Effect of Neonatal Unit Interventions Designed to Increase Breastfeeding in Preterm Infants: An Overview of Systematic Reviews.

INTRODUCTION: This overview aims to systematically review evidence regarding effects of interventions undertaken in neonatal units to increase breastfeeding in preterm infants. METHODS: We followed Cochrane methodology. Systematic reviews published to October 31, 2022, reporting meta-analysis of effects from original studies on breastfeeding rates in preterm infants of neonatal unit interventions designed to increase breastfeeding were included. RESULTS: Avoidance of bottles during breastfeed establishment (comparator breastfeeds with bottle-feeds) demonstrated clear evidence of benefit for any breastfeeding at discharge and exclusive breastfeeding 3 months post-discharge, and possible evidence of benefit for exclusive breastfeeding at discharge, and any breastfeeding post-discharge. Kangaroo mother care (KMC) (comparator usual care) demonstrated clear evidence of benefit for any and exclusive breastfeeding at discharge and possible benefit for any breastfeeding post-discharge. Quality improvement (QI) bundle(s) to enable breastfeeds (comparator conventional care) showed possible evidence of benefit for any breastfeeding at discharge. Cup feeding (comparator other supplemental enteral feeding forms) demonstrated possible evidence of benefit for exclusive breastfeeding at discharge and any breastfeeding 3 months after. Early onset KMC (commenced <24 h post-birth), oral stimulation, and oropharyngeal colostrum administration, showed no evidence of benefit. No meta-analyses reported pooled effects for gestational age or birthweight subgroups. CONCLUSION: There is ample evidence to support investment in KMC, avoidance of bottles during breastfeed establishment, cup feeding, and QI bundles targeted at better supporting breastfeeding in neonatal units to increase prevalence of breastfeeding in preterm infants and promote equal access to breastmilk. Stratifying effects by relevant subgroups is a research priority.

Treatment of HMG-CoA Lyase Deficiency-Longitudinal Data on Clinical and Nutritional Management of 10 Australian Cases.

3-Hydroxy-3-Methylglutaryl-CoA Lyase (HMGCL) deficiency can be a very severe disorder that typically presents with acute metabolic decompensation with features of hypoketotic hypoglycemia, hyperammonemia, and metabolic acidosis. A retrospective chart and literature review of Australian patients over their lifespan, incorporating acute and long-term dietary management, was performed. Data from 10 patients contributed to this study. The index case of this disorder was lost to follow-up, but there is 100% survival in the remainder of the cases despite several having experienced life-threatening episodes. In the acute setting, five of nine patients have used 900 mg/kg/day of sodium D,L 3-hydroxybutyrate in combination with intravenous dextrose-containing fluids (delivering glucose above estimated basal utilization requirements). All patients have been on long-term protein restriction, and those diagnosed more recently have had additional fat restriction. Most patients take L-carnitine. Three children and none of the adults take nocturnal uncooked cornstarch. Of the cohort, there were two patients that presented atypically-one with fulminant liver failure and the other with isolated developmental delay. Dietary management in patients with HMGCL deficiency is well tolerated, and rapid institution of acute supportive metabolic treatment is imperative to optimizing survival and improve outcomes in this disorder.

Early versus delayed introduction of human milk fortification in enterally fed preterm infants: A systematic review and meta-analysis.

AIM: To assess effects of early versus delayed introduction of human milk fortification in preterm infants. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PubMed and CINAHL for randomised controlled trials evaluating start time for human milk fortification in preterm infants (March 2020). Two authors assessed trial eligibility and risk of bias, extracted data and assessed evidence certainty. RESULTS: We identified 1307 publications and included three trials (378 infants). Meta-analysis comparing fortification commencing at an enteral feed volume of ≤40 mL/kg/day versus ≥75 mL/kg/day, showed little to no difference in rates of necrotising enterocolitis (3 trials), sepsis (3 trials), feeding intolerance (2 trials) (low-quality evidence) and infant growth (1 trial, very low-quality evidence). CONCLUSIONS: Whether early introduction of fortification, at an enteral feed volume of ≤40 mL versus delayed at ≥75 mL/kg/day improves growth or influences adverse feeding outcomes is very uncertain.

Impact of initial flow rate of high-flow nasal cannula on clinical outcomes in infants with bronchiolitis.

