Effect of brewer's yeast or beta-glucan on breast milk supply following preterm birth: the BLOOM study - protocol for a multicentre randomised controlled trial.

BACKGROUND: Many individuals who experience preterm birth struggle with early breast milk supply, which can translate into suboptimal longer-term breastfeeding outcomes. Further investigations into the potential role of early non-pharmacological and pharmacological interventions in improving breast milk production soon after birth is growing. While natural galactagogues, such as brewer's yeast, are widely perceived by women to be safer than pharmaceutical galactagogues and are taken by many women, evidence to support their efficacy is largely absent. The BLOOM study has been designed to determine the efficacy and safety of brewer's yeast and beta-glucans, derived from Saccharomyces cerevisiae, when administered soon after birth for increasing early breast milk supply in mothers who have delivered preterm. METHODS: The BLOOM study is a multicentre, double-blinded, randomised controlled trial that will assess if brewer's yeast or beta-glucan can increase early breast milk production following preterm birth. Target population are mothers of preterm infants born at less than 34 weeks' gestation who intend to provide breast milk for their infant, are less than 72 h following birth and able to give informed consent. Participants will be randomly allocated into three parallel groups at 1:1:1 ratio (n = 33 per group) to receive either brewer's yeast, beta-glucan or placebo capsules for seven days. The primary outcome is total expressed breast milk volume over a 24-hour period on day 7 of intervention. Participants and their infants will be followed until the infant reaches term corrected age or is discharged home from the neonatal unit (whichever occurs first). DISCUSSION: The use of brewer's yeast as a galactagogue to enhance milk production is extremely common amongst breastfeeding mothers, however, there are no trials evaluating its efficacy and safety. This will be the first randomised controlled trial to evaluate the efficacy and safety of two commonly used galactagogues, brewer's yeast and beta-glucan, compared with placebo in improving maternal breast milk supply following preterm birth. The trial will also evaluate whether early intervention with galactagogues soon after a preterm birth improves longer-term breastfeeding outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000968774 (registered on 8 July 2022) and UTN U1111-1278-8827.

Reducing intravenous antibiotics in neonates born ≥35 weeks' gestation: A quality improvement study.

AIM: To assess the impact of the Early Onset Sepsis (EOS) calculator, implemented as a quality improvement study, to reduce the rate of unnecessary antibiotics in neonates born ≥35 weeks' gestation. METHODS: An audit of routinely collected hospital data from January 2008 to March 2014 (retrospective) and from January 2018 to September 2019 (prospective) determined baseline incidence of EOS intravenous antibiotic use in neonates born ≥35 weeks' gestation in a tertiary level perinatal centre. Plan-do-study-act (PDSA) cycles were applied to implement the EOS calculator. Statistical process control methodology and time series analysis assessments were used to assess the potential impact of the PDSA cycles on the rate of intravenous antibiotics, blood culture collection, EOS, length of stay and health care costs (not adjusted for potential confounders). RESULTS: In the study population, from January 2008 to March 2014, the baseline incidence of intravenous antibiotic use was 10.49% (2970/28290), whilst only 0.067% (19/28290) neonates had culture proven EOS. From January 2018 to October 2019, prior to implementation of the EOS calculator, 13.3% (1119/8411) neonates were treated with intravenous antibiotic and the use decreased to 8.3% (61/734) post-implementation. The rate of blood culture collection decreased from 14.4% (1211/8411) to 11.9% (87/734). There were no cases of missed EOS. Length of stay decreased from 2.68 to 2.39 days, with an estimated cost saving of $366 per patient per admission. CONCLUSION: Implementing the EOS calculator in a tertiary hospital setting reduced invasive investigations for EOS and intravenous antibiotic use among neonates ≥35 weeks' gestation. This can result in reduced length of neonatal hospital stays, and associated health care cost savings and may reduce separation of mother and baby.

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.

Neonatal magnesium sulphate for neuroprotection: A systematic review and meta-analysis.

AIM: To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE). METHOD: This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability). RESULTS: Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53-0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58-0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34-1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86-10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14-1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision. INTERPRETATION: Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.

Longitudinal trends in domperidone dispensing to mothers of very preterm infants and its association with breast milk feeding at infant discharge: a retrospective study.

OBJECTIVE: This study aims: (a) to evaluate patterns of domperidone dispensing to mothers of very preterm (<32 weeks gestation) infants born before and after 2014 when international recommendations were made to limit its use and (b) to examine characteristics associated with domperidone dispensing and impacts on breast milk feeding rates at infant hospital discharge. DESIGN: Retrospective audit using linked electronic medical records and hospital pharmacy records. SETTING: Tertiary-referral neonatal intensive care unit at the Women's and Children's Hospital in South Australia. PATIENTS: Mothers of preterm infants admitted to neonatal intensive care from January 2004 to December 2018. MAIN OUTCOME MEASURES: Rate of domperidone dispensing compared pre-2014 and post-2014 recommendations using interrupted time series analyses, and breast milk feeding rates at infant discharge based on domperidone treatment status, adjusted for other factors known to influence breast milk production. RESULTS: Overall, domperidone was dispensed to 691 (41%) of 1688 mothers. Prior to 2014 recommendations, the proportion of women dispensed domperidone was stable. Following the recommendations, there was a significant reduction in trend (-2.55% per half year, 95% CI -4.57% to -0.53%;), reflecting less domperidone dispensing.Breast milk feeding rates at discharge remained consistently lower in infants of women dispensed domperidone than those who were not (adjusted OR 0.58, 95% CI 0.45 to 0.75). CONCLUSION: Domperidone dispensing in mothers of hospitalised very preterm infants has declined over time following international regulatory warnings. Breast milk feeding rates remain lower in mothers prescribed domperidone, suggesting further research is needed to optimise lactation support for mothers of very preterm infants.

