Recurrent congenital cytomegalovirus infection in a sequential pregnancy with severe sequelae, and a possible association with prophylactic valacyclovir treatment: a case report.

Recurrent congenital cytomegalovirus infections in consecutive pregnancies are rarely reported. Due to the risk of fetal infection from preconception maternal infection, a 6-month interval after primary maternal infection is generally advised before a new conception. Recently, high-dose valacyclovir treatment was shown to prevent fetal infection in first trimester primary infections. We present a case of first trimester primary infection treated with high-dose valacyclovir but resulting in polymerase chain reaction-confirmed fetal infection. Cytomegalovirus-specific immunoglobulin G titers remained very low during treatment and rose only after cessation of antiviral treatment. Six months after primary seroconversion, in a sequential pregnancy, recurrent fetal infection was diagnosed and resulted in severe fetal sequella. Whole genome sequencing of both amniotic fluid isolates proved them to be identical. Both pregnancies were terminated. We hypothesize that valacyclovir treatment, although unsuccessful in preventing fetal infection, had delayed the adaptive maternal immune response and might have contributed to fetal infection during the sequential pregnancy. We suggest that a longer delay might be warranted after valacyclovir treatment and before a new conception.

[Cytomegalovirus screening during pregnancy : an ongoing debate still in 2022]. / Dépistage du cytomégalovirus pendant la grossesse : toujours débattu en 2022.

Cytomegalovirus infection remains the main congenital infectious cause of abnormal development, notably neurological or auditory. In case of early maternal infection, vertical transmission is lower than later in pregnancy, but fetal/neonatal sequelae are more frequent and severe. Until recently, there was no available treatment to prevent transmission and complications and only preventive measures were recommended. Based on a recent literature review, we will discuss the possible indication for CMV screening before conception and/or in the first trimester of pregnancy, in order to improve patient's information, prevention and treatment.

Le cytomégalovirus constitue la première cause infectieuse congénitale d'anomalie du développement, notamment aux niveaux neurologique et auditif. En cas d'infection maternelle précoce, le risque de transmission verticale est moindre que plus tard durant la grossesse, mais les séquelles fœtales/néonatales sont plus sévères. Jusqu'à présent, il n'existait pas de traitement efficace et seules les mesures de prévention primaire permettaient de combattre cette infection. Après une revue critique de la littérature récente, nous proposons de discuter l'intérêt d'un dépistage précoce en préconceptionnel et/ou au premier trimestre de la grossesse afin de permettre la mise en place des mesures de prévention et également l'introduction d'un traitement préventif/thérapeutique si nécessaire.

Lack of Fetal Protection against Bovine Viral Diarrhea Virus in a Vaccinated Heifer.

The aim of the report was to present the circulation of BVDV (bovine viral diarrhea virus) in the cattle population and determine the cause of the failure of vaccination failure leading to the birth of the PI (persistently infected) calf. The case study was carried out at the BVDV-free animal breeding center and cattle farm, where the vaccination program against BVDV was implemented in 2012, and each newly introduced animal was serologically and virologically tested for BVDV. In this case, a blood sample was taken from a 9-month-old breeding bull. Positive RT-PCR and negative ELISA serology results were obtained. The tests were repeated at 2-week intervals, and the results confirmed the presence of the virus and the absence of specific antibodies, i.e., persistent infection. Additionally, sequencing and phylogenetic analysis were performed, and the BVDV-1d subgenotype was detected. The results of this study showed that pregnant heifers and cows that are vaccinated multiple times with the killed vaccine containing BVDV-1a may not be fully protected against infection with other subgenotypes of BVDV, including their fetuses, which can become PI calves.

Fit mothers for a healthy future: Breaking the intergenerational cycle of non-alcoholic fatty liver disease with maternal exercise.

SPECIAL ISSUE: 'FOIEGRAS-Bioenergetic Remodelling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease'. BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non-pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases. METHODS: Following detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed. RESULTS: PE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles-metabolic, endocrine and epigenetic-could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances. CONCLUSIONS: The better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.

A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).

Secondary prevention of congenital cytomegalovirus infection with valacyclovir following maternal primary infection in early pregnancy.

