NECNCT05293353
Neokare Safety and Tolerability Assessment in Neonates With GI Problems
An observational study of NEC and Gastroschisis, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
With an increasing body of evidence to support a causal link between drinking milk that contain cow's milk protein (CMP) and the development of gastrointestinal disturbance in infants, many clinicians avoid the use of CMP containing feed in high risk babies. Read more about this study
- Who is it for?
- Ages Up to 44 weeks
- Conditions the study is for
- NEC, Gastroschisis, Intestinal Perforation
- What is being tested?
- NeoKare Breast Milk Fortifier
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Jun 2022to Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 44 weeks
- All sexes
- Child
Study population: The aim of these inclusion criteria is to select a group of babies typically requiring nutritional supplementation of breast milk but in whom there is currently a reluctance to provide cow's milk-based breastmilk fortifiers.
Who may be able to join
- All of the following must be met:
- Current weight greater than ≥ 1.5kg (this will reduce to current weight of ≥ 1.0kg following midpoint review if no safety concerns
- Deemed by attending clinician that fortification of breast milk is desirable either to meet nutritional requirements or optimise growth
- Exclusive maternal or donor breast milk feeding (at time of starting fortifier)
- At least one of the following diagnostic criteria:
- Any previous gastrointestinal tract surgery. This may include but is not limited:
Show all 19Show fewer
- Surgery for NEC
- Gastroschisis
- Spontaneous Intestinal Perforation
- Intestinal Atresias and Webs
- Malrotation
- Hirschsprung's disease
- Volvulus
- Exomphalos
- Meconium Ileus/plugs
- Anorectal anomalies
- Medically treated gastrointestinal disease including but not limited to necrotising enterocolitis (based on nationally agreed case definitions), meconium ileus of prematurity (clinical diagnosis), milk curd obstruction (clinical diagnosis)
- Previously suspected intolerance of cow's milk protein-based breast milk fortifier in the absence of other gastrointestinal disease (clinical diagnosis)
- Congenital gastrointestinal anomaly (not requiring surgery)
Who cannot join
- Any of the following will result in exclusion:
- Known congenital metabolic disorder
- Formula fed prior to diagnosis being made
- Bilateral grade III or IV intra-ventricular haemorrhage
- Any infant who has had gastrointestinal tract surgery and received feed other than breast milk following surgery and prior to commencing the study
- Refusal of consent, refusal for the use of pasteurised donor human milk
- The reason for these exclusion criteria is to exclude any baby in whom the primary outcome may be adversely influenced by co-existing medical morbidities
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, SO16 6YD
Andrew Guy, +442381205146, andrew.guy@uhs.nhs.uk
Mark Johnson, PhD
About this study
Official title: A Prospective Tolerability and Safety Study of a Powdered Human Milk-based Breastmilk Fortifier (Neokare) in Neonates With Gastrointestinal Problems
With an increasing body of evidence to support a causal link between drinking milk that contain cow's milk protein (CMP) and the development of gastrointestinal disturbance in infants, many clinicians avoid the use of CMP containing feed in high risk babies.
Delivery of adequate nutritional intake is one of the great challenges in the care of newborn infants, particularly those born preterm or with gastrointestinal problems. Whilst there are recognised benefits of human milk, a diet of exclusive human milk may not meet the nutritional demands of the infant. To close this gap, breast milk fortifier (BMF) is typically added to human milk. However, addition of BMF may be associated with gastrointestinal disturbance, possibly due to the fact that it contains CMP.
Read more
This research study is to test the tolerability and safety of a new human milk-based BMF in neonates with gastrointestinal problems. It is hoped that this may provide an opportunity for high risk infants, to receive the benefits of human milk whilst minimising the risks reported to be associated with CMP.
Eligible infants will be those in whom nutritional supplementation of breast is deemed clinically necessary, a weight of greater than 1.0kg at the time of starting fortifier and at least one of:
- previous gastrointestinal surgery
- congenital gastrointestinal anomaly
- medically treated gastrointestinal disease
- previously suspected intolerance of CMP based breast milk fortifier in the absence of other gastrointestinal disease
Infants will be started on human milk-based BMF once they are tolerating 100 mls per kilo per day of human breast milk. The human milk-based fortifier will be commenced at half the recommended dose for 48 hours then increase to full strength. This will be continued until the infant reaches 44 weeks corrected gestational age, or until such time as they are deemed to no longer require the additional nutrition.
