A protocol for a randomised controlled trial exploring human milk, nutrition, growth, and breastfeeding rates at discharge: the Hummingbird study

A protocol for a randomised controlled trial exploring human milk, nutrition, growth, and breastfeeding rates at discharge: the Hummingbird study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol A protocol for a randomised controlled trial exploring human milk, nutrition, growth, and breastfeeding rates at discharge: the Hummingbird study Kristina Chmelova, Janet Berrington, Natalie Shenker, Stefan Zalewski, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2263972/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Mother’s own breast milk (MOM) is the optimal nutrition for preterm infants as it reduces the incidence of key neonatal morbidities and improves long-term outcomes. However, MOM shortfall is common and either preterm formula (PF) or pasteurised donor human milk (DHM) may be used, although practice varies widely. Limited data suggest that the use of DHM may impact on maternal beliefs and behaviours and may therefore impact on breastfeeding rates. The aim of this pilot study is to determine if the duration of DHM exposure impacts on breastfeeding rates, and maternal breastfeeding self-efficacy. Methods The Human Milk, Nutrition, Growth, and Breastfeeding Rates at Discharge (Hummingbird) study is a feasibility and pilot, non-blinded, randomised controlled trial (RCT) with a contemporaneous qualitative evaluation. Babies born at less than 33 weeks gestation or with birth weight <1500 grams whose mothers intend to provide MOM are randomly assigned to either control arm (DHM used to make up shortfall until full feeds, then PF used thereafter) or intervention arm (DHM used to make up shortfall until 36 weeks corrected age or discharge if sooner). The primary outcome is breastfeeding rates at discharge. Secondary outcomes include growth, key neonatal morbidities, length of stay, breastfeeding self-efficacy and postnatal depression using validated questionnaires. Qualitative interviews using a topic guide will explore perceptions around use of DHM and will be analysed using thematic analysis. Discussion The provision of DHM is a complex intervention as it impacts on infant health and disease, as well as impacting on maternal and healthcare staff belief and behaviour. This is the first RCT to investigate the impact of DHM duration on breastfeeding rates and maternal self-efficacy. Trial registration: Trial was registered prospectively on 4 th May 2021 (ISRCTN 57339063). breast milk donor human milk preterm breastfeeding nutrition Figures Figure 1 Background Approximately 60,000 babies are born prematurely (<37 weeks) in the UK each year. While most are born late preterm (34 -37 weeks), around 10,000 babies are born very preterm (<32 weeks’ gestation) ( 1 ). Preterm babies often need neonatal intensive care and prolonged hospital stay. While survival rates of extremely preterm (<28 weeks) infants have notably improved over the past two decades, death is still relatively common ( 2 , 3 ), with late onset sepsis (LOS) and necrotising enterocolitis (NEC) being the most prevalent ( 4 ). Preterm infants are at significant risk of long-term complications such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and cognitive impairment ( 3 ). Nutritional management impacts on short and long-term neonatal outcomes ( 5 ) but remains challenging as macronutrient intakes can sometimes be hard to meet. ( 6 ). Mother’s own milk Mother’s own milk (MOM) provides the basis of the optimal diet for preterm babies ( 7 ) due to the composition of key proteins and lipids, but also because it provides hormones, enzymes, growth factors and other unique and dyad-specific bioactive nutrients such as human milk oligosaccharides (HMOs) which facilitate early colonisation of the gut and may reduce NEC. Use of MOM is associated with decreased risk of major neonatal morbidities such as NEC, LOS, ROP or BPD ( 8-11 ), and this effect is dose-responsive ( 12 ). Whilst an exclusive MOM diet has been associated with slower growth in very low birth weight (VLBW) infants compared to growth with PF use ( 13 , 14 ), cognitive, cardiac and metabolic outcomes are better in the first year ( 15 , 16 ) and throughout the life-course ( 17 , 18 ). Challenges of expressing MOM and breastfeeding in NICU Despite strong evidence about the benefits of MOM, low breastfeeding rates remain a major health concern. Over 90% of mothers now provide at least some breastmilk after preterm delivery, but breastfeeding rates at discharge for preterm infants vary considerably from 19-70% across Europe ( 19 ). In addition to the challenges many women experience when breastfeeding, mothers of preterm babies may also be unwell, they must cope with the stress of having a preterm, often sick infant who is physically separated from them from birth, and they need to maintain breastmilk expression for several weeks. Furthermore, the initiation of lactogenesis is often impaired after preterm birth ( 20 , 21 ). Delayed initiation, first expression of colostrum more than 6 hours after delivery, is associated with three-fold decrease in milk volumes at 3 weeks postpartum ( 22 ). In view of these challenges, effective support and counselling for mothers who express milk in the NICU is vital. Assessment tools have been developed to identify mothers who are at risk of discontinuing breastfeeding early, but most are only validated for term infants and their reliability varies ( 23 ). Despite targeted support, shortfall of MOM is common in neonatal intensive care units ( NICU)s with more than 80% of infants requiring additional milk at some point ( 1 ). Donor Human Milk The World Health Organisation, American Association for Pediatrics and European Society of Paediatric Gastroenterology, Hepatology and Nutrition recommend the use of donor human milk (DHM) for feeding premature infants as a first alternative when there is a MOM shortfall ( 7 , 24 , 25 ), despite the relatively lack of high-quality RCTs and the heterogeneity of many studies. A recent Cochrane review suggested that DHM may reduce risk of NEC compared to PF, with at least 33 infants needing to receive DHM to prevent one NEC case. The data do not support a reduction in mortality or longer-term neurodevelopmental benefits, and many studies were noted to have been conducted more than 20 years ago. ( 26 ). Zipitis et al. demonstrated differences in DHM use amongst UK NICUs ( 27 ), with some only providing DHM for the first 10 days of a baby’s life whereas other units use DHM until closer to discharge. Battersby et al. showed that variation between NICUs is not related to the presence of a local milk bank and is most likely linked to uncertainties around DHM use ( 28 ). One key uncertainty is whether DHM affects duration of breastmilk expression or breastfeeding. A systematic review of 10 studies showed that DHM may have a positive impact on any breastfeeding but does not appear to affect rates of exclusive breastfeeding on discharge ( 29 ). A large observational study analysing DHM availability in 56 NICUs in the USA showed positive effects on breastfeeding in NICUs where a DHM programme was implemented, along with a decrease in NEC rate ( 30 ). A historical cohort comparison study pre- and post-DHM introduction demonstrated increased breastfeeding at discharge and increased consumption of MOM ( 31 ). In contrast, another single-centre retrospective study showed that MOM provision decreased over a two-year period following the implementation of a donor milk program where preterm infants consumed less MOM in the first 14 days in the post-DHM cohort. ( 32 ). Esquerra-Zwiers et al. showed similarly reduced exclusive MOM use in the first two weeks of life with DHM availability compared to a pre-DHM cohort. However, in these studies enteral feeds were commenced earlier, and infants were exposed to formula