Should we give antibiotics to neonates with mild non-progressive symptoms? A comparison of serial clinical observation and the neonatal sepsis risk calculator

ObjectiveTo compare two strategies [the neonatal sepsis risk calculator (NSC) and the updated serial clinical observation approach (SCO)] for the management of asymptomatic neonates at risk of early-onset sepsis (EOS) and neonates with mild non-progressive symptoms in the first hours of life.MethodsThis was a single-center, retrospective cohort study conducted over 15 months (01/01/2019–31/03/2020). All live births at ≥34 weeks of gestation were included. Infants were managed using SCO and decisions were compared with those retrospectively projected by the NSC. The proportion of infants recommended for antibiotics or laboratory testing was compared in both strategies. McNemar's non-parametric test was used to assess significant differences in matched proportions.ResultsAmong the 3,445 neonates (late-preterm, n = 178; full-term, n = 3,267) 262 (7.6%) presented with symptoms of suspected EOS. There were no cases of culture-proven EOS. Only 1.9% of the neonates were treated with antibiotics (median antibiotic treatment, 2 days) and 4.0% were evaluated. According to NSC, antibiotics would have been administered in 5.4% of infants (absolute difference between SCO and NSC, 3.51%; 95% CI, 3.14–3.71%; p <0.0001) and 5.6% of infants would have undergone “rule out sepsis” (absolute difference between SCO and NSC, 1.63%, 95% CI 1.10–2.05; p <0.0001).ConclusionSCO minimizes laboratory testing and unnecessary antibiotics in infants at risk of EOS or with mild non-progressive symptoms, without the risk of a worse neonatal outcome. The NSC recommends almost three times more antibiotics than the SCO without improving neonatal outcomes

Neurodevelopmental Outcome and Neuroimaging of Very Low Birth Weight Infants from an Italian NICU Adopting the Family-Centered Care Model

Background: Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a pertinent public health concern. Family-centered care has emerged as a holistic philosophy that promotes effective alliances among patients, families, and healthcare providers to improve the quality of care. Aims: This longitudinal prospective study aims to evaluate the neurodevelopmental outcomes and brain MRI findings in a cohort of preterm newborns admitted to a neonatal intensive care unit (NICU) adopting a family-centered care model. Methods: Very low birth weight (VLBW) infants admitted to the NICU of Modena between 2015 and 2020 were enrolled. Infants who underwent conventional brain magnetic resonance imaging (MRI) at term-equivalent age were included. Neurodevelopmental follow-up was performed until the age of 24 months by a multidisciplinary team using the Amiel-Tison neurological assessment and the Griffiths Mental Developmental Scales (GMDS-R). Neurodevelopmental outcomes were classified as major sequelae (cerebral palsy, DQ ≤ 70, severe sensory impairment), minor sequelae (minor neurological signs such as clumsiness or DQ between 71 and 85), and normal outcomes (no neurological signs and DQ > 85). Risk factors for severe outcomes were assessed. Results: In total, 49 of the 356 infants (13.8%) died before hospital discharge, and 2 were excluded because of congenital disorders. Of the remaining 305 infants, 222 (72.8%) completed the 24 month follow-up and were included in the study. Neurodevelopmental outcomes were classified as normal (n = 173, 77.9%), minor (n = 34, 15.3%), and major sequelae (n = 15, 6.8%). Among 221 infants undergoing brain MRI, 76 (34.4%) had major lesions (intraventricular hemorrhage, hemorrhagic parenchymal infarction, periventricular leukomalacia, and large cerebellar hemorrhage). In the multivariate regression model, the retinopathy of prematurity (OR 1.8; p value 0.016) and periventricular–intraventricular hemorrhage (OR 5.6; p value < 0.004) were associated with major sequelae. Conclusions: We reported low rates of severe neurodevelopmental outcomes in VLBW infants born in an Italian NICU with FCC. Identifying the risk factors for severe outcomes can assist in tailoring and optimizing early interventions on an individual basis, both within the NICU and after discharge

LA MENINGITE NEL NEONATO E NEL PICCOLO LATTANTE

Bacterial meningitis may cause long term disabilities or death, particularly at younger ages. Early diagnosis and prompt antibiotic therapy are essential for improving outcome. The diagnosis of meningitis in newborns and young infants is a challenge because symptoms and signs are frequently vague and non-specific, in particular at the onset of the disease. Cerebrospinal fluid culture and analysis remain nowadays the gold standard for diagnosis. Clinicians often defer lumbar puncture because of concerns of complications, although data concerning the risks of lumbar puncture at younger ages are poorly defined. Perhaps a combination of laboratory markers and selected clinical symptoms at the onset of meningitis would identify neonates with higher risk of meningitis who should necessarily undergo lumbar puncture. Currently, clinicians should be aware that the advantage of an early diagnosis of meningitis through lumbar puncture overcomes the risks related to the procedure

Neonatal seizures treatment based on conventional multichannel EEG monitoring: an overview of therapeutic options

Introduction: Seizures are the main neurological emergency during the neonatal period and are mostly acute and focal. The prognosis mainly depends on the underlying etiology. Conventional multichannel video-electroencephalographic (cEEG) monitoring is the gold standard for diagnosis, but treatment remains a challenge. Areas covered: : This review, based on PubMed search over the last 4 decades, focuses on the current treatment options for neonatal seizures based on cEEG monitoring. There is still no consensus on seizure therapy, owing to poor scientific evidence. Traditionally, the first-line treatments are phenobarbital and phenytoin, followed by midazolam and lidocaine, but their efficacy is limited. Therefore, current evidence strongly suggests the use of alternative antiseizure medications. Randomized controlled trials of new drugs are ongoing. Expert opinion: : Therapy for neonatal seizures should be prompt and tailored, based on semeiology, mirror of the underlying cause, and cEEG features. Further research should focus on antiseizure medications that directly act on the etiopathogenetic mechanism responsible for seizures and are therefore more effective in seizure control

