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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bollani, Auriti, Achille, Garofoli, De Rose, Meroni, Salvatori and Tzialla.)

Zika virus (ZIKV) infection has been linked to congenital defects in fetuses and infants, as exemplified by the microcephaly epidemic in Brazil. Given the overlapping presence of Dengue virus (DENV) in the majority of ZIKV epidemic regions, advanced diagnostic approaches need to be evaluated to establish the role of pre-existing DENV immunity in ZIKV infection. From 2015 to 2017, five pregnant women with suspected ZIKV infection were investigated in Pavia, Italy. Among the five pregnant women, three were DENV-ZIKV immunologically cross-reactive, and two were DENV-naïve. Advanced diagnosis included the following: (i) NS1 blockade-of-binding (BOB) ELISA assay for ZIKV specific antibodies and (ii) ELISpot assay for the quantification of effector memory T cells for DENV and ZIKV. These novel assays allowed to distinguish between related flavivirus infections. The three DENV-experienced mothers did not transmit ZIKV to the fetus, while the two DENV-naive mothers transmitted ZIKV to the fetus. Pre-existing immunity in DENV experienced mothers might play a role in cross-protection .

Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.

Infants born to mothers who seroconverted for toxoplasmosis during pregnancy are at risk of sequelae. In the case of a negative work-up at birth, congenital infection can be ruled out only by monitoring the disappearance of maternal immunoglobulin G (IgG) transmitted through the placenta, which can be achieved by regular blood sampling during the first year. To alleviate the discomfort of this follow-up, we developed an indirect enzyme-linked immunosorbent assay to detect specific IgG diffusing passively from the blood through the gingival epithelium by collecting oral fluid on microsponges. To assess the feasibility of the test, 212 patients were first enrolled. Levels of specific IgG in oral fluid were significantly higher in seropositive (n = 195) than in seronegative (n = 17) patients (mean optical densities, 1.145 ± 0.99 versus 0.092 ± 0.127; P < 0.0001). In a population of 93 patients <15 months of age born to mothers who displayed toxoplasmic infection during pregnancy, 70 were free of congenital infection and were followed up until their serology turned negative, and 23 were congenitally infected. The same patterns of IgG were observed in the oral fluid and sera in each group. Using a cutoff of 0.04 (optical density value), the sensitivity and specificity of the test were 67.9% and 80.3%, respectively, and the probability of not having a congenital infection when the test on oral fluid was negative was 99%. Although the performance of the test needs to be improved, oral fluid sampling appears to be a promising tool for monitoring infants with suspected congenital toxoplasmosis., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

ATP synthase or complex V (cV) of the oxidative phosphorylation system is responsible for the production of ATP, dissipating the electrochemical gradient generated by the mitochondrial respiratory chain. In addition to maternally transmitted cV dysfunction caused by mutations in mtDNA genes (MT-ATP6 or MT-ATP8), encoding cV subunits, recessive mutations in the nuclear TMEM70 are the most frequent cause of ATP synthase deficiency.We report on a cohort of ten Italian patients presenting with neonatal lactic acidosis, respiratory distress, hypotonia, cardiomyopathy and psychomotor delay and harbouring mutations in TMEM70, including the common splice mutation and four novel variants. TMEM70 protein was virtually absent in all tested TMEM70 patients' specimens.The exact function of TMEM70 is not known, but it is considered to impact on cV assembly since TMEM70 mutations have been associated with isolated cV activity reduction. We detected a clear cV biochemical defect in TMEM70 patients' fibroblasts, whereas the assay was not reliable in frozen muscle. Nevertheless, the evaluation of the amount of holocomplexes in patients with TMEM70 mutations showed a nearly absent cV in muscles and a strong decrease of cV with accumulation of sub-assembly species in fibroblasts. In our cohort we found not only cV deficiencies but also impairment of other OXPHOS complexes. By ultrastructural analysis of muscle tissue from one patient with isolated cV deficiency, we found a severely impaired mitochondrial morphology with loss of the cristae. These findings indicate that cV impairment could indirectly alter other respiratory chain complex activities by disrupting the mitochondrial cristae structure.