later in life in after DHM introduction ( 33 ). Tshamala et al. also reported earlier start of enteral feeding and unchanged proportion of infants fed exclusively with maternal breastmilk at discharge after implementation of a DHM programme ( 34 ). More recently, Mondkar et al. showed that DHM use in addition to optimising breastfeeding support and kangaroo care led to improved exclusive human milk feeding ( 35 ).To date, no RCT has studied the relationship between donor milk availability and breastfeeding at hospital discharge. Preterm formula The composition of PF is designed to meet the high nutritional demands of the preterm infant. This has resulted in improved weight gain, linear growth, and head growth of preterm infants ( 26 ). However, no RCTs have shown improved long-term growth or neurodevelopmental outcomes compared to use of MOM or DHM ( 26 , 36 ). PF may provide a more consistent delivery of macro- and micro-nutrients but lacks non-nutritive content, so called bionutrients or immunonutrients, which might be key in reducing disease (e.g. NEC), establishing diverse gut microbiota and improving long-term outcomes ( 37 , 38 ). The cost of PF (around £5 per litre) is almost 30-fold lower than the cost of DHM (between £125-150 per litre). However, if supplemental DHM feeding prevented NEC, total costs for hospitalisation would favour DHM compared to PF use in case of MOM shortfall ( 39 , 40 ). Summary of key issues: donor human milk as a 'complex intervention’ In summary, MOM is the optimal source of nutrition for preterm infants. Despite this evidence, breastfeeding rates in the UK are amongst the lowest in the world ( 41 ), and breastfeeding rates in the North East of England are some of the lowest in the UK ( 42 ). This is also reflected in breastmilk feeding of premature infants. Currently, around 90-95% of mothers in the North East start expression of breastmilk for their preterm baby, but only 35% are still providing breastmilk at discharge compared to the national average of 60% ( 42 ). Improving availability of MOM in NICUs is crucial to reducing key neonatal morbidities. The use of DHM is increasing in most UK neonatal units and is recommended by ESPGHAN when there is a shortfall of mother’s own milk, largely because meta-analysis suggests a lower rate of NEC ( 26 ). However, because DHM also affects growth, which may in turn be associated with longer term brain and metabolic outcomes, the optimal strategy for improving lifelong health remains uncertain. Observational data show that availability of DHM impacts on breastmilk expression and breastfeeding duration demonstrating that DHM affects beliefs and behaviours of mothers, healthcare staff or perhaps both, and DHM is therefore a ‘complex intervention’. Complex interventions in healthcare impact on biology (i.e. health and disease), behaviour and belief (e.g., breastfeeding rates). They may have multiple relevant outcomes and mechanistic causal pathways; and may be affected by context e.g. NICUs with differing background rates of NEC or breastfeeding. There is often long lag time between intervention and outcome (metabolic and cognitive outcomes in adulthood) ( 43 ). Provision of DHM may be the best example of a complex intervention in neonatal medicine, and uncertainties around the optimal strategy are unlikely to be resolved with a single RCT. However, this trial could lay foundation for further trials to investigate the optimal implementation and use of DHM (Figure 1). Methods/design The HUMMINGBIRD study is a randomised open-label controlled trial set in two tertiary neonatal units in the North East of England. It is designed to compare two different nutritional strategies which use DHM to make up any shortfall in MOM for preterm infants (Table 1). Table 1. Summary of study methods Setting Tertiary level NICUs in North East England Population Preterm infants <33 weeks or with a birth weight <1500g admitted in the first seven days of life Intervention Use of DHM to make up any shortfall in MOM until 36 weeks corrected age (or discharge if this comes earlier) Control Use of DHM to make up any shortfall in MOM until full feeds are achieved (tolerating 150mls/kg/day for 48 hours) Design Randomised open-label controlled trial Timeframe Until 36 weeks corrected gestation or hospital discharge if earlier Population Infants born before 33 completed weeks of gestation or with a birth weight of less than 1500 g whose mothers intend to express breastmilk after delivery and are willing to accept DHM are eligible. Only infants with written informed consent from parents and randomised within seven days of birth can be included. Infants who were born with major congenital or life-threatening abnormalities or who were exposed to formula milk prior randomisation are excluded. Intervention: DHM duration This study aims to assess the impact on breastfeeding at discharge, therefore infants in the intervention group will only continue to receive DHM if their mother is still expressing breastmilk. Where the infant has not received any mother’s own breastmilk for one week, or where the mother has told clinical staff she is no longer expressing, the use of DHM will be discontinued and the baby will receive a standard formula milk designed for preterm infants. Control: DHM duration Full feeds are defined as a volume of 150 ml/kg/day tolerated for 48 hours. If a shortfall of MOM occurs beyond this point, infants in the control group will receive preterm formula milk. Randomisation Infants are randomised with a secured, password protected web-based randomisation tool using a minimisation algorithm ( www.sealedenvelope.com ) that incorporates the following variables: gestation (<28 weeks yes/no), and twin/triplet status (yes/no). Twins, triplets, and higher multiples are co-randomised to the same trial arm. Study Outcomes Primary outcome Any breastfeeding, or mother still actively expressing milk, at 36 weeks corrected age or discharge if this is earlier. Secondary outcomes – growth, feeding and neonatal outcomes Growth – weekly weight, length and head circumference, absolute changes (g/kg/day and mm/week) and change in standard deviation score Neonatal morbidities: Episodes of confirmed NEC Bell stage 2 or greater Late onset sepsis confirmed and clinically suspected according to existing case definitions ( 44 ) Chronic lung disease (oxygen requirement or respiratory support at 36 weeks) Retinopathy of prematurity (ROP) Intraventricular haemorrhage and/or cystic periventricular leukomalacia Days of intensive, high and low dependency care ( 45 ); corrected age at discharge, total length of stay (days) Total volume (litres) of milk (MOM, DHM and formula) received from birth to 36 weeks Age at starting breastmilk fortifier and number of days when fortifier is provided Type of feeding at discharge (direct breast feeding, tube feeding etc.) Type of milk and feeding at 6- and 12-weeks post discharge Secondary outcomes – maternal questionnaires and qualitative data A validated questionnaire, Breastfeeding Self-Efficacy Scale – Short Form (BSES-SF) adapted for preterm infants ( 46 ), is given to mothers at two time points – around 10 days postnatal age and again at 35-36 weeks corrected age or prior to discharge if sooner. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire will also administered to mothers around day 10 postpartum ( 47 , 48 ). BSES-SF and EPDS scores will serve as a tool to stratify mothers into two groups (scores in the bottom and top quartile of scores). This will be used as a guide to ensure that both groups will be represented in the subset of interviewed mothers. Qualitative interviews with mothers will be conducted to explore perceptions around donor milk use and barriers and facilitators to expressing MOM. These one-to-one, online or in-person semi-structured in-depth interviews will be recorded and transcribed. We estimate that 15-20 interviews will be recorded although final number of interviews will be determined by thematic saturation generated through interpretation of data ( 49 ). Hypothesis, sample size and power We hypothesise that longer access to DHM (intervention arm) will improve the rate of breastfeeding at discharge from the current rate of 35% to the UK national average of 60%. Fifty-eight infants per trial group will be required to detect an improvement in breastfeeding rates at discharge from 35% to 60%. Assuming 10% of infants do not survive, at least 130 infants need to be recruited to complete the trial. We estimate that up to 20% of infants may be discharged before 36 weeks corrected age to a local neonatal unit that does not have continued access to DHM. We will therefore need to recruit between 130 and 156 infants in order for the study to be powered at 80%, and we estimate this will take 18-24 months recruitment. Analysis Data will be analysed using an intention-to-treat approach, but additional analysis will be performed only using breastfeeding outcome data for those completing the study (i.e., excluding transfers) and the first baby from a multiple pregnancy enrolled. Categorical data will be presented as counts and frequencies and will be compared using chi squared or Fisher exact test as appropriate. Continuous data will be presented as mean (SD) or median (IQR) and the Shapiro-Wilk test will be used to test the normality of the data. Group differences in continuous data will be compared using Student’s t-test or Mann-Whitney U test for normally and non-normally distributed data respectively. All tests will be performed two tailed and p<0.05 will be deemed statistically significant. Qualitative data will be analysed using reflexive thematic analysis ( 50 ). Discussion The benefits of MOM for preterm infants are well recognised but uncertainties remain around the optimal strategy for DHM use, especially whether it impacts on breastfeeding success. DHM is a complex intervention as it impacts on infant health and disease as well as maternal and healthcare staff behaviours and beliefs. To our knowledge, HUMMINGBIRD is the first RCT to investigate DHM as a complex intervention. A single RCT of a complex intervention is unlikely to resolve all uncertainties, unless there is a large impact on serious disease or mortality. In this respect, current systematic reviews of the role of DHM maybe of low certainty and do not clearly identify the optimal strategy. Studies incorporating quantitative and qualitative methods may better elucidate the role of DHM in NICUs and help optimise the design of future studies. Abbreviations BPD bronchopulmonary dysplasia BSES-SF breastfeeding self-efficacy scale – short form DHM donor human milk EPDS Edinburgh Postnatal Depression Scale HMO human milk oligosaccharides IRAS Integrated Research Application System LOS late onset of sepsis MOM mother’s own milk NICU neonatal intensive care unit PF preterm formula RCT randomised controlled trial REC Research Ethics Committee ROP retinopathy of prematurity Declarations ETHIC S APPROVAL AND CONSENT TO PARTICIPATE Nottingham 2 Research Ethics Committee granted approval for HUMMINGBIRD Study on 6 th April 2021 (IRAS Project ID 281071) and recruitment commenced on 7 th June 2021. A trial steering committee including independent members and parents will oversee trial conduct and progress. The trial is compliant with the UNICEF Baby Friendly Initiative. CONSENT FOR PUBLICATION Not applicable. AVAILABILITY OF DATA AND MATERIALS Not applicable. COMPETING INTERESTS NS is the cofounder of the Human Milk Foundation, a UK charity that provides donor human milk. NE and JB report research grants paid to their institution from National Institutes for Health Research, Action Medical Research, Prolacta Biosciences US, Danone Early Life Nutrition and NeoKare but received no personal fee, and have no other financial conflicts related to industry funding. NE reports lecture honoraria from Nestle Nutrition Institute, and Astarte Medical. FUNDING This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors and was supported using internal departmental funds. AUTHORS’ CONTRIBUTIONS NE had original idea for Hummingbird trial after discussions with NS and played a key role in developing the protocol. JB contributed to study design and protocol development. All authors contributed to the writing and review of this paper and gave final approval for its submission. 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NE and JB report research grants paid to their institution from National Institutes for Health Research, Action Medical Research, Prolacta Biosciences US, Danone Early Life Nutrition and NeoKare but received no personal fee, and have no other financial conflicts related to industry funding. NE reports lecture honoraria from Nestle Nutrition Institute, and Astarte Medical. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2263972","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":151934017,"identity":"10492942-2c69-449c-aef1-1f80729589ca","order_by":0,"name":"Kristina Chmelova","email":"","orcid":"","institution":"Newcastle upon Tyne Hospitals NHS Foundation Trust","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kristina","middleName":"","lastName":"Chmelova","suffix":""},{"id":151934018,"identity":"841af841-8ff3-4a97-9d77-c602dcb57247","order_by":1,"name":"Janet Berrington","email":"","orcid":"","institution":"Newcastle upon Tyne Hospitals NHS Foundation Trust","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Janet","middleName":"","lastName":"Berrington","suffix":""},{"id":151934019,"identity":"5c7f20e7-6026-47b2-8208-64030691c5b4","order_by":2,"name":"Natalie Shenker","email":"","orcid":"","institution":"Imperial College London","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Natalie","middleName":"","lastName":"Shenker","suffix":""},{"id":151934020,"identity":"5df0ec52-435d-42b5-a086-b50f3f72b885","order_by":3,"name":"Stefan Zalewski","email":"","orcid":"","institution":"Newcastle upon Tyne Hospitals NHS Foundation Trust","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stefan","middleName":"","lastName":"Zalewski","suffix":""},{"id":151934021,"identity":"46fa8271-9724-43e8-bcdb-07de07c64f97","order_by":4,"name":"Judith Rankin","email":"","orcid":"","institution":"Newcastle University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Judith","middleName":"","lastName":"Rankin","suffix":""},{"id":151934022,"identity":"2ecc84ae-f7bc-4541-bc39-4afb93ab50e4","order_by":5,"name":"Nicholas Embleton","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABQklEQVRIie2RMUvDUBDHLzx4WV7p+kq1foUrgYaCNF/lPQpOjTgWGuiDQh3MB4gU/AxOdY0E0iXFVXFJETq1EDfBKqZah9pUV4f3W+7g+HF3/AE0mv8IAQpw9tlSSNfFVJuRuam8SMGNItYdC78mjOxRYEfh4nfFNsk8zbDlgHlxkoruqmZXlrdPzGs5DiEhvHggL9WW0hxQux5gWyo2vUGRoNUcnbYtFrelT6gw/BjkaHsLRoxWGRIB3B1zOUR5/dhpVF1FBCMMoaRAXhUqfQeOlrnynisPif3qqr7DSDkz3vYqkaF4KVdUrtyzBnFVZPiEAVlv2TmMNioBTuSQufkvsWVh0rGqq3gi/YhidBBz68f7eBfNedbtOWVzOk4zr1bDSVJ/DryeY54PZrOFd3wYhDvBfKdTQFgUpEaj0Wj+5APKNmlNgrnSEgAAAABJRU5ErkJggg==","orcid":"","institution":"Newcastle upon Tyne Hospitals NHS Foundation Trust","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nicholas","middleName":"","lastName":"Embleton","suffix":""}],"badges":[],"createdAt":"2022-11-11 16:29:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2263972/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2263972/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":29144994,"identity":"391f8373-7c1f-4a86-a8d1-4b8dc83c2076","added_by":"auto","created_at":"2022-11-16 16:03:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":130430,"visible":true,"origin":"","legend":"\u003cp\u003eLogic model depicting DHM as complex intervention.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2263972/v1/a78c54650680a7607341c025.png"},{"id":29268177,"identity":"b82e383a-5b4e-47ba-9df0-22ce802ccc98","added_by":"auto","created_at":"2022-11-19 02:29:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":632226,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2263972/v1/1a9f9432-ca7f-4b9a-8d27-ac24540b1779.pdf"}],"financialInterests":"Competing interest reported. NS is the cofounder of the Human Milk Foundation, a UK charity that provides donor human milk. NE and JB report research grants paid to their institution from National Institutes for Health Research, Action Medical Research, Prolacta Biosciences US, Danone Early Life Nutrition and NeoKare but received no personal fee, and have no other financial conflicts related to industry funding. NE reports lecture honoraria from Nestle Nutrition Institute, and Astarte Medical.","formattedTitle":"A protocol for a randomised controlled trial exploring human milk, nutrition, growth, and breastfeeding rates at discharge: the Hummingbird study","fulltext":[{"header":"Background","content":"\u003cp\u003eApproximately 60,000 babies are born prematurely (\u0026lt;37 weeks) in the UK each year. While most are born late preterm (34 -37 weeks), around 10,000 babies are born very preterm (\u0026lt;32 weeks\u0026rsquo; gestation) (\u003ca href=\"#_ENREF_1\" title=\", #12\"\u003e1\u003c/a\u003e). Preterm babies often need neonatal intensive care and prolonged hospital stay. While survival rates of extremely preterm (\u0026lt;28 weeks) infants have notably improved over the past two decades, death is still relatively common\u0026nbsp;(\u003ca href=\"#_ENREF_2\" title=\"Santhakumaran, 2018 #15\"\u003e2\u003c/a\u003e, \u003ca href=\"#_ENREF_3\" title=\"Platt, 2014 #16\"\u003e3\u003c/a\u003e), with late onset sepsis (LOS) and necrotising enterocolitis (NEC) being the most prevalent\u0026nbsp;(\u003ca href=\"#_ENREF_4\" title=\"Berrington, 2012 #3\"\u003e4\u003c/a\u003e). Preterm infants are at significant risk of long-term complications such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and cognitive impairment\u0026nbsp;(\u003ca href=\"#_ENREF_3\" title=\"Platt, 2014 #16\"\u003e3\u003c/a\u003e).\u0026nbsp;Nutritional management impacts on short and long-term neonatal outcomes\u0026nbsp;(\u003ca href=\"#_ENREF_5\" title=\"Embleton, 2013 #18\"\u003e5\u003c/a\u003e)\u0026nbsp;but remains challenging as macronutrient intakes can sometimes be hard to meet.\u0026nbsp;(\u003ca href=\"#_ENREF_6\" title=\"Ziegler, 2009 #24\"\u003e6\u003c/a\u003e). \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eMother\u0026rsquo;s own milk\u003c/h2\u003e\n\u003cp\u003eMother\u0026rsquo;s own milk (MOM) provides the basis of the optimal diet for preterm babies\u0026nbsp;(\u003ca href=\"#_ENREF_7\" title=\"Agostoni, 2010 #22\"\u003e7\u003c/a\u003e)\u0026nbsp;due to the composition of key proteins and lipids, but also because it provides hormones, enzymes, growth factors and other unique and dyad-specific bioactive nutrients such as human milk oligosaccharides (HMOs) which facilitate early colonisation of the gut and may reduce NEC. Use of MOM is associated with decreased risk of major neonatal morbidities such as NEC, LOS, ROP or BPD\u0026nbsp;(\u003ca href=\"#_ENREF_8\" title=\"Patel, 2013 #72\"\u003e8-11\u003c/a\u003e), and this effect is dose-responsive\u0026nbsp;(\u003ca href=\"#_ENREF_12\" title=\"Ahrabi, 2013 #29\"\u003e12\u003c/a\u003e). Whilst an exclusive MOM diet has been associated with slower growth in very low birth weight (VLBW) infants compared to growth with PF use\u0026nbsp;(\u003ca href=\"#_ENREF_13\" title=\"Embleton, 2001 #45\"\u003e13\u003c/a\u003e, \u003ca href=\"#_ENREF_14\" title=\"Embleton, 2007 #46\"\u003e14\u003c/a\u003e), cognitive, cardiac and metabolic outcomes are better\u0026nbsp;in the first year\u0026nbsp;(\u003ca href=\"#_ENREF_15\" title=\"Rozé, 2012 #141\"\u003e15\u003c/a\u003e, \u003ca href=\"#_ENREF_16\" title=\"El-Khuffash, 2021 #204\"\u003e16\u003c/a\u003e)\u0026nbsp;and throughout the life-course\u0026nbsp;(\u003ca href=\"#_ENREF_17\" title=\"Owen, 2005 #76\"\u003e17\u003c/a\u003e, \u003ca href=\"#_ENREF_18\" title=\"Singhal, 2001 #92\"\u003e18\u003c/a\u003e).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eChallenges of expressing MOM and breastfeeding in NICU\u003c/h2\u003e\n\u003cp\u003eDespite strong evidence about the benefits of MOM, low breastfeeding rates remain a major health concern. Over 90% of mothers now provide at least some breastmilk after preterm delivery, but breastfeeding rates at discharge for preterm infants vary considerably from 19-70% across Europe\u0026nbsp;(\u003ca href=\"#_ENREF_19\" title=\"Bonet, 2011 #152\"\u003e19\u003c/a\u003e). In addition to the challenges many women experience when breastfeeding, mothers of preterm babies may also be unwell, they must cope with the stress of having a preterm, often sick infant who is physically separated from them from birth, and they need to maintain breastmilk expression for several weeks. Furthermore, the initiation of lactogenesis is often impaired after preterm birth\u0026nbsp;(\u003ca href=\"#_ENREF_20\" title=\"Dewey, 2001 #42\"\u003e20\u003c/a\u003e, \u003ca href=\"#_ENREF_21\" title=\"Henderson, 2008 #203\"\u003e21\u003c/a\u003e). Delayed initiation, first expression of colostrum more than 6 hours after delivery, is associated with three-fold decrease in milk volumes at 3 weeks postpartum\u0026nbsp;(\u003ca href=\"#_ENREF_22\" title=\"Parker, 2012 #43\"\u003e22\u003c/a\u003e).\u003c/p\u003e\n\u003cp\u003eIn view of these challenges, effective support and counselling for mothers who express milk in the NICU is vital. Assessment tools have been developed to identify mothers who are at risk of discontinuing breastfeeding early, but most are only validated for term infants and their reliability varies\u0026nbsp;(\u003ca href=\"#_ENREF_23\" title=\"Ho, 2010 #48\"\u003e23\u003c/a\u003e). Despite targeted support, shortfall of MOM is common in neonatal intensive care units ( NICU)s with more than 80% of infants requiring additional milk at some point\u0026nbsp;(\u003ca href=\"#_ENREF_1\" title=\", #12\"\u003e1\u003c/a\u003e).\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eDonor Human Milk\u003c/h3\u003e\n\u003cp\u003eThe World Health Organisation, American Association for Pediatrics and European Society of Paediatric Gastroenterology, Hepatology and Nutrition recommend the use of donor human milk (DHM) for feeding premature infants as a first alternative when there is a MOM shortfall\u0026nbsp;(\u003ca href=\"#_ENREF_7\" title=\"Agostoni, 2010 #22\"\u003e7\u003c/a\u003e, \u003ca href=\"#_ENREF_24\" title=\"Organization, 2011 #146\"\u003e24\u003c/a\u003e, \u003ca href=\"#_ENREF_25\" title=\"Barness, 1993 #147\"\u003e25\u003c/a\u003e), despite the relatively lack of high-quality RCTs and the heterogeneity of many studies.\u0026nbsp;A recent\u0026nbsp;Cochrane review suggested that DHM may reduce risk of NEC compared to PF, with at least 33 infants needing to receive DHM to prevent one NEC case. The data do not support a reduction in mortality or longer-term neurodevelopmental benefits, and many studies were noted to have been conducted more than 20 years ago.\u0026nbsp;(\u003ca href=\"#_ENREF_26\" title=\"Quigley, 2018 #6\"\u003e26\u003c/a\u003e).