Neonatal septic shock, a focus on first line interventions

Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out

Late-Onset Sepsis Mortality among Preterm Infants: Beyond Time to First Antibiotics

Objective: To investigate the impact of timing, in vitro activity and appropriateness of empirical antimicrobials on the outcome of late-onset sepsis among preterm very low birth weight infants that are at high risk of developing meningitis. Study design: This retrospective study included 83 LOS episodes in 73 very low birth weight infants born at ≤32 weeks’ gestation with positive blood and/or cerebrospinal fluid culture or polymerase chain reaction at >72 h of age. To define the appropriateness of empirical antimicrobials we considered both their in vitro activity and their ideal delivery through the blood-brain barrier when meningitis was confirmed or not ruled out through a lumbar puncture. The primary outcome was sepsis-related mortality. The secondary outcome was the development of brain lesions. Timing, in vitro activity and appropriateness of empirical antimicrobials, were compared between fatal and non-fatal episodes. Uni- and multi-variable analyses were carried out for the primary outcome. Results: Time to antibiotics and in vitro activity of empirical antimicrobials were similar between fatal and non-fatal cases. By contrast, empirical antimicrobials were appropriate in a lower proportion of fatal episodes of late-onset sepsis (4/17, 24%) compared to non-fatal episodes (39/66, 59%). After adjusting for Gram-negative vs. Gram-positive pathogen and for other supportive measures (time to volume administration), inappropriate empirical antimicrobials remained associated with mortality (aOR, 10.3; 95% CI, 1.4–76.8, p = 0.023), while timing to first antibiotics was not (aOR 0.9; 95% CI, 0.7–1.2, p = 0.408; AUC = 0.88). The association between appropriate antimicrobials and brain sequelae was also significant (p = 0.024). Conclusions: The risk of sepsis-related mortality and brain sequelae in preterm very low birth weight infants is significantly associated with the appropriateness (rather than the timing and the in vitro activity) of empirical antimicrobials. Until meningitis is ruled out through lumbar puncture, septic very low birth weight infants at high risk of mortality should receive empiric antimicrobials with high delivery through the blood-brain barrier

Late-Onset Sepsis Mortality among Preterm Infants: Beyond Time to First Antibiotics

Objective: To investigate the impact of timing, in vitro activity and appropriateness of empirical antimicrobials on the outcome of late-onset sepsis among preterm very low birth weight infants that are at high risk of developing meningitis. Study design: This retrospective study included 83 LOS episodes in 73 very low birth weight infants born at ≤32 weeks’ gestation with positive blood and/or cerebrospinal fluid culture or polymerase chain reaction at >72 h of age. To define the appropriateness of empirical antimicrobials we considered both their in vitro activity and their ideal delivery through the blood-brain barrier when meningitis was confirmed or not ruled out through a lumbar puncture. The primary outcome was sepsis-related mortality. The secondary outcome was the development of brain lesions. Timing, in vitro activity and appropriateness of empirical antimicrobials, were compared between fatal and non-fatal episodes. Uni- and multi-variable analyses were carried out for the primary outcome. Results: Time to antibiotics and in vitro activity of empirical antimicrobials were similar between fatal and non-fatal cases. By contrast, empirical antimicrobials were appropriate in a lower proportion of fatal episodes of late-onset sepsis (4/17, 24%) compared to non-fatal episodes (39/66, 59%). After adjusting for Gram-negative vs. Gram-positive pathogen and for other supportive measures (time to volume administration), inappropriate empirical antimicrobials remained associated with mortality (aOR, 10.3; 95% CI, 1.4–76.8, p = 0.023), while timing to first antibiotics was not (aOR 0.9; 95% CI, 0.7–1.2, p = 0.408; AUC = 0.88). The association between appropriate antimicrobials and brain sequelae was also significant (p = 0.024). Conclusions: The risk of sepsis-related mortality and brain sequelae in preterm very low birth weight infants is significantly associated with the appropriateness (rather than the timing and the in vitro activity) of empirical antimicrobials. Until meningitis is ruled out through lumbar puncture, septic very low birth weight infants at high risk of mortality should receive empiric antimicrobials with high delivery through the blood-brain barrier

Sudden Unexpected Postnatal Collapse and Therapeutic Hypothermia: What’s Going On?

Sudden unexpected postnatal collapse (SUPC) is a rare event, potentially associated with catastrophic consequences. Since the beginning of the 2000s, therapeutic hypothermia (TH) has been proposed as a treatment for asphyxiated neonates after SUPC. However, only a few studies have reported the outcome of SUPC after TH. The current study presents the long-term neurodevelopmental outcome of four cases of SUPC treated with TH in a single Italian center. Furthermore, we reviewed the previous literature concerning 49 cases of SUPC treated with TH. Among 53 total cases (of whom four occurred in our center), 15 (28.3%) died before discharge from the NICU. A neurodevelopmental follow-up was available only for 21 (55.3%) out of the 38 surviving cases, and seven infants developed neurodevelopmental sequelae. TH should be considered in neonates with asphyxia after SUPC. However, SUPC is a rare event, and there is a lack of comparative clinical data to establish the risk/benefit of TH after SUPC with different degrees of asphyxia. Analysis of large cohorts of newborns with SUPC, whether treated with TH or untreated, are needed in order to better identify infants who should undergo TH

Neurodevelopmental Outcome after Culture-Proven or So-Called Culture-Negative Sepsis in Preterm Infants

(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case–control study included infants with birth weight p = 0.002) and all sepsis (OR 3.68, CI 1.2–11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority