Evaluation of a new tool - "Step by step with my baby" - to support parental involvement in the care of preterm infants.

BACKGROUND AND AIMS: Parental guidance is essential for supporting parental involvement, maintaining the quality and safety of infant care, and limiting parental stress. The efficiency of a new tool to support parental empowerment - "Step by step with my baby" - was evaluated. The perception of this tool by parents and nurses was studied. METHODS: This was a prospective, observational study conducted from September 2019 to December 2020 at a level-3 neonatal center. A total of 79 newborns (<33 weeks of gestational age or small for gestational age), 84 parents, and 94 nurses were included. The new tool that was evaluated is in the form of a drawing of flowers to be colored according to the parents' ability to care for their newborn. Six domains were explored and given a score (total of 35 points) according to the parents' ability to care for each item: behavior, skin-to-skin contact, carrying, oral and tube feeding, and routine care. The use and relevance of this tool were evaluated by parents and caregivers. RESULTS: At a mean of 19 days of life, parents required caregiver support regardless of the skill domain (6/35). After 26 days, the mean score increased to 19.4 (p < 0.05). Parents felt autonomous in changing diapers and monitoring temperature but always required help for skin-to-skin contact, carrying, and feeding with or without a tube. The progression was not affected by the presence of siblings, the distance from home, and staying in the parental hospital room. For 67 % of the parents, the tool gave them a better understanding of their newborn and helped them be more confident (69 %) without feeling judged (81 %). These feelings were upheld by nurses. CONCLUSIONS: This tool was efficient for evaluating parents' autonomy and helped them take ownership of the care provided.

Changes of Infant- and Family-Centered Care Practices Administered to Extremely Preterm Infants During Implementation of the NIDCAP Program.

Introduction: Many studies have evaluated the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP), but few studies have assessed changes in infant- and family-centered developmental care (IFCDC) practices during its implementation. Objectives: The primary objective of this single center study was to investigate the impact of the implementation of the NIDCAP program on IFCDC practices used for management of extremely preterm infants (EPIs). The secondary objective was to determine during implementation the impact of this program on the short-term medical outcomes of all EPIs hospitalized at our center. Methods: All EPIs (<28 weeks gestational age) who were hospitalized at Strasbourg University Hospital from 2007 to 2014 were initially included. Outborn infants were excluded. The data of EPIs were compared for three time periods: 2007 to 2008 (pre-NIDCAP), 2010 to 2011, and 2013 to 2014 (during-NIDCAP implementation) using appropriate statistical tests. The clinical and caring procedures used during the first 14 days of life were analyzed, with a focus on components of individualized developmental care (NIDCAP observations), infant pain management (number of painful procedures, clinical pain assessment), skin-to-skin contact (SSC; frequency, day of initiation, and duration), and family access and involvement in the care of their children (duration of parental presence, parental participation in care). The short-term mortality and morbidity at discharge were evaluated. Results: We examined 228 EPIs who received care during the three time periods. Over time, painful procedures decreased, but pain evaluations, parental involvement in care, individualized observations, and SSC increased (all p < 0.01). In addition, the first SSC was performed earlier (p = 0.03) and lasted longer (p < 0.01). There were no differences in mortality and morbidity, but there were reductions in the duration of mechanical ventilation (p = 0.02) and the time from birth to first extubation (p = 0.02), and an increase of weight gain at discharge (p = 0.02). Conclusion: NIDCAP implementation was accompanied by progressive, measurable, and significant changes in IFCDC strategies. There were, concomitantly, moderate but statistically significant improvements in multiple important outcome measures of all hospitalized EPI.

Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study.