\u0026nbsp;Zipitis et al. demonstrated differences in DHM use amongst UK NICUs\u0026nbsp;(\u003ca href=\"#_ENREF_27\" title=\"Zipitis, 2015 #38\"\u003e27\u003c/a\u003e), with some only providing DHM for the first 10 days of a baby\u0026rsquo;s life whereas other units use DHM until closer to discharge. Battersby et al. showed that variation between NICUs is not related to the presence of a local milk bank and is most likely linked to uncertainties around DHM use\u0026nbsp;(\u003ca href=\"#_ENREF_28\" title=\"Battersby, 2018 #13\"\u003e28\u003c/a\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOne key uncertainty is whether DHM affects duration of breastmilk expression or breastfeeding. A systematic review of 10 studies showed that DHM may have a positive impact on \u003cem\u003eany\u003c/em\u003e breastfeeding but does not appear to affect rates of \u003cem\u003eexclusive\u003c/em\u003e breastfeeding on discharge (\u003ca href=\"#_ENREF_29\" title=\"Williams, 2016 #10\"\u003e29\u003c/a\u003e). A large observational study analysing DHM availability in 56 NICUs in the USA showed positive effects on breastfeeding in NICUs where a DHM programme was implemented, along with a decrease in NEC rate\u0026nbsp;(\u003ca href=\"#_ENREF_30\" title=\"Kantorowska, 2016 #83\"\u003e30\u003c/a\u003e). A historical cohort comparison study pre- and post-DHM introduction demonstrated increased breastfeeding at discharge and increased consumption of MOM\u0026nbsp;(\u003ca href=\"#_ENREF_31\" title=\"Parker, 2016 #88\"\u003e31\u003c/a\u003e). In contrast, another single-centre retrospective study showed that MOM provision decreased over a two-year period following the implementation of a donor milk program where preterm infants consumed less MOM in the first 14 days in the post-DHM cohort.\u0026nbsp;(\u003ca href=\"#_ENREF_32\" title=\"Parker, 2019 #65\"\u003e32\u003c/a\u003e). Esquerra-Zwiers et al. showed similarly reduced exclusive MOM use in the first two weeks of life with DHM availability compared to a pre-DHM cohort. However, in these studies enteral feeds were commenced earlier, and infants were exposed to formula later in life in after DHM introduction\u0026nbsp;(\u003ca href=\"#_ENREF_33\" title=\"Esquerra-Zwiers, 2021 #60\"\u003e33\u003c/a\u003e). Tshamala et al. also reported earlier start of enteral feeding and unchanged proportion of infants fed exclusively with maternal breastmilk at discharge after implementation of a DHM programme\u0026nbsp;(\u003ca href=\"#_ENREF_34\" title=\"Tshamala, 2018 #79\"\u003e34\u003c/a\u003e). More recently, Mondkar et al. showed that DHM use in addition to optimising breastfeeding support and kangaroo care led to improved exclusive human milk feeding\u0026nbsp;(\u003ca href=\"#_ENREF_35\" title=\"Mondkar, 2022 #206\"\u003e35\u003c/a\u003e).To date, no RCT has studied the relationship between donor milk availability and breastfeeding at hospital discharge.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003ePreterm formula\u003c/h2\u003e\n\u003cp\u003eThe composition of PF is designed to meet the high nutritional demands of the preterm infant. This has resulted in improved weight gain, linear growth, and head growth of preterm infants\u0026nbsp;(\u003ca href=\"#_ENREF_26\" title=\"Quigley, 2018 #6\"\u003e26\u003c/a\u003e). However, no RCTs have shown improved long-term growth or neurodevelopmental outcomes compared to use of MOM or DHM\u0026nbsp;(\u003ca href=\"#_ENREF_26\" title=\"Quigley, 2018 #6\"\u003e26\u003c/a\u003e, \u003ca href=\"#_ENREF_36\" title=\"Hay, 2017 #67\"\u003e36\u003c/a\u003e). PF may provide a more consistent delivery of macro- and micro-nutrients but lacks non-nutritive content, so called bionutrients or immunonutrients, which might be key in reducing disease (e.g. NEC), establishing diverse gut microbiota and improving long-term outcomes\u0026nbsp;(\u003ca href=\"#_ENREF_37\" title=\"Masi, 2021 #121\"\u003e37\u003c/a\u003e, \u003ca href=\"#_ENREF_38\" title=\"Stewart, 2018 #207\"\u003e38\u003c/a\u003e). The cost of PF (around \u0026pound;5 per litre) is almost 30-fold lower than the cost of DHM (between \u0026pound;125-150 per litre). However, if supplemental DHM feeding prevented NEC, total costs for hospitalisation would favour DHM compared to PF use in case of MOM shortfall\u0026nbsp;(\u003ca href=\"#_ENREF_39\" title=\"Trang, 2018 #70\"\u003e39\u003c/a\u003e, \u003ca href=\"#_ENREF_40\" title=\"Zanganeh, 2021 #208\"\u003e40\u003c/a\u003e). \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eSummary of key issues: donor human milk as a \u0026apos;complex intervention\u0026rsquo;\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eIn summary, MOM is the optimal source of nutrition for preterm infants. Despite this evidence, breastfeeding rates in the UK are amongst the lowest in the world\u0026nbsp;(\u003ca href=\"#_ENREF_41\" title=\"Wilson, 2018 #62\"\u003e41\u003c/a\u003e), and breastfeeding rates in the North East of England are some of the lowest in the UK\u0026nbsp;(\u003ca href=\"#_ENREF_42\" title=\", 2020 #103\"\u003e42\u003c/a\u003e). This is also reflected in breastmilk feeding of premature infants. Currently, around 90-95% of mothers in the North East start expression of breastmilk for their preterm baby, but only 35% are still providing breastmilk at discharge compared to the national average of 60%\u0026nbsp;(\u003ca href=\"#_ENREF_42\" title=\", 2020 #103\"\u003e42\u003c/a\u003e). Improving availability of MOM in NICUs is crucial to reducing key neonatal morbidities. The use of DHM is increasing in most UK neonatal units and is recommended by ESPGHAN when there is a shortfall of mother\u0026rsquo;s own milk, largely because meta-analysis suggests a lower rate of NEC\u0026nbsp;(\u003ca href=\"#_ENREF_26\" title=\"Quigley, 2018 #6\"\u003e26\u003c/a\u003e). However, because DHM also affects growth, which may in turn be associated with longer term brain and metabolic outcomes, the optimal strategy for improving lifelong health remains uncertain. Observational data show that availability of DHM impacts on breastmilk expression and breastfeeding duration demonstrating that DHM affects beliefs and behaviours of mothers, healthcare staff or perhaps both, and DHM is therefore a \u0026lsquo;complex intervention\u0026rsquo;. Complex interventions in healthcare impact on biology (i.e. health and disease), behaviour and belief (e.g., breastfeeding rates). They may have multiple relevant outcomes and mechanistic causal pathways; and may be affected by context e.g. NICUs with differing background rates of NEC or breastfeeding. There is often long lag time between intervention and outcome (metabolic and cognitive outcomes in adulthood)\u0026nbsp;(\u003ca href=\"#_ENREF_43\" title=\"Skivington, 2021 #143\"\u003e43\u003c/a\u003e).\u003c/p\u003e\n\u003cp\u003eProvision of DHM may be the best example of a complex intervention in neonatal medicine, and uncertainties around the optimal strategy are unlikely to be resolved with a single RCT. However, this trial could lay foundation for further trials to investigate the optimal implementation and use of DHM (Figure 1).\u003c/p\u003e"},{"header":"Methods/design","content":"\u003cp\u003eThe HUMMINGBIRD study is a randomised open-label controlled trial set in two tertiary neonatal units in the North East of England. It is designed to compare two different nutritional strategies which use DHM to make up any shortfall in MOM for preterm infants (Table 1).\u003c/p\u003e\n\u003cp\u003eTable 1. Summary of study methods\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.640599001663894%\"\u003e\n \u003cp\u003eSetting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.35940099833611%\"\u003e\n \u003cp\u003eTertiary level NICUs in North East England\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.640599001663894%\"\u003e\n \u003cp\u003ePopulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.35940099833611%\"\u003e\n \u003cp\u003ePreterm infants \u0026lt;33 weeks or with a birth weight \u0026lt;1500g admitted in the first seven days of life\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.640599001663894%\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.35940099833611%\"\u003e\n \u003cp\u003eUse of DHM to make up any shortfall in MOM until 36 weeks corrected age (or discharge if this comes earlier)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.640599001663894%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.35940099833611%\"\u003e\n \u003cp\u003eUse of DHM to make up any shortfall in MOM until full feeds are achieved (tolerating 150mls/kg/day for 48 hours)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.640599001663894%\"\u003e\n \u003cp\u003eDesign\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.35940099833611%\"\u003e\n \u003cp\u003eRandomised open-label controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.640599001663894%\"\u003e\n \u003cp\u003eTimeframe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.35940099833611%\"\u003e\n \u003cp\u003eUntil 36 weeks corrected gestation or hospital discharge if earlier\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch2\u003ePopulation\u003c/h2\u003e\n\u003cp\u003eInfants born before 33 completed weeks of gestation or with a birth weight of less than 1500 g whose mothers intend to express breastmilk after delivery and are willing to accept DHM are eligible. Only infants with written informed consent from parents and randomised within seven days of birth can be included. Infants who were born with major congenital or life-threatening abnormalities or who were exposed to formula milk prior randomisation are excluded.