The FEED1 Trial: Protocol for a Randomised Controlled Trial of Full Milk Feeds Versus Intravenous Fluids with Gradual Feeding for Preterm Infants (30-33 Weeks Gestational Age)


 BackgroundIn the UK, approximately 8% of live births are preterm (before 37 weeks gestation), more than 90% of whom are born between 30 and 36 weeks, forming the largest proportion of a neonatal units’ workload. Neonatologists are cautious in initiating full milk feeds for preterm infants due to fears of necrotising enterocolitis (NEC). There is now evidence to dispute this fear. Small studies have shown that feeding preterm infants full milk feeds enterally from birth could result in a shorter length of hospital stay, which is important to parents, clinicians and NHS services without increasing the risk of NEC. This trial aims to investigate whether full milk feeds initiated in the first 24 hours after birth reduces the length of hospital stay in comparison to introduction of gradual milk feeding with IV fluids.MethodsFEED1 is a multi-centre, open, parallel group, randomised, controlled superiority trial of full milk feeds initiated on the day of birth versus gradual milk feeds for infants born at 30+0 to 32+6 (inclusive) weeks gestation. Recruitment will take place in around 40 UK neonatal units. Mothers will be randomised 1:1 to full milk feeds, starting at 60 ml/kg day, or gradual feeds, as per usual local practice. Mother’s expressed breast milk will always be the first choice of milk, though will likely be supplemented with formula or donor breast milk in the first few days. Feeding data will be collected until full milk feeds are achieved (>140 ml/kg/day for 3 consecutive days). The primary outcome is length of infant hospital stay. Additional data will be collected 6 weeks post-discharge. Follow-up at 2 years (corrected gestational age) is planned. The sample size is 2088 infants to detect a between group difference in length of stay of two days. Accounting for multiple births, this requires 1700 women to be recruited. Primary analysis will compare the length of hospital stay between groups, adjusting for minimisation variables and accounting for multiple births.DiscussionThis trial will provide high-quality evidence on feeding practices for preterm infants. Full milk feeds from day of birth could result in infants being discharged sooner.Trial RegistrationISRCTN, ISRCTN89654042 prospectively registered on 23 September 2019; http://www.isrctn.com/ISRCTN89654042


Abstract Background
In the UK, approximately 8% of live births are preterm (before 37 weeks gestation), more than 90% of whom are born between 30 and 36 weeks, forming the largest proportion of a neonatal units' workload. Neonatologists are cautious in initiating full milk feeds for preterm infants due to fears of necrotising enterocolitis (NEC). There is now evidence to dispute this fear. Small studies have shown that feeding preterm infants full milk feeds enterally from birth could result in a shorter length of hospital stay, which is important to parents, clinicians and NHS services without increasing the risk of NEC. This trial aims to investigate whether full milk feeds initiated in the rst 24 hours after birth reduces the length of hospital stay in comparison to introduction of gradual milk feeding with IV uids.
Methods FEED1 is a multi-centre, open, parallel group, randomised, controlled superiority trial of full milk feeds initiated on the day of birth versus gradual milk feeds for infants born at 30 +0 to 32 +6 (inclusive) weeks gestation. Recruitment will take place in around 40 UK neonatal units. Mothers will be randomised 1:1 to full milk feeds, starting at 60 ml/kg day, or gradual feeds, as per usual local practice. Mother's expressed breast milk will always be the rst choice of milk, though will likely be supplemented with formula or donor breast milk in the rst few days. Feeding data will be collected until full milk feeds are achieved (>140 ml/kg/day for 3 consecutive days). The primary outcome is length of infant hospital stay. Additional data will be collected 6 weeks post-discharge. Follow-up at 2 years (corrected gestational age) is planned. The sample size is 2088 infants to detect a between group difference in length of stay of two days. Accounting for multiple births, this requires 1700 women to be recruited. Primary analysis will compare the length of hospital stay between groups, adjusting for minimisation variables and accounting for multiple births.