AIM: Bronchiolitis is a common condition in the paediatric population. Severe cases often receive respiratory support with high-flow nasal cannula (HFNC). Significant variation in the application of HFNC exists throughout Australia and internationally. This study aimed to determine if the flow rate used initially and when ceasing HFNC at the end of the illness alters clinical outcomes. METHODS: A retrospective analysis was conducted of 251 children less than 12 months of age when admitted to the Women's and Children's Hospital Adelaide with bronchiolitis requiring HFNC therapy between the period of April 2016 to April 2019. The primary outcome was to determine if commencing HFNC therapy at different rates (1 L/kg/min, 1.5 L/kg/min and 2 L/kg/min) affected length of stay or treatment failure (escalation in physiological parameters or respiratory support). RESULTS: Treatment failure occurred in 33%, 13% and 26% of those starting at 1 L/kg/min, 1.5 L/kg/min and 2 L/kg/min, respectively. Commencing HFNC therapy at 1 L/kg/min increased length of stay by an average of 30 h (P < 0.001) and the likelihood of treatment failure (P < 0.002) compared with starting at 1.5 L/kg/min. There was no statistical difference in outcomes between starting at 1.5 L/kg/min and 2 L/kg/min. There was no significant difference in the length of stay from the starting of weaning HFNC to time of discharge. CONCLUSIONS: The commencing flow rates of initial HFNC therapy impact individual patient's outcomes, including length of stay and rates of treatment failure. Clinicians should consider commencing HFNC at 1.5 L/kg/min or 2 L/kg/min in infants that have failed low-flow oxygen therapy.

Safety and efficacy of human milk-based fortifier in enterally fed preterm and/or low birthweight infants: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the efficacy and safety of fortification of human milk with human milk-based fortifier versus cow's milk-based fortifier for use in preterm and/or very low birthweight infants. DESIGN: Randomised or quasi-randomised controlled trials comparing the effect of human milk fortification with human milk-based milk fortifier versus cow's milk-based fortifier in infants born <34 weeks' gestation and/or with birth weight <1500 g were identified by searching databases, clinical trial registries and reference lists until 5 November 2019. Two authors independently extracted data and assessed evidence quality. Meta-analyses were conducted using fixed or random effects models, as appropriate. MAIN OUTCOME MEASURES: Necrotising enterocolitis (Bell's stage II or higher) and late-onset sepsis. RESULTS: Of 863 unique records identified, 16 full-text trials were screened and 2 trials involving 334 infants were included. Primary outcome data were available for 332 infants. Use of human milk-based fortifier compared with cow's milk-based fortifier reduced the risk of necrotising enterocolitis (risk ratio 0.47, 95% CI 0.22 to 0.98). There was no clear evidence of an effect on late-onset sepsis or any other outcomes. The quality of evidence was low to very low due to imprecision and lack of blinding in one study. CONCLUSIONS: Findings suggest that there is a reduction in the incidence of necrotising enterocolitis with human milk-based fortifiers compared with cow's milk-based fortifiers. The overall quality of evidence is low. Further appropriately powered trials are required before this intervention can be routinely recommended for preterm infants.

What clinical practice strategies have been shown to decrease incidence rates of intraventricular haemorrhage in preterm infants?

AIM: To answer the clinical question 'In infants about to be delivered and admitted to neonatal units, what clinical practice strategies, compared to standard care, have been shown to decrease incidence rates of intraventricular haemorrhage (IVH)?' METHODS: MEDLINE via Ovid (1943 to 5 January 2018), Embase via Ovid (1974 to 5 January 2018) and the Cochrane Library (5 January 2018) were searched for relevant articles. RESULTS: A total of 478 articles, after the removal of duplicates, were found and screened by title and abstract. Forty full-text articles were subsequently reviewed, and 19 were included as relevant to the structured clinical question. An additional article was included based on expert advice. CONCLUSION: There are various levels of research evidence for clinical practice strategies to decrease the incidence rates of IVH. Higher-quality evidence suggests that antenatal corticosteroids decrease the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit are associated with decreased rates of IVH.

Does early compared to late fortification of human milk for preterm infants improve clinical outcomes?