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eIntervention: DHM\u0026nbsp;duration\u003c/h2\u003e\n\u003cp\u003eThis study aims to assess the impact on breastfeeding at discharge, therefore infants in the intervention group will only continue to receive DHM if their mother is still expressing breastmilk. Where the infant has not received any mother\u0026rsquo;s own breastmilk for one week, or where the mother has told clinical staff she is no longer expressing, the use of DHM will be discontinued and the baby will receive a standard formula milk designed for preterm infants.\u003c/p\u003e\n\u003ch2\u003eControl: DHM duration\u003c/h2\u003e\n\u003cp\u003eFull feeds are defined as a volume of 150 ml/kg/day tolerated for 48 hours. If a shortfall of MOM occurs beyond this point, infants in the control group will receive preterm formula milk.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eRandomisation\u003c/h2\u003e\n\u003cp\u003eInfants are randomised with a secured, password protected web-based randomisation tool using a minimisation algorithm (\u003ca href=\"http://www.sealedenvelope.com\"\u003ewww.sealedenvelope.com\u003c/a\u003e) that incorporates the following variables: gestation (\u0026lt;28 weeks yes/no), and twin/triplet status (yes/no). Twins, triplets, and higher multiples are co-randomised to the same trial arm.\u003c/p\u003e\n\u003ch2\u003eStudy Outcomes\u003c/h2\u003e\n\u003ch2\u003ePrimary outcome\u003c/h2\u003e\n\u003cp\u003eAny breastfeeding, or mother still actively expressing milk, at 36 weeks corrected age or discharge if this is earlier. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eSecondary outcomes \u0026ndash; growth, feeding and neonatal outcomes\u003c/h2\u003e\n\u003col\u003e\n \u003cli\u003eGrowth \u0026ndash; weekly weight, length and head circumference, absolute changes (g/kg/day and mm/week) and change in standard deviation score\u003c/li\u003e\n \u003cli\u003eNeonatal morbidities:\u003col style=\"list-style-type: lower-alpha; font-weight: initial;\"\u003e\n \u003cli\u003eEpisodes of confirmed NEC Bell stage 2 or greater\u003c/li\u003e\n \u003cli\u003eLate onset sepsis confirmed and clinically suspected according to existing case definitions\u0026nbsp;(\u003ca href=\"#_ENREF_44\" title=\"Dong, 2015 #144\"\u003e44\u003c/a\u003e)\u003c/li\u003e\n \u003cli\u003eChronic lung disease (oxygen requirement or respiratory support at 36 weeks)\u003c/li\u003e\n \u003cli\u003eRetinopathy of prematurity (ROP)\u003c/li\u003e\n \u003cli\u003eIntraventricular haemorrhage and/or cystic periventricular leukomalacia\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/li\u003e\n \u003cli\u003eDays of intensive, high and low dependency care\u0026nbsp;(\u003ca href=\"#_ENREF_45\" title=\"Medicine, 2011 #145\"\u003e45\u003c/a\u003e); corrected age at discharge, total length of stay (days)\u003c/li\u003e\n \u003cli\u003eTotal volume (litres) of milk (MOM, DHM and formula) received from birth to 36 weeks\u003c/li\u003e\n \u003cli\u003eAge at starting breastmilk fortifier and number of days when fortifier is provided\u003c/li\u003e\n \u003cli\u003eType of feeding at discharge (direct breast feeding, tube feeding etc.)\u003c/li\u003e\n \u003cli\u003eType of milk and feeding at 6- and 12-weeks post discharge\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch2\u003eSecondary outcomes \u0026ndash;\u0026nbsp;maternal questionnaires and qualitative data\u003c/h2\u003e\n\u003cp\u003eA validated questionnaire, Breastfeeding Self-Efficacy Scale \u0026ndash; Short Form (BSES-SF) adapted for preterm infants\u0026nbsp;(\u003ca href=\"#_ENREF_46\" title=\"Wheeler, 2013 #50\"\u003e46\u003c/a\u003e), is given to mothers at two time points \u0026ndash; around 10 days postnatal age and again at 35-36 weeks corrected age or prior to discharge if sooner. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire will also administered to mothers around day 10 postpartum\u0026nbsp;(\u003ca href=\"#_ENREF_47\" title=\"Cox, 1987 #150\"\u003e47\u003c/a\u003e, \u003ca href=\"#_ENREF_48\" title=\"Smith-Nielsen, 2018 #149\"\u003e48\u003c/a\u003e). BSES-SF and EPDS scores will serve as a tool to stratify mothers into two groups (scores in the bottom and top quartile of scores). This will be used as a guide to ensure that both groups will be represented in the subset of interviewed mothers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQualitative interviews with mothers will be conducted to explore perceptions around donor milk use and barriers and facilitators to expressing MOM. These one-to-one, online or in-person semi-structured in-depth interviews will be recorded and transcribed. We estimate that 15-20 interviews will be recorded although final number of interviews will be determined by thematic saturation generated through interpretation of data\u0026nbsp;(\u003ca href=\"#_ENREF_49\" title=\"Braun, 2021 #154\"\u003e49\u003c/a\u003e).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eHypothesis, sample size and power\u003c/h2\u003e\n\u003cp\u003eWe hypothesise that longer access to DHM (intervention arm) will improve the rate of breastfeeding at discharge from the current rate of 35% to the UK national average of 60%. Fifty-eight infants per trial group will be required to detect an improvement in breastfeeding rates at discharge from 35% to 60%. Assuming 10% of infants do not survive, at least 130 infants need to be recruited to complete the trial. We estimate that up to 20% of infants may be discharged before 36 weeks corrected age to a local neonatal unit that does not have continued access to DHM. We will therefore need to recruit between 130 and 156 infants in order for the study to be powered at 80%, and we estimate this will take 18-24 months recruitment. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAnalysis\u003c/h2\u003e\n\u003cp\u003eData will be analysed using an intention-to-treat approach, but additional analysis will be performed only using breastfeeding outcome data for those completing the study (i.e., excluding transfers) and the first baby from a multiple pregnancy enrolled. Categorical data will be presented as counts and frequencies and will be compared using chi squared or Fisher exact test as appropriate. Continuous data will be presented as mean (SD) or median (IQR) and the Shapiro-Wilk test will be used to test the normality of the data. Group differences in continuous data will be compared using Student\u0026rsquo;s t-test or Mann-Whitney U test for normally and non-normally distributed data respectively. All tests will be performed two tailed and p\u0026lt;0.05 will be deemed statistically significant. Qualitative data will be analysed using reflexive thematic analysis\u0026nbsp;(\u003ca href=\"#_ENREF_50\" title=\"Braun, 2006 #96\"\u003e50\u003c/a\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe benefits of MOM for preterm infants are well recognised but uncertainties remain around the optimal strategy for DHM use, especially whether it impacts on breastfeeding success. DHM is a complex intervention as it impacts