Is 25OH Vitamin D Excess before 36 Weeks Corrected Age an Independent Risk Factor for Bronchopulmonary Dysplasia or Death?

Low 25-Hydroxyvitamin D (25(OH)D) in preterm infants is a risk factor for bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate a beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and histological alterations in the lung evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120 nmol/L are also a risk factor for BPD or death. This retrospective single-center cohort study included only infants born at <31 weeks gestational age without major malformations with at least a determination of 25(OH)D at <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120 nmol/L (50.5% vs. 43.9%, p = 0.53). The logistic regression identified weight (OR 0.997, 95% CI [0.995-0.998]) and term (OR 0.737, 95% CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95% CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

Impact of a nurse education programme on oral feeding in a neonatal unit.

BACKGROUND: Premature neonates often experience feeding difficulties during their hospital stay, and evidence-based interventions have been shown to improve feeding outcomes. AIM: This study investigated whether an infant-cue based nurse educational feeding bundle accelerates the achievement of independent oral feeding in neonates in a neonatal intensive care unit. STUDY DESIGN: A quality improvement study with a pre, during and post intervention test design. All premature neonates admitted to the unit were eligible. The feeding programme included a four-month nurse training module and nurse coaching. RESULTS: A hundred and twenty-five nurses or nurse assistants attended the programme and 706 neonates were included. The median time to independent oral feeding (IOF) was 40, 36 and 37 days, respectively, for pre, during and post intervention. The reduction in time to IOF observed during the post-intervention period compared with the baseline period was significant (HR = 1.32, CI 95%: 1.01-1.74). No difference was noted in the length of hospital stay between the three study periods. CONCLUSIONS: An infant-cue based nurse educational feeding bundle can promote earlier achievement of IOF in preterm neonates. RELEVANCE TO CLINICAL PRACTICE: This quality improvement study demonstrates the impact that a nurse-driven intervention in neonatal care can have on improving practice. Feeding interventions involve the early introduction of oral feeding, non-nutritive sucking (NNS), and oral motor stimulation, and should be individualized for each neonate. These individualized feeding interventions applied by all nurses and assistant nurses, can facilitate the achievement of earlier independent oral feeding in preterm infants and should be included in neonatal critical care nurse education programs.

A Positive Impact of an Observational Study on Breastfeeding Rates in Two Neonatal Intensive Care Units.

We aimed to investigate whether the participation in an observational study on breastfeeding (Doal) modified breastfeeding outcomes in enrolling neonatal intensive care units (NICUs). This bi-centric before-and-after study included neonates who were admitted during a 4-month period before and a 4-month period after the implementation of Doal. Breastfeeding intention and breastfeeding rates at discharge were compared between the two periods. The association between inclusion in Doal and breastfeeding at discharge was assessed among the infants fulfilling the inclusion criteria of Doal. The present study included 655 neonates. After adjustments, both breastfeeding (aOR 1.21, 95%CI [1.1; 1.4], p = 0.001) and exclusive breastfeeding (aOR 1.8, 95%CI [1.4; 2.3], p < 0.001) at discharge increased in the period after. Breastfeeding intention was higher in one center in the period after (79%) compared to before (59%, p = 0.019). Compared to the period before, neonates who were not included in Doal in the period after had a lower chance to be breastfed at discharge, whereas those included were more frequently exclusively breastfed. The participation in an observational study on breastfeeding was associated with an increase in breastfeeding outcomes in enrolling neonatal intensive care units (NICUs). Patients who are not included deserve attention as they are at risk to be disadvantaged regarding breastfeeding success.

Local protocol helped to deliver vitamin D levels more accurately in preterm infants.

AIM: This study retrospectively evaluated the effectiveness and safety of a local hospital protocol of vitamin D supplementation for preterm infants, which was modified in 2016. METHODS: We focussed on 99 preterm infants born before 31 weeks of gestation and admitted to the neonatal intensive care unit at the Femme Mere Enfant Hospital, Bron, France, from 1 January to 31 December 2018. Calcium and urinary calcium were measured, and 25-hydroxy vitamin D (25(OH)D) levels were monitored monthly and supplementation was adjusted, with 50-120 nmol/L considered normal. The results are presented as medians and interquartile ranges. RESULTS: The infants were enrolled at a gestational age of 28.0 [26.9-29.1] weeks and birth weight of 960 [800-1160] g. When they were discharged at 37.3 [35.2-39.8] weeks, the overall 25(OH)D level was 98 [79-140] nmol/L: 4% had low levels, 63% had normal levels and 33% had high levels. Vitamin D supplementation was withdrawn for 60% more than one month before discharge. Rickets or fractures were not reported. CONCLUSION: The modified protocol limited underdosing and significant overdosing, but moderate hypervitaminosis D was still frequent. Urgent studies are needed to determine the optimal supplementation and clinical impact of 25(OH)D on comorbidities in preterm infants.

Breastfeeding peer counselling for mothers of preterm neonates: protocol of a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Among preterm infants, mother's own milk feeding reduces neonatal morbidity and decreases the length of hospital stay. However, breastfeeding rates and duration are lower than among term infants. It is reported that peer counselling is effective in increasing breast feeding in term infants in low-income and middle-income countries, but results are mixed in high-income countries. We aim to investigate herein whether peer counselling may be a feasible and effective breastfeeding support among preterm infants in French-speaking high-income countries. METHODS AND ANALYSIS: Eight European centres will participate in this stepped-wedge cluster randomised controlled trial. We plan to include 2400 hospitalised neonates born before 35 gestational weeks. Each centre will begin with an observational period. Every 3 months, a randomised cluster (centre) will begin the interventional period with peer counsellors until the end of the study. The counsellors will be trained and supervised by the trained nurses. They will have a weekly contact with participating mothers, with a face-to-face meeting at least once every fortnight. During these meetings, peer counsellors will listen to mothers' concerns, share experiences and help the mother with their own knowledge of breast feeding. The main outcome is breastfeeding rate at 2 months corrected age. Secondary outcomes are breastfeeding rates at hospital discharge and at 6 months, breastfeeding duration and severe neonatal morbidity and mortality. The mental health of the mother, mother-infant bonding and infant behaviour will be assessed using self-report questionnaires. A neurodevelopmental follow-up, a cost-effectiveness analysis and a cost-consequence at 2 years corrected age will be performed among infants in a French subgroup. ETHICS AND DISSEMINATION: French, Belgian and Swiss ethics committees gave their agreement. Publications in peer-reviewed journals are planned on breast feeding, mental health and economic outcomes. TRIAL REGISTRATION NUMBER: NCT03156946.

Early Use of Mother's Own Raw Milk, Maternal Satisfaction, and Breastfeeding Continuation in Hospitalised Neonates: A Prospective Cohort Study.

BACKGROUND: Despite the critical importance of breast milk for preterm and sick neonates, there is no consensus regarding the use of raw mother's own milk (MOM) in neonatal units. OBJECTIVES: This study aimed to describe the use of raw MOM in hospitalised neonates before day 7 (early use), and to investigate: (i) related factors, (ii) maternal satisfaction, and (iii) the association with breastfeeding continuation. METHODS: This prospective cohort included 516 neonates intended to be breastfed in 2 French neonatal units. Neonates receiving raw MOM before day 7 were compared to those who did not. The association between early use of MOM and breastfeeding continuation at hospital discharge, and up to 6 months later, was measured by logistic regression. RESULTS: More than one-third (36.2%) of breastfed neonates did not receive any MOM during their first week, mainly due to organisational constraints and staff reluctance. Maternal satisfaction related to early raw MOM use was high (96%), and was coupled with a more frequent maternal feeling of being supported in breastfeeding (p = 0.003). There was a significant association between early use of MOM and breastfeeding continuation at discharge (OR 2.92, 95% CI 1.94-4.40, p < 0.0001), which persisted 6 months later (OR 2.70, 95% CI 1.21-6.03, p = 0.023). This association appeared independent in multivariable analyses (at discharge: aOR 2.03, 95% CI 1.27-3.25, p = 0.003; 6 months later: aOR 2.46, 95% CI 1.02-5.92, p = 0.045). CONCLUSION: While the early use of raw MOM in hospitalised neonates can be limited by multiple factors, it appears supportive for mothers, and might represent a simple opportunity to improve breastfeeding in neonatal units.

Shielding Parenteral Nutrition From Light Improves Survival Rate in Premature Infants.

BACKGROUND: Intravenous nutrition preparations that are not photoprotected generate oxidants, which are deleterious for cell survival. The question remains: are these observations of clinical relevance in individuals receiving parenteral nutrition (PN), especially in those who exhibit immature antioxidant defenses such as premature infants? OBJECTIVE: To review clinical trials reporting the effect of light-exposed vs light-protected PN to determine whether photoprotection reduces neonatal mortality in preterm infants. DATA SOURCE: Electronic databases, abstracts in relevant journals, and references in manuscripts between 1980 and 2014. SELECTION CRITERIA: Newborn, premature infants, PN, photoprotection, shielding from light, randomization, mortality, death. METHODS: Consensus for inclusion reached by 2 reviewers; meta-analysis of trials and observational studies reporting mortality at 36 weeks' gestational age or hospital discharge. RESULTS: Four trials meeting selection criteria, which involved a total of 800 newborn premature infants, were included. Across trials, gestational age (mean ± SD) ranged from 26 ± 1 to 31 ± 2 weeks, birth weight from 775 ± 161 to 1588 ± 366 g, and mortality from 5%-32%. Mortality in the light-protected group was half of that in the light-exposed group (95% confidence interval, 0.32-0.87) and twice as high in males compared with females (χ2, P = .01). CONCLUSION: Shielding PN from light has vital repercussions that call for action to provide photoprotected delivery systems and infusion sets in premature infants. Further studies should be extended to the increasing number of children and adults receiving long-term home PN to evaluate the effects of light protection on severe complications that impede their quality of life.