Discussion
This trial will provide high-quality evidence on feeding practices for preterm infants. Full milk feeds from day of birth could result in infants being discharged sooner.
Trial Registration ISRCTN, ISRCTN89654042 prospectively registered on 23 September 2019; http://www.isrctn.com/ISRCTN89654042 Background In preterm infants, early establishment of enteral feeding is associated with reduced sepsis, improved growth (1), and enhanced neurodevelopment (2). Achieving full milk feeds sooner and improving growth without infection or necrotising enterocolitis (NEC) may help the infant be ready for home earlier, reducing the length of hospital stay. Despite evidence to the contrary (3), clinicians often delay initiating feeds or increment feeds slowly due to fear of NEC. The recently completed Speed of Increasing milk Feeds Trial (SIFT) provides rm evidence from over 2,800 infants that faster advancement of milk feeds does not increase the risk of NEC even in the most premature infants (4). In this large, multi-centre trial comparing fast (30ml/kg/d) vs. slow (18ml/kg/d) feed increments in 2804 infants born before 32 weeks gestation, the risks of NEC or death were not increased by the faster increment in feeds. Faster fed infants achieved full feeds quicker and received IV uids for fewer days. A recent Cochrane review assessing advancement of feed volumes in preterm infants concluded that slow advancement of enteral feed volumes results in several days of delay in establishing full milk feeds, and may increase the risk of invasive infection (1) possibly due to increased iatrogenic infections from a longer duration of IV line placement.
These results indicate that there may be bene t from a faster approach to feeding. In infants between 30 +0 to 32 +6 weeks this could be achieved by providing their full uid requirements solely as enteral feeds from day of birth without using IV uids or parenteral nutrition i.e. "full milk" feeds from the day of birth. A Cochrane review on early full enteral feeding in preterm infants included 6 randomised controlled trials involving 601 stable infants weighing between 1000-1500g at birth (5). A meta-analysis of length of hospital stay (4 studies, 398 infants) showed a mean difference of -2.26 days in infants given early full enteral feeds. There was no difference in NEC. However, all studies were conducted in India and were biased in several areas when assessed for methodological rigour. One small study included in the review included 46 infants (birth weight 1200-1500 grams; mean gestation 31 weeks) who were randomised to receive full milk from 1 hour after birth or IV uids and slow feed increments (20ml/kg/d) (6). They found that infants randomised to full milk feeding regained birth weight quicker, had improved growth at discharge, shorter duration of hospital stay, and fewer cases of sepsis without an increased risk of NEC. Additionally, in a trial of 180 infants, Nangia showed a mean difference of -3.6 days in time taken to reach full enteral feeds in infants fed early enteral feeds, and a reduction of 4.1 days in length of hospital stay (7). These ndings suggest it is potentially safe and may be better to start full milk feeds on day of birth without increasing the risk of NEC and possibly reducing the risk of sepsis. An observational study also showed that implementing full milk feeds from birth is feasible and acceptable, with the infants receiving full enteral milk feeds having signi cantly fewer cases of NEC and sepsis, less antibiotics, less parenteral nutrition, and a shorter average hospital stay (8). These studies were all conducted in India where the preterm population, healthcare resources, infrastructure and delivery systems as well as treatments and risk factors are different to that in the UK. There have been no studies in the UK or other similar high resource settings investigating the strategy of feeding preterm infants "full milk" feeds from day of birth.

Justi cation for study population
In 2018, in England and Wales, there were 656,925 live births of which 51,864 (7.9%) were preterm (born before 37 completed weeks gestation) (9). Providing optimal nutrition is a cornerstone of neonatal care and the subject of many recent research studies including SIFT (10), ADEPT (11), NEON (12) and SCAMP (13). These and other similar studies focus on extremely preterm infants (born before 30 weeks) at highest risk of adverse outcomes (death or NEC). However, more than 90% of preterm infants are born at or after 30 weeks, including the 12% of preterm infants who are eligible for FEED1. More mature preterm infants (≥ 34 weeks) typically do not require special care. Infants born at 30, 31 or 32 weeks comprise over 40% of preterm infants routinely admitted to neonatal units (in 2018 there were 5879 infants in this group in England and Wales) and form the largest proportion of workload for neonatal services. Treatments that reduce length of stay in this group of preterm infants could therefore impact the largest number of infants in neonatal units and their families.

