Impact of mRNA-based vaccines in the prevention of adverse outcomes of COVID-19 infection in pregnancy: a single-center cohort study.

Several data have suggested that pregnant women have an increased risk of severe COVID-19 compared to those who are not pregnant. Moreover, different studies have showed that severe COVID-19 is limited mostly to unvaccinated women. The aim of the present study was to ascertain the different maternal and fetal outcomes in pregnant women with COVID-19 according to their vaccination status. A retrospective cohort study was carried out including all women admitted to the high-risk pregnancy unit of our center with COVID-19 between December 2021 and February 2022. Among the 163 women included in the study, 60 were vaccinated with an mRNA vaccine and 103 were unvaccinated. Pregnancy outcome and obstetrical and neonatal complications were encountered. Vaccinated women showed higher educational levels and lower prevalence of cases, with BMI >25 compared to unvaccinated women. Moreover, vaccinated women were admitted mostly for obstetrical indications rather than for COVID-related symptoms. In addition, the risk of developing COVID-19 pneumonia was significantly higher in unvaccinated women (p = 0.01) compared with vaccinated ones. Furthermore, pregnancy and neonatal outcomes showed some differences in the two cohorts. In unvaccinated women, the rate of C-section was higher (p = 0.03), and the mean birthweight percentile in their infants was impaired by COVID-19 infection (p = 0.01) when compared to those born to vaccinated women. Based on these results, we suggest that women who received a full course of vaccination were protected from the severity of the disease, having milder symptoms of SARS-Cov2 infection, while also presenting a more favorable pregnancy outcome.

Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond.

During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

Low complement levels are related to poor obstetric outcomes in women with obstetric antiphospholipid syndrome. The EUROAPS Registry Study Group.

INTRODUCTION: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease related to antiphospholipid antibodies (aPL) with primaryinflammatory injury followed by clot cascade activation and thrombus formation. Complement system activation and their participation in aPL-related thrombosis is unclosed. METHODS: We haveanalysed adverse pregnancy outcomes (APO) related to low complement (LC) levels in a cohort of 1048 women fulfilling classification criteria for OAPS. RESULTS: Overall, 223 (21.3%) women presented LC values, during pregnancy. The length of pregnancy was shorter in OAPS women with LC compared to those with normal complement (NC) (median: 33 weeks, interquartile range: [24-38] vs. 35 weeks [27-38]; p = 0.022). Life new-born incidence was higher in patients with NC levels than in those with LC levels (74.4% vs. 67.7%; p = 0.045). Foetal losses were more related to women with triple or double aPL positivity carrying LC than NC values (16.3% vs. 8.0% NC; p = 0.027). Finally, some placental vasculopathies were affected in OAPS patients with LC as late Foetal Growth Restriction (FGR >34 weeks) rise to 7.2% in women with LC vs. 3.2% with NC (p = 0.007). DISCUSSION: Data from our registry indicate that incidence of APO was higher in OAPS women with LC levels and some could be reverted by the correct treatment.

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

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

Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

The Detrimental Effect of Thyroiditis on Pregnancy Outcome of Patients Affected by Autoimmune Diseases: An Open Question.

