases in RuV infection in LG-induced ER-stressed trophoblasts were observed. No significant increase in apoptosis of RuV-infected cells was noted at days 2 and 5 pi, and substantial viral progeny production was observed until day 5 pi. An approximate fivefold increase in viral binding was noted for the LG-stressed cells. Although the detailed mechanisms underlying viral entry into LG-stressed cells are not known and require further investigation, these findings suggest that a certain degree of LG stress in early pregnancy may facilitate infection and cause CRS.

Congenital Toxoplasmosis: The State of the Art.

Infection with the protozoan parasite Toxoplasma gondii occurs worldwide and usually causes no symptoms. However, a primary infection of pregnant women, may infect the fetus by transplacental transmission. The risk of mother-to-child transmission depends on week of pregnancy at the time of maternal infection: it is low in the first trimester, may reach 90% in the last days of pregnancy. Inversely, however, fetal disease is more severe when infection occurs early in pregnancy than later. Systematic serologic testing in pregnant women who have no antibodies at the beginning of pregnancy, can accurately reveal active maternal infection. Therefore, the risk of fetal infection should be assessed and preventive treatment with spiramycin must be introduced as soon as possible to reduce the risk of mother-to-child transmission, and the severity of fetal infection. When maternal infection is confirmed, prenatal diagnosis with Polymerase Chain Reaction (PCR) on amniotic fluid is recommended. If fetal infection is certain, the maternal treatment is changed to a combination of pyrimethamine-sulfonamide and folinic acid. Congenitally infected newborns are usually asymptomatic at birth, but at risk for tardive sequelae, such as blindness. When congenital infection is evident, disease include retinochoroiditis, cerebral calcifications, hydrocephalus, neurocognitive impairment. The diagnosis of congenital infection must be confirmed at birth and management, specific therapy, and follow-up with multidisciplinary counseling, must be guaranteed.

COVID-19-associated pathological changes in placentae of third-trimester pregnant women

Background and aim Recently, many instances of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [coronavirus disease 2019 (COVID-19)] placental invasion in late pregnancy have been reported, and this is still not completely clear. Controversy data are sequentially published, so more studies are needed to investigate placental pathology as it gives vital information on placental changes, mechanisms of maternal–fetal infection transmission, and viral effects on the placenta as inflammatory or vascular changes. We aimed to find out the placental pathological changes in term placentae and to detect SARS-CoV-2 RNA in specimens fixed in formalin and embedded in paraffin. Patients and methods A total of 30 placentae were obtained from COVID-19-infected pregnant women. They were examined for pathological changes by histopathology; immunohistochemistry for CD3, CD20, CD15, CD68, angiotensin-converting enzyme 2, cytokeratin, and PDL-1; and reverse transcription-PCR to recognize viral RNA. Results According to the COVID-19 status at the delivery time, four groups were identified. Group 1 (12 patients with COVID-19 at the delivery time) showed chronic villitis and placental maternal and fetal malperfusion. Group 2 (seven cases that turned negative by PCR of the nasopharyngeal swab prior to delivery by 5–8 days) showed maternal malperfusion but no villitis. Both groups were SARS-CoV-2 RNA positive by PCR of the nasopharyngeal swab. Group 3 (five cases that turned negative 1 day before delivery) showed maternal–fetal malperfusion and mild chronic subchorionitis and deciduitis. Only three had SARS-CoV RNA. Group 4 (six cases with a persistent negative swab for 20 days before delivery) showed focal villitis (much less than other groups) and maternal malperfusion. Only two had SARS-CoV-2 RNA. Immunophenotyping of cases in the four groups detected mixed inflammatory infiltrate with variable diffuse angiotensin-converting enzyme 2 immunostaining of villus and extravillous trophoblasts. Cytokeratin staining detected thinning and discontinuity of syncytiotrophoblast and strong PD-L1 expression was seen in villitis areas. Conclusion SARS-CoV-2-positive women exhibited a diverse range of results; thus, pregnant women should not be considered a homogeneous group as outcomes are dependent on a multitude of interdependent circumstances.

A Systematic Review of Maternal TORCH Serology as a Screen for Suspected Fetal Infection

(Abstracted from Prenat Diagn 2022;42:87–96) “TORCH” is an acronym describing a group of congenital infections that can cause significant risk for perinatal morbidity and mortality; these infections include toxoplasmosis, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV). However, although a TORCH serology panel is often ordered during pregnancy, the diagnostic yield of this approach continues to be questioned.

Antiviral medication to prevent fetal transmission of maternal CMV during pregnancy

Background. Cytomegalovirus infection represents the most frequent congenital viral infection, with serious consequences on newborns. Neurosensorial hearing loss is the principal outcome, but also, the infection can cause other central nervous system’s anomalies. Although CMV infection can have a major impact on fetal development, there are not clear directions to follow yet, to prevent or treat this condition. Therefore, our purpose with this paper is to update the knowledge regarding the treatment options in order to prevent fetal transmission of maternal CMV infection, based on the latest data from the specialized literature in this field. Methods. Electronic research and analysis of the relevant articles published mainly in the last 5 years were performed, consulting the web platforms PubMed, ScienceDirect, Mendeley and ClinicalTrials.gov. Results and conclusions. To date, there is not enough evidence to reach a consensus on therapeutic methods to prevent or to treat fetal CMV infections and, as a consequence, antenatal screening is not justified. Many pharmaceutical companies work on vaccines to prevent CMV infection, but the results are only from studies’ second phase. Information on efficiency of hyperimmunoglobulin is mixt and it is necessary to clarify the dosage. Among antiviral agents, valaciclovir, which was studied in recent clinical trials, seems to have the best efficiency to prevent fetal transmission of maternal CMV infection and the best safety profile. Valganciclovir has possible embryotoxic effects, but higher potency and information on it are available only from case reports. The interest of scientific community on this topic is high, thus many studies are underway to bring new clarifications.

O-054 COVID-19 during pregnancy, maternal immune response and neonatal cell-specific immunity

Pathogens are a major threat to maternal health and the progression of pregnancy. The immune response during normally progressing pregnancies, primarily the suppression of inflammation, likely accounts for this high susceptibility of pregnant women to infections. An increased morbidity and mortality related to influenza, COVID-19 and malaria has been reported for pregnant women, compared to non-pregnant women. Especially influenza infections during pregnancy have been well studied, as humans are severely and recurrently affected by seasonal epidemics and random pandemics. Besides severe maternal symptoms such as acute cardiopulmonary events, pneumonia, and acute respiratory distress syndrome, maternal influenza infection also causes foetal complications, such as intrauterine growth restriction, preterm birth or even foetal death. However, vertical transmission of the influenza virus across the placenta and infection of the foetus has not been observed, suggesting that the pregnancy pathologies are maternally derived.In addition to influenza-mediated adverse conditions, the recent COVID-19 pandemic has underscored that infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) can also lead to severe illnesses in pregnant women, accompanied by a higher risk for foetal loss or preterm birth. Fortunately, with the ongoing pandemic, large cohort studies and meta-analyses revealed that vertical transmission and related fetal infection is a rare complication affecting only 1-3% of SARS-CoV-2 infections in pregnancy. These low risk for placental infection is likely due to the inefficient SARS-CoV-2 virus replication in placental tissues. Since understanding SARS-CoV-2-related pathogenicity during pregnancy is highly relevant, we initiated a study early in 2020, to which we have recruited more than 160 pregnant women with COVID-19. Our comprehensive placental analyses unearthed a paucity of SARS-CoV-2 viral expression ex vivo in term placentae under acute infection and in convalescent pregnant women. Furthermore, we could show inefficient SARS-CoV-2 replication in placental tissues in vitro, which provides a rationale for the low ex vivo viral expression. We detected specific SARS-CoV-2 T cell responses in mothers within a few days upon infection, which is undetectable in cord blood. Reports by others have shown that maternal SARS-CoV-2 during pregnancy may cause placental insufficiency, defined by increased perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. These changes can cause extensive placental damage leading to placental malperfusion and insufficiency that is incompatible with intrauterine survival. Considering that multiple SARS-CoV-2 variants of concern which emerged until today may affect pregnant women differently and bear a differential risk for pregnancy complication. This, continuous vigilance is needed in order to provide best protection of the highly vulnerable group of pregnant women and their unborn children.Trial registration number

Detection of PRRSV-2 alone and co-localized with CD163 positive macrophages in porcine placental areolae