Low phosphatemia in extremely low birth weight neonates: A risk factor for hyperglycemia?

BACKGROUND & AIMS: Hyperglycemia occurs in more than half of the extremely low birth weight (ELBW) neonates during the first weeks of life, and is correlated with an increased risk of morbi-mortality. Hypophosphatemia is another frequent metabolic disorder in this population. Data from animal, adult studies and clinical observation suggest that hypophosphatemia could induce glucose intolerance. Our aim was to determine whether a low phosphatemia is associated with hyperglycemia in ELBW neonates. METHODS: This observational study included ELBW infants admitted in a tertiary neonatal care center (2010-2011). According to the center's policy, they received parenteral nutrition from birth and human milk from day 1. Phosphatemia and glycemia were measured routinely during parenteral nutrition. Hyperglycemia was defined by two consecutives values >8.3 mmol/L (150 mg/dL). Statistical analysis used a joint model combining a mixed-effects and a survival submodels to measure the association between phosphate and hyperglycemia. RESULTS: The study included 148 patients. Mean gestational (Standard Deviation) age was 27.3 (1.6) weeks; mean birth weight was 803 (124) grams; 57% presented hyperglycemia. The multivariate joint model showed that the hazard of hyperglycemia at a given time was multiplied by 3 for each 0.41 mmol/L decrease of phosphate level at this time (p = 0.002) and by 3.85 for the same decreased of phosphate the day before (p = 0.0015). CONCLUSION: To our knowledge, this is the first study suggesting that low phosphatemia can be associated with hyperglycemia in ELBW neonates. Further studies will have to demonstrate whether better control of phosphatemia could help in preventing hyperglycemia.

Shielding Parenteral Nutrition Solutions From Light: A Randomized Controlled Trial.

INTRODUCTION: Oxidant stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Light induces peroxide generation in parenteral nutrition (PN) solutions, creating an oxidant stress. Shielding PN from light decreases its peroxide content, which has nutrition and biochemical benefits in animals and humans. This study aims at determining whether full light protection of PN decreases the rate of bronchopulmonary dysplasia and/or death in very low-birth-weight infants. METHODS: Multicenter randomized controlled trial of photoprotection, using amber bags and tubing initiated during compounding of PN and maintained throughout infusion in the light-protected (LP) group. The control group (light exposed [LE]) received PN exposed to ambient light. Depending on centers, lipids were infused either separately or as all-in-one PN. RESULTS: In total, 590 infants born <30 weeks gestational age were included. At randomization, LE and LP groups did not differ clinically except for maximal FiO2 before 12 hours. The rate of BPD/death was not different between groups at 28 days (77% LP vs 72% LE, P = .16) or at 36 weeks corrected age (30% LP vs 27% LE, P = .55). Multivariate analysis showed no significant effect of photoprotection on BPD and/or death. The rate of BPD/death was significantly lower (odds ratio, 0.54; 95% confidence interval, 0.32-0.93; P = .02) in infants receiving all-in-one PN vs those who received lipids separately. CONCLUSION: This study did not show significant beneficial effects of photoprotection. Since the decreased rate of BPD/death found with all-in-one PN relates to a center-dependent variable, this warrants further investigation.

[Issues surrounding the breastfeeding of hospitalized newborns]. / Les enjeux de l'allaitement maternel pour les nouveau-nés hospitalisés.

The nutritional and physiological qualities of breast milk make it the best food for newborns, favouring their wellbeing and growth. The implementation of a programme encouraging the breastfeeding of hospitalised newborns in care departments requires specific methods of organisation, as well as constant and adapted support from health professionals.

Outcome and prognostic factors in neonates with septic shock.

