Reference Ranges for Arterial Oxygen Saturation, Heart Rate, and Cerebral Oxygen Saturation during Immediate Postnatal Transition in Neonates Born Extremely or Very Preterm.

OBJECTIVE: To define percentile charts for arterial oxygen saturation (SpO2), heart rate (HR), and cerebral oxygen saturation (crSO2) during the first 15 minutes after birth in neonates born very or extremely preterm and with favorable outcome. STUDY DESIGN: We conducted a secondary-outcome analysis of preterm neonates included in the COSGOD III trial with visible cerebral oximetry measurements and with favorable outcome, defined as survival without cerebral injuries until term age. We excluded infants with inflammatory morbidities within the first week after birth. SpO2 was obtained by pulse oximetry, and electrocardiogram or pulse oximetry were used for measurement of HR. CrSO2 was assessed with near-infrared spectroscopy. Measurements were performed during the first 15 minutes after birth. Percentile charts (10th to 90th centile) were defined for each minute. RESULTS: A total of 207 preterm neonates with a gestational age of 29.7 (23.9-31.9) weeks and a birth weight of 1200 (378-2320) grams were eligible for analyses. The 10th percentile of SpO2 at minute two, five, ten and 15 was 32%, 52%, 83% and 85%, respectively. The 10th percentile of HR at minute two, five, ten and 15 was 70bpm, 109bpm, 126bpm and 134bpm, respectively. The 10th percentile of crSO2 at minute two, five, ten and 15 was 15%, 27%, 59% and 63%, respectively. CONCLUSIONS: This study provides new centile charts for SpO2, HR, and crSO2 for extremely preterm neonates with favorable outcome. Implementing these centiles in guiding interventions during the stabilization process after birth might help to more accurately target oxygenation during postnatal transition period.

Parental stress, depression, anxiety and participation in care in neonatal intensive care unit: a cross-sectional study in Italy comparing mothers versus fathers.

BACKGROUND: This study aimed at documenting the levels of stress, depression, anxiety and participation in care among mothers versus fathers of newborns hospitalised in a third-level neonatal intensive care unit (NICU) in Northern Italy. METHODS: Parental stress, depression and anxiety were assessed by the Parental Stressor Scale in NICU (PSS:NICU), the Edinburgh Postnatal Depression Scale (EPDS) and the State-Trait Anxiety Inventory (STAI). Participation in care was evaluated with the Index of Parental Participation. Differences between mothers and fathers were assessed with the Mood's median test and z-test, respectively for continuous and discrete variables. Multivariate analyses controlling for potential confounders were performed to confirm gender differences. RESULTS: 191 parents (112 mothers and 79 fathers) were enrolled. Mothers reported significantly higher median scores for stress (2.9 vs 2.2, p<0.001) and trait anxiety (37 vs 32, p=0.004) and higher depression rates (EPDS ≥12: 43.8% vs 19.0%, p<0.001). 'High stress' (PSS:NICU ≥3) was reported by 45.5% of mothers compared with 24.1% of fathers (p=0.004). The frequency of the three conditions simultaneously was significantly higher among mothers (20.0% vs 3.8%, p=0.016), with the vast majority of mothers (76.0%) suffering from at least one condition compared with less than half of fathers (45.3%, p<0.001). Participation in care was more frequent in mothers (median score: 19 vs 15, p<0.001), with the exception of activities related to advocacy (median 5 vs 4, p=0.053). In a multivariate analysis, gender differences in mental health outcomes did not change. CONCLUSIONS: Routine screening of mental distress among parents of infants in NICU is warranted, and gender differences need to be acknowledged in order to deliver tailored support and to promote collaboration with the family of vulnerable newborns. Knowledge and skills on how to prevent and cope with mental distress of parents should be part of the core curriculum of staff working in NICU.

Decreased incidence of late-onset sepsis during the SARS-CoV-2 pandemic in Italy: a multicentric study on a cohort of infants requiring major surgery.