Background: Early diagnosis is essential to improve the treatment and prognosis of newborn infants with nosocomial bacterial infections. Although cytokines and procalcitonin (PCT) have been evaluated as early inflammatory markers, their diagnostic properties have rarely been compared. Objectives: This study evaluated and compared the ability of individual inflammatory markers available for clinician (PCT, semi-quantitative determination of IL-8) and of combinations of markers (CRPi plus IL-6 or quantitative or semi-quantitative determination of IL-8) to diagnose bacterial nosocomial infections in neonates. Methods: This prospective two-center study included neonates suspected of nosocomial infections from September 2008 to January 2012. Inflammatory markers were measured initially upon suspicion of nosocomial infection, and CRP was again measured 12-24 h later. Newborns were retrospectively classified into two groups: those who were infected (certainly or probably) and uninfected (certainly or probably). Results: The study included 130 infants of median gestational age 28 weeks (range, 24-41 weeks). Of these, 34 were classified as infected and 96 as uninfected. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) for PCT were 59.3% (95% confidence interval [CI], 38.8-77.6%), 78.5% (95% CI, 67.8-86.9%), 48.5% (95% CI, 30.8-66.5%), 84.9% (95% CI, 74.6-92.2%), 2.7 (95% CI, 1.6-4.9), and 0.5 (95% CI, 0.3-0.8), respectively. Semi-quantitative IL-8 had the highest specificity (92.19%; 95% CI, 82.70-97.41%), PPV (72.22%; 95% CI, 46.52-90.30%) and LR+ (6.17, 95% CI, 2.67-28.44), but had low specificity (48.15%; 95% CI, 28.67-68.05%). Of all markers tested, the combination of IL-6 and CRPi had the highest sensitivity (78.12%; 95% CI, 60.03-90.72%), NPV (91.3%; 95% CI, 82.38-96.32%) and LR- (0.29; 95% CI, 0.12-0.49). The combination of IL-6 and CRPi had a higher area under the curve than PCT, but with borderline significance (p = 0.055). Conclusions: The combination of IL-6 and CRPi was superior to other methods, including PCT, for the early diagnosis of nosocomial infection in neonates, but was not sufficient for sole use. The semi-quantitative determination of IL-8 had good diagnostic properties but its sensitivity was too low for use in clinical practice.

Very preterm infants can detect small variations in light levels in incubators.

AIM: This prospective observational study was designed to improve our understanding of the responses of very preterm infants to light level variations in incubators and to evaluate what determined those reactions. METHODS: The physiological responses of 27 very preterm infants were analysed following variations in the light level environments of their incubators over 10 hours. Heart and respiratory rates, systemic oxygen saturation and regional cerebral oxygen saturations were recorded using near-infrared spectroscopy, and the variation of each parameter was analysed. RESULTS: We analysed 332 light level changes. Heart rate increased by 3.8 beats per minute (range -2.6 to 12.6), respiratory rate by six cycles per minute (-1.5 to 26) and regional cerebral oxygen saturation by 1.1% (-0.5% to 3.9%) (p < 0.05 each) when delta lux was over 50. Only respiratory rate decreased significantly, by -8.4 cycles per minute (-28 to -0.4), when delta lux was 50 or lower (p < 0.05). The initial level of illumination altered the very preterm infants' responses, with higher reactivity for higher ambient light levels. CONCLUSION: Very preterm infants reacted to moderate variations in illumination in their incubator, within recommended ranges of light levels, suggesting that they may detect even small light level variations.

Safety and effectiveness of skin-to-skin contact in the NICU to support neurodevelopment in vulnerable preterm infants.

Skin-to-skin contact (SSC) is a cornerstone of neurodevelopmentally supportive and family-oriented care for very low-birth-weight preterm infants (VPIs). However, performing SSC with unstable and/or ventilated VPIs remains challenging for caregiving teams and/or controversial in the literature. We first aimed to assess the safety and effectiveness of SSC with vulnerable VPIs in a neonatal intensive care unit over 12 months. Our second aim was to evaluate the impact of the respiratory support (intubation or not) and of the infant's weight (above or below 1000 g) on the effects of SSC. Vital signs, body temperature, and oxygen requirement data were prospectively recorded by each infant's nurse before (baseline), during (3 time points), and after their first or first 2 SSC episodes. We compared the variations of each parameter from baseline (analysis of variance for repeated measures with post hoc analysis when appropriate). We studied 141 SSCs in 96 VPIs of 28 (24-33) weeks' gestational age, at 12 (0-55) days of postnatal age, and at a postmenstrual age of 30.5 (±1.5) weeks. During SSC, there were statistically significant increases in oxygen saturation (Sao2) (P < .001) with decreases in oxygen requirement (P = .043), a decrease in heart rate toward stability (P < .01) but a transient and moderate decrease in mean axillary temperature following the transfer from bed to mother (P < .05). Apneas/bradycardias requiring minor intervention occurred in 19 (13%) SSCs, without need for SSC termination. These variations were similar for intubated newborns (18%) as compared with newborns on nasal continuous positive airway pressure (52%) or breathing room air (30%). However, ventilated infants exhibited a significant increase in transcutaneous partial pressure of carbon dioxide (TcPco2) (P = .01), although remaining in a clinically acceptable range, and a greater decrease in oxygen requirements during SSC (P < .001) than nonventilated infants. Skin-to-skin contact in the neonatal intensive care unit seems safe and effective even in ventilated VPIs. Recording physiologic data of infants before, during, and after SCC provides data needed to secure changes of practice in SCC.

Moderate acoustic changes can disrupt the sleep of very preterm infants in their incubators.