Patient Blood Management in Neonates.

Patient blood management (PBM) is an evidence-based care package to improve patient outcomes by optimizing a patient's blood, minimizing blood loss, and the effective management and, when appropriate, the tolerance of anemia. It is relatively well-developed in adult medicine and remains in its infancy in neonatology. This review explores why evidence-based guidelines are insufficient, discusses the variations in neonatal transfusion practice and why this matters, and provides the key updates in neonatal transfusion practice. The authors give examples of a successful neonatal PBM program and single-center projects.

Women's experiences with using domperidone as a galactagogue to increase breast milk supply: an australian cross-sectional survey.

BACKGROUND: Domperidone is one of the most commonly utilised pharmacological galactagogues, with evidence of increasing use in clinical practice. However, the use of domperidone as a galactagogue remains controversial, with mixed evidence on safety and efficacy, leading to variable clinical practice recommendations. We sought to evaluate contemporary patterns of domperidone use and examine maternal experiences related to perceived safety and effectiveness. METHODS: In 2019, we conducted an online, cross-sectional survey of Australian breastfeeding women to examine individual experiences related to domperidone use, in addition to perceptions of safety and effectiveness. RESULTS: Among 1876 survey responses, 19% (n = 355) reported using domperidone. Domperidone use was significantly higher in women who were primiparous, gave birth preterm, delivered by caesarean section, had self-perceived low milk supply, and saw a lactation consultant. Nearly 20% of women commenced domperidone use in the first week postpartum (19%, n = 67). The median duration of use was six weeks (interquartile range 3-16 weeks). Maximum reported doses of domperidone used ranged from 20 mg/day to 160 mg/day. Half (n = 178, 50%) of women reported using a dose of 30 mg/day or less, 44% (n = 155) reported using a dose between 31 and 60 mg/day, and 6% (n = 22) reported using a dose greater than 61 mg/day. Nearly half of the respondents reported domperidone as 'very' or 'extremely effective' (45%, n = 161), with only 8% (n = 27) reporting it was 'not at all effective'. Almost half (n = 172, 48%) of all women using domperidone reported side effects, including weight gain (25%), headaches (17%) and dry mouth (13%). Higher doses were associated with an increased likelihood of any side effects (≤ 30 mg/day, 38%; >31-≤60 mg/day, 48%, > 61 mg/day 73%; P < 0.004), with 31 (9%) stopping domperidone because of side effects. CONCLUSION: We identified widespread variation in domperidone utilisation patterns, with domperidone broadly perceived to be effective in increasing breast milk supply. Side effects associated with domperidone treatment were common, appeared to be dose-related, and were frequently associated with treatment cessation. These findings highlight the importance of improved clinical practice recommendations and generation of evidence from additional high-quality clinical trials evaluating the efficacy and safety of domperidone. More conclusive clinical trials are needed to determine the efficacy, as well as optimal dose and duration, of domperidone use.

Breastfeeding outcomes in late preterm infants: A multi-centre prospective cohort study.

OBJECTIVES: To describe (1) infant feeding practices during initial hospitalisation and up to 6 months corrected age (CA) in infants born late preterm with mothers intending to breastfeed, (2) the impact of early feeding practices on hospital length of stay and (3) maternal and infant factors associated with duration of breastfeeding. METHODS: We conducted a prospective cohort study of infants born at 34+0 to 36+6 weeks gestational age during 2018-2020. Families were followed up until the infant reached 6 months of age (corrected for prematurity). Feeding practices during the birth hospitalisation, length of initial hospital stay, and the prevalence of exclusive or any breastfeeding at 6 weeks, 3 months, and 6 months CA were examined. Associations between maternal and infant characteristics and breastfeeding at 6 weeks, 3 months and 6 months CA were assessed using multivariable logistic regression models. RESULTS: 270 infants were enrolled, of these, 30% were multiple births. Overall, 78% of infants received only breastmilk as their first feed, and 83% received formula during the hospitalisation. Seventy-four per cent of infants were exclusively breastfed at discharge, 41% at 6 weeks CA, 35% at 3 months CA, and 29% at 6 months CA. The corresponding combined exclusive and partial breastfeeding rates (any breastfeeding) were 72%, 64%, and 53% of babies at 6 weeks CA, 3 months CA, and 6 months CA, respectively. The mean duration of hospitalisation was 2.9 days longer (95% confidence interval (CI) 0.31, 5.43 days) in infants who received any formula compared with those receiving only breastmilk (adjusted for GA, maternal age, multiple birth, site, and neonatal intensive care unit admission). In multivariable models, receipt of formula as the first milk feed was associated with a reduction in exclusive breastfeeding at 6 weeks CA (odds ratio = 0.22; 95% CI 0.09 to 0.53) and intention to breastfeed >6 months with an increase (odds ratio = 4.98; 95% CI 2.39 to 10.40). Intention to breastfeed >6 months remained an important predictor of exclusive breastfeeding at 3 and 6 months CA. CONCLUSIONS: Our study demonstrates that long-term exclusive breastfeeding rates were low in a cohort of women intending to provide breastmilk to their late preterm infants, with approximately half providing any breastmilk at 6 months CA. Formula as the first milk feed and intention to breastfeed >6 months were significant predictors of breastfeeding duration. Improving breastfeeding outcomes may require strategies to support early lactation and a better understanding of the ongoing support needs of this population.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