Justi cation for comparators
Infants that are fully milk fed need less monitoring and could be moved to lower dependency care. Adequate enteral nutrition could promote weight gain and reduce the risk of infections, potentially making infants ready for home sooner and reducing the length of hospital stay. This would make scarce higher dependency cots for sicker infants more readily available and avoid transferring infants further a eld to access resources.
Strategies that aim to safely achieve a shorter hospital stay could improve care for all infants who require neonatal care. Full milk feeds may also reduce the cost of care by decreasing use of parenteral nutrition, IV uids, and reducing iatrogenic infections.
Preterm birth is associated with long term morbidities and large lifetime nancial costs, placing strain on NHS nances and social care resources. Full milk feeds may improve nutrition and reduce morbidities such as sepsis, thereby improving neurodevelopmental outcomes and lifelong quality of life for this large group of infants. Such an approach that improves the care of preterm infants while simultaneously reducing the cost of care would achieve the NHS "Five Year Forward View" aim of achieving e ciency savings while maintaining and improving quality of care and safety (14). There are also potential bene ts for mothers and families from a less medical model of care, with opportunities for involvement in care, shorter mother-infant separation, improved satisfaction and mental health outcomes.
The FEED1 Trial addresses three of the top six research priorities identi ed by the James Lind Alliance (15): "What is the optimum milk feeding strategy and guidance (including quantity and speed of feeding and use of donor and formula milk) for the best long-term outcomes of premature infants?
How can infection in preterm infants be better prevented?
Which interventions are most effective to prevent necrotising enterocolitis in premature infants?" This paper is reported in accordance with the Standard Protocol Items: Recommendations for Interventional trials (SPIRIT) guidelines (16).

Objectives
To determine whether, in infants born at 30 +0 to 32 +6 weeks gestation, full milk feeds initiated in the rst 24 hours after birth reduces the length of infant hospital stay in comparison to IV uids or parenteral nutrition with gradual milk feeding.

Methods / Design
This is a multi-centre, open, parallel group, randomised (1:1) controlled superiority trial of full milk feeds versus gradual milk feeds.
Mothers and infants will be recruited from around 40 neonatal units (predominantly local neonatal units (LNUs) and Neonatal Intensive Care Units (NICUs) in the UK. A list of participating sites can be found at www.feed1.ac.uk. The full protocol and other trial documentation, including participant information sheets and consent forms, can also be found on the trial website. An embedded Study Within a Trial (SWAT) is also included which is investigating methods of training sites. Details of the SWAT can be found on the SWAT repository (17) (18) and will be reported separately.

Eligibility
Inclusion criteria include i) infants born at 30 +0 to 32 +6 weeks gestation (inclusive) and ii) infants <3 hours (180 minutes) old (since recorded time of birth). Infants requiring respiratory support (such as via continuous positive airway pressure) or other supportive treatments will be included in the study if the clinician is in equipoise about the infant being randomised to either the "full milk" or the "gradual milk" arm. Similarly, well infants should only be included if the attending clinician is in equipoise about the best feeding regime and the infant being randomised to either "full milk" or "gradual milk" groups. Exclusion criteria include i) infants with known congenital abnormalities of the gastrointestinal tract or other congenital conditions that make enteral feeding unsafe, ii) infants who are small for gestational age (SGA) (birthweight <10 th centile) and have evidence of reversed end-diastolic ow on antenatal umbilical artery doppler ultrasound, iii) mothers who have participated in the trial during a previous pregnancy.

Interventions
For infants in the full milk group (intervention), uids will be started as milk at 60 ml/kg/day, increased as per their individual requirements and in line with standard neonatal practice. The choice of feeding intervals will be determined by local policy and clinician's preference. Wherever possible, mother's expressed breast milk will always be the rst preference for infant milk feeds. It is likely that mother's breast milk will need to be supplemented with additional milk, i.e. either infant formula milk or donor breast milk in the rst few days. The decision as to the type of milk used will be made by the mother and the site, in line with the site's local policy. For infants in the gradual milk group (control), uids will be given in accordance with standard practice at the site. This may include milk feeds, starting at a maximum of 30 ml/kg/day on day 1 with a minimum of 30 ml/kg/day of supplementary IV uids or parenteral nutrition. Adherence to the randomised allocation will be monitored on a regular basis by the Trial Management Group.