Changes in the organization of the clinical care wards, requested by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, have influenced the environmental circulation of other pathogens. The implementation of prevention procedures may have led to a decrease in the incidence of healthcare-associated infections. We aimed to investigate the impact of prevention and control measures for preventing the COVID-19 spread on the incidence of bacterial sepsis and invasive fungal infections in neonates and infants requiring major surgery. We compared the incidence of bacterial and fungal sepsis and their risk factors observed before the SARS-CoV-2 pandemic (from 01/10/2018 to 29/02/2020) with those observed during the pandemic (from 01/03/2020 to 07/05/2021) in 13 level III Neonatal Intensive Care Units in Italy, through a secondary analysis of data, collected during a prospective multicenter study (REF). The patients enrolled were infants within three months of life, hospitalized in the two periods in the participating centers to undergo major surgery. Among 541 enrolled patients, 324 (59.9%) were born in the pre-pandemic period and 217 (40.1%) during the pandemic. The incidence density (ID) of any infection in the pre-pandemic period was 16.0/1000 patient days versus 13.6/1000 patient days in the pandemic period (p < 0.001). One hundred and forty-five (145/324; 44.8%) patients developed at least one episode of bacterial sepsis in the pre-pandemic period, versus 103/217 (31.8%) patients, during the pandemic (p = 0.539). Concerning fungal sepsis, 12 (3.7%) patients had one episode in the pre-pandemic period versus 11 (5.1%) patients during the pandemic (p = 0.516). The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics pre-surgery, and that of proton pump inhibitors during the SARS-CoV-2 pandemic compared with the previous period. CONCLUSIONS: In our cohort of patients with major surgical needs, the reduction of CVC days, pre-surgery antibiotics administration, and current use of proton pump inhibitors, during the SARS-CoV-2 pandemic, led to a decrease in the incidence of late-onset sepsis. WHAT IS KNOWN: • Most cases of late-onset sepsis in neonates are referred to as central line-associated bloodstream infections. • In adults, the COVID-19 outbreak negatively influenced healthcare-associated infection rates and infection clusters within hospitals. WHAT IS NEW: • In neonates and infants undergoing major surgery the incidence density of infections was lower in the pandemic period than before. • The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics before surgery, and that of proton pump inhibitors during the pandemic compared with previously.

Extrauterine growth restriction in very low birth weight infants according to different growth charts: A retrospective 10 years observational study.

BACKGROUND: Extrauterine growth restriction (EUGR) is common among very low birth weight (VLBW) infants and associated with poor neurodevelopmental outcomes. There are two types of EUGR definitions (cross-sectional and longitudinal) and many growth charts for monitoring postnatal growth. Aims of our study were 1) to compare the rate of small for gestational rate (SGA) and EUGR in a population of VLBW infants, both according to different growth charts (Fenton, INeS charts and Intergrowth-21) and different definitions; 2) to identify risk factors for EUGR. METHODS: This is a single centre retrospective observational study, including all VLBW infants born between January 2009 and December 2018. Anthropometric measures were obtained at birth and at discharge and presented as z-scores according to three growth charts (Fenton, INeS charts, Intergrowth-21). Maternal, clinical and nutritional data were retrieved from clinical records. RESULTS: 228 VLBW were included. Percentage of SGA did not change significantly according to the three different growth charts (Fenton 22.4%, INeS charts 22.8%, Intergrowth 28.2%, p 0.27). Prevalence of EUGR was significantly higher when INeS and Fenton charts were used, compared to Intergrowth charts regardless of EUGR-definition (cross sectional-EUGR: Fenton 33.5%, INeS charts 40.9%, Intergrowth-21 23.8%, p 0.001; longitudinal-EUGR (loss of 1SDS): Fenton 15%, INeS charts 20.4%, Intergrowth 4%, p <0.001). In our population a longer time to reach 100 ml/kg/day of enteral feeding increased of 18% the risk of longitudinal EUGR. Late onset sepsis and retinopathy of prematurity were associated with an increased risk of longitudinal EUGR, although not significantly, while having a preeclamptic mother was associated with a reduced risk. CONCLUSIONS: We confirmed a wide variability of EUGR rates when using different charts and definitions, highlighting that Intergrowth-21 charts identify less EUGR when compared to INeS and Fenton charts. Standardized criteria for defining EUGR are warranted in order to facilitate comparisons between studies and to improve the nutritional management of VLBW infants.

