The effect of daily probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight.

BACKGROUND: Necrotizing enterocolitis remains a leading cause of morbidity and mortality in premature infants. The role of prophylactic probiotics in its prevention is unclear. This study evaluates the effect of routine probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight in the neonatal intensive care unit. METHODS: This retrospective cohort study compared infants cared for at a single institution before and after implementation of routine probiotic administration (2014- 2018). Babies born after July 2016 received probiotics containing Bifidobacterium and Lactobacillus daily until 35 weeks corrected gestational age. Baseline characteristics, necrotizing enterocolitis incidence and severity, infections, mortality, and length of stay were compared between groups. RESULTS: Of the 665 infants included in the study, 310 received probiotics and 355 did not. The 2 groups did not differ with regard to gestational age, birth anthropometrics, mode of delivery, comorbidities, and type of enteral feed. The incidence of necrotizing enterocolitis (Bell's stage 2 of 3) was similar between groups (4% v. 5%, p = 0.35), as was its severity (p = 0.10). In addition, there were no significant differences in mortality and length of stay between the groups. Significantly fewer infants receiving probiotics developed infections (27% v. 34%, p = 0.046), with the rate of urinary tract infections having the largest reduction. CONCLUSION: The routine use of Bifidobacterium and Lactobacillus probiotics in infants with very low birth weight did not significantly affect the incidence and severity of necrotizing enterocolitis. However, the use of probiotics was associated with fewer overall infections.

An alternative approach to developing guidelines for the management of an anticipated extremely preterm infant.

Objectives To identify the probability of survival and severe neurodevelopmental impairment (sNDI) at which perinatal physicians would or would not offer or recommend resuscitation at birth for extremely preterm infants. Methods A Delphi process consisting of five rounds was implemented to seek consensus (>80% agreement) amongst British Columbia perinatal physicians. The first-round consisted of neonatal and maternal-fetal-medicine Focus Groups. Rounds two to five surveyed perinatal physicians, building upon previous rounds. Draft guidelines were developed and agreement sought. Results Based on 401 responses across all rounds, consensus was obtained that resuscitation should not be offered if survival probability <5%, not recommended if survival probability 5 to <10%, resuscitation recommended if survival without sNDI probability >70 to 90% and resuscitation standard care if survival without sNDI >90%. Conclusions This physician consensus-based, objective framework for the management of an anticipated extremely preterm infant is a transparent alternative to existing guidelines, minimizing gestational-ageism and allowing for individualized management utilizing up-to-date data. Further input from other key stakeholders will be required prior to guideline implementation.

High-dose parenteral amino acid intake in very low birthweight infants: what is the current evidence?

PURPOSE OF REVIEW: There is uncertainty regarding optimal dosing for parenteral amino acids in preterm infants and wide variability exists in clinical practice. There is new data from clinical trials trying to address these concerns. We review the recent evidence on parenteral high-dose amino acid intake in very low birth weight (VLBW) neonates with a focus on relevant clinical outcomes. RECENT FINDINGS: Preterm infants often receive less protein than intended in the first week of life. Parenteral amino acid administration in doses that exceed requirements, however, leads to increased oxidation and higher blood urea concentrations. Amino acid doses greater than 3.5 g/kg/day have not shown to improve mortality, neonatal morbidities including sepsis, necrotizing enterocolitis, chronic lung disease, growth parameters or neurodevelopmental outcomes at 2 years of age. SUMMARY: Parenteral amino acid administration in VLBW infants should be initiated soon after birth at a dose of at least 1.5 g/kg/day to maintain anabolism. The maximum dose for parenteral amino acid should be between 2.5 and 3.5 g/kg/day, with adequate nonprotein calories and micronutrients to ensure efficient protein utilization and growth.

Needs assessment of ethics and communication teaching for neonatal perinatal medicine programs in Canada.

