Activin-A exerts a crucial anti-inflammatory role in neonatal infections.

BACKGROUND: Activin-A is a cytokine with a critical role in infections and associated inflammation in experimental models and humans. Still, the effects of activin-A on neonatal infections remain elusive. Here, we investigated the expression of activin-A in the serum of septicemic preterm and term neonates and in peripheral blood leukocytes stimulated with inflammatory agents in vitro. The role of activin-A in the regulation of inflammatory responses by neonatal leukocytes was delineated. METHODS: Peripheral blood was obtained from 37 septicemic neonates between the first and fifth days postinfection and from 35 healthy controls. Isolated monocytes and lymphocytes were stimulated with lipopolysaccharide (LPS) or phytohemagglutinin (PHA) in vitro in the presence of activin-A. Cell proliferation, cytokine, and chemokine release were investigated. RESULTS: Activin-A was significantly increased in the serum of preterm septicemic neonates. Neonatal leukocytes secreted copious amounts of activin-A following stimulation, pointing to these cells as an essential source of activin-A in the circulation. Of note, treatment of neonatal leukocytes with activin-A during PHA and LPS stimulation resulted in significantly decreased interleukin (IL)-1ß, IL-6, and CXCL8 production, concomitant with a striking increase in the anti-inflammatory mediator, IL-10. CONCLUSION: Our findings uncover activin-A as a novel immunomodulatory agent critical for the control of inflammatory responses in septicemic neonates.

Pharyngeal sampling for PCR-testing in the investigation of SARS-COV-2 vertical transmission in pregnancy.

The novel COVID-19 global pandemic has raised, among many others, major concerns regarding the impact of infection during pregnancy. Current evidence suggests that vertical transmission from mother to baby, antenatally or intrapartum, does occur, but is uncommon. According to the published reports of infants born to COVID-19-affected mothers, as well as the anecdotal experience of current practices worldwide, it appears that investigations regarding the potential of SARS-COV-2 vertical transmission in pregnancy have so far been based, to a large extent, on PCR testing of neonatal pharyngeal swab samples. Given that the transplacental route of intrauterine transmission for SARS-COV-2 is less likely to immediately involve the upper respiratory tract of the newborn, contrary to what happens after birth, it would be advisable to include appropriate biological samples, such as cord blood, placenta, amniotic fluid and neonatal blood, along with the pharyngeal samples, in order to contribute significantly to such investigations. It is important to point out that negative PCR tests of neonatal pharyngeal samples do not exclude the possibility of intrauterine viral transmission, while positive pharyngeal swabs are more likely to reflect intrapartum or postpartum contaminants, rather than antenatal intrauterine transmission, in the absence of other criteria. Revision and enhancement of the so far prevailing practices appear important, in order to facilitate the development of good clinical practice for managing neonates and ensuring safety of families and healthcare providers.

Non-steroid anti-inflammatory drugs in the treatment of patent ductus arteriosus in European newborns.

INTRODUCTION: Patent ductus arteriosus (PDA) is a common cause of morbidity and mortality among very low birth weight infants and must be treated on an individual basis. Non-steroid anti-inflammatory drugs (NSAIDs) have been used in the treatment of PDA. However, no general guidelines have been followed. AIM: To know the European reality on NSAIDs in the treatment of PDA in preterm newborns. METHODS: A questionnaire was sent to 24 European Societies of Neonatology and Perinatology to be filled, at least, by two neonatal intensive care units (NICUs) in each country, and to three representatives NICUs in Europe. RESULTS: We received 45 filled forms from 19 countries: 1 (2%) from North, 12 (27%) from East, 6 (13%) from West, and 26 (58%) from South Europe. Intravenous (iv) indomethacin is used in 32 (71%) NICUs (88% use a 30-60 min perfusion), iv ibuprofen in 16 (36%), and oral ibuprofen in 13 (29%). In 45% of NICUs a second course is used; 27% prescribed a third one. Prolonged treatment, 4-6 days, is mentioned by 45% of NICUs, in extremely low birth eight infants and after the failure of 3 courses of treatment. Prophylactic treatment is used in two NICUs, 24% treat no hemodynamically significant PDA, 96% treat with NSAIDs hemodynamically significant PDA and one NICU uses surgical closure as first line treatment. The ibuprofen/indomethacin contra-indications and preferences are similar to the literature. Pedea is the iv ibuprofen solution used and oral ibuprofen is a solution with 20 mg/ml. The choices are influenced by economical reasons in 22% of NICUs. CONCLUSION: Our data show a wide variation among NICUs and countries, regarding the use of NSAIDs to treat PDA, and that no general guidelines are followed. Guidelines or recommendations are necessary to standardize treatment of PDA in Europe, in order to give to all newborns identical health care opportunities.