AIM: To evaluate the impact of moderate noise on the sleep of very early preterm infants (VPI). METHODS: Observational study of 26 VPI of 26-31 weeks' gestation, with prospective measurements of sound pressure level and concomitant video records. Sound peaks were identified and classified according to their signal-to-noise ratio (SNR) above background noise. Prechtl's arousal states during sound peaks were assessed by two observers blinded to the purpose of the study. Changes in sleep/arousal states following sound peaks were compared with spontaneous changes during randomly selected periods without sound peaks. RESULTS: We identified 598 isolated sound peaks (5 ≤ SNR < 10 decibel slow response A (dBA), n = 518; 10 ≤ SNR < 15 dBA, n = 80) during sleep. Awakenings were observed during 33.8% (95% CI, 24-43.7%) of exposures to sound peaks of 5-10 dBA SNR and 39.7% (95% CI, 26-53.3%) of exposures to sound peaks of SNR 10-15 dBA, but only 11.7% (95% CI, 6.2-17.1%) of control periods. The proportions of awakenings following sound peaks were higher than the proportions of arousals during control periods (p < 0.005). CONCLUSIONS: Moderate acoustic changes can disrupt the sleep of VPI, and efficient sound abatement measures are needed.

Spontaneous cries can alter the physiological well-being and cerebral oxygenation of very preterm infants.

INTRODUCTION: Infant crying is a major expression of distress and can occur without any exogenous stimulation. Little is known, however, about the effects of crying on physiological homeostasis in very preterm infants (VPIs). METHODS: Environmental, behavioral (video and audio recording) and physiologic (heart rate [HR], respiratory rate [RR], and systemic [SaO(2)] and regional cerebral oxygenation [rSO(2)]) parameters were prospectively evaluated over 10h in 18 VPIs (median gestational age, 28 [27-31] weeks). Only episodes of "spontaneous" and isolated cries were analyzed. Changes in parameters were compared over 5-second periods between baselines and 40s following the onset of crying. Two periods were distinguished: 0-20s (a) and 20-40s (b). Minimal and/or maximal values in these periods were also compared to the baseline. RESULTS: Of the 18 VPIs initially studied, 13 (72%) presented crying episodes (CE). They experienced 210 "spontaneous" and isolated CE, with a median of 9 [range, 1-63] CEs per child. Physiological values varied significantly from the baseline with mainly a mean decrease in HR of -4.8±5.3 beats/min (b) after an initial mean increase of +2.6±2.0 beats/min (a); a mean decrease in RR of -3.8±4.8 cycles/min (a), followed by a mean increase of +5.6±7.3 cycles/min (b) and mean unidirectional decreases in SaO(2) and rSO(2) (minimal values) of -1.8±2.3% and -2.5±3.0%, respectively. CONCLUSION: Spontaneous cries can alter the homeostasis of VPIs. Their possible adverse consequences and high occurrence emphasize the need for better prevention and response to them.

Infants born very preterm react to variations of the acoustic environment in their incubator from a minimum signal-to-noise ratio threshold of 5 to 10 dBA.

INTRODUCTION: Very early preterm infants (VPIs) are exposed to unpredictable noise in neonatal intensive care units. Their ability to perceive moderate acoustic environmental changes has not been fully investigated. RESULTS: Physiological values of the 598 isolated sound peaks (SPs) that were 5-10 and 10-15 dB slow-response A (dBA) above background noise levels and that occurred during infants' sleep varied significantly, indicating that VPIs detect them. Exposure to 10-15 dBA SPs during active sleep significantly increased mean heart rate and decreased mean respiratory rate and mean systemic and cerebral oxygen saturations relative to baseline. DISCUSSION: VPIs are sensitive to changes in their nosocomial acoustic environment, with a minimal signal-to-noise ratio (SNR) threshold of 5-10 dBA. These acoustic changes can alter their well-being. METHODS: In this observational study, we evaluated their differential auditory sensitivity to sound-pressure level (SPL) increments below 70-75 dBA equivalent continuous level in their incubators. Environmental (SPL and audio recording), physiological, cerebral, and behavioral data were prospectively collected over 10 h in 26 VPIs (GA 28 (26-31) wk). SPs emerging from background noise levels were identified and newborns' arousal states at the time of SPs were determined. Changes in parameters were compared over 5-s periods between baseline and the 40 s following the SPs depending on their SNR thresholds above background noise.

N-glycans of core2 beta(1,6)-N-acetylglucosaminyltransferase-I (C2GnT-I) but not those of alpha(1,3)-fucosyltransferase-VII (FucT-VII) are required for the synthesis of functional P-selectin glycoprotein ligand-1 (PSGL-1): effects on P-, L- and E-selectin binding.