Timing of Symptoms of Early-Onset Sepsis after Intrapartum Antibiotic Prophylaxis: Can It Inform the Neonatal Management?

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003-2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): multicentre randomised phase 3 clinical trial.

OBJECTIVE: To investigate whether monitoring of cerebral tissue oxygen saturation using near infrared spectroscopy in addition to routine monitoring combined with defined treatment guidelines during immediate transition and resuscitation increases survival without cerebral injury of premature infants compared with standard care alone. DESIGN: Multicentre, multinational, randomised controlled phase 3 trial. SETTING: 11 tertiary neonatal intensive care units in six countries in Europe and in Canada. PARTICIPANTS: 1121 pregnant women (<32 weeks' gestation) were screened prenatally. The primary outcome was analysed in 607 of 655 randomised preterm neonates: 304 neonates in the near infrared spectroscopy group and 303 in the control group. INTERVENTION: Preterm neonates were randomly assigned to either standard care (control group) or standard care plus monitoring of cerebral oxygen saturation with a dedicated treatment guideline (near infrared spectroscopy group) during immediate transition (first 15 minutes after birth) and resuscitation. MAIN OUTCOME MEASURE: The primary outcome, assessed using all cause mortality and serial cerebral ultrasonography, was a composite of survival without cerebral injury. Cerebral injury was defined as any intraventricular haemorrhage or cystic periventricular leukomalacia, or both, at term equivalent age or before discharge. RESULTS: Cerebral tissue oxygen saturation was similar in both groups. 252 (82.9%) out of 304 neonates (median gestational age 28.9 (interquartile range 26.9-30.6) weeks) in the near infrared spectroscopy group survived without cerebral injury compared with 238 (78.5%) out of 303 neonates (28.6 (26.6-30.6) weeks) in the control group (relative risk 1.06, 95% confidence interval 0.98 to 1.14). 28 neonates died (near infrared spectroscopy group 12 (4.0%) v control group 16 (5.3%): relative risk 0.75 (0.33 to 1.70). CONCLUSION: Monitoring of cerebral tissue oxygen saturation in combination with dedicated interventions in preterm neonates (<32 weeks' gestation) during immediate transition and resuscitation after birth did not result in substantially higher survival without cerebral injury compared with standard care alone. Survival without cerebral injury increased by 4.3% but was not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT03166722.

Impact of a quality improvement intervention on neonatal mortality in a regional hospital in Burkina Faso.

BACKGROUND: The neonatal period is the most vulnerable time in terms of a child's survival, with mortality during this period accounting for approximately half of the deaths before the age of 5 years. The Neonatal Essential Survival Technology (NEST) project is a program aiming to reduce mortality by improving the quality of neonatal care in sub-Saharan Africa. This study presents the evaluation of the first phase of the NEST intervention program at Saint Camille Hospital Ouagadougou (HOSCO), Burkina Faso, in terms of the reduction in neonatal mortality. METHODS: This is a retrospective analysis, based on "pre-intervention" data collected in 2015, and "post-intervention" data collected in 2018, including all infants admitted to the neonatal unit of HOSCO. The intervention period (2016 and 2017) comprised a structured quality improvement process conducted by a multidisciplinary working group that focused on improving infrastructure, equipment, training and use of clinical protocols, team working within the neonatal unit and with other hospital departments, and communication with referring healthcare facilities. Mortality data were compared pre- vs. post-intervention using a logistic regression model. RESULTS: The analysis included 1427 infants in the pre-intervention period, and 819 post-intervention. In both time periods, more than 75% of admissions were infants with low birth weight, and nearly 50% were very low birth weight. Post-intervention, while there was a decrease in overall admission, the proportion of multiple births increased from 20% to 24% (p = .01). The overall mortality rate was 44.9% (641/1427) pre-intervention, and 42.2% (346/819) post-intervention (OR 0.90, 95% confidence interval (CI) 0.76-1.07; p = .23). Adjusting for clinically relevant factors, the intervention was not associated with a change in overall mortality (OR 1.39, 95% CI 0.91-2.12; p = .13), but was associated with a reduced likelihood of mortality in outborn infants compared to inborn infants (OR 0.57, 95% CI 0.36-0.92; p = .02). CONCLUSIONS: The first phase of the NEST quality improvement program was associated with a decrease in mortality in outborn infants admitted to the neonatal unit at HOSCO. Long-term assessment is expected to provide a more comprehensive evaluation of the program in a low-income setting.