OBJECTIVE: To explore ethics education needs in Canadian Neonatal Perinatal Medicine (NPM) training programs. METHODS: A retrospective review of NPM trainees' performance at the National NPM Objective Structured Clinical Examination (OSCE) was undertaken for 2012 to 2017 and two distinct cross-sectional online surveys were carried out. One survey targeted recently graduated neonatologists (RGNs) who completed 2 years' training in a Canadian NPM program between 2010 and 2015; the other survey was sent to Canadian NPM training program directors (PDs). The domains of interest were: perception of education, ethics and communication topics, educational strategies, assessment of trainees' competencies, and barriers to neonatal ethics education. RESULTS: NPM trainees generally performed less well in stations involving ethics and communication relative to other domains on the National OSCE. Forty-seven RGNs (44.3%) and 12 PDs (92.3%) completed the survey. Over 90% of PDs and RGNs agreed on the importance of training in ethics and communication. Both groups highly valued training on topics related to communication. Preferred teaching strategies were experiential: observation and feedback. PDs mentioned the importance of using validated tools to regularly and formally assess trainees. They recognized challenges in regard to financial resources, physical space, and faculty training in patient-physician communication. CONCLUSIONS: National OSCE results indicate the need to improve neonatal ethics and communication training in Canadian NPM programs. RGNs and PDs identified important topics, as well as teaching and evaluation strategies. These results can be used to develop a training program for ethics and communication in NPM.

Navigating the Dangerous Terrain of Moral Distress: Understanding Response Patterns in the NICU.

Moral distress is a well-recognized and ubiquitous aspect of health care professional practice in the neonatal intensive care unit (NICU) context. We used interpretive description methodology to guide a critical exploration of the dynamics of moral distress experience as reflected in the accounts of 28 health care professionals working in this setting. We learned about the kinds of clinical scenarios which triggered distressing experiences, and that the organizational and relational context of clinical work constituted a complex and dynamic working environment that profoundly affected both the individual and the collective experiences with moral distress in these situations. These findings shed light on possibilities for supporting NICU practitioners and developing the collaborative team cultures that may reduce the risk of unresolved effects of moral distress to the benefit of patients as well as the professionals who care for them.

Best Practice in Provider/Parent Interaction.

In this 3-year prospective grounded theory study in three pediatric settings, we aimed to develop a conceptualization of best practice health care providers (BPHCPs) in interaction with parents of children with complex, chronic, life-threatening conditions. Analysis of semistructured interviews with 34 parents and 80 health care professionals (HCPs) and 88 observation periods of HCP/parent interactions indicated that BPHCPs shared a broad worldview; values of equity, family-centered care, and integrity; and a commitment to authentic engagement. BPHCPs engaged in direct care activities, in connecting behaviors, and in exquisitely attuning to particularities of the situation in the moment, resulting in positive outcomes for parents and HCPs. By focusing on what HCPs do well, findings showed that not only is it possible for HCPs to practice in this way, but those who do so are also recognized as being the best at what they do. We provide recommendations for practice and initial and ongoing professional education.

The relationship between paediatric practitioners and 'industry'.

Paediatric practitioners interact with industry representatives for many purposes but most often to receive information on new and existing products. While practitioners believe they are immune to the marketing influences exerted by these representatives, research has demonstrated otherwise. The literature suggests that the public is aware of such influences and that most people feel industry influence on practitioners is inappropriate. National guidelines go some way toward regulating practitioner-industry interactions, although they are not always clear or sufficient. The present practice point explores the context for these relationships, raises some ethical issues specific to paediatric practitioners and provides recommendations for maintaining professional integrity in the patient-physician relationship. Paediatric practitioners have a professional duty to ensure that their own interactions with industry are conducted with the best interests of the patient front and centre.

Outcome of patients with gastroschisis managed with and without multidisciplinary teams in Canada.

OBJECTIVE: To describe the outcomes of gastroschisis (GS) patients managed with and without a multidisciplinary team during the postoperative period in Canada. METHOD: The Canadian Pediatric Surgery Network (CAPSNet) collects patient data from all Canadian tertiary perinatal centres. The outcomes of 396 GS patients born between 2005 and 2009 who were managed with and without a multidisciplinary team were analyzed. RESULTS: Significantly more parenteral nutrition (PN) days (P=0.003) and longer lengths of stay (P=0.018) were observed among patients in centres with multidisciplinary teams. Higher mortality rate and earlier death were observed in centres without multidisciplinary teams, especially for high-risk patients, although this was not statistically significant. With regard to low-risk patients, those in centres with multidisciplinary teams had significantly more PN days (P=0.019). CONCLUSIONS: GS patients managed by multidisciplinary teams had significantly more PN days and longer lengths of stay compared with patients who were not managed by multidisciplinary teams. This difference may be due to improved survival of high-risk patients in centres with multidisciplinary teams, and a uniform feeding approach for all patients.

