Use and experiences of galactagogues while breastfeeding among Australian women

Background: Galactagogues are substances thought to increase breast milk production, however evidence to support their efficacy and safety remain limited. We undertook a survey among Australian women to examine patterns of use of galactagogues and perceptions regarding their safety and effectiveness. Methods: An online, cross-sectional survey was distributed between September and December 2019 via national breastfeeding and preterm birth support organisations, and networks of several research institutions in Australia. Women were eligible to participate if they lived in Australia and were currently/previously breastfeeding. The survey included questions about galactagogue use (including duration and timing), side effects and perceived effectiveness (on a scale of 1 [Not at all effective] to 5 [Extremely effective]). Results: Among 1876 respondents, 1120 (60%) reported using one or more galactagogues. Women were 31.5 ± 4.8 years (mean ± standard deviation) at their most recent birth. Sixty-five percent of women were currently breastfeeding at the time of the survey. The most commonly reported galactagogues included lactation cookies (47%), brewer's yeast (32%), fenugreek (22%) and domperidone (19%). The mean duration of use for each galactagogue ranged from 2 to 20 weeks. Approximately 1 in 6 women reported commencing galactagogues within the first week postpartum. Most women reported receiving recommendations to use herbal/dietary galactagogues from the internet (38%) or friends (25%), whereas pharmaceutical galactagogues were most commonly prescribed by General Practitioners (72%). The perceived effectiveness varied greatly across galactagogues. Perceived effectiveness was highest for domperidone (mean rating of 3.3 compared with 2.0 to 3.0 among other galactagogues). Over 23% of domperidone users reported experiencing multiple side effects, compared to an average of 3% of women taking herbal galactagogues. Conclusions: This survey demonstrates that galactagogues use is common in Australia. Further research is needed to generate robust evidence about galactagogues' efficacy and safety to support evidence-based strategies and improve breastfeeding outcomes.Grace M. McBride, Robyn Stevenson, Gabriella Zizzo, Alice R. Rumbold, Lisa H. Ami, Amy K. Keir, Luke E. Grzeskowia

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

Improving the admission temperatures of preterm infants in the neonatal unit

Published Online First 2 August 2021Use of plan-do-study-act cycles to increase the proportion of preterm infants born at <32 weeks’ gestation admitted to a neonatal unit with a body temperature of 36.5–37.4°C.Amy K Keir, Angela Cavallar

Fluid Therapy: Friend or Foe?

Many questions surround fluid bolus therapy and subsequent fluid management in neonatal critical care as they do in pediatric and adult critical care. This review explores the known key clinical aspects of fluid bolus therapy and fluid balance in the first 7 days of life and provides suggestions for further work in this area. It draws on the pediatric and adult critical care literature to provide thought-provoking data around the potential harms of excessive intravenous fluids, which may prove relevant to neonatology. Current data suggest that fluid bolus therapy and early-life positive fluid balance in neonates may be associated with harm.Erin Grace, Amy K. Kei

'I wish I'd had the option': views about donor human milk among parents with babies born moderate-late preterm

First published: 02 May 2021When enough mother's own milk is not available, the benefits of pasteurised donor human milk (donor milk) are well-established for infants born very preterm (<32 weeks' gestation).1 Infants born moderate-to-late preterm (32–36 weeks' gestation) make up the majority of preterm births and frequently face challenges establishing breastfeeding,2 often necessitating the use of supplementary nutrition in the first weeks of life. While varied, the most common practice in Australia and New Zealand is to give infant formula.3 In other countries, particularly the USA, donor milk is used for some moderate to late preterm and term infants, but little evidence exists to inform care practices in these groups.4 Parental interest is likely one force driving practice change in donor milk use, however, little is known about Australian parents' views about donor milk. We conducted an exploratory survey of Miracle Babies Foundation members, the largest preterm birth support and advocacy group in Australia, who had babies born moderate to late preterm. The Lifeblood Human Research Ethics Committee approved the survey. The survey was advertised via the Miracle Babies Facebook page between January and March 2020. Parents were eligible if they had a baby that was born between 32 + 0 and 36 + 6 weeks' gestation. The survey asked about parents' experiences with feeding their baby and their perspectives on donor milk. Here we share their responses to prompt further discussions about the role of donor milk for moderate to late preterm infants. Overall, 67 parents responded to the survey; of these, more than half (n = 42, 63%) reported that they or their partner had trouble making enough milk for their baby (Table 1). Of those, several (n = 12, 29%) said that they sought human milk from another source, most commonly a friend or family member or a hospital milk bank.Laura D Klein, Amy K Keir, Melinda Cruz, Alice R Rumbol

Impact of human donor milk on maternal milk use at discharge: assessment using control charts

Amy K Keir, Laura Summers, Jennifer Gillis, Andrew J McPhee, Alice Rumbol

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.Erin Grace, Cathie Hilditch, Judith Gomersall, Carmel T Collins, Alice Rumbold, Amy K Keir ... et al

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

First published online: March 3, 2022Background: 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.Grace McKenzie McBride, Robyn Stevenson, Gabriella Zizzo, Alice R Rumbold, Lisa H Amir, Amy K Keir, Luke Edward Grzeskowia

Antenatal magnesium sulfate to prevent cerebral palsy

First published July 7, 2021.Magnesium sulfate given to women before birth at <30 weeks’ gestation reduces the risk of cerebral palsy in their children. Our study aimed to assess the impact of a local quality improvement programme, primarily using plan-do-study-act cycles, to increase the use of antenatal magnesium sulfate. After implementing our quality improvement programme, an average of 86% of babies delivered at <30 weeks’ gestation were exposed to antenatal magnesium sulfate compared with a historical baseline rate of 63%. Our study strengthens the case for embedding quality improvement programmes in maternal perinatal care to reduce the impact of cerebral palsy on families and society.Amy K Keir, Emily Shepherd, Sarah McIntyre, Alice Rumbold, Charlotte Groves, Caroline Crowther, Emily Joy Callande