Read the detailed description
BACKGROUND There is an increasing body of evidence to support a causal link between ingestion of cow's milk protein (CMP) containing milks and the development of gastrointestinal disturbance in preterm and term infants. In particular the development of necrotising enterocolitis (NEC) has been associated with use of CMP containing feed in both epidemiological studies and a small number of prospective trials. It may be that this is due to a lack of the protective effect of breast milk, rather than CMP pe se. In addition to NEC, CMP containing feed may be implicated in the development of other gastrointestinal disturbance in preterm infants and as such many clinicians avoid the use of CMP containing feed in high risk infants. One such group are preterm infants who have already had an episode of NEC. Others include those born with a congenital anomaly of the gastrointestinal tract such as gastroschisis.
One of the great challenges in the care of the preterm neonate is the delivery of adequate nutritional intake to support growth and development. Whilst there are recognised benefits of human milk for preterm infants, a diet of exclusive human milk does not meet the nutritional and metabolic demands of the preterm infant(4). To close this nutritional gap, breast milk fortifier (BMF) is typically added to human milk. BMF is manufactured from cow's milk, and so contains hydrolysed CMP. However, there is concern that this addition of BMF may be associated with gastrointestinal disturbance, and this may be due to the fact that it contains elements of CMP. In view of this potential association, there is an understandable reluctance to use standard BMF in infants who have already had evidence of gastrointestinal disturbance, such as NEC or gastrointestinal surgery.
RATIONALE Recently a human milk based breast milk fortifier (NeoKare) has become available and is currently being evaluated in the preterm population when compared to current standard feeding practice. Provision of such an exclusive human milk diet may not carry the same risk of gastrointestinal disturbance and may represent an opportunity for high-risk preterm infants that have had NEC, undergone gastrointestinal surgery or had other gastrointestinal disturbance felt to be related to type of milk, to receive the benefits of human milk together with the nutritional benefits of milk fortification, whilst minimising the risks reported to be associated with exposure to CMP. Being able to improve nutrient intakes in this way using human milk based fortifier, may reduce the need for parenteral nutrition, and in turn reduce the risk of complications of parenteral nutrition, length of stay and hospital costs. To date this human milk-based breast milk fortifier has not been formally evaluated in this group of infants.
There is a need to establish if NeoKare is tolerated by infants with pre-existing gastrointestinal disturbance, and see if it can be safely used in this population. There is also a need to see if it enables better nutrition and growth, and earlier cessation of PN, and in turn a shorter length of stay, These may have cost related benefits, which also need to be explored.
Primary objective The primary aim of the study is to investigate the tolerability of a powdered human milk-based breast milk fortifier (Neokare) in infants cared for on a neonatal unit with pre-existing gastrointestinal disturbance (previous gastrointestinal surgery, medically treated gastrointestinal disease, previously suspected intolerance of cow's milk protein-based breast milk fortifier in the absence of other gastrointestinal disease or a congenital gastrointestinal anomaly not requiring surgery). This will be compared to a retrospective control group of similar infants born prior to the study who were not managed using the NeoKare product
Secondary objectives The main secondary aim of the study is to investigate the safety of a powdered human milk-based breast milk fortifier (Neokare) in infants cared for on a neonatal unit with pre-existing gastrointestinal disturbance (previous gastrointestinal surgery, medically treated gastrointestinal disease, previously suspected intolerance of cow's milk protein-based breast milk fortifier in the absence of other gastrointestinal disease or a congenital gastrointestinal anomaly not requiring surgery) This will be compared to a retrospective control group of similar infants born prior to the study who were not managed using the NeoKare product Other secondary aims of the study are to see if, in infants cared for on a neonatal unit with pre-existing gastrointestinal disturbance (previous gastrointestinal surgery, medically treated gastrointestinal disease, previously suspected intolerance of cow's milk protein-based breast milk fortifier in the absence of other gastrointestinal disease or a congenital gastrointestinal anomaly not requiring surgery), the use of a powdered human milk-based breast milk fortifier (Neokare) leads to improvements in growth, nutrition, length of stay, time on parenteral nutrition and other clinical outcomes compared to a retrospective control group of similar infants born prior to the study who were not managed using the NeoKare product. Cost of care will also be compared.
