Breastfeeding Infants Receiving Respiratory Support Trial
Breastfeeding Infants Receiving Respiratory Support Trial
The purpose of this study is to assess whether two methods of breathing support in babies
 called 'Humidified High-Flow Nasal Cannula' oxygen (HHFNC) and 'nasal Continuous Positive
 Airways Pressure' (nCPAP) are compatible with breastfeeding. Many babies who are premature or
 unwell after birth require help with their breathing. This is often achieved by blowing a
 continuous flow of air through the nose and down into the lungs in order to reduce the amount
 of effort the baby needs to inflate the lungs during breathing.

 Currently some centres allow babies to breastfeed whilst undergoing breathing support whilst
 other centres do not in case there is an increased risk of choking or other harmful events.
 In the latter case, babies are fed using a nasogastric tube (NGT) that runs from the baby's
 nostrils into their stomach.

 At this centre, babies are allowed to breastfeed whilst simultaneously on either HHFNC or
 nCPAP. This is because the concerns over the choking risk are not evidence based. This study
 aims to conclusively prove that thisfeeding protocol is safe and then to expand into other
 areas of research to find out the following:

 -  Whether breastfeeding during nCPAP or HHFNC leads to babies establishing full
 breastfeeding sooner (and subsequently reduce the length of their stay in hospital)

 -  What the effects of breastfeeding of nCPAP or HHFNC are on a baby's parents (e.g.
 whether it enhances bonding)

 -  If nCPAP and HHFNC have different effects on breastfeeding As part of this study the
 investigators will observe stable babies on nCPAP or HHFNC during breastfeeding
 episodes. The investigators will monitor the babies for signs of distress or instability
 and whether they are more stable when breastfeeding is not occurring. This will be
 compared to an episode where the same baby is fed by NGT to see which technique is
 better.
BACKGROUND Breastfeeding infants receiving respiratory support (nCPAP or HHFNC) is a
 controversial topic. Expert consensus has been that feeding should be delayed until
 respiratory support (including nCPAP or HHFNC) is no longer needed. Data from animal models
 suggests that nasal CPAP can affect swallowing behaviour in infant animals but the magnitude
 and clinical significance of any effect is unclear even in animals. Studies in adults are
 also lacking but some have shown that swallowing can be impaired during CPAP therapy. There
 is no research into whether HHFNC has similar effects in any of the above populations. There
 is currently no published data on the safety or efficacy of breastfeeding infants receiving
 respiratory support via nasal CPAP or HHFNC.

 nCPAP is a key intervention in the current care of many babies as it is the preferred mode of
 non-invasive respiratory support and compared to conventional mechanical ventilation it has
 been shown to reduce the incidence of bronchopulmonary dysplasia . HHFNC oxygen has emerged
 as another method of respiratory support. It has been shown that it is non-inferior to nCPAP
 following extubation although it is clear that the mechanics of flow delivery differ from
 nCPAP. There is some evidence that HHFNC use is associated with a reduction in some adverse
 effects when compared with nCPAP, such as nasal trauma.

 Some infants, especially infants born very preterm, spend prolonged periods on nasal CPAP or
 HHFNC. Normal oral feeding is often delayed in these children because respiratory support is
 needed. It has been shown that premature infants can show breastfeeding cues from a very
 early stage and if infants are given the opportunity breastfeeding can be well established.
 Recent studies have shown that early introduction of oral feeding in preterm neonates is not
 associated with adverse outcomes and leads to earlier establishment of full oral feeding and
 discharge home.

 RATIONALE FOR CURRENT STUDY There is uncertainty surrounding the safety of breastfeeding
 babies on nasal nCPAP or HHFNC. There is great disparity in clinical practice between
 neonatal units. At our department babies on respiratory support have traditionally been
 offered the chance to breastfeed. Local experience is that this is not associated with
 adverse events. When compared to other units internationally (as part of the Vermont-Oxford
 Network of neonatal units) our unit does not have an excess of complications due to this
 practice.