OBJECTIVE: Cytomegalovirus (CMV) maternal primary infection (MPI) in early pregnancy is the main risk factor for congenital CMV (cCMV) infection with long-term sequelae. Our aim was to evaluate, in a single center offering CMV serology screening at 11-14 gestational weeks, secondary prevention of cCMV by administration of high-dosage maternal oral valacyclovir (VACV) in the first trimester of pregnancy. METHODS: This was a case-control study in a longitudinal cohort of pregnancies with CMV-MPI diagnosed prior to 14 weeks of gestation by serology screening (immunoglobulin (Ig) M and IgG measurement and IgG avidity) between 2009 and 2020. From October 2019 onwards, all women presenting at our center with MPI before 14 weeks' gestation were offered treatment with high-dosage oral VACV (8 g/day, 4 g twice/day). We used propensity score matching to compare fetal infection rates in cases treated with maternal oral VACV (8 g/day) with those in untreated controls. Fetal infection was assessed following amniocentesis at 17-22 weeks of gestation, by polymerase chain reaction (PCR) analysis of amniotic fluid for viral DNA. RESULTS: Of 310 cases of CMV-MPI identified, 269 underwent amniocentesis for PCR. Of these, 66 were offered, and 65 accepted, treatment with VACV. From the remaining untreated cases, we selected 65 controls, matched for proportion of periconceptional infections and gestational age at amniocentesis. VACV was initiated at a median gestational age of 12.71 (interquartile range (IQR), 10.00-13.86) weeks and the median duration of treatment was 35 (IQR, 26-54) days. On multivariate logistic regression, fetal infection was lower in the treated group (odds ratio, 0.318 (95% CI, 0.120-0.841); P = 0.021). One treated patient developed acute renal failure 4 weeks after initiation of VACV therapy, but this resolved within 5 days after treatment was stopped. CONCLUSION: This study confirms the acceptability, tolerance and benefit of secondary prevention by VACV of cCMV infection in a clinical setting with a well-established routine maternal serum screening policy in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Intervención educativa en prevención preconcepcional de efectos embriofetales de la diabetes mellitus. Policlínico Universitario Carlos Verdugo, 2018-2019 / Educational intervention in preconceptional prevention of embryo fetal effects of diabetes mellitus. University Policlinic Carlos Verdugo, 2018-2019

RESUMEN Introducción: los efectos embriofetales derivados de la exposición a la diabetes mellitus, durante el período prenatal de la vida, se extienden a la etapa posnatal con importantes repercusiones para la salud, incluyendo el efecto transgeneracional de la enfermedad. Objetivo: evaluar la efectividad de una intervención educativa para incrementar el nivel de conocimientos en prevención preconcepcional de efectos embriofetales de la diabetes mellitus en mujeres en edad fértil, pertenecientes al Consultorio 1 del Policlínico Universitario Carlos Verdugo, del municipio Matanzas, entre enero de 2018 y diciembre de 2019. Materiales y métodos: se realizó un estudio de intervención que constó de tres etapas. Un universo de 198 mujeres en edad fértil pertenecientes al Consultorio 1 del Policlínico Universitario Carlos Verdugo, durante el período señalado. Se empleó la encuesta para medir factores de riesgo de diabetes mellitus y conocimientos de las féminas en prevención preconcepcional de los efectos embriofetales de la enfermedad. Resultados: la edad superior a 30 años y la presencia de sobrepeso u obesidad fueron los factores de riesgo más detectados. Resultó calificado de malo el nivel de conocimientos en prevención preconcepcional de efectos embriofetales de la diabetes, previo a la intervención. Conclusiones: después de la implementación del programa educativo, se elevó el conocimiento sobre prevención preconcepcional de efectos embriofetales de la diabetes mellitus en las mujeres en edad fértil del consultorio 1 del Policlínico Universitario Carlos Verdugo, del municipio Matanzas, lo que demostró su efectividad (AU).

