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The article describes the case of severe renal failure in a 36-week old baby girl whose mother had taken Olmesartan for hypertension during her last month of pregnancy. The baby died of cardio-circulatory failure 45 days after her birth with kidneys showing severe tubular dysgenesis. Also included is information on sartans as treatment for arterial hypertension and role of renin-angiotensin components in kidney development. The study concludes that exposure to sartans during the last month of pregnancy can cause congenital malformations, renal impairment, and fetal or neo-natal death.

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). Targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, the inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference < 10th centile, failed hearing screen, and prematurity. During the first three years of use of this program (2021-2023), 940 (12.3%) of 7651 live-born infants were tested. The most common indication was birthweight < 10th centile (n = 633, 67.3%). Eleven neonates were diagnosed as congenitally infected, for a prevalence of 1.17% (95%CI 0.48-1.86) on tested neonates and of 0.14% (95%CI 0.06-0.23) on live-born infants. None of the cCMV-infected newborns had a failed hearing screen as a testing indication. Implementation of an expanded cCMV screening program appears feasible and of clinical value.

We aimed to establish reference ranges for USCOM parameters in preterm infants, determine factors that affect cardiac output, and evaluate the measurement repeatability. This retro-prospective study was performed at Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. We included infants below 32 weeks of gestational age (GA) and/or 1500 g of birth weight (BW). We excluded infants with congenital heart diseases or hemodynamic instability. Measurements were performed at 3 ± 1, 7 ± 2, and 14 ± 2 postnatal days. We analyzed 204 measurements from 92 patients (median GA = 30.57 weeks, BW = 1360 g). The mean (SD) cardiac output (CO) was 278 (55) ml/min/kg, cardiac index (CI) was 3.1 (0.5) L/min/m 2 , and systemic vascular resistance (SVRI) was 1292 (294) d*s*cm -5 /m 2 . CO presented a negative correlation with postmenstrual age (PMA), while SVRI presented a positive correlation with PMA. The repeatability coefficient was 31 ml/kg/min (12%).  Conclusion: This is the first study describing reference values for USCOM parameters in hemodynamically stable preterm infants and factors affecting their variability. Further studies to investigate the usefulness of USCOM for the longitudinal assessment of patients at risk for cardiovascular instability or monitoring the response to therapies are warranted. What is Known: • The ultrasonic cardiac output monitoring (USCOM) has been widely used on adult and pediatric patients and reference ranges for cardiac output (CO) by USCOM have been established in term infants. What is New: • We established reference values for USCOM parameters in very preterm and very-low-birth-weight infants; the reference ranges for CO by USCOM in the study population were 198-405 ml/kg/min. • CO normalized by body weight presented a significant negative correlation with postmenstrual age (PMA); systemic vascular resistance index presented a significant positive correlation with PMA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy., Methods: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves., Results: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age <37 weeks) was significantly higher in the first and third waves (15.6-12.5%). The risk of intrauterine transmission was always very low, while the risk of postnatal transmission during rooming-in was higher and peaked at 4.5% during the fourth wave. A total of 80% of positive neonates were asymptomatic., Conclusion: The risk of adverse maternal and neonatal outcomes was significantly higher during the first and third waves, dominated by unsequenced variants and the Delta variant, respectively. Postnatal transmission accounted for most neonatal infections and was more frequent during the Omicron period. However, the paucity of symptoms in infected neonates should lead us not to separate the dyad., Competing Interests: Declaration of Competing Interest All authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Indomethacin is administered as a tocolytic agent for threatening preterm labor <28weeks of gestation. Only a few, not conclusive, studies have investigated its nephrotoxicity in very low birth weight (VLBW) infants. We investigated whether indomethacin increases the incidence of acute kidney injury (AKI) among VLBW infants., Methods: This is a retrospective study including all VLBW infants born at our center between January 1, 2005, and December 31, 2013. Indomethacin was administered to women with preterm labor and intact membranes. Neonatal AKI was defined according to KDIGO classification. Univariate analyses were performed comparing VLBW infants exposed to and not exposed to indomethacin. In the multivariable model, the association of indomethacin and AKI was adjusted for patent ductus arteriosus, use of nephrotoxic medications, birth weight, and gestational age., Results: Five hundred seventy-five VLBW infants were included, 49 (8.5%) of whom were exposed to indomethacin in utero. The univariate analysis showed that infants exposed to indomethacin had lower birth weight, lower gestational age, and higher incidence of AKI than infants not exposed. The multivariable model adjusted for confounding factors confirmed an increased risk of AKI in relation to gestational age at birth <27 weeks, but not to indomethacin., Conclusions: Our data suggest that extreme prematurity, but not the use of indomethacin, is associated with AKI.

