Effect of standardized vs. local preoperative enteral feeding practice on the incidence of NEC in infants with duct dependent lesions: Protocol for a randomized control trial.

Background: Infants with duct dependent heart lesions often require invasive procedures during the neonatal or early infancy period. These patients remain a challenge for pediatric cardiologists, neonatologists, and intensive care unit personnel. A relevant portion of these infant suffer from respiratory, cardiac failure and may develop NEC, which leads to inadequate growth and nutrition, causing delayed or complicated cardiac surgery. Methods: This randomized control trial will recruit term infants diagnosed with a duct dependant lesion within the first 72 h of life. After obtaining written parental consent patients will be randomized to either the physician led enteral feeding or protocol-based feeding group. The intervention will continue up to 28 days of life or day of cardiosurgical treatment, whichever comes first. The primary outcomes include NEC and death related to NEC. Secondary outcomes include among others, number of interrupted feedings, growth velocity, daily protein and caloric intake, days to reach full enteral feeding and on mechanical ventilation. Discussion: Our study will be the first randomized control trial to evaluate if standard (as in healthy newborns) initiation and advancement of enteral feeding is safe, improves short term outcomes and does not increase the risk of NEC. If the studied feeding regime proves to be intact, swift implementation and advancement of enteral nutrition may become a recommendation. Trial registration: The study protocol has been approved by the local ethical board. It is registered at ClinicalTrials.gov NCT05117164.

Usefulness of two types of pain monitors in newborns treated in NICU, in the opinion of experts: Results of the survey.

Pain experienced in the neonatal period has been shown to have serious short- and long-term consequences. It is also known that painkillers have side effects and should not be abused. The basis of proper pain management is assessment of pain, which in newborns is very difficult due to the lack of verbal communication. In these patients, behavioural scales are used to assess pain, but they have numerous shortcomings. For this reason, many newborns treated in the ICU are at risk of pain, so instrumental methods of detecting and assessing the severity of pain are being sought. During three months, seven Polish NICUs conducted research with the use of NIPE and SCA monitors. After this time, the heads of these departments filled in questionnaires regarding their individual opinions on the usefulness of these devices. All respondents found pain monitors useful in the NICU. The NIPE monitor was rated slightly higher, as its usefulness in assessing the effectiveness of analgosedation and in the management of patients in the postoperative period was better rated. The high acceptance of both devices by legal guardians of newborns is noteworthy. It should be stated that in newborns, any way to improve pain monitoring is valuable. In the opinion of Polish experts, pain monitors are useful in NICU. The NIPE monitor was assessed a little higher and was considered useful in the assessment of analgosedation and in postoperative treatment. Pain monitors can provide valuable support for pain assessment in newborns treated in the NICU.

Newborn infant parasympathetic evaluation for the assessment of analgosedation adequacy in infants treated by mechanical ventilation - a multicenter pilot study.

INTRODUCTION: Adequate analgosedation is important in infants treated in pediatric/neonatal intensive care units (P/NICUs), because both too deep and insufficient analgosedation is disadvantageous. To assess the severity of pain, several behavioral and behavioral-physiological scales are used, but their usefulness is limited. It is therefore justified to search for additional methods to assess the adequacy of analgosedation in these patients. The aim of the present study is to evaluate the usefulness of Newborn Infant Parasympathetic Evaluation (NIPE) in the assessment of analgosedation quality in infants requiring mechanical ventilation, who are treated in P/NICUs. MATERIAL AND METHODS: We performed simultaneously 180 COMFORT-B assessments and heart rate variability measurements using a NIPE monitor in 30 mechanically ventilated infants receiving analgosedation. A generalized linear mixed model with the logit link function was used in order to perform logistic regression analysis to assess the relationship between NIPEi/NIPEm and deep sedation. RESULTS: The multivariable logistic regression model showed that NIPEi and NIPEm values were higher when analgosedation was deep as compared to when it was moderate or insufficient (OR (95% CI): NIPEm - 1.065 (1.007-1.126), p = 0.03; NIPEi - 1.068 (1.016-1.123), p = 0.01). CONCLUSIONS: The NIPE indexes are significantly higher in patients whose assessment on the behavioral scale indicates deep analgosedation as compared to those in whom it indicates moderate or insufficient analgosedation. Allowing continuous monitoring, the NIPE device may be a valuable assisting tool in the assessment of analgosedation quality in mechanically ventilated newborns and infants.

Available Instruments to Assess Pain in Infants.

Pain assessment in newborns and infants is challenging for clinicians. Although behavioral and behavioral-physiological scales are validated pain assessment instruments, their use in this age group has significant limitations. In this review, we summarize the methods currently available for assessing pain in neonates and infants. It is possible that these pain detection methods are also useful for assessing the quality of anesthesia and analgosedation in these populations. Further research should be aimed at confirming the usefulness of these tools in infants and identifying additional pain assessment options for clinical practice.