ABSTRACT Introduction: the embryo-fetal effects derived of the exposition to diabetes mellitus during the prenatal period of the life, extend to the postnatal stage, with important repercussions for health, including the disease's transgenerational effect. Objective: to assess the effectiveness of an educational intervention for increasing knowledge on pre-conceptional prevention of embryo-fetal effects of diabetes mellitus in fertile-aged women belonging to Family Doctor's office 1, of the University Policlinic Carlos Verdugo, municipality of Matanzas, from January 2018 to December 2019. Materials and methods: an interventional study was carried out, divided into three stages. The universe were 198 fertile-aged women belonging to Family Doctor's office 1, of the University Policlinic Carlos Verdugo, during the stated period. A survey was used to measure diabetes mellitus risk factors and women's knowledge on pre-conceptional preventing the disease's embryo-fetal effects. Results: age over 30 and being overweight or obese were the most frequently found risk factors. The knowledge level on pre-conceptional preventing diabetes mellitus embryo-fetal effects was poor before the intervention. Conclusions: after implementing the educational program, knowledge on pre-conceptional prevention of diabetes mellitus embryo-fetal effects increased among fertile-aged women of the Family Doctor's 1, of the policlinic Carlos Verdugo, of the municipality of Matanzas, demonstrating its effectiveness (AU).

Leaf ethanolic extract of Etlingera hemesphaerica Blume mitigates defects in fetal anatomy and endochondral ossification due to mercuric chloride during the post-implantation period in Mus musculus.

This study aimed to investigate the effectiveness of leaf ethanolic extract of Etlingera hemisphaerica (LE3H) in reducing defects in fetal anatomy and endochondral ossification in mice induced by HgCl2 during the post-implantation period. Pregnant mice were divided into four groups, each consisting of 10 dams, and received drink and food ad libitum. The first group was administered LE3H (E1), the second one HgCl2 (E2), the third one HgCl2+LE3H (E3), and the fourth was control (E0), administered double-distilled water only. HgCl2 (5 mg/kg bw) was administrated by injection intraperitoneally on gestation day (GD)9 and LE3H (0.39 mg/g bw) was administered by gavage on GD10. The treated and control animals were killed by cervical dislocation on GD18, dissected, and the morphologically normal living fetuses (MNLF) were collected. The MNLF of E0, E1, E2, and E3 from 5 dams were fixed with Bouin solution, and observed using the free hand razor blade technique for soft tissue examination. The remaining MNLF were fixed with 96% ethanol, and then stained with Alizarin Red S and Alcian Blue for ossification examination. Index of length of ossified part (ILOP) of humerus, index of width of ossified part (IWOP) of humerus, ILOP of femur, and IWOP of femur were calculated. E2 had higher cases of anatomical defects (74,6%) than E3 (48.9%), E1 (15.0%), and E0 (0%). E2 had humerus IWOP of 0.82±0.03, which was significantly lower than that of E0 (0.89±0.04) and E1 (0.89±0.03), while that of E1 and E0 was not significantly different from each other. Meanwhile, IWOP in E3 (0.88±0.03) was significantly higher than that in E2, but not different from that in E1 and E0. Thus, LE3H mitigated defects in fetal anatomy and endochondral ossification induced by HgCl2 in mice.

Knowledge of Preconception Healthcare and Associated Factors: A Study among Mothers in Jinka Town, Southern Region, Ethiopia.

BACKGROUND: Preconception healthcare is promising to improve the reproductive health status of women and couples if they receive care three months to two years before conception. In the current context of Ethiopia, however, preconception healthcare is overlooked in the continuum of care. Therefore, this study aimed to assess the knowledge of preconception healthcare and associated factors: a study among mothers in Jinka town, southern region, Ethiopia. METHODS: A community-based cross-sectional study was employed among 522 randomly selected women of childbearing age who are living in Jinka town from March to April 2018. The study considers all the kebeles in the town. Study subjects were determined using proportionate-to-population size allocation. Then, a systematic random sampling technique was applied. Data were collected using a semistructured and pretested questionnaire. Descriptive summary data and binary logistic regression analysis were carried out to identify factors with the 95% confidence level and a p value of less than 0.05. RESULTS: A total of 513 study subjects participated in this study. The overall preconception healthcare knowledge score of women in Jinka town was 51.1%. In the multivariable analysis, housewives (AOR = 2.93; 95% CI: 1.38-6.19), an education level of at least college (AOR = 3.79; 95% CI: 1.75-8.23), no history of neonatal death (AOR = 4.13; 95% CI = 1.39-12.25), and the use of family planning methods (AOR = 2.38; 95% CI: 1.49-3.79) increased the probability of preconception healthcare knowledge compared to the counterparts. CONCLUSION: In this study, women's knowledge of preconception healthcare was found borderline. The identified factors were housewife, education level of at least college, no history of neonatal death, and using family planning methods. Therefore, emphasizing these factors for the enhancement of women's knowledge of preconception healthcare is a necessary step.