Few data are available evaluating obstetrical outcome when thyroiditis coexist with autoimmune diseases. Objectives of our study were: 1) To assess the prevalence of thyroiditis in pregnant women with autoimmune diseases; 2) To evaluate the effects on pregnancy outcome when different autoimmune diseases are associated with thyroiditis. Two groups of pregnant women were analysed: a study group of pregnant women with autoimmune diseases (n = 268) versus a control group of pregnant women (n = 1,150). In both groups the research for thyroid antibodies, anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies, was performed. The positivity had a prevalence of 17.54% in women with autoimmune diseases (n = 47) versus 5.57% in the control group (n = 64) (p-value < 0.00001). Only major rheumatic diseases (MRD) were analysed for pregnancy outcome (week of delivery, birth weight and birth weight percentile): systemic lupus erythematosus (SLE) n = 36, antiphospholipid syndrome (APS) n = 44 and connective tissue diseases (CTD) n = 23. MRD were divided according to positive or negative results for thyroid antibodies. Thyroiditis in CDT patients showed a detrimental effect on pregnancy outcome, in terms of earlier week of delivery: 37.86 ± 0.90 (mean ± SD) in CTD with thyroiditis versus 38.56 ± 0.73 (mean ± SD) in CTD without thyroiditis (p-value = 0.03) and lower birth weight: 2,790.71 g ± 257.17 SD in CTD with thyroiditis versus 3,019.33 g ± 305.48 g in CTD without thyroiditis (p-value < 0.05). In SLE and APS thyroiditis did not appear to influence pregnancy outcome. However, we suggest investigating anti-thyroid antibodies in all autoimmune diseases with special attention to pregnant women with thyroiditis and CTD.

'Non-criteria antiphospholipid antibodies': bridging the gap between seropositive and seronegative antiphospholipid syndrome.

OBJECTIVE: We aimed to analyse the prevalence of non-criteria anti-phospholipid (aPL) antibodies and their role in the diagnosis, treatment and prognosis in a cohort of patients with clinical features consistent with a diagnosis of antiphospholipid syndrome (APS), but persistently negative for criteria aPL - anti-cardiolipin antibodies (aCL), anti-ß2-glycoprotein I antibodies (aß2-GPI) and lupus anticoagulant (LA) - named seronegative APS (SN-APS). METHODS: Sera from SN-APS patients were tested for aCL by TLC-immunostaining, anti-vimentin/cardiolipin (aVim/CL) and anti-phosphatidylserine/prothrombin (anti-PS/PT) by ELISA. Control groups of our study were APS patients and healthy controls. RESULTS: We enrolled 114 consecutive SN-APS patients, 69 (60.5%) resulted positive for at least one non-criteria test in two occasions 12 weeks apart. Among the persistently positive patients to these tests, 97% resulted positive for aCL by TLC-immunostaining, 52.3% for aVim/CL and 17.4% for aPS/PT. SN-APS patients with double positivity (aCL by TLC-immunostaining and aVim/CL) showed a likelihood positive ratio of 8 to present mixed thrombotic and obstetrical features. Among SN-APS patients tested positive, after the therapeutic changes, three cases of recurrent thrombosis were observed [median follow-up 41 months (IQR 39.5)]. Twenty pregnancies were recorded in 17 SN-APS patients after the detection of unconventional aPL and 12 of them (60%) experienced a good outcome under conventional treatment for APS. CONCLUSIONS: This is the largest monocentric study demonstrating that aCL tested by TLC-immunostaining and aVim/CL can detect aPL positivity in SN-APS. It may encourage clinicians to monitor and provide adequate targeted therapy, which improve SN-APS prognosis.

Is Cardiomegaly an Indication of "Heart-Sparing Effect" in Small Fetuses?

INTRODUCTION: This study aimed to test the hypothesis that cardiac size is maintained in small fetuses presenting with cardiomegaly. MATERIALS AND METHODS: We identified singleton fetuses with estimated fetal weight <10th centile and with cardiomegaly without another more likely cardiac or extra-cardiac cause. We used Z-scores for cardiac and thoracic circumferences normalized for gestational age (GA), biparietal diameter (BPD), head circumference (HC), and femur length (FL), obtained from 188 normally grown fetuses. RESULTS: When comparing chest size, small fetuses had significantly lower thoracic circumferences median Z-scores (IQR) for GA = -4.82 (-6.15 to -3.51), BPD = -2.42 (-4.04 to -1.48), HC = -2.72 (-4.53 to -1.90), and FL = -1.60 (-2.87 to -0.71); p < 0.001 for all. When comparing heart size, small fetuses showed lower cardiac circumferences median Z-scores (IQR) for GA = -1.59 (-2.79 to -0.16); p < 0.001, similar cardiac circumferences Z-scores for BPD = 0.29 (-0.65 to 1.28); p = 0.284 and HC = 0.11 (-1.13 to 0.96); p = 0.953, and higher cardiac circumferences Z-scores for FL = 0.94 (-0.05 to 2.13); p < 0.001. CONCLUSIONS: Our results show that in small fetuses with cardiomegaly, the heart maintains normal dimensions when normalized to cranial diameters and higher dimensions when normalized to long bones. This provides insight into cardiac adaptation to adverse intrauterine environment.