on infant health and disease as well as maternal and healthcare staff behaviours and beliefs. To our knowledge, HUMMINGBIRD is the first RCT to investigate DHM as a complex intervention. A single RCT of a complex intervention is unlikely to resolve all uncertainties, unless there is a large impact on serious disease or mortality. In this respect, current systematic reviews of the role of DHM maybe of low certainty and do not clearly identify the optimal strategy. Studies incorporating quantitative and qualitative methods may better elucidate the role of DHM in NICUs and help optimise the design of future studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBPD bronchopulmonary dysplasia\u003c/p\u003e\n\u003cp\u003eBSES-SF breastfeeding self-efficacy scale \u0026ndash; short form\u003c/p\u003e\n\u003cp\u003eDHM donor human milk\u003c/p\u003e\n\u003cp\u003eEPDS Edinburgh Postnatal Depression Scale\u003c/p\u003e\n\u003cp\u003eHMO human milk oligosaccharides\u003c/p\u003e\n\u003cp\u003eIRAS Integrated Research Application System\u003c/p\u003e\n\u003cp\u003eLOS late onset of sepsis\u003c/p\u003e\n\u003cp\u003eMOM mother\u0026rsquo;s own milk\u003c/p\u003e\n\u003cp\u003eNICU neonatal intensive care unit\u003c/p\u003e\n\u003cp\u003ePF preterm formula\u003c/p\u003e\n\u003cp\u003eRCT randomised controlled trial\u003c/p\u003e\n\u003cp\u003eREC Research Ethics Committee\u003c/p\u003e\n\u003cp\u003eROP retinopathy of prematurity\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eETHIC\u003c/strong\u003e\u003cstrong\u003eS APPROVAL AND CONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNottingham 2 Research Ethics Committee \u0026nbsp;granted approval for HUMMINGBIRD Study on 6\u003csup\u003eth\u003c/sup\u003e April 2021 (IRAS Project ID 281071) and recruitment commenced on 7\u003csup\u003eth\u003c/sup\u003e June 2021. A trial steering committee including independent members and parents will oversee trial conduct and progress. The trial is compliant with the UNICEF Baby Friendly Initiative. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIALS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNS is the cofounder of the Human Milk Foundation, a UK charity that provides donor human milk.\u0026nbsp;NE and JB report research grants paid to their institution from National Institutes for Health Research, Action Medical Research, Prolacta Biosciences US, Danone Early Life Nutrition and NeoKare but received no personal fee, and have no other financial conflicts related to industry funding. NE reports lecture honoraria from Nestle Nutrition Institute, and Astarte Medical.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors and was supported using internal departmental funds.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS\u0026rsquo; CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNE had original idea for Hummingbird trial after discussions with NS and played a key role in developing the protocol. JB contributed to study design and protocol development. All authors contributed to the writing and review of this paper and gave final approval for its submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBirth characteristics in England and Wales: 2019 Office for National Statistics [Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/livebirths/bulletins/birthcharacteristicsinenglandandwales/2019#gestational-age.\u003c/li\u003e\n\u003cli\u003eSanthakumaran S, Statnikov Y, Gray D, Battersby C, Ashby D, Modi N. Survival of very preterm infants admitted to neonatal care in England 2008\u0026ndash;2014: time trends and regional variation. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2018;103(3):F208-F15.\u003c/li\u003e\n\u003cli\u003ePlatt MJ. Outcomes in preterm infants. Public Health. 2014;128(5):399-403.\u003c/li\u003e\n\u003cli\u003eBerrington JE, Hearn RI, Bythell M, Wright C, Embleton ND. Deaths in preterm infants: changing pathology over 2 decades. J Pediatr. 2012;160(1):49-53.e1.\u003c/li\u003e\n\u003cli\u003eEmbleton ND. Early nutrition and later outcomes in preterm infants. World Rev Nutr Diet. 2013;106:26-32.\u003c/li\u003e\n\u003cli\u003eZiegler EE, Carlson SJ. Early nutrition of very low birth weight infants. J Matern Fetal Neonatal Med. 2009;22(3):191-7.\u003c/li\u003e\n\u003cli\u003eAgostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010;50(1):85-91.\u003c/li\u003e\n\u003cli\u003ePatel AL, Johnson TJ, Engstrom JL, Fogg LF, Jegier BJ, Bigger HR, et al. Impact of early human milk on sepsis and health-care costs in very low birth weight infants. J Perinatol. 2013;33(7):514-9.\u003c/li\u003e\n\u003cli\u003eSullivan S, Schanler RJ, Kim JH, Patel AL, Traw\u0026ouml;ger R, Kiechl-Kohlendorfer U, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010;156(4):562-7.e1.\u003c/li\u003e\n\u003cli\u003eBharwani SK, Green BF, Pezzullo JC, Bharwani SS, Bharwani SS, Dhanireddy R. Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update. J Perinatol. 2016;36(11):913-20.\u003c/li\u003e\n\u003cli\u003eVillamor-Mart\u0026iacute;nez E, Pierro M, Cavallaro G, Mosca F, Villamor E. Mother\u0026apos;s Own Milk and Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis. Front Pediatr. 2019;7:224.\u003c/li\u003e\n\u003cli\u003eAhrabi AF, Schanler RJ. Human milk is the only milk for premies in the NICU! Early Hum Dev. 2013;89 Suppl 2:S51-3.\u003c/li\u003e\n\u003cli\u003eEmbleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics. 2001;107(2):270-3.\u003c/li\u003e\n\u003cli\u003eEmbleton ND. Optimal protein and energy intakes in preterm infants. Early Hum Dev. 2007;83(12):831-7.\u003c/li\u003e\n\u003cli\u003eRoz\u0026eacute; JC, Darmaun D, Boquien CY, Flamant C, Picaud JC, Savagner C, et al. The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and LIFT. BMJ Open. 2012;2(2):e000834.\u003c/li\u003e\n\u003cli\u003eEl-Khuffash A, Lewandowski AJ, Jain A, Hamvas A, Singh GK, Levy PT. Cardiac Performance in the First Year of Age Among Preterm Infants Fed Maternal Breast Milk. JAMA Netw Open. 2021;4(8):e2121206.\u003c/li\u003e\n\u003cli\u003eOwen CG, Martin RM, Whincup PH, Smith GD, Cook DG. Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics. 2005;115(5):1367-77.\u003c/li\u003e\n\u003cli\u003eSinghal A, Cole TJ, Lucas A. Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet. 2001;357(9254):413-9.\u003c/li\u003e\n\u003cli\u003eBonet M, Blondel B, Agostino R, Combier E, Maier RF, Cuttini M, et al. Variations in breastfeeding rates for very preterm infants between regions and neonatal units in Europe: results from the MOSAIC cohort. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2011;96(6):F450-F2.\u003c/li\u003e\n\u003cli\u003eDewey KG. Maternal and Fetal Stress Are Associated with Impaired Lactogenesis in Humans. The Journal of Nutrition. 2001;131(11):3012S-5S.\u003c/li\u003e\n\u003cli\u003eHenderson JJ, Hartmann PE, Newnham JP, Simmer K. Effect of preterm birth and antenatal corticosteroid treatment on lactogenesis II in women. Pediatrics. 2008;121(1):e92-100.\u003c/li\u003e\n\u003cli\u003eParker LA, Sullivan S, Krueger C, Kelechi T, Mueller M. Effect of early breast milk expression on milk volume and timing of lactogenesis stage II among mothers of very low birth weight infants: a pilot study. J Perinatol. 2012;32(3):205-9.\u003c/li\u003e\n\u003cli\u003eHo YJ, McGrath JM. A review of the psychometric properties of breastfeeding assessment tools. J Obstet Gynecol Neonatal Nurs. 2010;39(4):386-400.\u003c/li\u003e\n\u003cli\u003eOrganization WH. Guidelines on optimal feeding of low birth-weight infants in low-and middle-income countries: World Health Organization; 2011.\u003c/li\u003e\n\u003cli\u003eBarness LA. Pediatric nutrition handbook. 1993.\u003c/li\u003e\n\u003cli\u003eQuigley M, Embleton ND, McGuire W. Formula versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2018;6(6):Cd002971.\u003c/li\u003e\n\u003cli\u003eZipitis CS, Ward J, Bajaj R. Use of donor breast milk in neonatal units in the UK. Arch Dis Child Fetal Neonatal Ed. 2015;100(3):F279-81.