Melatonin for the prevention of fetal injury associated with intrauterine inflammation.

Intrauterine inflammation is shown to be associated with preterm birth, fetal inflammatory response syndrome, and other pregnancy-related comorbidities such as central nervous system diseases including cerebral palsy and periventricular leukomalacia, pulmonary diseases such as bronchopulmonary dysplasia and respiratory distress syndrome, and necrotizing enterocolitis, to name a few. Many animal studies on intrauterine inflammation demonstrate that ascending infection of reproductive organs or the production of proinflammatory cytokines by some stimuli in utero results in such manifestations. Melatonin, known for its primary function in maintaining circadian rhythm, is now recognized as one of the most potent antioxidant and anti-inflammatory drugs. In some studies, melatonin injection in pregnant animals with intrauterine inflammation significantly reduced the number of preterm births, the severity of structural disintegration of the fetal lungs observed in bronchopulmonary dysplasia, and perinatal brain injuries with improvement in neuromotor function. These implicated benefits of melatonin in pregnant women with intrauterine inflammation seem promising in many research studies, strongly supporting the hypothesis that melatonin has antioxidative and anti-inflammatory properties that can potentially be taken by pregnant women who are at risk of having intrauterine inflammation. In this review, the potential of melatonin for improving outcomes of the pregnancies with intrauterine inflammation will be discussed.

Maternal and fetal outcomes in phaeochromocytoma and pregnancy: a multicentre retrospective cohort study and systematic review of literature.

BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

Budesonide with surfactant decreases systemic responses in mechanically ventilated preterm lambs exposed to fetal intra-amniotic lipopolysaccharide.

BACKGROUND: Chorioamnionitis is associated with increased rates of bronchopulmonary dysplasia (BPD) in ventilated preterm infants. Budesonide when added to surfactant decreased lung and systemic inflammation from mechanical ventilation in preterm lambs and decreased the rates and severity of BPD in preterm infants. We hypothesized that the addition of budesonide to surfactant will decrease the injury from mechanical ventilation in preterm lambs exposed to intra-amniotic (IA) lipopolysaccharide (LPS). METHODS: Lambs at 126 ± 1 day GA received LPS 10 mg IA 48 h prior to injurious mechanical ventilation. After 15 min, lambs received either surfactant mixed with: (1) saline or (2) Budesonide 0.25 mg/kg, then ventilated with normal tidal volumes for 4 h. Injury markers in the lung, liver, and brain were compared. RESULTS: Compared with surfactant alone, the addition of budesonide improved blood pressures, dynamic compliance, and ventilation, while decreasing mRNA for pro-inflammatory cytokines in the lung, liver, and multiple areas of the brain. LPS caused neuronal activation and structural changes in the brain that were not altered by budesonide. Budesonide was not retained within the lung beyond 4 h. CONCLUSIONS: In preterm lambs exposed to IA LPS, the addition of budesonide to surfactant improved physiology and markers of lung and systemic inflammation. IMPACT: The addition of budesonide to surfactant decreases the lung and systemic responses to injurious mechanical ventilation preterm lambs exposed to fetal LPS. Budesonide was present in the plasma by 15 min and the majority of the budesonide is no longer in the lung at 4 h of ventilation. IA LPS and mechanical ventilation caused structural changes in the brain that were not altered by short-term exposure to budesonide. The budesonide dose of 0.25 mg/kg being used clinically seems likely to decrease lung inflammation in preterm infants with chorioamnionitis.

Melatonin for prevention of fetal lung injury associated with intrauterine inflammation and for improvement of lung maturation.