Continuous Glucose Monitoring in Women with Normal OGTT in Pregnancy.

Continuous glucose monitoring (CGM) might be an effective tool to improve glycemic control in gestational diabetes mellitus (GDM). Few data are available about its utilization as a diagnostic tool to find potential alterations of glycemia in subjects with normal oral glucose tolerance test (OGTT). In this preliminary prospective real-life observational study, we aimed to analyze the glycemic pattern in normal and gestational diabetes mellitus (GDM) women by continuous glucose monitoring (CGM) in order to detect potential differences between the two groups and glycemic alterations despite a normal OGTT. After the screening for GDM, subjects were connected to a CGM system for seven consecutive days. The areas under the curve of the first 60 minutes after each meal and 60 minutes before breakfast were analyzed. Women with normal OGTT that during CGM showed impaired glycemic values (more than 95 fasting or more than 140 one hour after meals or more than 120 two hours after meals) performed one week of self-monitoring of blood glucose (SMBG). After OGTT, 53 women considered normal and 46 affected by GDM were included. CGM parameters did not show any differences between the two groups with impaired glycemic excursions found in both groups. After CGM period, 33 women with normal OGTT showed abnormal glycemic patterns. These 33 women then performed one week of SMBG. After evaluation of one week of SMBG, 21 required diet therapy and 12 required insulin treatment and were followed until the delivery. An increase in gestational weight gain was observed in normal women with normal OGTT but this was not significant. No significant data were found regarding neonatal outcomes in the two groups of women. In conclusion, CGM use in pregnancy might help to detect glycemic fluctuations in women with normal OGTT, improving their treatment and outcomes.

Bleeding and antithrombotic therapy during pregnancy in women with poor aPL-related obstetric outcomes: A survey of 1075 cases from EUROAPS registry∗.

BACKGROUND: The combination of low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH) until the end of gestation are the currently the accepted standard of care for the treatment of antiphospholipid-related obstetric disorders. In refractory cases, hydroxychloroquine (HCQ) can be added to this standard of care. OBJECTIVE: To evaluate the haemostatic safety of LDA and LMWH (medium to high prophylactic doses) during pregnancy and the puerperium in women with both full-blown obstetric antiphospholipid syndrome (OAPS) (Sydney criteria) and noncriteria - incomplete - OAPS. STUDY DESIGN: Retrospective/prospective multicentre observational study. Obstetric background, laboratory categories, delivery mode, antithrombotic regimens and bleeding complications were compared. SETTING: A total of 30 tertiary European hospitals. PATIENTS: Mainly, Caucasian/Arian pregnant women were included. Other ethnicities were minimally present. Women were controlled throughout pregnancy and puerperium. MAIN OUTCOME MEASURES: The primary end-point was to evaluate the number of major and minor haemorrhagic complications in this cohort of women. Neuraxial anaesthetic bleeding complications were particularly assessed. Secondly, we aimed to compare local/general bleeding events between groups. RESULTS: We studied 1650 women, of whom 1000 fulfilled the Sydney criteria of the OAPS and 650 did not (noncriteria OAPS). Data on antithrombotic-related complications were available in 1075 cases (65.15%). Overall, 53 (4.93%) women had bleeding complications, with 34 being considered minor (3.16%) and 19 major (1.76%). Neither obstetric complications nor laboratory categories were bleeding-related. Assisted vaginal delivery and caesarean section were related to local haemorrhage. Heparin doses and platelet count were not associated with major bleeding. CONCLUSIONS: LDA and medium to high prophylactic LMWH during pregnancy in women with full-blown OAPS/noncriteria OAPS are safe. A slight increase in bleeding risk was noted in instrumental deliveries. No women who underwent spinal or epidural anaesthesia suffered bleeding complications. No haemorrhage was observed in cases where HCQ was added to standard therapy.