Parental Stress, Depression, and Participation in Care Before and During the COVID-19 Pandemic: A Prospective Observational Study in an Italian Neonatal Intensive Care Unit.

Background: Recent studies reported, during the COVID-19 pandemic, increased mental distress among the general population and among women around the childbirth period. COVID-19 pandemic may undermine the vulnerable well-being of parents in Neonatal Intensive Care Units (NICUs). Objective: Our study aimed to explore whether parental stress, depression, and participation in care in an Italian NICU changed significantly over three periods: pre-pandemic (T0), low (T1), and high COVID-19 incidence (T2). Methods: Enrolled parents were assessed with the Parental Stressor Scale in the NICU (PSS:NICU), Edinburgh Postnatal Depression Scale (EPDS), and Index of Parental Participation (IPP). Stress was the study primary outcome. A sample of 108 parents, 34 for each time period, was estimated to be adequate to detect a difference in PSS:NICU stress occurrence level score (SOL) of 1.25 points between time periods. To estimate score differences among the three study periods a non-parametric analysis was performed. Correlation among scores was assessed with Spearman rank coefficient. Results: Overall, 152 parents were included in the study (62 in T0, 56 in T1, and 34 in T2). No significant differences in the median PSS:NICU, EPDS, and IPP scores were observed over the three periods, except for a slight increase in the PSS:NICU parental role sub-score in T2 (T0 3.3 [2.3-4.1] vs. T2 3.9 [3.1-4.3]; p = 0.038). In particular, the question regarding the separation from the infant resulted the most stressful aspect during T2 (T0 4.0 [4.0-5.0] vs. T2 5.0 [4.0-5.0], p = 0.008). The correlation between participation and stress scores (r = 0.19-022), and between participation and depression scores (r = 0.27) were weak, while among depression and stress, a moderate positive correlation was found (r = 0.45-0.48). Conclusions: This study suggests that parental stress and depression may be contained during the COVID-19 pandemic, while participation may be ensured.

Understanding Factors in Group B Streptococcus Late-Onset Disease.

Group B streptococcus (GBS) infection remains a leading cause of sepsis, pneumonia, and meningitis in infants. Rates of GBS early onset disease have declined following the widcespread use of intrapartum antibiotic prophylaxis; hence, late-onset infections (LOGBS) are currently a common presentation of neonatal GBS dicsease. The pathogenesis, mode of transmission, and risk factors associated with LOGBS are unclear, which interfere with effective prevention efforts. GBS may be transmitted from the mother to the infant at the time of delivery or during the postpartum period via contaminated breast milk, or as nosocomial or community-acquired infection. Maternal GBS colonization, prematurity, young maternal age, HIV exposure, and ethnicity (Black) are identified as risk factors for LOGBS disease; however, further studies are necessary to confirm additional risk factors, if any, for the implementation of effective prevention strategies. This narrative review discusses current and previous studies that have reported LOGBS. Few well-designed studies have described this condition; therefore, reliable assessment of maternal GBS colonization, breastfeeding, and twin delivery as risk factors for LOGBS remains limited.