Inflammation is associated with injury to immature lungs, and melatonin administration to preterm newborns with acute respiratory distress improves pulmonary outcomes. We hypothesized that maternally administered melatonin may reduce inflammation, oxidative stress, and structural injury in fetal lung and help fetal lung maturation in a mouse model of intrauterine inflammation (IUI). Mice were randomized to the following groups: control (C), melatonin (M), lipopolysaccharide (LPS; a model of IUI) (L), and LPS with melatonin (ML). Pro-inflammatory cytokines, components of the Hippo pathway, and Yap1/Taz were analyzed in the fetal lung at E18 by real-time RT-qPCR. Confirmatory histochemistry and immunohistochemical analyses (surfactant protein B, vimentin, HIF-1ß, and CXCR2) were performed. The gene expression of IL1ß in the fetal lung was significantly increased in L compared to C, M, and ML. Taz expression was significantly decreased in L compared to C and M. Taz gene expression in L was significantly decreased compared with those in ML. Immunohistochemical analyses showed that the expression of HIF-1ß and CXCR2 was significantly increased in L compared to C, M, and ML. The area of surfactant protein B and vimentin were significantly decreased in L than C, M, or ML in the fetal and neonatal lung. Antenatal maternally administered melatonin appears to prevent fetal lung injury induced by IUI and to help lung maturation. The results from this study results suggest that melatonin could serve as a novel safe preventive and/or therapeutic medicine for preventing fetal lung injury from IUI and for improving lung maturation in prematurity.

Inhibition of Na+/K+ ATPase blocks Zika virus infection in mice.

Zika virus (ZIKV) is an infectious disease that has become an important concern worldwide, it associates with neurological disorders and congenital malformations in adults, also leading to fetal intrauterine growth restriction and microcephaly during pregnancy. However, there are currently no approved vaccines or specific antiviral drugs for preventing or treating ZIKV infection. Here, we show that two FDA-approved Na+/K+-ATPase inhibitors, ouabain and digoxin, can block ZIKV infection at the replication stage by targeting Na+/K+-ATPase. Furthermore, ouabain reduced the viral burden of ZIKV in adult mice, penetrated the placental barrier to enter fetal tissues, and protected fetal mice from ZIKV infection-induced microcephaly in a pregnant mouse model. Thus, ouabain has therapeutic potential for ZIKV.

Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers.

BACKGROUND: Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB). OBJECTIVES: Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. METHODS: This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash. RESULTS: By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). CONCLUSIONS: These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573).

Factors preventing materno-fetal transmission of SARS-CoV-2.

Although many pregnant women have been infected by coronavirus, the presence of intrauterine vertical transmission has not been conclusively reported yet. What prevents this highly contagious virus from reaching the fetus? Is it only the presence of a strong placental barrier, or is it the natural absence of the some receptor that the viruses use for transmission? We, therefore, need to comprehensively understand the mechanism of action of the mammalian epithelial barriers located in two different organs with functional similarity. The barriers selected as potential targets by SARS-CoV-2 are the alveolo-capillary barrier (ACB), and the syncytio-capillary barrier (SCB). Caveolae are omega-shaped structures located on the cell membrane. They consist of caveolin-1 protein (Cav-1) and are involved in the internalisation of some viruses. By activating leukocytes and nuclear factor-κB, Cav-1 initiates inflammatory reactions. The presence of more than one Cav-1 binding sites on coronavirus is an important finding supporting the possible relationship between SARS-CoV-2-mediated lung injury. While the ACB cells express Cav-1 there is no caveolin expression in syncytiotrophoblasts. In this short review, we will try to explain our hypothesis that the lack of caveolin expression in the SCB is one of the most important physiological mechanisms that prevents vertical transmission of SARS-CoV-2. Since the physiological Cav-1 deficiency appears to prevent acute cell damage treatment algorithms could potentially be developed to block this pathway in the non-pregnant population affected by SARS-CoV-2.

Perinatal Use of Melatonin for Offspring Health: Focus on Cardiovascular and Neurological Diseases.

Cardiovascular and neurological diseases can originate in early life. Melatonin, a biologically active substance, acts as a pleiotropic hormone essential for pregnancy and fetal development. Maternal melatonin can easily pass the placenta and provide photoperiodic signals to the fetus. Though melatonin uses in pregnant or lactating women have not yet been recommended, there is a growing body of evidence from animal studies in support of melatonin as a reprogramming strategy to prevent the developmental programming of cardiovascular and neurological diseases. Here, we review several key themes in melatonin use in pregnancy and lactation within offspring health and disease. We have particularly focused on the following areas: the pathophysiological roles of melatonin in pregnancy, lactation, and fetal development; clinical uses of melatonin in fetal and neonatal diseases; experimental evidence supporting melatonin as a reprogramming therapy to prevent cardiovascular and neurological diseases; and reprogramming mechanisms of melatonin within developmental programming. The targeting of melatonin uses in pregnancy and lactation will be valuable in the prevention of various adult chronic diseases in later life, and especially cardiovascular and neurological diseases.