Outcomes
The primary outcome is length of infant hospital stay. Since hospitals could apply different discharge criteria, a secondary outcome of time until objective discharge criteria are met has also been included. The statistician, blinded to treatment allocation, will use the date at which each infant rst met all three of the following criteria: i) current weight >1700g, ii) infant is able to take at least one full suck feed assessed as adequate, iii) infant has been off additional temperature support for >24 hours. Daily data will be collected to determine the day on which the infant achieved all the three features to determine the time until objective discharge criteria are met. Secondary outcomes are listed in Table 1.  (4) Outcome measures included have been guided by the Core Outcomes in Neonatology (COIN) core outcome set (20). Discussions are ongoing to obtain separate funding in order to collect longer-term follow-up data at two years corrected gestational age. In addition, the research team are in discussions with researchers based in other countries, such as Canada and Australia, to set-up parallel studies. This will be to provide su cient power to assess outcomes of NEC and sepsis; these outcomes occurred in 1% and 12% of infants retrospectively in the SIFT Trial among those who would have been eligible for FEED1.

Sample size and recruitment
Our sample size calculation has been based upon detecting a between group difference in means of length of stay of two days. Input from our parent representatives suggests that from a family perspective even a short reduction in length of hospital stay could make a huge difference to parents. In addition, from a cost-saving perspective, a reduction in length of stay of 2 days for this population of infants could result in £5.6m annual savings for the NHS in England and Wales and >12,000 days of increased neonatal cot capacity.
Data from audits and previous studies suggest that the distribution of length of hospital stay in this population is approximately normal. To detect a difference in means of two days between the two groups with 90% power, 1:1 allocation, and 5% two-sided signi cance requires 1778 infants, assuming a standard deviation of 13. Allowing for 2% non-collection of the primary outcome data due to death, no consent for data collection after oral assent and infants remaining in hospital at the end of data collection and accounting for clustering will require 2088 infants and recruitment of approximately 1770 women. The in ation to account for clustering assumes that 15% and 1.4% of pregnancies will be twin and triplets respectively, and that the intracluster correlation coe cient for length of hospital stay for infants from the same pregnancy is 0.82.

Participant enrolment and consent
The ow of women and infants throughout the trial is shown in Figure 1. As the infant must be randomised within 3 hours of birth, a time during which the woman is recovering from giving birth and that is emotionally fraught and potentially di cult for families, a two-stage consent pathway will be used. Wherever possible, women will be approached antenatally and asked to consider participation in the trial. At around the time of antenatal counselling consultation, women will be given study information, have the opportunity to discuss the study and ask questions and give full written informed consent if they are willing to do so. For these women, once they have given birth, infant eligibility will be checked and the infant(s) will be entered into the trial, unless the mother expresses she has changed her mind. For some women, receiving information and providing consent antenatally may not be possible due to the rapid and unexpected nature of preterm birth. During labour and postnatally, these women can be approached via an oral assent pathway. This involves a member of the neonatal team inviting the woman to participate and giving the minimal information required to make a decision. A shorter, simpli ed participant information sheet and/or a short animation lm may be used to support this discussion. The decision to participate will be documented in the medical notes and full written informed consent will be obtained at a later date (ideally <72 hours). This two-stage consent pathway has been used successfully in a previous neonatal trial (21) and features as part of guidance from the Royal College of Obstetricians and Gynaecologists (RCOG) (22). Sites will be fully trained in the two-stage consent pathway and will be provided with a range of supplementary materials to support oral assent conversations which include a recorded webinar, video showing examples of discussions and additional documentation. Women are asked to give their optional consent to be contacted for longer-term follow-up of their infant(s) and for later educational outcomes.

Randomisation and blinding
The unit of randomisation is the mother to ensure that a mother-infant(s) dyad is treated as a unit. This will also enable antenatal consent and facilitate early commencement of the intervention. In addition it will ensure that siblings from multiple pregnancies are assigned to the same group. Parents have told us this is important to them as they would not like to feed their infants differently unless there was a medical reason to do so. Randomisation will be performed on a 1:1 ratio, using a secure web-based system, developed and maintained by the Nottingham Clinical Trials Unit (NCTU), which will conceal allocation sequence. Randomisation will use a minimisation algorithm, with a random element, to ensure balance on important prognostic factors: neonatal unit, single or multiple birth, gestational age at birth, birthweight centile and whether IV uids were started prior to randomisation. Randomisation will be undertaken by the Principal Investigator, clinician or other study team member within 3 hours from the recorded time of birth. This is to ensure infants randomised to full milk feeds can receive the intervention with minimal risk of receiving IV uids and should help prevent contamination between groups.
It is not possible to blind investigators and families due to the nature of the intervention. However, the trial statistician will remain blinded throughout the trial. To objectively assess the primary outcome, a secondary outcome measure to objectively assess discharge criteria is included and a blinded endpoint review committee (BERC) will also be established to examine cases of lateonset sepsis and necrotising enterocolitis where the diagnosis is unclear.

