Safety of Cow’s Milk-Derived Fortifiers Used with an All-Human Milk Base Diet in Very Low Birthweight Preterm Infants

Background: Very low birthweight (VLBW) preterm infants fed mothers own milk (MOM) need nutritional supplementation, traditionally achieved with cow’s milk derived fortifier (CMDF) and preterm formula (PTF) if MOM is insufficient. CM products have been associated with diverse major morbidities. The current recommendation is to preferentially replace PTF with donor milk (DM) to produce a 100% human milk (HM) base diet, usually fortified with CMDF. Objective: To identify whether CMDF, even when fed with a 100% HM base diet, is related to an increased risk of major morbidities. Methods: We identified a randomized trial with an all-HM base diet, comparing CMDF with a fortifier derived from human milk (HMDF), and two additional studies of this design were generated from raw data as subgroup analyses of a randomized controlled trial and a quasi-experimental study. Using these studies, we calculated the impact of CMDF on major morbidities of death, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA). Results: Each study individually provided support for an increase in major morbidities with CMDF. Meta-analyses of pooled data showed that compared to HMDF, the CMDF group had large in- creases in NEC (RR = 3.3; P = .001), ROP (RR = 2.2; P = .007), PDA (RR = 1.6; P = .009), interruption of feeding (RR = 3.4; P = .001) and a positive mortality/morbidity index based on one or more of death, NEC, sepsis, ROP and BPD (RR = 1.4; P = .006). Conclusions: Despite the increased use of HM in modern neonatal care as a base diet, we found a greater risk of critical morbidities with CMDF compared with HMDF. This burden of morbidity provides evidence that the benefits of an HM base diet, might be, in part, counteracted by multiple adverse outcomes relating to the use of CMDF.

Download Full-text

Safety of Cow's Milk-Derived Fortifiers used with an All Human Milk Base Diet in Very Low Birthweight Preterm Infants: Part II

Neonatology Today ◽

10.51362/neonatology.today/202010151038 ◽

2020 ◽

Vol 15 (10) ◽

pp. 3-8

Author(s):

Alan Lucas ◽

Maushumi Assad ◽

Jan Sherman ◽

John Boscardin ◽

Steven Abrams

Keyword(s):

United States ◽

Human Milk ◽

Low Birthweight ◽

Neonatal Morbidity ◽

The United States ◽

Cow’S Milk ◽

Very Low Birthweight ◽

Vlbw Infants ◽

Cow's Milk ◽

Morbidity Index

Recently we published a meta-analyses of morbidity seen with the use of cow’s milk derived fortifier (CMDF) rather than human milk derived fortifier (HMDF) in very low birthweight (VLBW) infants. Here, we further analyse these data to estimate the annual population risk of CMDF-related major morbidity in the United States and Canada. The outcome used was a mortality/morbidity index which was positive if the infants had one or more of death, necrotising enterocolitis, sepsis retinopathy of prematurity or broncho- pulmonary dysplasia. Using the risk difference (RD) between the CMDF and HMDF groups we estimated, provisionally, that 4150 additional VLBW infants in the United States and Canada each year, or an additional infant approximately every 2 hours, may be expected to develop a positive mortality/morbidity index in relation to being fed CMDF – over and above the number of infants with a positive index if fed HMDF. We provide an in-depth discussion of the limitations of our estimate. This analysis provides preliminary evidence of the magnitude of population risk of major neonatal morbidity with use of CMDF versus HMDF in VLBW infants in current practice.

Download Full-text

13 MEASUREMENT OF PROTEIN TURNOVER USING D1-PHENYLALANINE, D2-TYROSINE AND 1-13C-LEUCINE IN VERY LOW BIRTHWEIGHT (VLBWI PRETERM INFANTS FED FORTIFIED HUMAN MILK OR SPECIAL FORMULA

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-199505000-00024 ◽

1995 ◽

Vol 20 (4) ◽

pp. 448

Author(s):

Letty van Toledo-Enginga ◽

Willem Kulik ◽

Cornelis Jakobs ◽

Harrie N. Lafaber

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Protein Turnover ◽

Low Birthweight ◽

Very Low Birthweight ◽

Special Formula

Download Full-text

Serum Immunoglobulins in Preterm Infants: Comparison of Human Milk and Formula Feeding

