Clinical trial NCT02865941: Target Fortification of Breast Milk: How Often Breast Milk Needs to be Measured?
Official title: Target Fortification of Breast Milk: The Effect of Different Schedules for Milk Analysis on the Growth and Development of Preterm Infants.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Postnatal Growth Disorder
Keywords: Target Fortification
Breast milk analysis
Nutrition
Macronutrient intake
Protein accretion
Lead sponsor: McMaster Children's Hospital
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 56
Sex: ALL
Maximum age (years): 29
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: It has been observed that target fortification on different schedules leads to meal to meal variation. It changes the ratio of protein to energy and the percentage of carbohydrate to non-protein energy which may, affect growth. In the past, the investigators have analyzed the outcomes of breast milk composition when target fortification is done with different analysis schedules. The investigators were able to measure the macronutrient intake for different milk analysis schedules via a theoretical model and show that the more frequent schedules reduce the variation of fortified-breast milk, whereas a reduced schedule leads to a high variation of macronutrients. It was observed that, in all the breast milk samples measured twice per week, infants achieved on average the recommended macronutrients in line with current recommendations. Nonetheless, the model only looks at the macronutrient intake and does not investigates the relationship between macronutrient variation and its effect on growth.

The aim of the current study is to compare a frequent schedule of measurement of macronutrient analysis with a reduced schedule of measurement and to study its affect on growth, protein accretion and metabolic parameter.


Eligibility criteria: Inclusion Criteria:

1. Gestational age \< 30 weeks (maternal dates or early fetal ultrasound);
2. Tolerating an enteral intake of ≥100 mL/kg/d for ≥ 24h;
3. Subject is anticipated to receive the intervention for ≥ 3 consecutive weeks after full enteral feeding (≥150 mL/kg/d) has been achieved;
4. Written informed consent has been obtained from the infant's legal representative.
5. Multiple births: Each infant will be included in the study if he/she meets the study criteria, and siblings will be individually randomized to one or other of the treatment arms.
6. Discussion with Most Responsible Physician (MRP) and the staff in order to discuss any potential transfer during the next 7 days.

Exclusion Criteria:

1. Gastrointestinal malformation, major congenital anomalies and chromosomal abnormalities;
2. Babies with enterostoma or short gut syndrome;
3. Infants fed more than 25% of mean caloric intake for a consecutive week with formula milk;
4. Fluid restriction \<140 mL/kg/d for ≥ 3 consecutive days;
5. Sepsis - all infants with gram-negative sepsis will be removed from the study;
6. Necrotizing enterocolitis, defined by feeding intolerance associated with positive x-ray findings (pneumatosis intestinalis - Bell Stage 2; air in the biliary tract or free air in the peritoneum - Bell Stage 3);
7. Renal disease, defined by symptoms (oliguria, anuria, proteinuria, hematuria) associated with an increased blood urea nitrogen \>10 mmol/L and creatinine of 130mmol/L
8. Participation in another clinical trial that may provide an alternative nutritional intervention, which might affect the outcomes of this study. outcomes of this study;
9. Probability of transfer to another neonatal intensive care unit or level II nursery outside the McMaster Children's Hospital, as discussed with the most responsible physician (MRP)

Primary outcomes:
measure: Growth during first three weeks of intervention
timeFrame: first three weeks during intervention before 36 weeks of gestation
Secondary outcomes:
measure: Daily Nutrient intake (kcal, lactose, protein, fat) measured with conventional milk analysis
timeFrame: from inclusion at postmenstrual age <30 weeks until 36 weeks of gestation
measure: Weight Gain
timeFrame: from inclusion at postmenstrual age <30 weeks until 36 weeks of gestation or discharge
measure: Oxidative stress by 8-Oxo-2'-deoxyguanosine metabolites in urine
timeFrame: from inclusion at postmenstrual age <30 weeks until discharge
measure: Protein synthesis analyzed by nitrogen excretion in urine [µmol/mL]
timeFrame: first three weeks during intervention before 36 weeks of gestation
measure: Feeding intolerance questionaire
timeFrame: from inclusion at postmenstrual age <30 weeks until discharge
measure: Fat mass [g]
timeFrame: from inclusion at postmenstrual age <30 weeks until discharge
measure: Lean mass [g]
timeFrame: from inclusion at postmenstrual age <30 weeks until discharge
measure: Head circumference [cm]
timeFrame: from inclusion at postmenstrual age <30 weeks until discharge
measure: Body length [cm]
timeFrame: from inclusion at postmenstrual age <30 weeks until discharge
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Faculty of Health Science, McMaster Children's Hospital
state: Ontario
Study officials:
affiliation: McMaster Children's Hospital
name: Christoph Fusch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rochow N, Fusch G, Choi A, Chessell L, Elliott L, McDonald K, Kuiper E, Purcha M, Turner S, Chan E, Xia MY, Fusch C. Target fortification of breast milk with fat, protein, and carbohydrates for preterm infants. J Pediatr. 2013 Oct;163(4):1001-7. doi: 10.1016/j.jpeds.2013.04.052. Epub 2013 Jun 12.
citation: Choi A, Fusch G, Rochow N, Sheikh N, Fusch C. Establishment of micromethods for macronutrient contents analysis in breast milk. Matern Child Nutr. 2015 Oct;11(4):761-72. doi: 10.1111/mcn.12053. Epub 2013 Jun 18.
citation: Fusch G, Choi A, Rochow N, Fusch C. Quantification of lactose content in human and cow's milk using UPLC-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Dec 1;879(31):3759-62. doi: 10.1016/j.jchromb.2011.09.053. Epub 2011 Oct 6.
citation: Fusch G, Rochow N, Choi A, Fusch S, Poeschl S, Ubah AO, Lee SY, Raja P, Fusch C. Rapid measurement of macronutrients in breast milk: How reliable are infrared milk analyzers? Clin Nutr. 2015 Jun;34(3):465-76. doi: 10.1016/j.clnu.2014.05.005. Epub 2014 May 17.
citation: Fusch G, Mitra S, Rochow N, Fusch C. Target fortification of breast milk: levels of fat, protein or lactose are not related. Acta Paediatr. 2015 Jan;104(1):38-42. doi: 10.1111/apa.12804. Epub 2014 Oct 2.
citation: Rochow N, Landau-Crangle E, Fusch C. Challenges in breast milk fortification for preterm infants. Curr Opin Clin Nutr Metab Care. 2015 May;18(3):276-84. doi: 10.1097/MCO.0000000000000167.
citation: Rochow N, Fusch G, Zapanta B, Ali A, Barui S, Fusch C. Target fortification of breast milk: how often should milk analysis be done? Nutrients. 2015 Apr 1;7(4):2297-310. doi: 10.3390/nu7042297.
citation: Fusch G, Kwan C, Huang RC, Rochow N, Fusch C. Need of quality control programme when using near-infrared human milk analyzers. Acta Paediatr. 2016 Mar;105(3):324-5. doi: 10.1111/apa.13305. Epub 2016 Jan 19. No abstract available.
citation: Choi A, Fusch G, Rochow N, Fusch C. Target Fortification of Breast Milk: Predicting the Final Osmolality of the Feeds. PLoS One. 2016 Feb 10;11(2):e0148941. doi: 10.1371/journal.pone.0148941. eCollection 2016.
citation: Kotrri G, Fusch G, Kwan C, Choi D, Choi A, Al Kafi N, Rochow N, Fusch C. Validation of Correction Algorithms for Near-IR Analysis of Human Milk in an Independent Sample Set-Effect of Pasteurization. Nutrients. 2016 Feb 26;8(3):119. doi: 10.3390/nu8030119.