Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland.

BACKGROUND: Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. OBJECTIVE: To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. STUDY DESIGN: Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, ß2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). RESULTS: Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, ß2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and ß2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. CONCLUSION: The combination of thrombocytes, ß2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

Incidence and Management of Neonatal Pneumothorax in a 10-Hospital Regional Perinatal Network in Switzerland: A Retrospective Observational Study.

OBJECTIVE: Pneumothorax (PTX) is a potentially life-threatening condition that affects neonates, with an incidence of 0.05 to 2%. Its management includes conservative treatment, chest tube (CT) drainage, and needle aspiration (NA). Aims were to evaluate the incidence of PTX in a 10-hospital perinatal network, its clinical characteristics and risk factors, and to compare the different treatment options. STUDY DESIGN: All neonates diagnosed with PTX and hospitalized in the network were included in this retrospective observational trial over a period of 30 months. Primary outcome was the incidence of PTX. Secondary outcomes were the treatment modality, the length of stay (LOS), and the number of chest X-rays. RESULTS: Among the 173 neonates included, the overall incidence of PTX was 0.56 per 100 births with a large range among the hospitals (0.12-1.24). Thirty-nine percent of pneumothoraces were treated conservatively, 41% by CT drainage, 13% by NA, and 7% by combined treatment. Failure rate was higher for NA (37%) than for CT drainage (9%). However, the number of X-rays was lower for patients treated by NA, with a median of 6 (interquartile range [IQR] 4-6.25), than by CT drainage, with a median of 9 (IQR 7-12). LOS was shorter for NA than for CT drainage, with a median of 2 (IQR 1-4.25) and 6 days (IQR 3-15), respectively. Complications, including apnea and urinary retention, occurred in 28% of patients managed with CT drainage, whereas none was observed with NA. CONCLUSION: High variability of PTX incidence was observed among the hospitals within the network, but these values correspond to the literature. NA showed to reduce the number of X-rays, the LOS, and complications compared with CT drainage, but it carries a high failure rate. This study helped provide a new decisional management algorithm to harmonize and improve PTX treatment within our network. KEY POINTS: · Neonatal PTX is a frequent pathology with a high incidence requiring urgent management.. · We report a large variability of PTX incidence between different hospitals of the same network.. · Needle aspiration carries higher failure rate, shorter hospital stay duration without complications reported..

Neuronal autosis is Na+/K+-ATPase alpha 3-dependent and involved in hypoxic-ischemic neuronal death.

Macroautophagy (hereafter called autophagy) is an essential physiological process of degradation of organelles and long-lived proteins. The discovery of autosis, a Na+/K+-ATPase (ATP1)-dependent type of autophagic cell death with specific morphological and biochemical features, has strongly contributed to the acceptance of a pro-death role of autophagy. However, the occurrence and relevance of autosis in neurons has never been clearly investigated, whereas we previously provided evidence that autophagy mechanisms could be involved in neuronal death in different in vitro and in vivo rodent models of hypoxia-ischemia (HI) and that morphological features of autosis were observed in dying neurons following rat perinatal cerebral HI. In the present study, we demonstrated that neuronal autosis could occur in primary cortical neurons using two different stimulations enhancing autophagy flux and neuronal death: a neurotoxic concentration of Tat-BECN1 (an autophagy-inducing peptide) and a hypoxic/excitotoxic stimulus (mimicking neuronal death induced by cerebral HI). Both stimulations induce autophagic neuronal death (dependent on canonical autophagic genes and independent on apoptotic, necroptotic or ferroptotic pathways) with all morphological and biochemical (ATP1a-dependent) features of autosis. However, we demonstrated that autosis is not dependent on the ubiquitous subunit ATP1a1 in neurons, as in dividing cell types, but on the neuronal specific ATP1a3 subunit. We also provided evidence that, in different in vitro and in vivo models where autosis is induced, ATP1a3-BECN1 interaction is increased and prevented by cardiac glycosides treatment. Interestingly, an increase in ATP1a3-BECN1 interaction is also detected in dying neurons in the autoptic brains of human newborns with severe hypoxic-ischemic encephalopathy (HIE). Altogether, these results suggest that ATP1a3-BECN1-dependent autosis could play an important role in neuronal death in HI conditions, paving the way for the development of new neuroprotective strategies in hypoxic-ischemic conditions including in severe case of human HIE.

Neonatal amygdala volumes, procedural pain and the association with social-emotional development in children born very preterm.

Very preterm birth (< 32 weeks' gestational age) is associated with later social and emotional impairments, which may result from enhanced vulnerability of the limbic system during this period of heightened vulnerability. Evidence suggests that early procedural pain may be a key moderator of early brain networks. In a prospective cohort study, neonates born very preterm (< 30 weeks' gestation) underwent MRI scanning at term-equivalent age (TEA) and clinical data were collected (mechanical ventilation, analgesics, sedatives). Procedural pain was operationalized as the number of skin breaking procedures. Amygdala volumes were automatically extracted. The Strengths and Difficulties questionnaire was used to assess social-emotional outcomes at 5 years of age (mean age 67.5 months). General linear models were employed to examine the association between neonatal amygdala volumes and social-emotional outcomes and the timing and amount of procedural pain exposure (early within the first weeks of life to TEA) as a moderator, adjusting for biological sex, gestational age, 5-year assessment age, days of mechanical ventilation and total cerebral volumes. A total of 42 preterm infants participated. Right amygdala volumes at TEA were associated with prosocial behaviour at age 5 (B = -0.010, p = 0.005). Procedural pain was found to moderate the relationship between right amygdala volumes in the neonatal period and conduct problems at 5 years, such that early skin breaking procedures experienced within the first few weeks of life strengthened the association between right amygdala volumes and conduct problems (B = 0.005, p = 0.047). Late skin breaking procedures, experienced near TEA, also strengthened the association between right amygdala volumes and conduct problems (B = 0.004, p = 0.048).

HIGHLIGHTS: ● Preterm birth is associated with social-emotional challenges.● Amygdala volumes at term equivalent age were assessed in relation to preschool social-emotional outcomes.● Larger right amygdala volumes at term-equivalent age were associated with impaired prosocial behaviour at age 5.● Procedural pain moderated the relationship between neonatal amygdala volumes and conduct problems at age 5, with early or late skin breaking procedures strengthening this association.● Dysregulated growth and maturation of the amygdala in preterm neonates were associated with differences in social functioning at 5 years old, with early life procedural pain playing a moderating role.