Newborn Infant Parasympathetic Evaluation Index for the Assessment of Procedural Pain in Nonanesthetized Infants: A Multicenter Pilot Study.

OBJECTIVE: The aim of this study is to evaluate the ability of the Newborn Infant Parasympathetic Evaluation (NIPE) index to detect the response to nociceptive stimuli in nonanesthetized infants and to compare these results to simultaneous scoring by behavioral scales. STUDY DESIGN: Thirty-six nonanesthetized infants admitted to neonatal/pediatric intensive care unit (N/PICUs) were enrolled to the study. Due to faulty records of the data, three patients had to be excluded. To detect pain caused by noxious stimuli, the heart-rate-variability-derived NIPE index and behavioral pain scales designed for measuring procedural pain in nonverbal children were used. RESULTS: Forty-one painful events were available for analysis. We observed in the whole group a statistically significant decrease in NIPE values at 1, 2, and 3 minutes after a painful stimulus, in comparison to the NIPE value at rest and the statistically significant differences between the minimum NIPE value within 3 minutes after the stimulus in comparison to NIPE value at rest in the whole group, as well as in the subgroups of moderate and severe pain. Receiver operating characteristic (ROC) analysis has shown the strong sensitivity and specificity of the NIPE in detecting the noxious stimuli (ROC AUC: 0.767). We also found that the stronger the sensation of pain was, the more rapidly NIPE reached its lowest value. DISCUSSION: Our study indicates that the painful procedures are associated with a significant decrease in the NIPE value within 3 minutes after a noxious stimulus. Based on our observation, the minimum value within 3 minutes from the painful procedure seems to be the most distinctive value.

Procedural Pain Assessment in Infants Without Analgosedation: Comparison of Newborn Infant Parasympathetic Evaluation and Skin Conductance Activity - A Pilot Study.

Objective: New technologies to measure pain responses, such as heart rate variability and skin conductance hold promise in the development of tools that can be reliable and quantifiable of detecting pain. The main objective of this study was to assess the capability of two monitors i.e., Newborn Infant Parasympathetic Evaluation (NIPE) and Skin Conductance Algesimeter for detecting procedural pain in non-anesthetized infants. Materials and Methods: Thirty-three non-anesthetized infants were enrolled to the study. To detect pain caused by heel stick, NIPE, and Skin Conductance monitors and behavioral pain scales were used. Three minutes before and just after heel stick, pain was evaluated by behavioral scales, and simultaneously over the whole period by NIPE and SCA. Results: A statistically significant decrease of NIPE Index and an increase of SCA values were found after the HS procedure. There were no statistically significant differences between the decrease in NIPEi values and the increase in PPS values between subgroups based on pain assessment by behavioral-scale scores. Conclusion: Both NIPE and SCA can be useful for detection of procedural pain and may constitue an additional valuable tool for better handling of pain among patients treated in NICUs. More studies on larger groups of patients are needed.

Skin conductance measurement for the assessment of analgosedation adequacy in infants treated with mechanical ventilation: A multicenter pilot study.

BACKGROUND: Patients treated in neonatal/pediatric intensive care units (N/PICUs) are frequently exposed to pain. To assess its severity, several behavioral and behavioral-physiological scales are used, but their usefulness is limited. It is therefore justified to search for additional methods to assess the adequacy of analgesia and sedation in these patients. OBJECTIVES: To evaluate the usefulness of skin conductance (SC) measurement in the assessment of analgosedation quality in infants requiring mechanical ventilation treated in N/PICUs. MATERIAL AND METHODS: Thirty infants aged 6-208 days treated in 6 N/PICUs, mechanically ventilated and receiving analgosedation, were included for the study. Simultaneous COMFORT-B assessment and SC measurement using SCA (skin conductance algesimeter) monitor were performed. Due to technical problems, not all of the SC records could be interpreted, and finally 412 simultaneous assessments on the COMFORT-B scale and SC measurements in 29 patients were analyzed. RESULTS: We found a statistically significant correlation between the COMFORT-B scoring and the SC measurements. Additionally, SC was significantly lower when the behavioral score indicated deep sedation, in comparison to periods when it indicated moderate or insufficient analgosedation. CONCLUSIONS: Skin conductance measurements are comparable with the COMFORT-B rating in mechanically ventilated infants receiving analgosedation. The SCA monitor may be of value in the assessment of analgosedation quality, and in particular may identify the situation where sedation is deep. Further research is needed regarding the suitability of this device in clinical practice.

Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis.