TRIAL DESIGN This will be a Prospective observational cohort study with a retrospective control group
- Conditions
- NEC, Gastroschisis, Intestinal Perforation, Atresia, Intestinal, Hirschsprung Disease, Exomphalos
- Being tested
- NeoKare Breast Milk Fortifier
- Medical subject headings
- Gastroschisis, Intestinal Perforation, Intestinal Atresia, Hirschsprung Disease, Hernia, Umbilical, Intestinal Volvulus, Anorectal Malformations, Meconium Ileus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeoKare Breast Milk FortifierOther
Powdered product made from human breast milk used to increase nutritional content of mother's own breast milk
| Study group | Role | What they receive |
|---|---|---|
| Breast Milk Fortification with NeoKare | Prospective cohort, 50 infants Receives: Other: NeoKare Breast Milk Fortifier | |
| No Breast Milk Fortification | Retrospective, historical cohort, approx 50 infants |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days of feed intolerance
Defined as number of days enteral feed was withheld for =>12 hours due to concerns about nasogastric aspirate colour or volume, vomiting, abdominal distension, stoma output, stooling or vomiting, as a proportion of the total number of days on which human milk-based breast milk fortifier was included in the feed
Measured: At 38 weeks postmenstrual age (an average of 8 weeks after initial surgery/gastrointestinal disturbance)
Secondary outcomes (60)
Number of adverse events per infant related to the administration of human milk-based breast milk fortifier.
Any adverse event felt to be directly related to the administration of human milk-based breast milk fortifier will be determined by the research team and the clinical team caring for the infant.
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily Energy intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily protein intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily fat intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily carbohydrate intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily zinc intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily selenium intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily copper intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin A intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin D intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin E intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin C intake between surgery/gastrointestinal disturbance and discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily Energy intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily protein intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily fat intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily carbohydrate intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily zinc intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily selenium intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily copper intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin A intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin D intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin E intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin C intake whilst on human milk based fortifier
Measured: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- weight gain in g/kg/day
Measured: At 36 weeks postmenstrual age
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Measured: At 36 weeks postmenstrual age
Growth since study enrollment- weight gain in g/kg/day
Measured: At Estimated date of delivery
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Measured: At Estimated date of delivery
Growth since study enrollment- weight gain in g/kg/day
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- weight gain in g/kg/day
Measured: At 3 months of age corrected for prematurity
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Measured: At 3 months of age corrected for prematurity
Growth since study enrollment- length in mm/week
Measured: At 36 weeks postmenstrual age
Growth since study enrollment- change in length standard deviation score based on UK reference data
Measured: At 36 weeks postmenstrual age
Growth since study enrollment- length in mm/week
Measured: At Estimated date of delivery
Growth since study enrollment- change in length standard deviation score based on UK reference data
Measured: At Estimated date of delivery
Growth since study enrollment- length in mm/week
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- change in length standard deviation score based on UK reference data
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- length in mm/week
Measured: At 3 months of age corrected for prematurity
Growth since study enrollment- change in length standard deviation score based on UK reference data
Measured: At 3 months of age corrected for prematurity
Growth since study enrollment- head circumference in mm/week
Measured: At 36 weeks postmenstrual age
Growth since study enrollment- change in head circumference standard deviation score based on UK reference data
Measured: At 36 weeks postmenstrual age
Growth since study enrollment- head circumference in mm/week
Measured: At Estimated date of delivery
Growth since study enrollment- change in head circumference standard deviation score based on UK reference data
Measured: At Estimated date of delivery
Growth since study enrollment- head circumference in mm/week
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- change in head circumference standard deviation score based on UK reference data
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- head circumference in mm/week
Measured: At 3 months of age corrected for prematurity
Growth since study enrollment- change in head circumference standard deviation score based on UK reference data
Measured: At 3 months of age corrected for prematurity
Number of Episodes of Central Line Associated Blood Stream infection (CLABSI) and NEC during hospital stay after initial initial surgery/gastrointestinal disturbance, defined using existing nationally agreed case definitions