Objectives: To evaluate the rate of postnatal infection during the first month of life in neonates born to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive mothers during the predominant circulation of the omicron (B.1.1.529) variant., Methods: This prospective, 10-center study enrolled mothers infected by SARS-CoV-2 at delivery and their infants, if both were eligible for rooming-in, between December 2021 and March 2022. Neonates were screened for SARS-CoV-2 RNA at 1 day of life (DOL), 2 to 3 DOL, before discharge, and twice after hospital discharge. Mother-infant dyads were managed under a standardized protocol to minimize the risk of viral transmission. Sequencing data in the study area were obtained from the Italian Coronavirus Disease 2019 Genomic platform. Neonates were included in the final analysis if they were born when the omicron variant represented >90% of isolates., Results: Eighty-two percent (302/366) of mothers had an asymptomatic SARS-CoV-2 infection. Among 368 neonates, 1 was considered infected in utero (0.3%), whereas the postnatal infection rate during virtually exclusive circulation of the omicron variant was 12.1%. Among neonates infected after birth, 48.6% became positive during the follow-up period. Most positive cases at follow-up were detected concurrently with the peak of coronavirus disease 2019 cases in Italy. Ninety-seven percent of the infected neonates were asymptomatic., Conclusions: The risk of early postnatal infection by the SARS-CoV-2 omicron variant is higher than that reported for previously circulating variants. However, protected rooming-in practice should still be encouraged given the paucity of symptoms in infected neonates., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Preterm birth alters nephrogenesis and reduces the total nephron number. Intrauterine growth restriction (IUGR) seems to worsen nephron loss, but only a few studies have investigated its role in neonatal kidney impairment. We investigated whether IUGR, defined as reduced estimated fetal growth and/or placental flow alterations and low birth weight z-score, increases the risk of developing acute kidney injury (AKI) in very preterm infants., Methods: We performed a retrospective study including infants born with a birth weight (BW) ≤ 1500 g and/or gestational age (GA) ≤ 32 weeks admitted to our center between January 2016 and December 2021. Neonatal AKI was defined according to the neonatal KDIGO classification based on the decline of urine output and/or creatinine elevation. We used multivariable linear regressions to verify the association between AKI and GA, BW z-score, IUGR definition, and hemodynamically significant patent ductus arteriosus (PDA)., Results: We included 282 infants in the analysis, with a median (IQR) GA = 29.4 (27.4, 31.3) weeks, BW = 1150 (870, 1360) g, and BW z-score =  - 0.57 (- 1.64, 0.25). AKI was diagnosed in 36 (13%) patients, and 58 (21%) had PDA. AKI was significantly associated with BW z-score (beta (std. error) =  - 0.08 (0.03), p = 0.008) and severe IUGR (beta (std. error) = 0.21 (0.08), p = 0.009), after adjusting for GA and PDA., Conclusions: Our data suggest that low BW z-score and IUGR could represent adjunctive risk factors for kidney impairment in preterm babies. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Physiologically, smooth muscle cells (SMC) and nitric oxide (NO) produced by endothelial cells strictly cooperate to maintain vasal homeostasis. In atherosclerosis, where this equilibrium is altered, molecules providing exogenous NO and able to inhibit SMC proliferation may represent valuable antiatherosclerotic agents. Searching for dual antiproliferative and NO-donor molecules, we found that furoxans significantly decreased SMC proliferation in vitro, albeit with different potencies. We therefore assessed whether this property is dependent on their thiol-induced ring opening. Indeed, while furazans (analogues unable to release NO) are not effective, furoxans' inhibitory potency parallels with the electron-attractor capacity of the group in 3 of the ring, making this effect tunable. To demonstrate whether their specific block on G1-S phase could be NO-dependent, we supplemented SMCs with furoxans and inhibitors of GMP- and/or of the polyamine pathway, which regulate NO-induced SMC proliferation, but they failed in preventing the antiproliferative effect. To find the real mechanism of this property, our proteomics studies revealed that eleven cellular proteins (with SUMO1 being central) and networks involved in cell homeostasis/proliferation are modulated by furoxans, probably by interaction with adducts generated after degradation. Altogether, thanks to their dual effect and pharmacological flexibility, furoxans may be evaluated in the future as antiatherosclerotic molecules.