AIM: This evidence-based review aims to answer the following structured clinical question: In preterm infants <37 weeks' gestation (patient), does early fortification of breast milk (intervention) compared to late fortification (control) improve growth outcomes at the time of discharge or affect length of hospital stay (outcome)? METHODS: MEDLINE, Embase, Maternity and Infant Care Database and Evidence-Based Medicine Reviews were searched for articles published from 2000 onwards that were relevant to the structured clinical question. The National Institute for Health and Care Excellence, National Health and Medical Research Council, Agency for Healthcare Research and Quality, National Institute of Health and Turning Research into Practice databases were also searched, and reference lists of relevant articles were reviewed. RESULTS: A total of 167 articles, after removal of duplicates, were found and screened by title and abstract. Five full-text articles were ultimately included in the review. CONCLUSIONS: The results of this review suggest that early fortification is safe and well tolerated. However, earlier fortification has not been shown to have a significant impact on growth outcomes at time of discharge or length of stay. More research is required to determine if early fortification of breast milk may have benefits regarding longer-term growth and neurodevelopmental outcomes.

What evidence-based strategies have been shown to improve breastfeeding rates in preterm infants?

Breast milk is the preferred form of nutrition for all infants and has been shown to reduce morbidity and improve health outcomes in preterm infants. However, mothers of preterm infants face many challenges initiating and sustaining breastfeeding within the neonatal unit. This scoping review examines evidence-based practices which aim to improve breastfeeding rates in preterm infants at the time of hospital discharge. A literature review identified 17 articles which are included in this review. Supporting evidence was found for the implementation of kangaroo mother care and/or skin-to-skin care, peer counsellors, provision of oropharyngeal colostrum in early infancy and use of donor human milk banks. However, overall it is apparent that high quality research including systematic review and data synthesis in the form of meta-analysis is required in this area to reach sound conclusions regarding recommendations of different interventions. This scoping review provides an important foundation for further research into this area.

Are there interventions that improve breastfeeding and the use of breast milk in late preterm infants?

To answer the clinical question 'Among late preterm infants are there any interventions that improve the rates of breastfeeding and the use of breast milk compared with current practice?'. MEDLINE via Ovid, Embase via Ovid, the Maternity and Infant Care Database and the Cochrane Library were searched for relevant articles. Articles were excluded if they did not discuss specific interventions to improve breastfeeding, for example, if they only commented on factors such as age, race and education. Articles were also excluded if they were not specific to the late preterm infant population. A total of 516 articles were found and screened by title and abstract independently by two reviewers. The full text of 17 articles was independently reviewed. The reference lists of these full-text articles were screened, and 14 abstracts were subsequently reviewed. The final analysis included three studies. There is limited high-quality research evidence for interventions to improve breastfeeding in late preterm infants. In the absence of robust academic research, clinical practice should be guided by clinical expertise and involve a multidisciplinary team, including qualified lactation consultants. While it seems reasonable for hospitals to support interventions that improve breastfeeding in term infants, managing late preterm infants as healthy term infants without additional specialist support may result in high breastfeeding failure rates among late preterm infants.

Do feeding practices during transfusion influence the risk of developing necrotising enterocolitis in preterm infants?

Our evidence-based review set out to answer the clinical question 'In a preterm infant (patient) with anaemia of prematurity, do feeding practices (intervention) during blood transfusion reduce the risk of developing transfusion-associated necrotising enterocolitis (outcome)'? We found limited evidence that withholding feeding during red blood cell transfusion in preterm infants may reduce the risk of development of transfusion-associated necrotising enterocolitis. As clinical equipoise seemingly exists, it seems reasonable for individual units to make their own decisions regarding whether to withhold or continue enteral feeds during red blood cell transfusion until further evidence is available. The UK-based Withholding Enteral Feeds Around Transfusion (WHEAT) trial, a nation-wide multi-centre 'opt-out' randomised controlled study, hopefully will definitively answer our clinical question. Further research in other areas of neonatal care, using this innovative study design, is needed and it is exciting to see such a study underway.

Does screening for congenital cytomegalovirus at birth improve longer term hearing outcomes?

Currently, the diagnosis of congenital cytomegalovirus (cCMV) infection in most highly resourced countries is based on clinical suspicion alone. This means only a small proportion of cCMV infections are diagnosed. Identification, through either universal or targeted screening of asymptomatic newborns with cCMV, who would previously have gone undiagnosed, would allow for potential early treatment with antiviral therapy, ongoing audiological surveillance and early intervention if sensorineural hearing loss (SNHL) is identified. This paper systematically reviews published papers examining the potential benefits of targeted and universal screening for newborn infants with cCMV. We found that the treatment of these infants with antiviral therapy remains controversial, and clinical trials are currently underway to provide further answers. The potential benefit of earlier identification and intervention (eg, amplification and speech therapy) of children at risk of later-onset SNHL identified through universal screening is, however, clearer.