C2GnT-I [core2 beta(1,6)-N-acetyglucosaminyltransferase-I] and FucT-VII [alpha(1,3)-fucosyltransferase-VII] are the key enzymes for the biosynthesis of sialyl-Lewis x determinants on selectin ligands and therefore they represent good drug targets for the treatment of inflammatory disorders and other pathologies involving selectins. In the present study, we examined the importance of N-glycosylation for the ability of C2GnT-I and FucT-VII to generate functional selectin ligands, particularly the PSGL-1 (P-selectin glycoprotein ligand-1). We found that (i) both enzymes have their two N-glycosylation sites occupied, (ii) for C2GnT-I, the N-glycan chain linked to Asn-95 significantly contributes to the synthesis of functional PSGL-1 and is required to localize the enzyme to the cis/medial-Golgi compartment, (iii) all N-glycosylation-deficient proteins of FucT-VII displayr a dramatic impairment of their in vitro enzymatic activities, but retain their ability to fucosylate the core2-modified PSGL-I and to generate P- and L-selectin binding, and (iv) the glycomutants of FucT-VII fail to synthesize sialyl-Lewis x or to generate E-selectin binding unless core2-modified PSGL-1 is present. All combined, our results show a differential functional impact of N-glycosylation on C2GnT-1 and FucT-VII and disclose that a strongly reduced FucT-VII activity retains the ability to fucosylate PSGL-1 on the core2-based binding site(s) for the three selectins.

Intramural bronchogenic cyst in the carina observed in a neonate and treated by needle aspiration: a case report.

We report the first case to be observed in a neonate of an intramural bronchogenic cyst in the carina. Considering the age of the infant, it was decided to administer curative treatment by needle aspiration. A rigid bronchoscopy was used. The outcome was favorable.

Neonatal necrotizing tracheobronchitis: three case reports.

Necrotizing tracheobronchitis is a serious affection observed in ventilated newborns, frequently infants with instable hemodynamic state. It is characterized by acute episodes of airway obstruction. The treatment consists of the desobstruction by rigid bronchoscopy. The vascular theory seems to be of utmost importance in the physiopathology. Three cases are reported.

Dynamic recruitment of the adaptor protein LAT: LAT exists in two distinct intracellular pools and controls its own recruitment.

The integral membrane adaptor protein linker for activation of T cells (LAT) couples the T-cell receptor (TCR) with downstream signalling and is essential for T-cell development and activation. Here, we investigate the dynamic distribution of LAT-GFP fusion proteins by time-lapse video imaging of live T lymphocytes interacting with antigen-presenting cells. We show that LAT forms two distinct cellular pools, one at the plasma membrane and one that co-distributes with transferrin-labelled intracellular compartments also containing the TCR/CD3-associated zeta chain. The distribution of LAT between these two pools is dependent on LAT intracytoplasmic residues. Whereas plasma membrane-associated LAT is recruited to immune synapses after a few seconds of cell conjugate formation, the intracellular pool is first polarized and then recruited after a few minutes. We further show that LAT intracytoplasmic amino acid residues, particularly the Tyr136, 175, 195 and 235 residues, are required for its own recruitment to the immune synapse and that a herein-identified juxtamembrane LAT region (amino acids 32-104) is involved in the localization of LAT in intracellular pools and in T-cell signalling. Altogether, our results demonstrate that LAT controls its own recruitment at the immune synapse, where it is required as a scaffold protein for the signalling machinery. The results also suggest that the intracellular pool of LAT might be required for T-cell activation.

Transgene expression of alpha(1,2)-fucosyltransferase-I (FUT1) in tumor cells selectively inhibits sialyl-Lewis x expression and binding to E-selectin without affecting synthesis of sialyl-Lewis a or binding to P-selectin.

During inflammation, E- and P-selectins appear on activated endothelial cells to interact with leukocytes through sialyl-Lewis x and sialyl-Lewis a antigens (sLe(x/a)). These selectins can also interact with tumor cells in a sialyl-Lewis-dependent manner and for this reason, they are thought to play a key role in metastasis. Diverting the biosynthesis of sialyl-Lewis antigens toward nonadhesive structures is an attractive gene therapy for preventing the hematogenous metastatic spread of cancers. We have previously shown that transfection of alpha(1,2)-fucosyltransferase-I (FUT1) in Chinese hamster ovary (CHO) cells had a slight effect on the overall sialylation while the synthesis of sLE(x) was dramatically prevented. We herein delivered the gene of FUT1 by a human immunodeficiency virus-derived lentiviral vector to three human cancer cell lines including pancreatic (BxPC3), hepatic (HepG2), and colonic (HT-29) cancer cells. We found that on FUT1 transduction, all cells exhibited a dramatic decrease in sLe(x) synthesis with a concomitant increase in Le(y) and Le(b) expression, without any detectable effect on the level of cell surface sLe(a) antigens. In parallel, FUT1-transduced HT-29 and HepG2 cells, but not BxPC3 cells, failed to interact with E-selectin as assessed by E-selectin-binding assay or dynamic adhesion to activated endothelial cells. We show also that transduced FUT1 efficiently fucosylates the P-selectin ligand PSGL-1 without altering P-selectin binding. These results have important implications for understanding cell-specific reactions underlying the synthesis of selectin ligands in cancer cells and may provide a basis for the development of anti-metastatic gene therapy.

TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts.

Recent studies suggest that rafts are involved in numerous cell functions, including membrane traffic and signaling. Here we demonstrate, using a polyoxyethylene ether Brij 98, that detergent-insoluble microdomains possessing the expected biochemical characteristics of rafts are present in the cell membrane at 37 degrees C. After extraction, these microdomains are visualized as membrane vesicles with a mean diameter of approximately 70 nm. These findings provide further evidence for the existence of rafts under physiological conditions and are the basis of a new isolation method allowing more accurate analyses of raft structure. We found that main components of T cell receptor (TCR) signal initiation machinery, i.e. TCR-CD3 complex, Lck and ZAP-70 kinases, and CD4 co-receptor are constitutively partitioned into a subset of rafts. Functional studies in both intact cells and isolated rafts showed that upon ligation, TCR initiates the signaling in this specialized raft subset. Our data thus strongly indicate an important role of rafts in organizing TCR early signaling pathways within small membrane microdomains, both prior to and following receptor engagement, for efficient TCR signal initiation upon stimulation.

The cytosolic and transmembrane domains of the beta 1,6 N-acetylglucosaminyltransferase (C2GnT) function as a cis to medial/Golgi-targeting determinant.

The beta 1,6 N-acetylglucosaminyltransferase (C2GnT) has been recently mapped to the cis/medial-Golgi compartment. To analyze the Golgi-targeting determinants of C2GnT, we constructed various deletion mutants of the enzyme fused to the enhanced green fluorescent protein (EGFP) and localized these proteins by fluorescence microscopy in living cells. We found that the N-terminal peptide encompassing amino acids 1 to 32 represents the minimal Golgi-targeting signal sufficient to localize EGFP to the same compartment as the full-length C2GnT. This peptide makes up the cytoplasmic and the transmembrane domains of the enzyme and was referred to as CTd (cytoplasmic and transmembrane domains). We compared the Golgi-targeting efficiency of the C2GnT-derived CTd with its homologous domains from other glycosyltransferases, including the H-type alpha(1,2)-fucosyltransferase (FucTI), the polypeptide N-acetylgalactosaminyltransferase-I (GalNAcT-I), the alpha(1,3)-fucosyltransferase VII (FucTVII), and the alpha(2,6)-sialyltransferase (ST6Gal-I) and found that the Golgi-targeting determinants of these glycosyltransferases were also composed of their cytosolic and transmembrane domains. To investigate whether the CTd of C2GnT could serve as a cis to medial Golgi-specific signal, we tested its ability to mislocalize two late-Golgi acting glycosyltransferases FucTI and FucTVII. We show that fusing the C2GnT-derived CTd with the catalytic domain of FucTVII resulted in a complete mislocalization of the enzyme to the C2GnT compartment, with a parallel alteration of sialyl-Lewis x synthesis and P-selectin binding. The intracellular distribution and activity of FucTI, however, were not affected. Thus, CTds of either early or late-Golgi acting glycosyltransferases represent the Golgi-targeting domains of these enzymes. In addition, we show that C2GnT-derived CTd can function as a cis/medial Golgi-targeting determinant.

Role of ICAM-3 in the initial interaction of T lymphocytes and APCs.

Antigen-independent adhesive interactions between T lymphocytes and antigen-presenting cells (APCs) are essential for scanning for specific antigens on the APC surface and for initiating the immune response. Here we show, through time-lapse imaging of live cells, that the intercellular adhesion molecule 3 (ICAM-3, also known as CD50) is clustered specifically at the region of the T lymphocyte surface that initiates contact with APCs. We describe the role of ICAM-3 in T cell-APC conjugate formation before antigen recognition, in early intracellular signaling and in cytoskeletal rearrangement. Our data indicate that ICAM-3 is important in the initial scanning of the APC surface by T cells and, therefore, in generating the immune response.