OBJECTIF: Décrire l'évolution des patients ayant un gastroschisis (GS) traités ou non par une équipe multidisciplinaire pendant la période postopératoire au Canada. MÉTHODOLOGIE: Le Réseau canadien de chirurgie pédiatrique (CAPSNet) collige les données sur les patients de tous les centres périnatals de soins tertiaires au Canada. L'évolution de 396 patients ayant un GS nés entre 2005 et 2009 et qui ont été traités ou non par une équipe multidisciplinaire a été analysée. RÉSULTATS: Les patients hospitalisés dans des centres dotés d'équipes multidisciplinaires passaient considérablement plus de jours sur alimentation parentérale (AP) (P=0,003) et étaient hospitalisés plus longtemps (P=0,018). Bien que ce résultat ne soit pas significatif, le taux de mortalité était plus élevé et les décès, plus rapides dans les centres ne disposant pas d'une équipe multidisciplinaire, surtout chez les patients à haut risque. Pour ce qui est des patients à faible risque, ceux qui étaient traités dans des centres disposant d'une équipe multidisciplinaire passaient considérablement plus de jours sur AP (P=0,019). CONCLUSIONS: Les patients ayant un GS traités par une équipe multidisciplinaire passaient considérablement plus de jours sur AP et étaient hospitalisés plus longtemps que ceux qui n'étaient pas traités par une telle équipe. Cette différence peut être attribuable au meilleur taux de survie des patients à haut risque dans les centres disposant d'équipes multidisciplinaires et à une approche uniforme en matière d'alimentation pour tous les patients.

Human Milk Calorie Guide: A Novel Color-Based Tool to Estimate the Calorie Content of Human Milk for Preterm Infants.

Fixed-dose fortification of human milk (HM) is insufficient to meet the nutrient requirements of preterm infants. Commercial human milk analyzers (HMA) to individually fortify HM are unavailable in most centers. We describe the development and validation of a bedside color-based tool called the 'human milk calorie guide'(HMCG) for differentiating low-calorie HM using commercial HMA as the gold standard. Mothers of preterm babies (birth weight ≤ 1500 g or gestation ≤ 34 weeks) were enrolled. The final color tool had nine color shades arranged as three rows of three shades each (rows A, B, and C). We hypothesized that calorie values for HM samples would increase with increasing 'yellowness' predictably from row A to C. One hundred thirty-one mother's own milk (MOM) and 136 donor human milk (DHM) samples (total n = 267) were color matched and analyzed for macronutrients. The HMCG tool performed best in DHM samples for predicting lower calories (<55 kcal/dL) (AUC 0.87 for category A DHM) with modest accuracy for >70 kcal/dL (AUC 0.77 for category C DHM). For MOM, its diagnostic performance was poor. The tool showed good inter-rater reliability (Krippendorff's alpha = 0.80). The HMCG was reliable in predicting lower calorie ranges for DHM and has the potential for improving donor HM fortification practices.

Pandemic planning: Developing a triage framework for Neonatal Intensive Care Unit.

Although the Covid-19 pandemic has not had a direct impact on neonates so far, it has raised concerns about resource distribution and showed that planning is required before the next crisis or pandemic. Resource allocation must consider unique Neonatal Intensive Care Unit (NICU) attributes, including physical space and equipment that may not be transferable to older populations, unique skills of NICU staff, inherent uncertainty in prognosis both antenatally and postnatally, possible biases against neonates, and the future pandemic disease's possible impact on neonates. We identified the need for a validated Neonatal Severity of Illness Prognostic Score to guide triage decisions. Based on this score, triage decisions are the responsibility of an informed triage team not involved in direct patient care. Support for the distress experienced by parents and staff is needed. This paper presents essential considerations in developing a practical framework for resources and triage in the NICU before, during and after a pandemic.

The Importance of the ileocecal valve and colon in achieving intestinal independence in infants with short bowel syndrome.

PURPOSE: Infants with short bowel syndrome (SBS) wean from parenteral nutrition (PN) support at variable rates. Small bowel length is a predictor, but the importance of the ileocecal valve (ICV) and colon are unclear. We aim to determine if the ICV and/or colon predict enteral autonomy. METHODS: Infants from a single intestinal rehabilitation program were retrospectively reviewed. Etiology of SBS, intestinal anatomy, and duration of nutritional support were collected for three years. The primary outcome was time to full enteral nutrition. ANCOVA and Cox proportional hazards model were used, with p < 0.05 significant. RESULTS: 55 infants with SBS were included. After accounting for the effect of small bowel, PN duration was shorter for infants with the ICV compared to those without (mean 218 vs. 538 days, p = 0.003), and had a more significant effect on infants with ≤50% of small bowel. Increased small bowel length was a positive predictor of weaning. Patients with ≤50% of colon spent less time on PN with the ICV, compared to without (mean 220 vs 715 days, p = 0.009). CONCLUSIONS: Preservation of the ICV was associated with shorter duration of PN support, while colon was not. Small bowel length is a positive predictor of enteral autonomy. LEVEL OF EVIDENCE: Level III retrospective comparative study TYPE OF STUDY: Retrospective review.