Association between body composition at term equivalent age and Bayley scores at 2 years in preterm infants.

OBJECTIVE: To evaluate whether in a historical cohort of preterm infants, body composition at term equivalent age (TEA) correlated with Bayley scores at 2 years of corrected age. STUDY DESIGN: Ninety-five preterm babies were admitted to our neonatal intensive unit and underwent air-displacement plethysmography assessment at TEA. Of these, 74 completed Bayley tests at 2 years. We used multiple linear regression analysis to assess the association of body composition with Bayley scores. RESULTS: Mean gestational age and birthweight of our population were respectively 29.8 (±2.2) weeks and 1150 (±330) grams. Higher fat-free mass (FFM) z-score was associated with higher language (adjusted r = 0.28, p = 0.03) and motor composite scores (adjusted r = 0.33, p = 0.03) in both univariate and multiple regression analysis including birth weight, sex, maternal university degree, mechanical ventilation, and bilingualism. CONCLUSIONS: In our study FFM at term equivalent age was associated with higher Bayley composite motor and language scores at 2 years.

Invasive Candida Infections in Neonates after Major Surgery: Current Evidence and New Directions.

Infections represent a serious health problem in neonates. Invasive Candida infections (ICIs) are still a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Infants hospitalized in NICUs are at high risk of ICIs, because of several risk factors: broad spectrum antibiotic treatments, central catheters and other invasive devices, fungal colonization, and impaired immune responses. In this review we summarize 19 published studies which provide the prevalence of previous surgery in neonates with invasive Candida infections. We also provide an overview of risk factors for ICIs after major surgery, fungal colonization, and innate defense mechanisms against fungi, as well as the roles of different Candida spp., the epidemiology and costs of ICIs, diagnosis of ICIs, and antifungal prophylaxis and treatment.

Change in body composition of premature infants from parenteral nutrition discontinuation to term equivalent age.

AIM: To compare body composition (BC) of premature infants at parenteral nutrition (PN) suspension and at term equivalent age (TEA). METHODS: Body weight, fat mass (FM), fat free mass (FFM) and FM as % of body weight were measured in infants born at <32 gestational weeks by air-displacement plethysmography at PN suspension and at TEA in a tertiary level hospital. Z-scores were calculated for BC and anthropometric measurements. Nutritional and clinical data were obtained during hospital stay. BC, weight and length were measured at birth in a sample of infants born at term for comparison. RESULTS: Thirty premature infants with birth weight of 1198 ± 270 g and gestational age of 29.8 ± 1.8 weeks were included. At PN suspension, at 32.6 ± 1.6 postconceptional weeks, FFM z-score was similar to FFM z-score measured at TEA, at 39.8 ± 0.7 postconceptional weeks (-1.43 ± 1.27 vs -1.78 ± 1.64, p = 0.26), while FM z-score and %FM z-score at PN suspension were lower than those measured at TEA (FM z-score: 0.23 ± 0.62 versus 2.04 ± 1.00, p < 0.0001 and %FM z-score: 0.66 ± 0.76 versus 2.08 ± 1.07, p < 0.0001). At TEA, weight and length of premature infants were similar to those of term-born infants (3130 ± 340 g vs 3350 ± 340 g; 49.2 ± 2.4 cm vs 50.2 ± 2.5 cm, respectively), but %FM was higher (21.3 ± 4.2% vs 9.2 ± 4.4%, p < 0.001); higher exclusive enteral caloric and protein intakes were associated with a decrease in FM z-scores from PN suspension to TEA. CONCLUSION: In our sample of premature infants, fat free mass z-score was similar, while fat mass and % fat mass z-scores increased substantially from parenteral nutrition suspension to term-equivalent age. Nutritional intakes during exclusive enteral nutrition did not seem to contribute to such increase.

