Human Milk Fortification

Human milk fortification
by Dr. M. Tauseef Omer


Human milk fortifier (HMF) also known as breast milk fortifier (BMF) helps meet the nutritional demands of preterm and low-birth-weight infants whose needs exceed what is provided by unfortified human milk alone.


Indications:
HMF is required for all babies born <34 weeks’ gestation or those weighing <1.8 kg who are fed exclusively on mother’s expressed breast milk or donor expressed breast milk 

The short term goal is adequacy of growth (weight 15 - 22 g/Kg/day), length (0.9 cm/week), OFC (0.9 cm/week). Reduced risk of retinopathy of prematurity, intraventricular haemorrhage, bronchopulmonary dysplasia ( Poor nutrition in the first weeks of life impairs lung repair and alveolar development). There is also reduced mortality.

Long term goal: Better brain growth, and hence neurodevelopmental outcomes (language, motor, cognitive). MRI studies show improved gray matter and cerebellar volumes in infants with good early growth, which correlates with stronger learning and motor skills later in childhood.

Avoid excessive catch-up growth as it is linked with obesity later in life, hypertension, and metabolic syndrome (insulin resistance, glucose intolerance, hypertension, dyslipidemia), and diabetes or ischemic heart disease later in life. Increased risk of chronic kidney disease (rapid growth stresses immature kidneys). Neurodevelopment is impaired due to altered white matter microstructure with excessive fat accumulation in the body. There is also early onset of puberty specially in girls as more adipose tissue secretes higher levels of Leptin, which stimulates hypothalamus to secrete GnRH surges earlier. Higher insulin levels also enhance ovarian and testicular steroidogenesis. So there is accelerated bone age and earlier pubertal milestones.

When to begin human milk fortification: Fortification should begin once the infant’s milk intake reaches 100 mL/kg/day.

Advancement of feeding volumes: Once BMF is introduced, the total milk volume should be advanced to a maintenance level of 165 mL/kg/day as tolerated

When to discontinue human milk fortification:
1. Discontinue when the infant reaches term age and 1.8 Kg weight.
2. If the baby is receiving >50% nutrition via preterm formula

Continue fortification after discharge in babies <1.8 Kg, < 37 weeks, or those showing slow growth velocity.

Types of HMF:
Bovine Milk-Based Fortifiers: These are the most commonly used in the  and provide protein from either intact or hydrolyzed cow's milk. They have evolved from powdered forms to sterile liquid concentrates, which are preferred because they eliminate the risk of bacterial contamination (e.g., Cronobacter sakazakii) associated with non-sterile powders.

Human Milk-Based Fortifiers: Produced from pasteurized donor human milk, these contain only human-sourced proteins, fats, and carbohydrates. They are often used for the most immature infants (e.g., birth weight <1000 g) due to concerns about bovine protein tolerance, though they are significantly more expensive.

Nutrient Modulars: Single nutrients, such as medium-chain triglyceride (MCT) oil


Methods to determine the amount of fortification:

1. Standard Fortification: This involves adding a fixed amount of fortifier to human milk to reach a target caloric density, typically 24 kcal/oz. While easy to implement, it fails to account for the natural variability in the protein and fat content of the base human milk.

2. Adjustable Fortification: This strategy uses the infant’s metabolic response, specifically blood urea nitrogen (BUN) levels, as a guide. If the BUN is low (<9 mg/dL), it may indicate a need for more protein; if high (>16 mg/dL), protein intake is reduced. This method has been shown to improve short-term growth and later neurodevelopmental scores.

3. Targeted (Individualized) Fortification: This is the most precise method, utilizing bedside human milk analyzers to measure the exact macronutrient content of a mother's milk. Specific modular components (protein, fat, or carbohydrate) are then added to meet the infant's exact requirements. Although labor-intensive, it can lead to significantly better weight and linear growth.


Nutritional Composition and Targets

To achieve optimal growth and body composition, fortified feeds aim for specific ranges:

Protein: Preterm infants require 3.5 to 4.4 g/kg/day of protein
Energy: The target is typically 110 to 130 kcal/kg/day. In cases of chronic illness like bronchopulmonary dysplasia (BPD), requirements may rise to 150 kcal/kg/day.
Minerals: Fortification is essential for skeleton mineralization
Targets include 150–220 mg/kg/day of calcium and 75–140 mg/kg/day of phosphorus
Serum phosphorus levels should be maintained above 4 mg/dL to avoid bone resorption
Vitamins: Most HMF products are enriched with vitamins A, D, E, and K, as well as water-soluble vitamins, to prevent deficiencies and support retinal and neural maturation




Procedure for fortification:

Counsel parents about need of milk fortification, and narrate the advantages and possible adverse effects with fortification. Get written consent from parents.