The porcine epitheliochorial placenta creates a barrier for the transplacental transfer of some nutrients from the dam to the fetus, as well as feto-lethal viruses such as porcine reproductive and respiratory syndrome virus 2 (PRRSV-2). Areolae are specialized structures within the porcine placenta with a high absorptive and substance transport capacity that facilitate embryonic development. The overarching aim of this study was to characterize the localization of PRRSV-2 in and adjacent to areolae to provide insight into whether transplacental transmission might occur through placental areolae. Control (CON) plus three phenotypic fetal groups were selected based on levels of virus in fetal placenta, sera and thymus, to determine if fetal resilience was related to differences in PRRSV-2 localization, alone or co-localized with CD163+ macrophages. These fetal groups represented a range of susceptibility: uninfected (UNINF) being resistant, infected in placenta only (PLCO) being resilient, and high viral load viable (HVL-VIA) being most susceptible. Finally, potential factors related to PRRSV-2 localization, including the severity of inflammation in endometrium and placenta, and intrauterine growth restriction, known resilience factors, were assessed. Thirty-one pregnant gilts were inoculated with PRRSV-2 at gestation day 86 ± 0.4. Seven pregnant gilts were sham-inoculated. Gilts were euthanized at 12 days post-infection. Presence of PRRSV and CD163+ macrophages were determined using immunofluorescence in cryosections of maternal-fetal interface (MFI) with and without areolae. In the maternal, fetal and cavity of areolar region PRRSV particles were found both independently and co-localized with CD163+ macrophages. Similarly, individual, and co-localized particles were observed in the maternal and fetal sides of the MFI region of infected fetuses. Weak positive correlations were observed between the counts of CD163+ macrophages and some inflammation scores in endometrial and placental tissues, but no correlations with PRRSV-2 localization. There were no differences across the four fetal groups evaluated. These results suggest that transplacental transmission of PRRSV may occur through the areolae, either as non-cell associated or in association with infected CD163 macrophages.

Understanding the Immune System in Fetal Protection and Maternal Infections during Pregnancy.

The fetal-maternal immune system determines the fate of pregnancy. The trophoblast cells not only give an active response against external stimuli but are also involved in secreting most of the cytokines. These cells have an essential function in fetal acceptance or fetal rejection. Other immune cells also play a pivotal role in carrying out a successful pregnancy. The disruption in this mechanism may lead to harmful effects on pregnancy. The placenta serves as an immune barrier in fetus protection against invading pathogens. Once the infections prevail, they may localize in placental and fetal tissues, and the presence of inflammation due to cytokines may have detrimental effects on pregnancy. Moreover, some pathogens are responsible for congenital fetal anomalies and affect almost all organs of the developing fetus. This review article is designed to address the bacterial and viral infections that threaten pregnancy and their possible outcomes. Moreover, training of the fetal immune system against the exposure of infections and the role of CD49a + NK cells in embryonic development will also be highlighted.

#73 Single Cell RNA Sequencing of Zika Infection in Neural Tissues Reveals an Astrocyte-Driven Innate Immune Response Governed by Interferon Beta.

Abstract Background Congenital infection with Zika virus (ZIKV) has been linked to severe of fetal brain disruption and other developmental anomalies referred to collectively as congenital Zika syndrome (CZS). Long-term follow up of ZIKV-exposed infants has shown that even those without overt findings of CZS can have significant cognitive and developmental difficulties. However, the pathogenesis of ZIKV-related microcephaly and cognitive dysfunction remain poorly understood. To begin answering these questions, we sought to define the consequences of ZIKV infection on specific cell types in the developing brain. Method We have used primary human fetal brain cultures and human induced pluripotent stem cell-derived neural progenitor cell lines to probe innate immune signaling to ZIVK infection in vitro. We used single-cell RNA sequencing (10x Genomics) to identify the cell type-specific transcriptional changes induced by ZIKV infection. Results We found that neural progenitor cells (NPCs) support higher ZIKV RNA copy number than do differentiated neural cells. Moreover, while IFN-β is the predominant cytokine released by differentiated cells in response to ZIKV infection, NPCs do not produce IFN-β. By additionally characterizing the transcriptional response to IFN-β treatment, we have been able to distinguish virus-stimulated genes (VSGs) from interferon-stimulated genes (ISGs) across cell types. We find extensive heterogeneity in cell type-specific VSG and ISG profiles. Astrocytes undergo the largest transcriptional changes in response to infection and are the main producers of IFN-β. Our findings also identify genes whose expression is altered during viral infection specifically in NPCs and neurons, providing candidate pathways that may underlie neural dysfunction. Conclusion Across cell types, the response to Zika infection closely matches the response to IFN-β, arguing that astrocyte-derived IFN-β is the main driver of the innate immune response to ZIKV in the developing brain. Our findings provide insight into the pathogenesis of CZS and offer novel targets for improving developmental outcomes after fetal ZIKV infection.

Infections and Pregnancy: Effects on Maternal and Child Health.