Trial assessments and procedures
All trial assessments and procedures are outlined in Table 2. Most outcome data will be collected during the infant's hospital admission. A daily feeding log will be completed until the infant receives 140 ml/kg/day of feeds, sustained for 3 consecutive days. For infants who are transferred to another hospital, i.e. a continuing care site, a paper transfer pack will accompany the infant with information on trial participation and data collection will continue. In order to collect data at 6 weeks corrected gestational age, an online questionnaire (or paper if preferred) will be sent to women; reminders will be sent to increase response-rates. Women who present in the late stages of labour or who have already given birth should be consented rst via oral assent followed by later written informed consent 2 Women who given oral assent trial should provide written consent within 72 hours of providing oral assent, where possible 3 Each episode of microbiologically-con rmed or clinically-suspected late-onset invasive infection should be reported throughout the treatment period until hospital discharge 4 To be reported if this infant has received at least 5 days of treatment for gut signs, if they are transferred with gut signs, or if they have died from gut signs Adverse events Serious adverse events, including death, will be reported as such by the Principal Investigator, or delegate, reporting within 24 hours of being made aware of the event. Adverse reactions collected as outcomes will not need to be reported separately. Late-onset sepsis (micobiologically con rmed or clinically suspected), necrotising enterocolitis (Bell's stage 2 or 3) or other known complications of prematurity will not be reported as serious adverse events.

Data management
All trial data will be collected by site staff delegated to do so and entered onto a trial speci c database with infants only identi ed by their unique trial number and initials. Using MACRO (Elsevier), the database will be developed and maintained by NCTU staff.
Access to the database will be restricted and secure. Sites will be provided with paper workbooks in order to assist them with data collection. Missing or spurious data will be queried in a timely manner throughout the trial. In order to facilitate contact with families at 6 weeks corrected gestational age, contact details will be collected and entered into an online secure system, developed and maintained by NCTU staff. This data is held separately to the deidenti ed trial data collected. Access to contact details is restricted to those involved in the follow-up phase, as authorised by the Chief Investigator.

Statistical analysis
Analysis and reporting of the trial will be in accordance with the Consolidated Standards of Reporting Trials (CONSORT) (23) guidelines. All analyses will be outlined in a detailed Statistical Analysis Plan agreed prior to database lock. The primary comparative analyses will be conducted according to randomised allocation with due emphasis on con dence intervals for between-group comparisons.
The primary outcome will be analysed using linear mixed models to compare the mean length of hospital stay between groups, adjusting for minimisation variables and accounting for the correlation between outcomes for infants born from a multiple pregnancy. The estimated between group effect will be presented using the difference in means, with a 95% con dence interval. Secondary outcomes will be analysed similarly using appropriate multilevel regression models, dependent on the type of outcome variable. The between group effect will be reported using an appropriate effect estimate along with a corresponding 95% con dence interval.
The primary approach to between-group comparative analyses will be by modi ed intention-to-treat (i.e. including all participants who have been randomised and without imputation of missing outcome data). In particular, the primary analysis will exclude the small number of deaths that might occur before discharge, but sensitivity analysis will be performed by imputing the primary outcome with the worst observed length of stay for infants who died prior to discharge to check that this does not in uence the ndings. A further sensitivity analysis will assess the effect of compliance with the allocated feeding strategy through complier average causal effect (CACE) analysis.
Appropriate interaction terms will be included in the primary regression analyses in order to conduct subgroup analyses according to gestation at birth and birth weight centile, but this analysis will be regarded as exploratory as the study is not powered to detect interactions. Interpretation of any subgroup effects will be based on the treatment-subgroup interaction and 95% con dence interval.
A within-trial economic analysis will be conducted from an NHS and personal social services perspective. Resource data will be collected prospectively and unit costs will be obtained from routine sources. The main cost-effectiveness analysis will be based on the cost per reduction in days in care. A longer-term projection of costs and bene ts will be estimated through decision analytical modelling. Appropriate sensitivity analyses will be undertaken to account for any uncertainty.