Acute liver failure in Still's disease relapse during pregnancy: case report and discussion of a possible trigger role of DILI.

BACKGROUND: Still's disease is a rare systemic inflammatory disease with frequent but generally mild liver involvement. The most common cause of acute liver failure in western countries is drug-induced liver injury, while it has rarely been reported in subjects suffering from Still's disease. CASE PRESENTATION: We report a case of a young woman presenting with SD reactivation in pregnancy and acute liver failure after delivery with a possible triggering role of drug induced liver injury. CONCLUSIONS: The prompt recognition of Still's disease reactivation allowed early introduction of steroid therapy and resolution of the clinical picture. We discuss potential factors precipitating ALF in this case, and implications for the diagnosis and management of such patients.

Delivery room interventions to improve the stabilization of extremely-low-birth-weight infants.

OBJECTIVE: To retrospectively verify whether the positioning of the umbilical venous catheter (UVC) in the delivery room (DR) and the early start of the preheated infusion of 10% glucose solution conditioned temperature and glycemia values of ELBW neonates in the first hours of life. METHODS: Neonates (N = 137) were divided into two groups on the basis of timing of positioning of the UVC. In Group I the UVC was placed in DR, while in Group II after Neonatal Intensive Care Unit (NICU) admission. Data were assessed in different times: body temperature at neonatal admission to NICU (T1); after 2 hours (T2); then, every 2 hours until normothermia; glycemia value at NICU admission, every 1-2 hours in the first 12 hours, every 4 hours from 12 to 24 hours, and every 6-12 hours until normalization. Time slot childbirth was also detected since only in the morning shift there was a dedicated resuscitation team always present in DR, while during the afternoon and night it was available on-call. Preventive measures to limit heat dispersion were adopted in both Groups. RESULTS: In Group I respect to Group II, both at T1 and T2: (a) the rate of normothermic neonates was higher and (b) the rate of neonates with moderate hypothermia was lower. The hourly temperature increase was similar between the groups and the time needed to reach normothermia was significantly lower in Group I than in Group II. Glycemic values at T1 were lower in Group II. In Group II, after UVC positioning and glucose solution administration, the 42.2% of infants immediately brought glycemia back to normal, while the 57.8% needed specific treatment. The majority of newborns of Group I was born during the morning shift. CONCLUSIONS: The early UVC placement by a dedicated interdisciplinary team is a relevant intervention to carry out during the "Golden minutes" to improve the ELBW stabilization soon after birth.

Impact of chorioamnionitis on maternal and fetal levels of proinflammatory S100A12.

Histologic chorioamnionitis (HCA) may lead to the fetal inflammatory response syndrome (FIRS). The aim of this pilot study was to evaluate S100A12, a marker of innate immune activation, in mothers with or without HCA and in their infants. Concentrations of S100A12, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated in maternal, cord, and neonatal blood of very preterm infants. Histologic examinations of the placenta and umbilical cords were performed. The 48 mother-neonate pairs enrolled were subdivided into two groups: HCA group (N = 15) and control group without HCA (N = 33). Maternal S100A12 levels were similar between HCA and control group. Similarly, S100A12 concentrations in cord and neonatal blood did not differ between the groups. However, high S100A12 concentrations were detected in cord and neonatal blood of two out of three neonates exposed to HCA associated with advanced funisitis. Concentrations of IL-6 and CRP were higher in maternal blood of the HCA group compared with controls (p < 0.05, p < 0.001; respectively), but no differences in cord or neonatal blood was found.Conclusion:S100A12 did neither identify mothers with HCA nor very preterm infants exposed to HCA. It is currently unknown if S100A12 may identify neonates with FIRS. What is known: • Histologic chorioamnionitis (HCA) may lead to the fetal inflammatory response syndrome (FIRS). • S100A12 represents an early, sensitive, and specific diagnostic marker of inflammatory processes. What is new: • S100A12 did neither identify mothers with HCA nor very preterm infants exposed to HCA. • It is currently still unclear if S100A12 has a potential in identifying preterm infants with FIRS.

