Individualized Fortification of Breast Milk
Condition: Breast Milk; Premature Infant
MeSH terms: Birth Weight
Study type: Observational

Summary: 
      Objectives: To compare the effects of two different methods of individualized protein
      fortification of breast milk on the early growth of VLBW preterm infants.

      Design: VLBW preterm infants ≤ 32 weeks of gestational age were included in the study and
      randomized into two groups according to the method of breast milk fortification. In the
      targeted protein fortification group, breast milk samples were analyzed daily via
      mid-infrared spectroscopy and additional protein was provided to maintain an intake of 4.5
      g/kg/day. In the adjustable protein fortification group, blood urea nitrogen (BUN) levels
      were monitored weekly, and if the level was < 5 mg/dL, the amount of protein fortification
      was gradually increased to an "estimated" maximum level of 4.5 g/kg/day, as per the policy of
      neonatal intensive care unit. The cumulative amounts of protein, energy, fat, and
      carbohydrate given to infants prior to study commencement and during the study period were
      calculated. Anthropometric measurements were performed in both groups weekly for 4 weeks to
      compare their growth, and blood data including pH, base deficit, and urea, creatinine, and
      albumin levels were collected.
    

Detailed description: 
      Optimal feeding during the early neonatal period is critical because inadequate nutrition,
      especially of very-low-birth-weight (VLBW) preterm infants, causes growth restrictions and
      has negative effects on neurocognitive development (1-5).

      Although breast milk is the first choice for nutrition of preterm infants (6, 7), it falls
      short of meeting all of the nutritional needs of VLBW infants unless fortified (8-10).
      Therefore, standard fortification (addition of a fixed amount of a commercial fortifier to
      breast milk) has become a commonly used method in neonatal intensive care units (NICUs) (11,
      12). Standard fortification is performed based on assumptions made about the protein level in
      breast milk. However, protein levels show inter- and intra-individual variation, and the
      assumed levels in the milk of the mothers of preterm infants (2.1-2.4 g/100 kcal) is reduced
      to <1.5 g/100 kcal after the 14th day of lactation (10, 13-17). The protein content of
      commercial fortifiers ranges from 0.7 to 1.1 g/100 mL, and they thus can only increase the
      amount of protein in breast milk to 3.25 g/100 kcal. Therefore, the standard fortification
      method fails to meet the daily protein need of 3.5-4.5 g/kg/day of VLBW infants that is
      recommended by the European Society for Pediatric Gastroenterology Hepatology and Nutrition
      (18, 19).

      Individualized fortification is another method recommended for optimizing breast milk
      fortification, and it is considered the best solution for addressing the protein deficiencies
      of VLBW preterm infants (10, 12). There are two valid methods of individualized
      fortification: "targeted fortification" based on analyses of breast milk proteins, and
      "adjustable fortification" based on the blood urea nitrogen (BUN) - reflected metabolic
      response of infants (10, 12). Despite these developments, there is still no consensus on the
      optimum fortification method; many different protocols are applied in NICUs worldwide (20,
      21).

      To the best of the investigators knowledge, no study has yet compared these two
      individualized fortification methods for nutrition of preterm infants. Therefore, the
      investigators compared the effects of targeted and adjustable protein fortification on the
      early growth of breastfed VLBW preterm infants.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Very-low-birth-weight preterm infants ≤ 32 weeks of gestational age were included in the
        study and randomized into two groups according to the method of breast milk fortification.
      
Keywords: Preterm infants; very low birth weight; breast milk; individualized fortification; targeted protein fortification; adjustable protein fortification; growth