\u003c/li\u003e\n\u003cli\u003eBattersby C, Marciano Alves Mousinho R, Longford N, Modi N. Use of pasteurised human donor milk across neonatal networks in England. Early Hum Dev. 2018;118:32-6.\u003c/li\u003e\n\u003cli\u003eWilliams T, Nair H, Simpson J, Embleton N. Use of Donor Human Milk and Maternal Breastfeeding Rates: A Systematic Review. J Hum Lact. 2016;32(2):212-20.\u003c/li\u003e\n\u003cli\u003eKantorowska A, Wei JC, Cohen RS, Lawrence RA, Gould JB, Lee HC. Impact of Donor Milk Availability on Breast Milk Use and Necrotizing Enterocolitis Rates. Pediatrics. 2016;137(3):e20153123.\u003c/li\u003e\n\u003cli\u003eParker MG, Burnham L, Mao W, Philipp BL, Merewood A. Implementation of a Donor Milk Program Is Associated with Greater Consumption of Mothers\u0026apos; Own Milk among VLBW Infants in a US, Level 3 NICU. J Hum Lact. 2016;32(2):221-8.\u003c/li\u003e\n\u003cli\u003eParker LA, Cacho N, Engelmann C, Benedict J, Wymer S, Michael W, et al. Consumption of Mother\u0026apos;s Own Milk by Infants Born Extremely Preterm Following Implementation of a Donor Human Milk Program: A Retrospective Cohort Study. J Pediatr. 2019;211:33-8.\u003c/li\u003e\n\u003cli\u003eEsquerra-Zwiers A, Schoeny ME, Engstrom J, Wicks J, Szotek J, Meier P, et al. The Interaction of Donor Human Milk Availability and Race/Ethnicity on Provision of Mother\u0026apos;s Own Milk for Very Low Birth Weight Infants. Breastfeed Med. 2021;16(1):46-53.\u003c/li\u003e\n\u003cli\u003eTshamala D, Pelecanos A, Davies MW. Factors associated with infants receiving their mother\u0026apos;s own breast milk on discharge from hospital in a unit where pasteurised donor human milk is available. Journal of Paediatrics and Child Health. 2018;54(9):1016-22.\u003c/li\u003e\n\u003cli\u003eMondkar J, Chawla D, Sachdeva RC, Manerkar S, Shanbhag S, Khan A, et al. Impact of mother-baby friendly initiative plus approach on improving human milk feeding for neonates in hospital: a quality improvement before-and-after uncontrolled study. Eur J Pediatr. 2022;181(1):107-16.\u003c/li\u003e\n\u003cli\u003eHay WW, Jr., Hendrickson KC. Preterm formula use in the preterm very low birth weight infant. Semin Fetal Neonatal Med. 2017;22(1):15-22.\u003c/li\u003e\n\u003cli\u003eMasi AC, Embleton ND, Lamb CA, Young G, Granger CL, Najera J, et al. Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis. Gut. 2021;70(12):2273-82.\u003c/li\u003e\n\u003cli\u003eStewart CJ, Ajami NJ, O\u0026apos;Brien JL, Hutchinson DS, Smith DP, Wong MC, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562(7728):583-8.\u003c/li\u003e\n\u003cli\u003eTrang S, Zupancic JAF, Unger S, Kiss A, Bando N, Wong S, et al. Cost-Effectiveness of Supplemental Donor Milk Versus Formula for Very Low Birth Weight Infants. Pediatrics. 2018;141(3).\u003c/li\u003e\n\u003cli\u003eZanganeh M, Jordan M, Mistry H. A systematic review of economic evaluations for donor human milk versus standard feeding in infants. Matern Child Nutr. 2021;17(2):e13151.\u003c/li\u003e\n\u003cli\u003eWilson E, Edstedt Bonamy AK, Bonet M, Toome L, Rodrigues C, Howell EA, et al. Room for improvement in breast milk feeding after very preterm birth in Europe: Results from the EPICE cohort. Matern Child Nutr. 2018;14(1).\u003c/li\u003e\n\u003cli\u003eNational Neonatal Audit Programme (NNAP) 2020 annual report on 2019 data2020 [cited 2022. Available from: https://www.rcpch.ac.uk/sites/default/files/2022-03/NNAP%20Annual%20Report%20on%202020%20data.pdf.\u003c/li\u003e\n\u003cli\u003eSkivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, et al. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. Bmj. 2021;374:n2061.\u003c/li\u003e\n\u003cli\u003eDong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2015;100(3):F257-63.\u003c/li\u003e\n\u003cli\u003eMedicine BAoP. Categories of Care 2011 2011 [Available from: https://www.bapm.org/resources/34-categories-of-care-2011.\u003c/li\u003e\n\u003cli\u003eWheeler BJ, Dennis CL. Psychometric testing of the modified breastfeeding self-efficacy scale (short form) among mothers of ill or preterm infants. J Obstet Gynecol Neonatal Nurs. 2013;42(1):70-80.\u003c/li\u003e\n\u003cli\u003eCox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987;150:782-6.\u003c/li\u003e\n\u003cli\u003eSmith-Nielsen J, Matthey S, Lange T, V\u0026aelig;ver MS. Validation of the Edinburgh Postnatal Depression Scale against both DSM-5 and ICD-10 diagnostic criteria for depression. BMC Psychiatry. 2018;18(1):393.\u003c/li\u003e\n\u003cli\u003eBraun V, Clarke V. To saturate or not to saturate? Questioning data saturation as a useful concept for thematic analysis and sample-size rationales. Qualitative Research in Sport, Exercise and Health. 2021;13(2):201-16.\u003c/li\u003e\n\u003cli\u003eBraun V, Clarke V. Using thematic analysis in psychology. Qualitative research in psychology. 2006;3(2):77-101.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"breast milk, donor human milk, preterm, breastfeeding, nutrition","lastPublishedDoi":"10.21203/rs.3.rs-2263972/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2263972/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMother’s own breast milk (MOM) is the optimal nutrition for preterm infants as it reduces the incidence of key neonatal morbidities and improves long-term outcomes. However, MOM shortfall is common and either preterm formula (PF) or pasteurised donor human milk (DHM) may be used, although practice varies widely. Limited data suggest that the use of DHM may impact on maternal beliefs and behaviours and may therefore impact on breastfeeding rates. The aim of this pilot study is to determine if the duration of DHM exposure impacts on breastfeeding rates, and maternal breastfeeding self-efficacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Human Milk, Nutrition, Growth, and Breastfeeding Rates at Discharge (Hummingbird) study is a feasibility and pilot, non-blinded, randomised controlled trial (RCT) with a contemporaneous qualitative evaluation. Babies born at less than 33 weeks gestation or with birth weight \u0026lt;1500 grams whose mothers intend to provide MOM are randomly assigned to either control arm (DHM used to make up shortfall until full feeds, then PF used thereafter) or intervention arm (DHM used to make up shortfall until 36 weeks corrected age or discharge if sooner). The primary outcome is breastfeeding rates at discharge. Secondary outcomes include growth, key neonatal morbidities, length of stay, breastfeeding self-efficacy and postnatal depression using validated questionnaires. Qualitative interviews using a topic guide will explore perceptions around use of DHM and will be analysed using thematic analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe provision of DHM is a complex intervention as it impacts on infant health and disease, as well as impacting on maternal and healthcare staff belief and behaviour. This is the first RCT to investigate the impact of DHM duration on breastfeeding rates and maternal self-efficacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration: \u003c/strong\u003eTrial was registered prospectively on 4\u003csup\u003eth\u003c/sup\u003e May 2021 (ISRCTN 57339063).\u003c/p\u003e","manuscriptTitle":"A protocol for a randomised controlled trial exploring human milk, nutrition, growth, and breastfeeding rates at discharge: the Hummingbird study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-16 16:02:58","doi":"10.21203/rs.3.rs-2263972/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"481f8d64-bdb6-4fd0-ac32-38ba210e2a18","owner":[],"postedDate":"November 16th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-11-19T02:29:10+00:00","versionOfRecord":[],"versionCreatedAt":"2022-11-16 16:02:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2263972","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2263972","identity":"rs-2263972","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}