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

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

Postnatal Health in Children Born to Women After Bariatric Surgery.

INTRODUCTION: The aim of this study is to evaluate short- and long-term consequences in children born to women after different bariatric surgery (BS) procedures. METHODS: A questionnaire survey was given to the mothers referred from 1994 to 2019 to our center for pregnancy and delivery management after BS procedures: (a) malabsorptive surgery, (b) restrictive procedures, and (c) combined restrictive-malabsorptive procedures. RESULTS: Data from 74 children born after BS, aged 0 month to 12 years, were analyzed. The prevalence of children with underweight was 5.4%, normal weight 59.5%, overweight 16.2%, and obesity 18.9%. The prevalence of obesity was higher in children pre-school aged than that in school-aged ones. Neurodevelopmental disorders were more frequent if maternal BMI before bariatric surgery was ≥ 41 kg/m2 (p = 0.008), as well as if the pregnancy occurred less than 18 months after BS (p = 0.028). In school-aged children conceived within 18 months after BS, the highest risk of neurodevelopmental disorders (p = 0.028) and overweight (p = 0.018) was observed. The prevalence of neurodevelopmental disorders was much higher for small for gestational age babies (p = 0.048). Children born after biliopancreatic diversion (BPD) showed less maternal breastfeeding, shorter breastfeeding duration, more overweight, and more occurrence of atopic dermatitis in comparison with children born after other bariatric procedures. CONCLUSIONS: Postnatal health in children born to women after BS was impaired by long-term consequences and by other diseases later in life. Children born after BPD were particularly at higher risk for short and long term consequences when compared to children born after other BS procedures.

Autoimmune Congenital Heart Block: A Review of Biomarkers and Management of Pregnancy.

Autoimmune Congenital Heart Block (CHB) is an immune-mediated disease due to transplacental passage of circulating anti-Ro/SSA and anti-La/SSB autoantibodies. It occurs in 2% of anti-Ro/SSA-exposed pregnancies, and recurrence rate is nine times higher in subsequent pregnancies. Aim of this review is to identify biomarkers of CHB and treatment strategies. The Ro-system is constituted by two polypeptides targeted by the anti-Ro52 and anti-Ro60 autoantibodies. The central portion of Ro52 (p200), more than the full amino-acid sequence of Ro-52, is recognized to be the fine specificity of anti-Ro associated to the highest risk of cardiac damage. If anti-p200 antibody should be tested, as biomarker of CHB, over standard commercial ELISAs is still debated. Recent studies indicate that type I-Interferon (IFN) can activate fibroblasts in fetal heart. In the mother the anti-Ro/La antibodies activate the type I IFN-signature, and maternal IFN-regulated genes correlate with a similar neonatal IFN-gene expression. Evaluation of maternal IFN-signature could be used as novel biomarker of CHB. The measurement of "mechanical" PR interval with weekly fetal echocardiogram (ECHO) from 16 to at least 24 weeks of gestation is strongly recommended for CHB prenatal diagnosis. However, ECHO screening presents some limitations due to difficult identification of first-degree block and possible occurrence of a complete block from a normal rhythm in few days. Maternal administration of Hydroxychloroquine from the tenth week of gestation, modulating toll-like receptor and autoantibody-dependent type I IFN activation on the fetus, has an important role in preventing CHB in pregnant women with high risk for recurrent CHB.