Mother should wash her hands and chest.
Express milk manually or with a breast pump (manual or electric) into a clean container.
Container may be stored in fridge and HMF should ideally be added to milk just before feed.
HMF mixed milk may be stored in refrigerator and used within 122 hours of preparation.
Once added, gently swirl the container to mix the components. 


Adverse effects relating the use of fortifiers:
Increase in infections and NEC in infants fed fortified vs unfortified human milk.

Delayed gastric Emptying: The addition of fortifiers can delay gastric emptying and increase gastric residuals, which may be mistaken for signs of feeding intolerance or necrotizing enterocolitis (NEC).

Osmolality: Fortification increases the osmolality of human milk, which may contribute to GI distress.

Nutrient Loss: Fat and nutrients from fortified milk can adhere to feeding bags and tubing, especially during continuous feeds. Placing the infusion syringe at a 45-degree angle can help ensure even distribution

Risk of hypernatremia, metabolic acidosis, hypocalcemia, hypophosphatemia, raised or low BUN in neonates <28 weeks of gestation or <1000g weight. Therefore, weekly monitoring of these parameters is recommended.

Monitoring:
Daily weight measurement.
Continuous monitoring for abdominal distension, stool pattern, and feed intolerance.
Weekly monitoring of serum electrolytes, renal function tests, arterial blood gases, serum calcium and serum phosphate.

Human milk fortifier available in Punjab, Pakistan.
Pre-Nan Human milk Fortifier
It is in powdered form, 1 gram powder in 1 sachet.
Mix 1 pack in 25 cc of expressed human milk
100% hydrolyzed whey protein: aids digestion and absorption
Increases the protein content of breast milk to 0.36 grams


Available from:
Pharmacia, near FMH Lahore
And from the internal Pharmacy of Hameed Latif Hospital, Lahore.


The following breakdown provides the nutritional contents for a single 1g sachet of Nestlé PreNAN Human Milk Fortifier.

Macronutrients
ComponentAmount per 1g sachet
Energy4.3 kcal (18.2 kJ)
Protein0.36 g (100% partially hydrolyzed whey)
Carbohydrates0.32 g (Sugars: 0.03 g)
Total Fat0.18 g
MCT (Medium Chain Triglycerides)0.1 g
DHA1.37 mg
Linoleic Acid8.38 mg
Alpha-linolenic Acid3.91 mg

Minerals & Trace Elements
  • Calcium: 18.9 mg
  • Phosphorus: 11 mg
  • Sodium: 9.18 mg
  • Potassium: 12.1 mg
  • Chloride: 8.03 mg
  • Magnesium: 1 mg
  • Iron: 0.45 mg
  • Zinc: 0.24 mg
  • Copper: 13 mcg
  • Manganese: 2 mcg
  • Selenium: 0.7 mcg
  • Iodine: 3.17 mcg

Vitamins
  • Vitamin A: 83.2 mcg RE
  • Vitamin D: 0.88 mcg
  • Vitamin E: 0.94 mg TE
  • Vitamin K: 1.88 mcg
  • Vitamin C: 4.69 mg
  • B-Complex: Includes B1, B2, B6, B12, Niacin, Folic Acid, Pantothenic Acid, and Biotin.

Additional Nutrients
  • Choline
  • Inositol
  • Taurine
  • L-Carnitine


Recommended intake

Premature and low birth weight infants: the standard dosage is 1 g of powder, or one single sachet, per 25 ml of breast milk. It is recommended to gradually increase the dose, starting with 1 g of PreNAN® Breast Milk Strengthener per 50 ml of breast milk. After assessing breast milk tolerance within 24 hours of administration, the amount can be increased to a full dose of 1 g of PreNAN® Breast Milk Strengthener per 25 ml of breast milk or follow hospital feeding guidelines.

How to use

When proceeding to prepare milk, wash your hands thoroughly. Immediately before use, sterilize all the items you will need (bottle, pacifier and cap, syringe). If you use frozen breast milk, thaw it gradually in the refrigerator (below 4°C). Do not thaw milk by leaving it at room temperature or thaw it in the microwave. Shake or stir the milk before pouring it into a bottle or syringe. Next, pour the measured, appropriate amount of breast milk you want to fortify into the container. Before you add Nestlé PreNAN®, warm your breast milk to body temperature. Do not heat in the microwave. A standard serving is prepared by adding powder from one sachet (1 g) for every 25 ml of lukewarm breast milk at 35-40°C. Your doctor may order you to prepare a serving with different proportions of milk and powder. Cover the container and shake it gently until the powder dissolves completely in the milk. Feed your baby immediately after preparing the milk. Prepare only one serving of milk each time. Do not store leftover milk that your baby has not accepted.

