FAQs for health professionals

Yes. Anyone consenting to the trial should have valid GCP training.

Yes, as long as they are trained on the trial, GCP trained, and delegated on the delegation log. Training should always be detailed in the training log.

The remote consent form has been introduced to consent any infant who may have transferred home or to another site prior to the consent process taking place but may be of particular use for the HIE group of babies. The question as to whether supplementation works to improve developmental outcomes in the HIE group of babies is an equally important question to answer as the pre-term group and it is vitally important that we include these babies in this trial. We appreciate that you may have approached the parents of a baby who is being cooled but they may transfer to a continuing care site quite quickly after cooling, prior to consent taking place. If the parents wish to take part we have developed the remote consent process so those babies can take part in the trial.

No, the remote consent form is signed by the health professional taking consent to verify that a full discussion has taken place. The health professional also initials each box with his or her own initials to verify that the parent has agreed to each point on the form. For further information on the consent process, please refer to guidance sheet 2.

The parent information leaflet contains the following: The long-chain polyunsaturated fatty acids are from a fish source. The supplements contain small amounts of cow's milk protein. The supplements do not contain pork. They are not certified kosher and halal compliant. You may wish to discuss this further with your religious leader.

We would expect the discussion to form part of the consent process and ensure that parents are not consented if they are not happy with any of these aspects.

Anyone who is trained and delegated can assess eligibility however if you have any local policies, which only permit certain individuals to confirm eligibility, then we would ask you to adhere to those requirements.

Yes. As long as they were born at <28 weeks of gestation, they can be approached up to discharge home from NNU and no more than 3 months post EDD. The HIE stratum must be 35 weeks of gestation or more, have received therapeutic hypothermia for HIE and be up to 40 weeks of gestation plus 28 days.

Unfortunately, the trial materials are only available in English. We appreciate that some parents may not be able to take part unless they have a family member who will help them understand the trial and to complete the questionnaires.

DOLFIN should not be given via a jejunal feeding route as jejunal feeds are digested differently and may be less well absorbed. If a baby receiving jejunal feeds can tolerate DOLFIN given via a gastric route then this is fine. The DOLFIN supplement can then be prepared as for administration ahead of a breast feed i.e. 1g in 3ml of milk ratio and given via nasogastric route before, or alongside a jejunal feed.

Yes, in the event of an emergency unblinding, the recruiting site has access to a single use access code which is in an envelope in your document box. You must be satisfied that it is a genuine emergency and is needed to guide the appropriate clinical management of the infant. If the infant is at a continuing care site, please contact the PI or research staff at the recruiting site to discuss unblinding.

Yes, twins, triplets or higher order multiples will be allocated to the same trial arm.

The amount of supplement is 1 gram per kilogram of body weight. This increases throughout the duration of the trial to a maximum of 12g, so no infant would have more than 12g of supplement a day, even if their weight goes over 12kg. Every gram of supplement needs to be mixed with a minimum of 3mls of milk and then the total volume of milk feed of 15mls per 1g of feed given.

There is variation within units as to when to start infants on full feeds, so please start the infant on supplement according to when full feeds start in your unit. Yes, you can start fortifier at the same time however, the exact timing of commencing the DOLFIN supplement would be at the discretion of the clinical team in charge of the infant's care.

There is a choice. We are leaving this flexible, as it will vary depending on the method of feeding. It can all be given in one feed if of sufficient volume, but some parents/clinicians may choose to split it across feeds. See guidance sheet 4b and the DOLFIN supplement dosing charts for further information.

There were no side effects or feeding difficulties reported in the pilot. Some of the infants became more aware of the taste and texture as they became older, however the pilot supplemented until 2 years of age whilst we are supplementing to 12 months post EDD in the main trial. The supplement has also been greatly refined since the pilot, thanks to the input of the parents who took part in the pilot.

The supplement contains substances that occur naturally in human milk and in foods eaten as part of a healthy diet; they are often used as food supplements (long chain polyunsaturated fatty acids, uridine-5'-monophosphate, cytidine-5'-monophosphate, and choline). The control product contains most of the same ingredients, but in much smaller proportions and concentrations - the ingredients are very similar to those found in standard infant formula milks.

Yes. We are aware of the need for appropriate ratios of omega 6:3 fatty acids in this supplement.

In line with the manufacturers recommendations it needs to be given within 1 hour.