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Days of Parenteral Nutrition (PN) during hospital stay after initial initial surgery/gastrointestinal disturbance, defined as each 24hour period an infants received at least some PN
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Cost of providing PN per day during hospital stay after initial initial surgery/gastrointestinal disturbance
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of days spent having level 3 care (according to British Association of Perinatal Medicine criteria with associated tariff cost) during hospital stay after initial initial surgery/gastrointestinal disturbance
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of days spent having level 2 care (according to British Association of Perinatal Medicine criteria with associated tariff cost) during hospital stay after initial initial surgery/gastrointestinal disturbance
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of days spent having level 1 care (according to British Association of Perinatal Medicine criteria with associated tariff cost) during hospital stay after initial initial surgery/gastrointestinal disturbance
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of days spent having 'normal' care (according to British Association of Perinatal Medicine criteria with associated tariff cost) during hospital stay after initial initial surgery/gastrointestinal disturbance
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of participants who develop PN associated liver disease stay after initial surgery/GI disturbance-defined as cholestasis (conjugated serum bilirubin 34.2 mmol/L) occurring in the setting of PN, when other specific causes of liver injury excluded
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Length of stay in the hospital (both overall and post-operatively)
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of episodes of unplanned gastrointestinal surgery during hospital stay after initial initial surgery/gastrointestinal disturbance
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of infants that discontinue fortifier during hospital stay after initial initial surgery/gastrointestinal disturbance
The number of infants who have the NeoKare fortifier stopped for clinical reasons. Reason for discontinuation will also be collected
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of infants who die during the study period and prior to hospital discharge
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Number of episodes of any infections/sepsis requiring antibiotic therapy > 7 days during hospital stay after initial initial surgery/gastrointestinal disturbance
Measured: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2022
- Study start9 Jun 2022
- Primary completionApr 2023 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NECStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Southampton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southampton, NeoKare Nutrition Ltd
- Responsible party
- Sponsor
- Investigators
- Mark Johnson, PhD, Principal investigator, University Hospital Southampton NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05293353
- Sponsor's protocol ID
- CHI1109
- Status last verified
- Oct 2022
- First submitted
- 17 Feb 2022
- Last updated
- 28 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Tolerability and Safety Study of a Powdered Human Milk-based Breastmilk Fortifier (Neokare) in Neonates With Gastrointestinal Problems
- ClinicalTrials.gov ID
- NCT05293353
- Acronym / sponsor ID
- CHI1109
- Conditions
- NEC, Gastroschisis, Intestinal Perforation, Atresia, Intestinal, Hirschsprung Disease, Exomphalos
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital Southampton NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Southampton, NeoKare Nutrition Ltd
- Study start
- 9 Jun 2022 (actual)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 24 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With an increasing body of evidence to support a causal link between drinking milk that contain cow's milk protein (CMP) and the development of gastrointestinal disturbance in infants, many clinicians avoid the use of CMP containing feed in high risk babies.
Delivery of adequate nutritional intake is one of the great challenges in the care of newborn infants, particularly those born preterm or with gastrointestinal problems. Whilst there are recognised benefits of human milk, a diet of exclusive human milk may not meet the nutritional demands of the infant. To close this gap, breast milk fortifier (BMF) is typically added to human milk. However, addition of BMF may be associated with gastrointestinal disturbance, possibly due to the fact that it contains CMP.
This research study is to test the tolerability and safety of a new human milk-based BMF in neonates with gastrointestinal problems. It is hoped that this may provide an opportunity for high risk infants, to receive the benefits of human milk whilst minimising the risks reported to be associated with CMP.
Eligible infants will be those in whom nutritional supplementation of breast is deemed clinically necessary, a weight of greater than 1.0kg at the time of starting fortifier and at least one of:
- previous gastrointestinal surgery
- congenital gastrointestinal anomaly
- medically treated gastrointestinal disease
- previously suspected intolerance of CMP based breast milk fortifier in the absence of other gastrointestinal disease
Infants will be started on human milk-based BMF once they are tolerating 100 mls per kilo per day of human breast milk. The human milk-based fortifier will be commenced at half the recommended dose for 48 hours then increase to full strength. This will be continued until the infant reaches 44 weeks corrected gestational age, or until such time as they are deemed to no longer require the additional nutrition.