Urine sodium to urine creatinine ratio as a marker of total body sodium in infants with intestinal failure.

PURPOSE: Urine sodium (UNa) is a measure of total body sodium in infants with intestinal failure (IF) but can be misleading as it does not reflect volume status. Urine sodium to urine creatinine ratio (UNa:UCr) may offer a more accurate measure, but is not routinely used. This study compares UNa:UCr to UNa as a maker of sodium status in infants with IF. METHODS: A retrospective review of infants with IF, from a single center, from 2018 to 2020 was conducted (REB H20-00,816). IF etiology, intestinal anatomy, nutritional intake, urine electrolytes and anthropometrics were collected. Linear mixed effects models adjusting for repeated measures were used to associate UNa and UNa:UCr with weight gain and sodium intake. RESULTS: Twenty-two infants with a median gestational age of 31 weeks were included. IF etiology included gastroschisis (41%), necrotizing enterocolitis (23%), and intestinal perforation (14%). Infants had an average of 3 paired UNa and UNa:UCr measures for a total of 74 paired measurements. UNa:UCr more strongly correlated with sodium intake compared to UNa (R = 0.25, p = 0.032 vs. R = 0.10, p = 0.38). Overall, neither UNa (p = 0.21) nor UNa:UCr (p = 0.16) were significantly correlated with weight gain. However, for infants receiving ≤50% nutrition enterally, weight gain correlated with UNa (p = 0.01) and UNa:UCr (p = 0.01). UNa:UCr >35 predicted adequate growth regardless of enteral intake (92% sensitivity, 59% specificity). CONCLUSION: UNa:UCr is a measure of total body sodium that correlates with sodium intake in infants with IF. Our study indicates UNa:UCr >35 is associated with adequate growth and can be used to guide further validation studies.

In Utero diagnosis and management of a fetus with homozygous α-Thalassemia in the second trimester: a case report and literature review.

Alpha thalassemia with the absence of 4 α-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous α-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia. Cordocentesis confirmed anemia and homozygous α-thalassemia (--/--). Intrauterine transfusion corrected anemia but fetal growth restriction and oligohydramnios persisted. Intrauterine exchange transfusion improved hemoglobin parameters, fetal growth, and oligohydramnios. The late preterm infant was delivered with classic limb reduction defects. Hemoglobin Bart's is nonfunctional for oxygen transport, and intrauterine exchange transfusion may be effective first-line therapy and further investigation is warranted.

The physician's relationship with the pharmaceutical industry: caveat emptor...buyer beware!

Historically physicians have had close relationships with the pharmaceutical or other medically related industry. This has come under close scrutiny by the public, with articles appearing in medical journals and the lay press. The reality is that physicians depend on industry to bring products to market as well as to assist in research and education, leaving physicians questioning what their relationship with industry should be. This review deals with this complex relationship, identifying ways that industry might affect decision making in the clinical context. We will highlight areas of potential concern in this relationship, identify attendant moral dilemmas, and provide some recommendations. Our intention in raising the consciousness of physicians and medical institutions to these potential areas of concern is to aid physicians in their efforts to provide the best medical care for patients and to practice with integrity.

Ethical care for infants with conditions not curable with intensive care.

Offering intensive care to neonates who have conditions that carry extremely poor prognoses is a source of great contention amongst neonatologists. The concept of best interests is commonly used as a rationale for refusing such care, despite the fact that parents of these infants often have a different view of what best interests means. This article takes up the question of what best interests should incorporate for infants with lethal conditions not curable with intensive care, and how and who should decide which treatment options should be implemented. Based on our recommendation that parents be apprised of the basis upon which physicians are evaluating treatment options, we offer a framework that allows all relevant parties to approach the issue of what is appropriate treatment from a similar place. We maintain that this approach will increase transparency, dialogue, understanding, and trust, which, in turn, may result in greater consensus.

Corrected fortification approach improves the protein and energy content of preterm human milk compared with standard fixed-dose fortification.