Post-translational modifications are necessary for collagen precursor molecules (procollagens) to acquire final shape and function. However, the mechanism and contribution of collagen modifications that occur outside the endoplasmic reticulum and Golgi are not understood. We discovered that VIPAR, with its partner proteins, regulate sorting of lysyl hydroxylase 3 (LH3, also known as PLOD3) into newly identified post-Golgi collagen IV carriers and that VIPAR-dependent sorting is essential for modification of lysines in multiple collagen types. Identification of structural and functional collagen abnormalities in cells and tissues from patients and murine models of the autosomal recessive multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome caused by VIPAR and VPS33B deficiencies confirmed our findings. Thus, regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis and for the development and function of multiple organs and tissues.

Determinants of Postpartum Vitamin D Status in the Caucasian Mother-Offspring Pairs at a Latitude of 52°N: A Cross-Sectional Study.

BACKGROUND: High prevalence of vitamin D deficiency in pregnancy is recorded. AIM: To establish determinants of postpartum 25-hydroxyvitamin D (25(OH)D) levels on mothers and offspring. METHODS: 25(OH)D level was measured in cord blood and maternal blood collected ≤3 weeks postpartum. Maternal socioeconomic status, vitamin D intake, sun exposure during pregnancy and maternal and neonatal fat mass (FM; dual X-ray absorptiometry) were assessed within 3 weeks postpartum. RESULTS: A total of 174 mother-offspring pairs were enrolled. Maternal 25(OH)D <20 ng/ml was seen in 32 (51%) of summer and 82 (74%) of winter deliveries. Women with 25(OH)D <20 ng/ml had a 2-fold lower percentage of vitamin D intake of ≥800 IU/day than women with 25(OH)D ≥20 ng/ml (p = 0.02). FM (%) was comparable between groups (p > 0.05). Multiple regression analysis revealed the delivery season, prenatal vitamin D intake ≥800 IU/day and duration of supplementation to be the determinants of maternal 25(OH)D level (R(2) = 0.26, p < 0.001). Maternal 25(OH)D level, season of birth and duration of maternal supplementation explained 83% of the variance in cord blood 25(OH)D level (R(2) = 0.83, p < 0.001). CONCLUSIONS: The key determinants of higher maternal vitamin D status were the summer-autumn season of delivery and prenatal use of ≥800 IU/day of vitamin D. The cord blood 25(OH)D level was mainly determined by maternal 25(OH)D level and season of birth.

Impact of vitamin D supplementation during lactation on vitamin D status and body composition of mother-infant pairs: a MAVID randomized controlled trial.

OBJECTIVE: The optimal vitamin D intake for nursing women is controversial. Deterioration, at least in bone mass, is reported during lactation. This study evaluated whether vitamin D supplementation during lactation enhances the maternal and infant's vitamin D status, bone mass and body composition. DESIGN AND METHODS: After term delivery, 174 healthy mothers were randomized to receive 1200 IU/d (800 IU/d+400 IU/d from multivitamins) or 400 IU/d (placebo+400 IU/d from multivitamins) of cholecalciferol for 6 months while breastfeeding. All infants received 400 IU/d of cholecalciferol. Serum 25-hydroxyvitamin D [25(OH)D], iPTH, calcium, urinary calcium, and densitometry were performed in mother-offspring pairs after delivery, and at 3 and 6 months later. RESULTS: A total of 137 (79%) (n = 70; 1200 IU/d, n = 67; 400 IU/d) completed the study. 25(OH)D was similar in both groups at baseline (13.7 ng/ml vs. 16.1 ng/ml; P = 0.09) and at 3 months (25.7 ng/ml vs. 24.5 ng/ml; P = 0.09), but appeared higher in the 1200 IU/d group at 6 months of supplementation (25.6 ng/ml vs. 23.1 ng/ml; P = 0.009). The prevalence of 25(OH)D <20 ng/ml was comparable between groups at baseline (71% vs. 64%, P = 0.36) but lower in the 1200 IU/d group after 3 months (9% vs. 25%, P = 0.009) and 6 months (14% vs. 30%, P = 0.03). Maternal and infants' iPTH, calciuria, bone mass and body composition as well as infants' 25(OH)D levels were not significantly different between groups during the study. Significant negative correlations were noted between maternal 25(OH)D and fat mass (R =  -0.49, P = 0.00001), android fat mass (R = -0.53, P = 0.00001), and gynoid fat mass (R = -0.43, P = 0.00001) after 6 months of supplementation. CONCLUSIONS: Vitamin D supplementation at a dose of 400 IU/d was not sufficient to maintain 25(OH)D >20 ng/ml in nursing women, while 1200 IU/d appeared more effective, but had no effect on breastfed offspring vitamin D status, or changes in the bone mass and the body composition observed in both during breastfeeding. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506557.