OBJECTIVE: Few accurate data are available on the outcome of septic shock in the neonatal period. The objective was to describe outcome and to determine variables associated with death or adverse outcome in neonates with septic shock. DESIGN: Retrospective cohort study. SETTING: A tertiary neonatal intensive care unit in a university hospital. PATIENTS: All patients admitted to the neonatal intensive care unit over a 6-yr period meeting the following criteria: hypotension and/or need for intravenous fluid administration or vasoactive drugs, in the presence of proven or highly probable infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Main outcomes were 28-day mortality and adverse outcome at 18 months of corrected age, defined as death or severe sequelae (cerebral palsy, severe developmental delay, hearing impairment, blindness, or short bowel syndrome). Forty-eight infants were included. Follow-up data at 18 months were obtained for 46 of 48 infants. The 28-day mortality was 40% (19 deaths). Adverse outcome at 18 months of corrected age was observed in 24 of 46 infants (52%; death = 19, severe sequelae = 5). Twenty-eight percent of the infants were alive and had a normal examination at 18 months. Infants with adverse outcome had significantly lower gestational age, birth weight, Apgar score, weight at onset of sepsis, and pH and more often had gram-negative infection, fetal growth restriction, hypoglycemia, and thrombocytopenia. Significant predictors (multivariate analysis) of 28-day mortality and of adverse outcome at 18 months of corrected age were weight (kg) at the onset of sepsis (odds ratio 0.14, 95% confidence interval 0.03-0.55; odds ratio 0.21, 95% confidence interval 0.06-0.74, respectively) and gram-negative infection (odds ratio 10.1, 95% confidence interval 1.5-65.7; odds ratio 45.5, 95% confidence interval 3-637, respectively). CONCLUSIONS: Septic shock in the neonatal period has a very poor outcome. Data underscore the extreme vulnerability of very low birth weight infants to septic shock, particularly to gram-negative species.

Influence of dietary cholesterol on vitamin d metabolism in formula-fed preterm neonates.

OBJECTIVES: Supplementation of preterm formulas with cholesterol could help to mimic the fat composition of human milk. However, this could possibly influence vitamin D 25-hydroxylation because this reaction is catalyzed in part by the mitochondrial cytochrome P-450, the enzyme responsible for the 27-hydroxylation of cholesterol. The purpose of this study was to verify whether the addition of cholesterol to preterm formulas could interfere with vitamin D metabolism in preterm neonates. METHODS: In a prospective study, 30 preterm neonates were randomly assigned to a low (< 0.03 g/L), medium (0.15 g/L), or high (0.30 g/L) cholesterol-content preterm formula until theoretical term (i.e., 40 weeks post-conceptional age). Anthropometric data and serum hydroxy-vitamin D and 1,25 dihydroxy-vitamin D concentrations were measured at study entry and theoretical term. In a subgroup of 14 subjects, serum cholesterol and lymphocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA were also assessed. RESULTS: (median [25, 75 centiles]): At theoretical term, there were no significant differences in serum hydroxy-vitamin D concentrations among the three groups, even after adjustment for confounding variables (65 [50, 78] nmol/L, 79 [59, 86] nmol/L, and 67 [43, 103] nmol/L, respectively, = 0.65) or 1,25 dihydroxy-vitamin D ( = 0.88). Furthermore, there were no significant differences in 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA copy numbers. CONCLUSIONS: In preterm neonates fed formulas with a cholesterol content similar to or higher than that of human milk, we did not observe deleterious effects on vitamin D metabolism. However, long-term effects of cholesterol supplementation require further studies.

Multivitamin solutions for enteral supplementation: a source of peroxides.

OBJECTIVE: We investigated whether solutions of enteral vitamin supplementation are involved in the generation of peroxides and whether that contamination is biologically significant. METHODS: Peroxide contents of oral multivitamin preparations were measured over 3 wk after the initial opening of the containers. In selected premature infants (younger than 35 wk gestation), urinary peroxides were measured after initiating oral multivitamin supplementation. RESULTS: Peroxides in multivitamin solutions for enteral use are predominantly organic peroxides because they resist catalase. After the initial opening of the containers, there was a two-fold increase in total peroxides levels (P < 0.05) even in the preparation without riboflavin, a catalyst for the generation of peroxides. Initiation of oral vitamin supplementation was associated with increased (P < 0.05) urine peroxide levels. The high organic peroxide load did not correlate with its urinary excretion, mostly in the form of H(2)O(2). The excretion of H(2)O(2) corresponded to its oral intake from the multivitamin solution. CONCLUSIONS: Compared with parenteral multivitamin solutions, the enteral preparations contained higher organic peroxide levels starting with the initial opening of the bottles. The increased urinary excretion of H(2)O(2) after enteral multivitamin supplementation suggested a systemic diffusion of peroxides or of components of the multivitamin preparation responsible for the generation of peroxides. This oxidant load was not quenched by the immature antioxidant defenses of premature infants.