OBJECTIVE: To evaluate whether a pragmatic corrected fortification (CF) model achieves recommended target protein and calorie content of human milk (HM) for preterm infants when compared with standard fixed-dose fortification (SF). DESIGN: In this prospective non-interventional study, we enrolled mothers of infants with birth weight ≤1500 g fed exclusive HM. Infants with chromosomal or intestinal disorders were excluded. A total of 405 HM samples from 29 mothers and 45 donor milk samples were analysed for macronutrient content using a real-time HM analyser. A stepwise CF model was derived based on published data on HM calorie and protein content corrected for lactation stage and milk type. We applied both models to the measured protein and calorie content for all HM samples and compared the proportion of samples achieving target nutrient requirement in each group. RESULTS: Target protein and calorie content of feed was achieved in 68% of HM samples with CF, compared with 5% samples with SF model (p<0.0001). For mother's own milk, none of the samples met the target macronutrient range with SF fortification during later lactation periods (≥week 5). With SF, over 40% of infants had poor growth (decline in weight z-score ≥0.8 SD) by 8 weeks. The final feed osmolality was acceptable for all fortification steps of the CF model. CONCLUSION: The proposed CF model significantly improved the final protein and calorie content of HM with acceptable osmolality. It provides a proactive option to improve nutrient intake in premature infants.

NeoCHIRP: A model for intestinal rehabilitation in the neonatal intensive care unit.

Multidisciplinary intestinal rehabilitation (IR) teams have transformed care in pediatric intestinal failure (IF).1 Although most children with IF are identified in the neonatal intensive care unit (NICU), IR teams may not be involved at this stage. We describe our collaborative model, blending NICU and IR expertise to optimize care. Over 6 years, the NeoCHIRP (Neonatal Children's IR Program) team followed 164 babies for weekly visits (median, 8; range, 1-27). Bedside rounds included CHIRP team physician and surgeons, neonatologist champion, attending neonatologist and fellow, NICU dietitian, bedside nurse, and family. Medical and nutrition status, nutrition history, and laboratory data were discussed, and a nutrition plan to support IR, considering the child's other medical needs, was created to guide the next week's management. Typical issues addressed included parenteral nutrition (PN) composition, enteral nutrition plan, oral feeding, management of small-intestinal bacterial overgrowth and sodium status, and cholestasis. A total of 164 babies were followed by the NeoCHIRP team. Of 153 survivors, IF resolved by discharge in 89% (136 of 153). Seventeen of 153 babies (11%) went on to require home PN and were transferred from NICU directly to the CHIRP team. By discharge, 99% of babies were orally fed (69/136, 50% fully, 67/136, 49% partially), and cholestasis improved or resolved in 80/105 (76%). Eleven babies (7%) died; four deaths were unrelated to IF, but in seven babies, IF was at least a contributing factor. In this high-risk cohort, most babies achieved good outcomes, and those who required longer-term IR transitioned smoothly to the CHIRP team.

The Extremely Preterm Infant: Ethical Considerations in Life-and-Death Decision-Making.

Care of the preterm infant has improved tremendously over the last 60 years, with attendant improvement in outcomes. For the extremely preterm infant, <28 weeks' gestation, concerns related to survival as well as neurodevelopmental impairment, have influenced decision-making to a much larger extent than seen in older children. Possible reasons for conferring a different status on extremely preterm infants include: (1) the belief that the brain is a privileged organ, (2) the degree of medical uncertainty in terms of outcomes, (3) the fact that the family will deal with the psychological, emotional, physical, and financial consequences of treatment decisions, (4) that the extremely preterm looks more like a fetus than a term newborn, (5) the initial lack of relational identity, (6) the fact that extremely preterm infants are technology-dependent, and (7) the timing of decision-making around delivery. Treating extremely preterm infants differently does not hold up to scrutiny. They are owed the same respect as other pediatric patients, in terms of personhood, and we have the same duties to care for them. However, the degree of medical uncertainty and the fact that parents will deal with the consequences of decision-making, highlights the importance of providing a wide band of discretion in parental decision-making authority. Ethical principles considered in decision-making include best interest (historically the sine qua non of pediatric decision-making), a reasonable person standard, the "good enough" parent, and the harm principle, the latter two being more pragmatic. To operationalize these principles, potential models for decision-making are the Zone of Parental Discretion, the Not Unreasonable Standard, and a Shared Decision-Making model. In the final analysis shared decision-making with a wide zone of parental discretion, which is based on the harm principle, would provide fair and equitable decision-making for the extremely preterm infant. However, in the rare circumstance where parents do not wish to embark upon intensive care, against medical recommendations, it would be most helpful to develop local guidelines both for support of health care practitioners and to provide consistency of care for extremely preterm infants.