Cerebral Hemodynamics During Neonatal Cerebrospinal Fluid Removal.

BACKGROUND: Standard treatment of neonatal posthemorrhagic hydrocephalus is cerebrospinal fluid removal. The aim of this study was to assess how much cerebrospinal fluid volume removal, by ventricular reservoir taps, is needed to improve cerebral hemodynamics and oxygenation in neonatal posthemorrhagic hydrocephalus. METHODS: Cerebral hemodynamics and oxygenation were continuously monitored by near-infrared spectroscopy in four newborns (one term and three preterm) during 28 ventricular reservoir taps. At each tap, 10 mL/kg of cerebrospinal fluid was removed. Near-infrared spectroscopy detected changes in the concentration of oxy-hemoglobin and total hemoglobin, considered as estimates of cerebral blood flow and volume, respectively. Cerebral tissue oxygenation index was also measured. During cerebrospinal fluid removal, variation in cerebral blood flow, volume, and oxygenation were analyzed by repeated measures analysis of variance. The associations between changes in cerebral hemodynamics and oxygenation, during cerebrospinal fluid removal and after its conclusion, were analyzed by Pearson's r correlation coefficient. RESULTS: A significant increase in cerebral blood flow and volume was already evident at 50% of targeted cerebrospinal fluid volume removal (P < 0.001). Although cerebral tissue oxygenation index absolute value remained unchanged, variations in cerebral blood flow and oxygenation were positively correlated, both during cerebrospinal fluid removal and after its conclusion (r = 0.57; P = 0.002). CONCLUSIONS: On the basis of the results from this small cohort, the volume of cerebrospinal fluid removal associated with an improvement in cerebral hemodynamics and perfusion seems to be less than the traditional 10 mL/kg. Further research is needed to define the potential role of near-infrared spectroscopy monitoring to individualize cerebrospinal fluid removal.

Secondary prevention of early-onset sepsis: a less invasive Italian approach for managing neonates at risk.

Strategies to prevent early-onset sepsis (EOS) have led to a substantial decline in many countries. However, one of the most controversial topics in neonatology is the management of asymptomatic full-term and late preterm neonates at risk for EOS, and guidelines lack substantial consensus regarding this issue. A strategy for managing neonates, entirely based on serial physical examinations, has been developed in two Italian regions. This strategy seems safe, while reducing laboratory tests and unnecessary antibiotics. In the current commentary we provide area-based data concerning the prevention of EOS in 2 northern Italian regions, and we detail the results of their strategy for managing healthy-appearing newborns at risk for EOS.

Higher growth, fat and fat-free masses correlate with larger cerebellar volumes in preterm infants at term.

AIM: Smaller cerebellar volumes in very low-birthweight (VLBW) infants at term have been related to adverse cognitive outcomes, and this study evaluated whether these volumes were associated with a growth in body composition during hospital stays. METHODS: We prospectively recruited 42 VLBW infants from an Italian neonatal unit between January 2013 and August 2015. Cerebellar volumes and body composition were measured by magnetic resonance imaging (MRI) and air-displacement plethysmography, respectively, at 40 weeks of gestational age and anthropometric and nutritional data were collected. We also included 20 term-born controls. RESULTS: The mean gestational age and birthweight of the VLBW infants were 29.4 (±1.9) weeks and 1120 (±290) g. There was a positive correlation between cerebellar volumes and daily weight gain from birth to term (R2 = 0.26, p = 0.001), weight (R2 = 0.25, p = 0.001), length (R2 = 0.16, p = 0.01), fat mass (R2 = 0.15, p = 0.01) and fat-free mass at term (R2 = 0.20, p = 0.003). In multiple regression analysis, daily weight gain, mechanical ventilation and postconceptional age at MRI were independently associated with cerebellar volumes. Anthropometric data and cerebellar volumes were similar between VLBW and control infants. CONCLUSION: Higher growth, higher fat mass and fat-free mass were associated with larger cerebellar volumes in VLBW infants at term.