Detailed description
BACKGROUND There is an increasing body of evidence to support a causal link between ingestion of cow's milk protein (CMP) containing milks and the development of gastrointestinal disturbance in preterm and term infants. In particular the development of necrotising enterocolitis (NEC) has been associated with use of CMP containing feed in both epidemiological studies and a small number of prospective trials. It may be that this is due to a lack of the protective effect of breast milk, rather than CMP pe se. In addition to NEC, CMP containing feed may be implicated in the development of other gastrointestinal disturbance in preterm infants and as such many clinicians avoid the use of CMP containing feed in high risk infants. One such group are preterm infants who have already had an episode of NEC. Others include those born with a congenital anomaly of the gastrointestinal tract such as gastroschisis.
One of the great challenges in the care of the preterm neonate is the delivery of adequate nutritional intake to support growth and development. Whilst there are recognised benefits of human milk for preterm infants, a diet of exclusive human milk does not meet the nutritional and metabolic demands of the preterm infant(4). To close this nutritional gap, breast milk fortifier (BMF) is typically added to human milk. BMF is manufactured from cow's milk, and so contains hydrolysed CMP. However, there is concern that this addition of BMF may be associated with gastrointestinal disturbance, and this may be due to the fact that it contains elements of CMP. In view of this potential association, there is an understandable reluctance to use standard BMF in infants who have already had evidence of gastrointestinal disturbance, such as NEC or gastrointestinal surgery.
RATIONALE Recently a human milk based breast milk fortifier (NeoKare) has become available and is currently being evaluated in the preterm population when compared to current standard feeding practice. Provision of such an exclusive human milk diet may not carry the same risk of gastrointestinal disturbance and may represent an opportunity for high-risk preterm infants that have had NEC, undergone gastrointestinal surgery or had other gastrointestinal disturbance felt to be related to type of milk, to receive the benefits of human milk together with the nutritional benefits of milk fortification, whilst minimising the risks reported to be associated with exposure to CMP. Being able to improve nutrient intakes in this way using human milk based fortifier, may reduce the need for parenteral nutrition, and in turn reduce the risk of complications of parenteral nutrition, length of stay and hospital costs. To date this human milk-based breast milk fortifier has not been formally evaluated in this group of infants.
There is a need to establish if NeoKare is tolerated by infants with pre-existing gastrointestinal disturbance, and see if it can be safely used in this population. There is also a need to see if it enables better nutrition and growth, and earlier cessation of PN, and in turn a shorter length of stay, These may have cost related benefits, which also need to be explored.
Primary objective The primary aim of the study is to investigate the tolerability of a powdered human milk-based breast milk fortifier (Neokare) in infants cared for on a neonatal unit with pre-existing gastrointestinal disturbance (previous gastrointestinal surgery, medically treated gastrointestinal disease, previously suspected intolerance of cow's milk protein-based breast milk fortifier in the absence of other gastrointestinal disease or a congenital gastrointestinal anomaly not requiring surgery). This will be compared to a retrospective control group of similar infants born prior to the study who were not managed using the NeoKare product
Secondary objectives The main secondary aim of the study is to investigate the safety of a powdered human milk-based breast milk fortifier (Neokare) in infants cared for on a neonatal unit with pre-existing gastrointestinal disturbance (previous gastrointestinal surgery, medically treated gastrointestinal disease, previously suspected intolerance of cow's milk protein-based breast milk fortifier in the absence of other gastrointestinal disease or a congenital gastrointestinal anomaly not requiring surgery) This will be compared to a retrospective control group of similar infants born prior to the study who were not managed using the NeoKare product Other secondary aims of the study are to see if, in infants cared for on a neonatal unit with pre-existing gastrointestinal disturbance (previous gastrointestinal surgery, medically treated gastrointestinal disease, previously suspected intolerance of cow's milk protein-based breast milk fortifier in the absence of other gastrointestinal disease or a congenital gastrointestinal anomaly not requiring surgery), the use of a powdered human milk-based breast milk fortifier (Neokare) leads to improvements in growth, nutrition, length of stay, time on parenteral nutrition and other clinical outcomes compared to a retrospective control group of similar infants born prior to the study who were not managed using the NeoKare product. Cost of care will also be compared.