PEDIATRICS ◽

10.1542/peds.72.3.312 ◽

1983 ◽

Vol 72 (3) ◽

pp. 312-316 ◽

Cited By ~ 2

Author(s):

Erkki Savilahti ◽

Anna-Liisa Järvenpää ◽

Niels C. R. Räihä

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Gestational Age ◽

Formula Feeding ◽

Cow’S Milk ◽

Serum Concentrations ◽

Cow's Milk ◽

Serum Immunoglobulins

Serum concentrations of immunoglobulins (IgA, IgG, and IgM) were studied in 64 preterm infants with gestational age of 31 to 36 weeks (mean 33.2 weeks), between 1 week and 4 months after birth. Infants were fed solely human milk or formula based on cow's milk. Infants fed formula exhibited significantly higher IgA levels at the age of 9 to 13 weeks than infants fed human milk. Infants given human milk who received more than 60% of their feeding in the hospital from their own mother had significantly higher IgA levels at the age of 3 weeks than did those receiving less than 30% of their feeding from their own mother. At 1 week of age, formula-fed infants with gestational age of 31 to 33 weeks had a significantly lower mean IgG concentration than those with gestational age of 34 to 36 weeks. However, the two term subgroups of infants receiving human milk, had similar mean concentrations of IgG and the value for infants of 31 to 33 weeks of gestation was significantly higher than that for formula-fed infants at the same gestational age. Serum IgM concentrations were similar whether infants were receiving human milk or formula. The formula feeding caused a more rapid maturation of IgA than did human milk. Results suggest that preterm infants may absorb IgA from the milk of their own mothers and that preterm infants with gestational age of 31 to 33 weeks may absorb IgG from human milk.

Download Full-text

Evaluation of A Concentrated Preterm Formula as a Liquid Human Milk Fortifier in Preterm Babies at Increased Risk of Feed Intolerance

Nutrients ◽

10.3390/nu10101433 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1433 ◽

Cited By ~ 3

Author(s):

Anish Pillai ◽

Susan Albersheim ◽

Julie Matheson ◽

Vikki Lalari ◽

Sylvia Wei ◽

...

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Clinical Decision ◽

Feeding Intolerance ◽

Serious Adverse Events ◽

Increased Risk ◽

Preterm Formula ◽

Feed Intolerance ◽

Preterm Babies ◽

Human Milk Fortifier

There are concerns around safety and tolerance of powder human milk fortifiers to optimize nutrition in preterm infants. The purpose of this study was to evaluate the tolerance and safety of a concentrated preterm formula (CPF) as a liquid human milk fortifier (HMF) for premature infants at increased risk of feeding intolerance. We prospectively enrolled preterm infants over an 18-month period, for whom a clinical decision had been made to add CPF to human milk due to concerns regarding tolerance of powder HMF. Data on feed tolerance, anthropometry, and serum biochemistry values were recorded. Serious adverse events, such as mortality, necrotizing enterocolitis (NEC), and sepsis, were monitored. A total of 29 babies received CPF fortified milk during the study period. The most common indication for starting CPF was previous intolerance to powder HMF. Feeding intolerance was noted in 4 infants on CPF. The growth velocity of infants was satisfactory (15.9 g/kg/day) after addition of CPF to feeds. The use of CPF as a fortifier in preterm babies considered at increased risk for feed intolerance seems well tolerated and facilitates adequate growth. Under close nutrition monitoring, this provides an additional option for human milk fortification in this challenging subgroup of preterm babies, especially in settings with limited human milk fortifier options.

Download Full-text

Evidence for Defective Skeletal Mineralization in Low-Birthweight Infants: The Absorption of Calcium and Fat

PEDIATRICS ◽

10.1542/peds.57.1.16 ◽

1976 ◽

Vol 57 (1) ◽

pp. 16-25

Author(s):

J. C. L. Shaw

Keyword(s):