Monitoring and governance
An independent data monitoring committee (DMC) will review unblinded trial data, including safety data, on an intermittent basis. The role of the DMC is outlined in a charter which outlines their terms of reference. Overall independent oversight will be provided by a Trial Steering Committee (TSC).
On-site monitoring will not be conducted routinely throughout the trial. Instead, regular central monitoring of trial data will be undertaken and this data will be used to assess if sites have met any triggers to activate a triggered monitoring visit. The Trial Management Group (TMG) are responsible for reviewing central monitoring reports and agreeing if triggered on-site monitoring visits are required. Any trial conduct audits will be carried out by the sponsor as per their local auditing plans.

Patient and public involvement (PPI)
Our research team includes a parent who has experience of having a preterm infant, born at 31 weeks gestation, and the research manager for Bliss, the UK's largest premature and sick baby charity, who represent parents with experience of preterm birth. In addition to our immediate research team PPI members, we have a group of three parents who provide additional parent input, and a PPI member on the independent trial steering committee. We involved parents throughout the design stage of this trial and continue to do so whilst it is being conducted.

Discussion
This is a pragmatic trial that has had strong patient and public involvement input from the outset. Having a preterm infant is a stressful, emotional experience and it has therefore been crucial for us to ensure the views of preterm infants are represented and that parents nd the trial acceptable. The results of this trial will provide high-quality evidence on feeding practices for preterm infants of 30-33 weeks gestation. Infants in the intervention group may be discharged from hospital sooner and parents have told us that even a small reduction in the length of hospital stay is important to them. In addition, a reduction in length of stay could result in increased cot capacity on neonatal units and a potential cost saving of £5.6.8 million annually (based upon a reduction of 2 days). Full milk feeds from birth may be an intervention that improves outcomes and care of preterm infants and their families whilst simultaneously reducing the cost of NHS care.
Since trial conception one challenge has been with respect to the type of milk available to the infant, since the intervention involves feeding infants full volumes of milk from day of birth. As in standard practice, the rst choice will always be the mother's own milk unless there are medical contraindications or the mother chooses to feed her infant with formula milk. It is likely for some infants that mother's own milk may not be su cient in volume during the rst few days of life. For infants in the intervention arm, where this is the case, formula milk or donor breast milk will be used to replace the intravenous uids or parenteral nutrition. Mothers will be supported in breast feeding and full milk feeding with mother's expressed breast milk will be established as soon as su cient volumes are available. Breast feeding will be supported and encouraged in both arms of the trial. Information is included about the bene ts of breast feeding in all study information. There is no involvement of any kind by any formula milk manufacturers or related organisations in this trial. Several outcomes related to breastfeeding are included. In addition, we will also undertake additional exploratory analyses to compare the primary outcome and key secondary outcomes between infants who have received donor breast milk and preterm formula milk to supplement mother's breast milk. Written informed consent to participate will be obtained from all participants.

Consent for publication
Not applicable

Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Anonymised participant data will be made available, upon request, in accordance with the NCTU standard operating procedure after publication of trial results.

Competing interests
The authors declare that they have no competing interests Funding This study is funded by the National Institute for Health Research (NIHR) [Health Technology Assessment programme (project reference 17/94/31)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder had no role in the design of this study and will have no role in the analysis, interpretation of data or decision to submit results in the future.
Author's contributions EM is the lead trial methodologist and wrote the rst draft of the manuscript. SO is the Chief Investigator and supported by JD; conceived the idea and led the funding proposal. GM is the Trial Manager and trial management oversight is provided by RH. JA represents Bliss, the UK's largest charity for premature and sick infants. CG, MJ, WM and SO are neonatologists and are involved in training sites. CK is a parent representative. HM is the health economist. AM is the Nottingham Clinical Trials Unit Director and provides overall trial oversight. CP is the trial statistician and statistical oversight is provided by RO. PP provides midwifery expertise and KW provides obstetric expertise. All authors critiqued the manuscript for important intellectual content and approved the nal version. This is a list of supplementary les associated with this preprint. Click to download. FEED1SPIRITchecklistrevised12Apr21.doc