Nutritional values

100 g of powder contains: energy value 1826 kJ/ 435 kcal, fat 18.1 g (including saturated fatty acids 12.2 g, including medium-chain triglycerides (MCT) 10.9 g), carbohydrates 32 g (including sugars 2.5 g), protein 36 g, salt 2.3 g; vitamin A 8320 µg, vitamin D 88 µg, vitamin E 94 mg, vitamin K 188 µg, vitamin C 469 mg, thiamine (B1) 3.5 mg, riboflavin (B2) 4.7 mg, niacin 35 mg, vitamin B6 3.1 mg, folic acid 938 µg, vitamin B12 4.7 µg, biotin 82 µg, pantothenic acid 16 mg; sodium 918 mg, potassium 1210 mg, chlorine 803 mg, calcium 1890 mg, phosphorus 1095 mg, magnesium 100 mg, iron 45 mg, zinc 24 mg, copper 1.3 mg, manganese 0.15 mg, fluorine <0.06 mg, selenium 70 µg, chromium <23 µg, molybdenum <20 µg, iodine 317 µg; linoleic acid 838 mg, ?-linolenic acid 391 mg, DHA (docosahexaenoic acid) 137 mg, choline 202 mg, inositol 108 mg, taurine 47 mg, L-carnitine 62 mg. Osmolarity 339 mOsm/l.
A 100 kcal serving contains: energy value 422 kJ/ 100 kcal, fat 4.2 g (including saturated fatty acids 2.8 g, including medium-chain triglycerides (MCT) 2.5 g), carbohydrates 7.5 g (including sugars 0.6 g), protein 8.2 g, salt 0.53 g; vitamin A 1915 µg, vitamin D 20 µg, vitamin E 22 mg, vitamin K 43 µg, vitamin C 108 mg, thiamine (B1) 0.8 mg, riboflavin (B2) 1.1 mg, niacin 8.1 mg, vitamin B6 0.7 mg, folic acid 216 µg, vitamin B12 1.1 µg, biotin 19 µg, pantothenic acid 3.8 mg; sodium 211 mg, potassium 278 mg, chlorine 185 mg, calcium 435 mg, phosphorus 252 mg, magnesium 23 mg, iron 10 mg, zinc 5.4 mg, copper 0.3 mg, manganese 0.035 mg, fluorine <0.014 mg, selenium 16 µg, chromium <5.3 µg, molybdenum <4.6 µg, iodine 73 µg; linoleic acid 193 mg, ?-linolenic acid 90 mg, DHA (docosahexaenoic acid) 32 mg, choline 46 mg, inositol 25 mg, taurine 11 mg, L-carnitine 14 mg. Osmolarity 339 mOsm/l.
1 sachet (1 g of powder) contains: energy value 18.2 kJ/ 4.3 kcal, fat 0.18 g (including saturated fatty acids 0.12 g, including medium-chain triglycerides (MCT) 0.1 g), carbohydrates 0.32 g (including sugars 0.03 g), protein 0.36 g, salt 0.02 g; vitamin A 83.2 µg, vitamin D 0.88 µg, vitamin E 0.94 mg, vitamin K 1.88 µg, vitamin C 4.69 mg, thiamine (B1) 0.04 mg, riboflavin (B2) 0.05 mg, niacin 0.35 mg, vitamin B6 0.03 mg, folic acid 9.38 µg, vitamin B12 0.05 µg, biotin 0.82 µg, pantothenic acid 0.16 mg; sodium 9.18 mg, potassium 12.1 mg, chlorine 8.03 mg, calcium 18.9 mg, phosphorus 11 mg, magnesium 1 mg, iron 0.45 mg, zinc 0.24 mg, copper 0.01 mg, manganese 0.002 mg, fluorine <0.0006 mg, selenium 0.7 µg, chromium <0.23 µg, molybdenum <0.2 µg, iodine 3.17 µg; linoleic acid 8.38 mg, ?-linolenic acid 3.91 mg, DHA (docosahexaenoic acid) 1.37 mg, choline 2.02 mg, inositol 1.08 mg, taurine 0.47 mg, L-carnitine 0.62 mg. Oosmolarity 339 mOsm/l.

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