Breast Milk ◽

Preterm Infants ◽

Milk Fat ◽

Low Birthweight ◽

Calcium Absorption ◽

Full Term ◽

Cow’S Milk ◽

Published Data ◽

Cow's Milk ◽

Fat Malabsorption

Using serial metabolic balance techniques, the absorption and retention of calcium and the absorption of fat have been measured over the first 30 to 70 days of life in 11 preterm and 2 full-term light-for-dates infants. They were fed either full-cream cow's milk, half-skimmed cow's milk, the proprietary filled milk S.M.A., or breast milk. The values for calcium intake, absorption, and retention were compared with the rate of accumulation of calcium by the fetus in utero, which was calculated from published data on the chemical composition of fetal bodies. Infants fed breast milk had an absolute dietary deficiency of calcium. Those fed other milks ingested sufficient but they did not absorb enough. Though calcium absorption increased with increasing postnatal age, intrauterine rates of calcium retention were never achieved on any of the milks. The average retention of calcium by preterm infants as a percentage of intrauterine accumulation was, for cow's milk 38%, for S.M.A. 27%, and for breast milk 17%. The full-term light-for-dates infants absorbed and retained more calcium than the preterm infants; it was on average 52% of the amount accumulated by the human fetus for an equivalent weight gain. The average absorption of fat by preterm infants was, from the cow's milk preparations 55%, from S.M.A. 61%, and from breast milk 84%. The light-for-dates infants absorbed on average 87% of the breast milk fat. There was no evidence that the amount of calcium absorbed was materially influenced by fat malabsorption. The principal determinants of the amount of calcium absorbed were the length of gestation and postnatal age of the infant.

Download Full-text

Weight Gain and Chemical Changes in Low Birthweight Infants After Change From Human Milk to Modified Cow's Milk

Archives of Disease in Childhood ◽

10.1136/adc.47.256.946 ◽

1972 ◽

Vol 47 (256) ◽

pp. 946-949 ◽

Cited By ~ 4

Author(s):

D. P. Davies ◽

R. Saunders ◽

O. P. Gray

Keyword(s):

Weight Gain ◽

Human Milk ◽

Low Birthweight ◽

Cow’S Milk ◽

Chemical Changes ◽

Cow's Milk

Download Full-text

The Evidence for Use of Human Milk in Very Low-birthweight Preterm Infants

NeoReviews ◽

10.1542/neo.8-11-e459 ◽

2007 ◽

Vol 8 (11) ◽

pp. e459-e466 ◽

Cited By ~ 15

Author(s):

A. L. Patel ◽

P. P. Meier ◽

J. L. Engstrom

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Low Birthweight ◽

Very Low Birthweight

Download Full-text

Safety and efficacy of human milk-based fortifier in enterally fed preterm and/or low birthweight infants: a systematic review and meta-analysis

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2020-319406 ◽

2020 ◽

pp. fetalneonatal-2020-319406

Author(s):

Erin Grace ◽

Cathie Hilditch ◽

Judith Gomersall ◽

Carmel T Collins ◽

Alice Rumbold ◽

...

Keyword(s):

Human Milk ◽

Low Birthweight ◽

Late Onset ◽

Meta Analysis ◽

Necrotising Enterocolitis ◽

Cow’S Milk ◽

Quality Of Evidence ◽

Cow's Milk ◽

Late Onset Sepsis

ObjectiveTo conduct a systematic review and meta-analysis of the efficacy and safety of fortification of human milk with human milk-based fortifier versus cow’s milk-based fortifier for use in preterm and/or very low birthweight infants.DesignRandomised or quasi-randomised controlled trials comparing the effect of human milk fortification with human milk-based milk fortifier versus cow’s milk-based fortifier in infants born <34 weeks’ gestation and/or with birth weight <1500 g were identified by searching databases, clinical trial registries and reference lists until 5 November 2019. Two authors independently extracted data and assessed evidence quality. Meta-analyses were conducted using fixed or random effects models, as appropriate.Main outcome measuresNecrotising enterocolitis (Bell’s stage II or higher) and late-onset sepsis.ResultsOf 863 unique records identified, 16 full-text trials were screened and 2 trials involving 334 infants were included. Primary outcome data were available for 332 infants. Use of human milk-based fortifier compared with cow’s milk-based fortifier reduced the risk of necrotising enterocolitis (risk ratio 0.47, 95% CI 0.22 to 0.98). There was no clear evidence of an effect on late-onset sepsis or any other outcomes. The quality of evidence was low to very low due to imprecision and lack of blinding in one study.ConclusionsFindings suggest that there is a reduction in the incidence of necrotising enterocolitis with human milk-based fortifiers compared with cow’s milk-based fortifiers. The overall quality of evidence is low. Further appropriately powered trials are required before this intervention can be routinely recommended for preterm infants.

Download Full-text