Forty‑one tumors were detected in a population of 1,649,003 cattle slaughtered in 4 abattoirs in Lombardy over a 5‑year period, for an overall prevalence of 2.5 tumors per 100,000 cattle. Tumors were classified according to the WHO histological classification of tumors of domestic animals. Alimentary and hemopoietic systems were commonly affected with 9 cases each. Other affected sites were the respiratory (n = 3), urinary (n = 2), endocrine (n = 2), musculoskeletal (n = 2), nervous (n = 1), and cardiovascular (n = 1) systems. The peritoneum was affected by 6 cases, while the primary location of 3 tumors of the connective tissues and 3 metastatic carcinomas was unidentified. Liver tumors and mesotheliomas, for which environmental risk factors are well‑known in humans, were common, as well as tumors typically encountered in pediatric human patients (tumors of mesenchymal tissues, pulmonary blastomas and nephroblastomas). These findings suggest the useful role of bovines as sentinel and model for human carcinogenesis. Our study indicates that the establishment of a bovine cancer registry in Lombardy is feasible considering its potential contribution to understanding the role of environmental risk factors in the genesis of tumors in animals and humans.

Aneuploidy is the condition of having an imbalanced karyotype, which is associated with tumor initiation, evolution, and acquisition of drug-resistant features, possibly by generating heterogeneous populations of cells with distinct genotypes and phenotypes. Multicellular eukaryotes have therefore evolved a range of extrinsic and cell-autonomous mechanisms for restraining proliferation of aneuploid cells, including activation of the tumor suppressor protein p53. However, accumulating evidence indicates that a subset of aneuploid cells can escape p53-mediated growth restriction and continue proliferating in vitro . Here we show that such aneuploid cell lines display a robust modal karyotype and low frequency of chromosomal aberrations despite ongoing chromosome instability. Indeed, while these aneuploid cells are able to survive for extended periods in vitro , their chromosomally unstable progeny remain subject to p53-induced senescence and growth restriction, leading to subsequent elimination from the aneuploid pool. This mechanism helps maintain low levels of heterogeneity in aneuploid populations and may prevent detrimental evolutionary processes such as cancer progression and development of drug resistance.

We describe a case of neonatal SARS-CoV-2 infection, in an infant diagnosed 3 days after birth, and manifesting with silent hypoxemia, requiring respiratory support., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Sartans are selective type 1 angiotensin II receptor antagonists that are used for treatment of arterial hypertension. We report a case of severe renal failure required dialysis after the use of olmesartan in the last month of pregnancy. Exposure to sartans during the last period of gestation seems to be associated with high risk of congenital malformations. It is important to stress that the use of these drugs during pregnancy must be avoided, especially in the third trimester.