 Establishing the safety of breastfeeding whilst receiving nCPAP or HHFNC will provide
 clinicians with the information necessary to decide when breastfeeding should be attempted in
 infants needing ongoing respiratory support.

 In addition the study team want to use this opportunity to establish the feasibility of
 future studies. If breastfeeding on nCPAP and HHFNC is safe the study team want to prepare
 for further investigation in this field looking at:

 -  Whether infants being breastfed on nCPAP and HHFNC can show progression from immature to
 mature feeding behaviours and if this ultimately leads to earlier establishment of full
 oral feeding.

 -  What impact being breastfed on nCPAP or HHFNC has on the parents of these babies. If
 breastfeeding on nCPAP and HHFNC help bonding this would be another important factor to
 consider.

 -  To prepare to compare HHFNC and nCPAP to see if the effects they have on breastfeeding
 differ. If nCPAP or HHFNC is superior to the other this may affect clinician decision on
 which to use.

 Clarity in this field will enable clinicians to make safe decisions about when infants
 receiving respiratory support should be allowed to breastfeed aiding delivery of optimal
 care.

 STUDY OBJECTIVES The primary objective of this prospective observational study is to test the
 hypothesis that breastfeeding infants undergoing nCPAP or HHFNC is safe.

 The secondary objective is to test the feasibility of future studies:

 -  To investigate the feasibility of testing the hypothesis that breastfeeding preterm
 infants while treated with nCPAP or HHFNC leads to faster establishment of full enteral
 feeds as this could allow patients to benefit from earlier discharge home. This study
 will show whether the methods used are acceptable to parents and capture the outcome
 data required. Data gathered will give information on the standard deviation of outcomes
 to enable accurate sample size calculation.

 -  To investigate the feasibility of assessing parental perception of breastfeeding babies
 receiving respiratory support and the effect it has on bonding. Questionnaire responses
 and feedback from parents will be reviewed to investigate their feeidng issues and
 concerns.

 -  To investigate the feasibility of comparing nCPAP and HHFNC to evaluate whether they
 have different effects breastfeeding for infants.

 STUDY DESIGN Prospective, observational, single centre safety study. Recruitment will occur
 over a one-year period. Parents will initially be approached by members of the healthcare
 team. With their consent they will then be contacted by a member of the BIRRST team and
 informed about the details of the study. Written consent from the parents must be obtained in
 order to include a patient. It will be explained to parents that it is common practise to
 offer infants to be breast fed while still on respiratory support in this unit.

 No change will be made to the management of babies enrolled in this study. Babies will be
 observed during feeding episodes but the timing of these feeds, whether a baby will be fed by
 breastfeeding or NGT and all details relating to how a feed is administered are decisions
 that will be made by the nursing team looking after a baby (in conjunction with the baby's
 parents). The study team will have no influence or say in these decisions and will just
 observe standard practice for this unit.

 50 infants will be recruited, 25 infants treated with nCPAP and 25 infants treated with HHFNC
 while breast feeding attempts are made. Each child is estimated to have between 4 and 6
 observations. There will be no crossover between the respiratory support modalities. Infants
 without any respiratory support will no longer be eligible or included in the study.

 130 paired observations of breastfeeding and NGT feeding during nCPAP treatment will be made.
 In addition 130 paired observations of breastfeeding and NGT feeding while babies are on
 HHFNC will be made. Each infant will serve as its own control as feeding episodes will be
 paired so that a breastfeed and an NGT feed are both observed within a 12 hour period. This
 will minimise variation caused by changes in the infants' condition.

 It is unlikely that infants will be able to obtain sufficient volume of milk while learning
 to breastfeed and so after each breastfeeding attempt the babies will be offered a top-up via
 NGT to ensure they receive their required feed volume.

 Once a baby is enrolled in the study feeding episodes will be regularly observed (as is
 feasible with respect to staff availability and parental presence). If a baby is too unwell
 to be observed this will be documented.

 Prior to the observation the baby's stability during the preceding hour will be evaluated and
 recorded. During a feeding episode all infants will be directly observed for a 30 minute
 period during which they will either receive a breast feed with a subsequent NGT top up or
 solely an NGT feed. Subsequently the baby's stability over the following hour will be
 retrospectively assessed. All infants will receive continuous nCPAP or HHFNC throughout.