The supplement needs to be given within 1 hour of mixing. Even on units with a milk kitchen, it may be preferable to make up the supplement at the cot-side and immediately, with the option to prepare the supplement in the milk kitchen if cot-side preparation is problematic.

You will not be able to identify from labelling or packaging which is the placebo and which is the active supplement. Each baby will be allocated a box with a pack ID on it at randomisation. Please ensure that the baby only receives supplement from that pack. There is a daily dosing log where you need to document the pack id to confirm that the baby has received the correct intervention.

There will be inter-current illnesses, which may result in readmissions and therefore will result in a short pause in supplementation. We do not anticipate that this is going to be problematic in terms of trial outcomes due to the long duration of supplementation. Individual paediatric units will have to follow their usual practice. Administration of the supplement in a situation where an infant is re-admitted will depend on how unwell the infant is, why they have been admitted and what the local policy is.

No. As these infants will be taking the supplement up to 12 months post EDD, we expect that there will be interruptions to supplementation and therefore any temporary discontinuation does not constitute a withdrawal.

No. The scoops and clips are re-useable and should not be disposed of until the entire supplement from that box is used.

No trial activities can take place without the necessary approvals being in place at a site. Even if the parents are trained to give the supplement, they will not be able to continue with supplementation at a non-approved continuing care site. Please email dolfin@npeu.ox.ac.uk as soon as possible if you know that one of your infants is being transferred and we will do all we can to get the necessary approvals in place.

No, you do not need to be delegated to administer the supplement.

If the baby cannot tolerate any milk or medication via a nasogastric route then the DOLFIN supplement should be paused until it can be re-introduced via a gastric route. The DOLFIN supplement can then be prepared as for administration ahead of a breast feed i.e. 1g in 3ml of milk ratio and given via nasogastric route before, or alongside a jejunal feed.

No, these are mandatory and are important to determine our primary and secondary outcomes.

Parents are sent questionnaires via a link to an SMS and/or email. It is therefore vitally important that a mobile number and /or email address is entered onto the database by the site once the baby is randomised. Questionnaires are sent by NPEU CTU and therefore require no site involvement.

Yes. Participating families are sent a £25 gift voucher as a thank you for their participation in the trial at the same time as the 2 year questionnaire is sent to them.

As long-term neurodevelopmental follow-up of the cohort in future studies is planned, participants will not be unblinded at the end of the trial or until all future follow-up studies are completed. If you do have any requests to unblind, please email NPEU CTU, who will consider the request in discussion with the Chief Investigators or delegate.

The DOLFIN App has been developed by the team at Newcastle to make the parent's experience of reporting infant weights and supplement adherence much easier. If parents do not want to or cannot use the App we do have alternative systems to use (e.g. SMS) but these are not as simple or as streamlined as the App.

Product development and testing work involving parents has resulted in a more refined product with improved sensory properties and acceptability. In addition to this parents will have the option to give this to breastfeeding infants predominately as a breast milk shot followed by a normal breast feed. We anticipate this will improve usability for breastfeeding parents.

The trial supports parents to take part who are breastfeeding and wish to continue breastfeeding. There is some funding available to cover the purchase of pumps for use on the unit, or to give to parents to take home. Details about the funding available and how and who to invoice are in the site agreement.

We have been unable to test the osmolality of breastmilk containing the DOLFIN supplement and breastmilk fortifier. It is preferable to try and provide these in separate feeds if possible. If the supplement is being made up as a breastmilk shot, addition of breastmilk fortifier makes the milk too thick to administer. A breastmilk shot containing the DOLFIN supplement can be given, and then milk containing breastmilk fortifier given separately by whichever method is typically used.

We have been unable to test the osmolality of breastmilk containing the DOLFIN supplement, however the medicines and supplements added to milk are the major contributors to osmolality. There is no reason that the DOLFIN supplement should significantly increase this. For this reason, there are no contraindicated medications or supplements and infants will be able to have all medicines and supplements normally prescribed during the course of the trial. However, we need to be mindful that if a mixture of supplements are added all in one feed you might end up with a substance too thick to administer via a syringe or teat.

In this situation, sites could consider using donated breast milk (DBM). The supplement can be mixed with water however, the supplement may precipitate in water meaning that less of the dose is received. For this reason, mixing with water should be a last resort.