Knowledge of Galactagogue Use During Breastfeeding in Australia: A Cross Sectional Online Survey.

BACKGROUND: Galactagogues have been used for centuries to induce, maintain, or increase a mother's milk supply. Recently, there has been an apparent increase in utilization and promotion of galactagogues, largely in the absence of data regarding their efficacy and safety. However, there is limited contemporary evidence about knowledge of these substances in the community or how and where individuals seek information. RESEARCH AIM: To evaluate knowledge about galactagogue use during breastfeeding among birth parents, including recognition of specific substances, perceptions of safety, and common information sources. METHOD: An online, prospective, cross-sectional survey of Australian birthing parents (N = 2055) who were currently breastfeeding or had previously breastfed their infants was conducted from September to December 2019. The survey included questions about recognition of galactagogues, perceptions of safety, and information-seeking behaviors. RESULTS: Among participants, 47% (n = 882) were primiparous and 65% (n = 1,219) were currently breastfeeding. The most recognized galactagogues included lactation cookies (89%; n = 1,828), brewer's yeast (79%; n = 1,629), fenugreek (74%; n = 1,519), and domperidone (69%; n = 1,420). Respondents cited the internet (52%; n = 1,066), lactation support providers (46%; n = 951), midwives (42%; n = 873), general practitioners (39%; n = 802), and social media (35%; n = 714) as common information sources. Lactation support providers and breastfeeding helplines were commonly rated as helpful; whereas, general practitioners and community pharmacists were often rated as unhelpful. While most participants perceived galactagogues to be safe, herbal or dietary galactagogues were perceived to be safer than pharmaceutical galactagogues. CONCLUSIONS: Our Australian community survey of individuals with current or previous breastfeeding experience identified widespread recognition of galactagogue use, with participants reporting a broad range of information-seeking behaviors and generally perceiving galactagogues as being safe to use.

Effects of COVID-19 pandemic restrictions on an Australian neonatal and paediatric retrieval service.

AIM: The COVID-19 pandemic and associated travel and social distancing restrictions have reduced paediatric intensive care unit admissions for respiratory illnesses. The effects on retrieval (transport) services remain unquantified. Our study examined the utility of statistical process control in assessing the impact of the COVID-19 pandemic on the number of neonatal and paediatric transfers in an Australian retrieval service. METHODS: Data collected prospectively from the SA Ambulance Service MedSTAR Emergency Retrieval database in South Australia were analysed from January 2015 to June 2021. Statistical process control methodology, a combination of a time series analysis and assessment for common and special cause variation, was used to assess the impact of the COVID-19 pandemic on retrieval workload (primary outcome of interest). RESULTS: A total of 5659 neonatal and paediatric transfers occurred during the study period and were included. A significant decrease in paediatric transfers occurred after the initial lockdown measures in March 2020 were announced in South Australia (special cause variation). However, a similar reduction was not observed for neonatal transfers (common cause variation). CONCLUSION: Our study demonstrates that statistical process control may be effectively used to understand the effects of external events and processes on usual activity patterns in the retrieval setting. We found a reduction in retrieval numbers for paediatric transfers but no effect on neonatal transfer numbers. The decline in paediatric transfers was primarily attributed to reduced respiratory cases.

Antenatal magnesium sulphate for preventing cerebral palsy: An economic evaluation of the impact of a quality improvement program.

Previous work demonstrated that implementing a quality improvement (QI) program improves the uptake of guideline-recommended antenatal magnesium sulphate, a critical intervention known to reduce cerebral palsy risk. Here we estimate potential cost savings attributable to the improved uptake. By expanding coverage from 63 to 83% of eligible women, we estimated that five children potentially would not have received a diagnosis of cerebral palsy, a potential cost saving of $AU4.8 million in lifetime healthcare costs. Our findings strengthen the case for embedding QI approaches in perinatal care to reduce the incidence of cerebral palsy.

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.