 During a feeding episode heart rate and oxygen saturation will be continuously monitored
 using pulse oximetry. Apnoea monitors will be used to assess episodes of apnoea. Axillary
 temperature will be assessed at the beginning and end of the feeding episode. The oxygen
 requirement will be measured from the CPAP/HHFNC machine.

 The stability of the neonate during each feeding episode will be compared with their
 stability over the preceding hour by reviewing the documented incidence of desaturations,
 bradycardias and apnoeas and the neonate's temperature on their observation chart.

 Quality of breastfeeding will be assessed using videos of breastfeeding episodes. These
 videos will be reviewed by trained assessors (Speech and Language Therapists with an interest
 in lactation from Imperial College Healthcare NHS Trust) who will use the PIBBS tool to
 assess the quality of feeding. They will look for feeding behaviours to assess the maturity
 of feeding.

 Serial feeding episodes will be compared to assess whether there is a progression from more
 immature to mature feeding as the babies have breastfeeding opportunities on CPAP or HHFNC.
 This data will be used to assess whether future studies in this area to explore how feeding
 behaviours progress would be beneficial.

 It will also be recorded at what corrected gestational age/actual age these babies establish
 oral feeding; how they are fed at discharge (breast or bottle) and what milk they are
 discharged home on. This data will allow planning of future studies to assess whether early
 attempts at breastfeeding whilst receiving CPAP or HHFNC help the establishment of full
 breastfeeding.

 The parental perception of feeding with respiratory support will be assessed using a parental
 questionnaire. This will use a visual analogue scale to assess whether parents feel that
 breastfeeding during respiratory support is beneficial to their infants overall care and what
 impact the feeding opportunities has had on their bonding with their baby. This data will be
 used to assess the feasibility of further studies in this area by establishing the parental
 tolerance of breastfeeding babies receiving respiratory support and developing a
 questionnaire that will effectively explore the parental experience.

 The data collected for nCPAP and HHFNC separately will be used to establish the sample size
 that will be required in future studies to compare the two modalities to see if there are
 significant differences between the two (in terms of safety, efficacy and parental
 tolerance).

 STATISTICS AND DATA ANALYSIS Analysis of the pilot study data suggested that desaturation was
 the most common adverse event associated with feeding during nCPAP or HHFNC treatment. The
 sample size has been calculated to show a significant difference based on the results from
 the pilot data.

 128 feeding episodes are required to get 80% power at the 5% significance level to find a
 difference in mean duration of desaturation episodes of 1.25 minutes, based on a standard
 deviation for changes in this outcome of 5 (taken from pilot data). This is felt to be a
 clinically significant increase in desaturation episodes over a 30 minute period.

 The feeding episodes may come from around 25 babies. As each baby acts as its own control
 (because each breastfeeding episode is paired with an episode of NGT feeding occurring within
 24 hours) the sample size is dependent on the number of feeding episodes observed, not the
 number of babies.

 Analysis: paired t-test of mean duration of desaturation. McNemar's test to compared paired
 proportions between groups.

 Data and all appropriate documentation will be stored for 5 years after the completion of the
 study, including the follow-up period.
Inclusion Criteria:

 -  Infants cared for at Imperial College Healthcare NHS trust neonatal unit at Queen
 Charlottes and Chelsea Hospital and St Marys Hospital. Infants will be eligible if
 they are over 30 weeks of gestational age and receive continuous treatment with nCPAP
 or HHFNC .

 Exclusion Criteria:

 -  Major congenital malformation or underlying genetic disorder

 -  signs of severe progressive respiratory distress

 -  FiO2 > 0.4

 -  PCo2 > 9kPa

 -  Need for high CPAP > 8cmH2O

 -  Need for HHFNC with flow rate of >8litres/min

 -  Severe temperature instability, not tolerating 30 min outside the incubator

 -  CPAP or HHFNC treatment stopped