Italy provides a free voluntary serological screening for toxoplasmosis in pregnancy supported by public health system, as there is an estimated congenital toxoplasmosis rate of 1-2/10,000. The aim of this study was to make an inventory of diagnostic and therapeutic protocols in use in Italy in the absence of a national guideline. A semistructured questionnaire was distributed to AMCLI (Italian Association of Clinical Microbiologists) members who were asked to involve other specialists to fill in the form. Data from 26 centers show: a) a general use of the IgG avidity test to solve diagnosis in IgG/IgM positive, pregnant women; b) a widespread attitude to spyramicin antenatal treatment in suspected, unconfirmed maternal infection; c) avoidance of invasive antenatal diagnosis only in suspected early or late (>24 weeks), even confirmed, maternal infection d) fetal diagnosis performed by PCR assays on amniotic fluid; e) variability of both indications and dosage of pyrimethamine-sulfadiazine (P-S) as fetal treatment; f) use of comparative mother and newborn IgG/IgM Immuneblot in most centers; g) no diagnostic tests performed on placenta and cord blood; h) spyramicin is no longer used in congenital infections; i) no P-S-based treatment for children at high risk of congenital infection (late maternal infection) in the absence of diagnosis. As there is the opportunity to test pregnant women for Toxoplasma gondii infection in Italy free of charge, standardized diagnostic and therapeutic national guidelines would focus on a more uniform approach.

Rationale: The new form of bronchopulmonary dysplasia (BPD) is characterized by lung immaturity with disrupted alveolar and capillary development after extremely premature birth, but the mechanism of impaired lung vascular formation is still not completely understood., Objectives: We tested the hypothesis that reduced numbers of circulating endothelial progenitor cells at birth are associated with the development of BPD., Methods: We studied ninety-eight preterm infants with gestational age of less than 32 weeks or a birth weight less than 1,500 g. Endothelial colony-forming cells (ECFCs) were assessed by clonogenic analysis in infants for whom cord blood was available. The proportion of circulating endothelial and hematopoietic cells was measured by flow cytometry at birth, at 48 hours, and at 7 days of life., Measurements and Main Results: ECFCs in cord blood were lower in infants who later developed BPD (median [range]: 0.00 [0.00-0.48] vs. 2.00 [0.00-21.87]; P = 0.002). ECFCs decreased with decreasing gestational age (r = 0.41; P = 0.02), but even at extremely low gestational ages, infants with higher numbers of ECFCs were protected from BPD. The endothelial and hematopoietic cell subsets studied by flow cytometry were comparable in infants with and without BPD and rapidly decreased after birth., Conclusions: ECFCs are low at extremely low gestational ages and increase during gestation; extremely preterm infants who display lower numbers at birth have an increased risk of developing BPD. Our findings suggest that decreased ECFCs following extremely preterm birth may be associated with the risk for developing lung vascular immaturity characteristic of new BPD.

Human cytomegalovirus (HCMV) immediate-early messenger RNA (IEmRNA) in sequential blood samples from 32 pregnant women with primary infection and from 14 congenitally infected newborns was qualitatively investigated by nucleic acid sequence-based amplification. IEmRNA was detected in 100%, 75%, 36.3%, 22.2%, and 0% of samples collected 1, 2, 3, 4-6, and >6 months after onset of primary HCMV infection, respectively, showing 83.7% sensitivity and 92.2% specificity, compared with results of quantitative DNAemia (detection of viral DNA in blood). In infected newborns, IEmRNA was positive in 100% of samples collected 1-7 days (median, 1.5 days) and in 46.4% of samples collected 27-260 days (median, 88 days) after birth, showing 75.7% sensitivity and 100% specificity, compared with DNAemia results. IEmRNA was not detected in HCMV-immune individuals with remote or recurrent HCMV infection or in uninfected newborns. IEmRNA determination appears to be a valuable tool for early diagnosis of both primary and congenital HCMV infection.