Pregnancy causes physiological and immunological adaptations that allow the mother and fetus to communicate with precision in order to promote a healthy pregnancy. At the same time, these adaptations may make pregnant women more susceptible to infections, resulting in a variety of pregnancy complications; those pathogens may also be vertically transmitted to the fetus, resulting in adverse pregnancy outcomes. Even though the placenta has developed a robust microbial defense to restrict vertical microbial transmission, certain microbial pathogens have evolved mechanisms to avoid the placental barrier and cause congenital diseases. Recent mechanistic studies have begun to uncover the striking role of the maternal microbiota in pregnancy outcomes. In this review, we discuss how microbial pathogens overcome the placental barrier to cause congenital diseases. A better understanding of the placental control of fetal infection should provide new insights into future translational research.

Necrotizing funisitis associated with Ureaplasma urealyticum infection: A clinicopathologic analysis of 14 cases

IntroductionNecrotizing funisitis is a distinct lesion of the umbilical cord associated with chorioamnionitis and bloodborne fetal infection. The lesion may be a response to microorganisms in Wharton's jelly. A common microorganism detected in chorioamnionitis is Ureaplasma urealyticum (U. urealyticum). This study hypothesizes that U. urealyticum DNA will be present in Wharton's jelly in necrotizing funisitis. MethodsNecrotizing funisitis was identified retrospectively from a 2-year pathology database and confirmed in review. Paraffin fixed embedded tissue sections of the lesion were prepared for polymerase chain reaction (PCR) by using primers to identify U. urealyticum. Twenty matched controls without funisitis were similarly processed. Clinical data included serological tests of common bloodborne infections in the mothers and infants, and U. urealyticum PCR results in the urine of the neonates. ResultsFourteen cases of necrotizing funisitis were identified in 7,416 examined placentas. Nine of these umbilical cords were positive by PCR for U. urealyticum (64.3%). Nineteen of twenty control cases were negative. Eight of ten neonates (80%) also had positive urine PCR tests for U. urealyticum. No infants or mothers had evidence of bloodborne fetal infection. DiscussionU. urealyticum DNA was present in Wharton's jelly by PCR testing in the majority of the necrotizing funisitis lesions tested. This result supports a possible causative role for U. urealyticum in many cases of necrotizing funisitis.

Stillbirth due to SARS-CoV-2 placentitis without evidence of intrauterine transmission to fetus: association with maternal risk factors.

ObjectivesTo describe the placental pathology, fetal autopsy findings and clinical characteristics of pregnancies that resulted in stillbirth owing to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) placentitis, and to identify potential risk factors.MethodsThis was a prospective multicenter study of non‐vaccinated pregnant women affected by coronavirus disease 2019 (COVID‐19) in Greece from April 2020 to August 2021. A total of 165 placentas were examined histologically and six cases of stillbirth associated with SARS‐CoV‐2 placentitis were retrieved. Complete fetal autopsy was performed in three of these cases. Gross, histopathological, immunohistochemical, molecular and electron microscopy examinations were carried out in the stillbirth placentas and fetal organs. The histological findings of cases with SARS‐CoV‐2 placentitis were compared with those in 159 cases with maternal COVID‐19 which resulted in a live birth. Regression analysis was used to identify predisposing risk factors for SARS‐CoV‐2 placentitis.ResultsThe placentas of all six stillborn cases showed severe and extensive histological changes typical of SARS‐CoV‐2 placentitis, characterized by a combination of marked intervillositis with a mixed inflammatory infiltrate and massive perivillous fibrinoid deposition with trophoblast damage, associated with intensely positive immunostaining for SARS‐CoV‐2 spike protein, the presence of virions on electron microscopy and positive reverse‐transcription polymerase chain reaction test of placental tissues. The histological lesions obliterated over 75% of the maternal intervillous space, accounting for intrauterine fetal death. Similar histological lesions affecting less than 25% of the placenta were observed in seven liveborn neonates, while the remaining 152 placentas of COVID‐19‐affected pregnancies with a live birth did not show these findings. Complete fetal autopsy showed evidence of an asphyctic mode of death without evidence of viral transmission to the fetus. The mothers had mild clinical symptoms or were asymptomatic, and the interval between maternal COVID‐19 diagnosis and fetal death ranged from 3 to 15 days. Statistically significant predisposing factors for SARS‐CoV‐2 placentitis included thrombophilia and prenatally diagnosed fetal growth restriction (FGR). Multiple sclerosis was seen in one case.ConclusionsSARS‐CoV‐2 placentitis occurred uncommonly in COVID‐19‐affected pregnancies of non‐vaccinated mothers and, when extensive, caused fetal demise, with no evidence of transplacental fetal infection. Thrombophilia and prenatally detected FGR emerged as independent predisposing factors for the potentially lethal SARS‐CoV‐2 placentitis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.