Awareness and Preventative Behaviours Regarding Toxoplasma, Listeria and Cytomegalovirus Among Pregnant Women

Aim Infection with toxoplasma, listeria and cytomegalovirus (CMV) infections can negatively affect pregnancy outcomes. Awareness of these infections, knowledge of preventive practices and pertinent behaviours was assessed. Methods A survey of patients at antenatal clinics in a Dublin maternity hospital was conducted over a six month period. Analysis was undertaken using SPSS. Results The response rate was 36% (287/800). One in two respondents were aware of toxoplasma, one in four of Listeria but only 1 in 10 of CMV. Overall, knowledge was highest among older, more educated pregnant women. Nativity had a significant effect on knowledge and behaviour, but increasing parity did not. However the majority practised key safe behaviours. Conclusion Information must be conveyed to pregnant women in a user friendly format and in a culturally sensitive way.

[Prevention and treatment of cytomegalovirus infection in pregnant women and newborns].

This review summarises the present knowledge of cytomegalovirus infection (CMV), which is the most common congenital infection. The awareness and knowledge of the disease is, however, limited among healthcare professionals. Neither screening of pregnant women nor testing of new-borns is routine. A lack of early identification can lead to an unnecessary increase in morbidity and mortality, as treat-ment must be started within the first months of life. The best weapon against congenital CMV is primary prevention in the form of information and thorough hand hygiene.

Prenatal Management of Pregnancies at Risk of Fetal Neonatal Alloimmune Thrombocytopenia (FNAIT): Scientific Impact Paper No. 61.

WHAT IS IT?: Fetal neonatal alloimmune thrombocytopenia (FNAIT), also known as neonatal alloimmune thrombocytopenia (NAIT) or fetomaternal alloimmune thrombocytopenia (FMAIT), is a rare condition which affects a baby's platelets. This can put them at risk of problems with bleeding, particularly into the brain. One baby per week in the UK may be seriously affected and milder forms can affect one in every 1000 births. HOW IS IT CAUSED?: Platelets are blood cells that are very important in helping blood to clot. All platelets have natural proteins on their surface called human platelet antigens (HPAs). In babies, half of these antigens are inherited from the mother and half from the father. During pregnancy, some of the baby's platelets can cross into the mother's bloodstream. In most cases, this does not cause a problem. But in cases of FNAIT, the mother's immune system does not recognise the baby's HPAs that were inherited from the father and develops antibodies, which can cross the placenta and attack the baby's platelets. These antibodies are called anti-HPAs, and the commonest antibody implicated is anti-HPA-1a, but there are other rarer antibody types. If this happens, the baby's platelets may be destroyed causing their platelet count to fall dangerously low. If the platelet count is very low there is a risk to the baby of bleeding into their brain before they are born. This is very rare but if it happens it can have serious effects on the baby's health. HOW IS IT INHERITED?: A baby inherits half of their HPAs from its mother and half from its father. Consequently, a baby may have different HPAs from its mother. As the condition is very rare, and even if the baby is at risk of the condition we have no way of knowing how severely they will be affected, routine screening is not currently recommended. WHAT CAN BE DONE?: FNAIT is usually diagnosed if a previous baby has had a low platelet count. The parents are offered blood tests and the condition can be confirmed or ruled out. There are many other causes of low platelets in babies, which may also need to be tested for. As the condition is so rare, expertise is limited to specialist centres and normally a haematologist and fetal medicine doctor will perform and interpret the tests together. Fortunately, there is an effective treatment for the vast majority of cases called immunoglobulin, or IVIg. This 'blood product' is given intravenously through a drip every week to women at risk of the condition. It may be started from as early as 16 weeks in the next pregnancy, until birth, which would be offered at around 36-37 weeks. Less common treatments that may be considered depending on individual circumstances include steroid tablets or injections, or giving platelet transfusions to the baby. WHAT DOES THIS PAPER TELL YOU?: This paper considers the latest evidence in relation to treatment options in the management of pregnancies at risk of FNAIT. Specifically, we discuss the role of screening, when IVIg should be started, what dose should be used, and what evidence there is for maternal steroids. We also consider in very rare selected cases, the use of fetal blood sampling and giving platelet transfusions to the baby before birth. Finally, we consider the approaches to blood testing mothers to tell if babies are at risk, which is offered in some countries, and development of new treatments to reduce the risk of FNAIT.