TRIAL DESIGN This will be a Prospective observational cohort study with a retrospective control group
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Breast Milk Fortification with NeoKare | – | Other: NeoKare Breast Milk FortifierProspective cohort, 50 infants |
| No Breast Milk Fortification | – | –Retrospective, historical cohort, approx 50 infants |
Who may qualify
- Ages
- Up to 44 weeks
- Sex
- All
- Age groups
- Child
- Study population
- The aim of these inclusion criteria is to select a group of babies typically requiring nutritional supplementation of breast milk but in whom there is currently a reluctance to provide cow's milk-based breastmilk fortifiers.
Key inclusion criteria (19 listed)
- Current weight greater than ≥ 1.5kg (this will reduce to current weight of ≥ 1.0kg following midpoint review if no safety concerns
- Deemed by attending clinician that fortification of breast milk is desirable either to meet nutritional requirements or optimise growth
- Exclusive maternal or donor breast milk feeding (at time of starting fortifier)
- At least one of the following diagnostic criteria:
Key exclusion criteria (7 listed)
- Known congenital metabolic disorder
- Formula fed prior to diagnosis being made
- Bilateral grade III or IV intra-ventricular haemorrhage
- Any infant who has had gastrointestinal tract surgery and received feed other than breast milk following surgery and prior to commencing the study
- Refusal of consent, refusal for the use of pasteurised donor human milk
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeoKare Breast Milk FortifierPowdered product made from human breast milk used to increase nutritional content of mother's own breast milk | Other | Breast Milk Fortification with NeoKare |
Primary outcome
Days of feed intolerance
Time frame: At 38 weeks postmenstrual age (an average of 8 weeks after initial surgery/gastrointestinal disturbance)
Defined as number of days enteral feed was withheld for =>12 hours due to concerns about nasogastric aspirate colour or volume, vomiting, abdominal distension, stoma output, stooling or vomiting, as a proportion of the total number of days on which human milk-based breast milk fortifier was included in the feed
60 secondary outcomes
Number of adverse events per infant related to the administration of human milk-based breast milk fortifier.
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily Energy intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily protein intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily fat intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily carbohydrate intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily zinc intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily selenium intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily copper intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin A intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin D intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin E intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin C intake between surgery/gastrointestinal disturbance and discharge
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Mean daily Energy intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily protein intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily fat intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily carbohydrate intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily zinc intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily selenium intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily copper intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin A intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin D intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin E intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Mean daily vitamin C intake whilst on human milk based fortifier
Time frame: During the intervention period (whilst receiving human milk-based fortifier, an average of 8weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- weight gain in g/kg/day
Time frame: At 36 weeks postmenstrual age
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Time frame: At 36 weeks postmenstrual age
Growth since study enrollment- weight gain in g/kg/day
Time frame: At Estimated date of delivery
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Time frame: At Estimated date of delivery
Growth since study enrollment- weight gain in g/kg/day
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- weight gain in g/kg/day
Time frame: At 3 months of age corrected for prematurity
Growth since study enrollment- change in weight standard deviation score based on UK reference data
Time frame: At 3 months of age corrected for prematurity
Growth since study enrollment- length in mm/week
Time frame: At 36 weeks postmenstrual age
Growth since study enrollment- change in length standard deviation score based on UK reference data
Time frame: At 36 weeks postmenstrual age
Growth since study enrollment- length in mm/week
Time frame: At Estimated date of delivery
Growth since study enrollment- change in length standard deviation score based on UK reference data
Time frame: At Estimated date of delivery
Growth since study enrollment- length in mm/week
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- change in length standard deviation score based on UK reference data
Time frame: At hospital discharge (an average of 10 weeks after initial surgery/gastrointestinal disturbance)
Growth since study enrollment- length in mm/week
Time frame: At 3 months of age corrected for prematurity
Growth since study enrollment- change in length standard deviation score based on UK reference data
Time frame: At 3 months of age corrected for prematurity
Growth since study enrollment- head circumference in mm/week
Time frame: At 36 weeks postmenstrual age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Johnson, PhD principal investigator
University Hospital Southampton NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of NEC and Gastroschisis, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrew Guy (+442381205146, andrew.guy@uhs.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days of feed intolerance (time frame: At 38 weeks postmenstrual age (an average of 8 weeks after initial surgery/gastrointestinal disturbance)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2022.