Formulas for Premature Infants: Fate of the Calcium and Phosphorus

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Formulas

for Premature

Infants:

Fate

of the

Calcium

and Phosphorus

Jatinder

Bhatia,

MD, and Samuel

J. Fomon,

MD

From the Division of Nutrition, Department of Pediatrics, University of Iowa, Iowa City

ABSTRACT. Formulas designed for feeding of premature

infants contain minerals added by the manufacturer.

Although it is known that these minerals may be poorly

suspended in the formula, little is known about concen-trations of minerals in formula delivered to the infant under conditions prevailing in premature infant nurser-ies. In partially empty bottles of Similac Special Care, concentrations of calcium and phosphorus of this residual

formula were found to be substantially greater than con-centrations in full bottles. Presumably, concentrations of calcium and phosphorus in formula delivered to the in-fants was relatively low. Enfamil Premature and SMA

Preemie infant formulas contain lesser quantities of

added calcium and demonstrated less tendency to

sedi-mentation. Substantial decrease in concentration of

cal-cium was observed with all three formulas during contin-uous infusion, but the decrease was greatest with Similac

Special Care. Little or no change in concentrations of

calcium and phosphorus were observed with simulated bolus feeding by gavage. Pediatrics 1983;72:37-40;

pre-mature infants, formula sedimentation, cakium, phospho-rus, intragastric infusion.

The protein source of formulas designed for the feeding of premature infants is generally a mixture of partially demineralized whey and nonfat cow’s milk. The quantities of certain minerals associated with these proteins are believed to be less than the

requirements for small premature infants and, for

this reason, a number of minerals are added in formula manufacturing. The solubility of some of

these mineral salts in aqueous solution is low, and

we wondered whether the minerals would be

deliv-ered to the infant under prevailing circumstances

of feeding. Sediments are commonly observed in

bottles of formula that have not been shaken, and

we have observed that vigorous shaking may be necessary to resuspend the sediment. The

manu-facturer’s literature’ indicates that losses of

mm-erals occur during continuous infusion of one pre-mature infant formula, and this has been confirmed

by Antonson et al.2 The present study was

under-taken to explore the extent of delivery of calcium and phosphorus from infant formulas to premature

infants under practical circumstances of feeding in

our premature nursery.

In our neonatal intensive care unit, small

pre-mature infants (<1,500 g) are often fed by nasogas-tric infusion, utilizing a pump. A three-hour feeding

period is followed by a one-hour rest period. The

feeding is withdrawn by syringe from the

ready-to-feed 120-mL feeding unit prepared by the manufac-turer. Instructions on these feeding units state

“shake well.” Syringes for feeding several infants

may be filled from the same feeding unit at approx-imately the same time (within 15 minutes) and the remainder is discarded.

To determine the stability of minerals in

formu-las designed for feeding small premature infants,

we made observations of four types: (1) Full and

partially empty (“used”) feeding units were ob-tamed from our neonatal intensive care unit and analyzed for calcium and phosphorus. The formula

in use at the time was Similac Special Care (Ross

Laboratories, Columbus, OH). (2) Under standard-ized conditions in the laboratory we determined

changes in concentrations of calcium and

phospho-flis due to “settling” over a ten-minute interval

using three commercially available formulas de-signed for feeding of small premature infants. (3)

The same three formulas were studied under

sim-ulated syringe-pump feeding circumstances, and (4) under simulated bolus gavage feeding

circumstan-ces.

MATERIALS

AND METHODS

Received for publication June 24, 1982; accepted Sept 2, 1982.

Reprint requests to (S.J.F.) Department of Pediatrics,

Univer-sity of Iowa Hospital, Iowa City, IA 52242.

American Academy of Pediatrics.

Formula

Obtained

from Premature

Nursery

Six full (120-mL) feeding units and 12 used units

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38 FORMULAS

FOR

PREMATURE

INFANTS

to 91 mL) were obtained from our neonatal inten-sive care unit during several nursing shifts. In the laboratory, each feeding unit was shaken vigorously

until no sediment was visible and the contents of

the unit were transferred to a beaker and stirred

for five minutes with a Teflon-coated magnetic stirrer. While the stirring continued, aliquots were removed, dried at 100#{176}C,and ashed for 24 hours at

525#{176}C.Calcium concentration was determined by atomic absorption spectrophotometry, and

phos-phorus concentration was measured by a modifi-cation of the method of Fiske and Subbarow.3

Rate of Settling

of Calcium

Formula from each of two ready-to-feed 120-mL

feeding units was mixed well and poured into a

beaker. The formula was stirred with a Teflon-coated magnetic stirrer for five minutes. At the end

of the five-minute period, while stirring continued,

a 5-mL aliquot of formula was removed for analysis and a 25-mL aliquot was placed in each of three

graduated cylinders. The height of the column of

formula in the cylinders was 15 cm and internal diameter of the cylinder was 1.5 cm. After one

minute, a 5-mL aliquot of formula was removed

from the top of the first cylinder. Formula from the

second cylinder was sampled in a similar manner after five minutes and that in the third cylinder was sampled after ten minutes. The experiment

was repeated three times with each of three

for-mulas: Similac Special Care, Enfamil Premature (Mead Johnson Company, Evansville, IN), and SMA Preemie (Wyeth Laboratories, Philadelphia).

Simulated

Syringe-Pump

Feeding

Feeding units (120 mL) were shaken by hand for

one minute and left undisturbed for one minute. At

the end of the one-minute period, a 5-mL aliquot

of formula was removed for the analysis from the

upper 2 cm of fluid in the feeding unit (prepump sample) and 40 mL of formula was drawn into a syringe. To the syringe was attached a 122-cm

length of polyvinyl chloride pump tubing (Extra-corporeal Medical Specialities, King of Prussia, PA) and this was connected to a 40-cm length of 5

French polyvinyl chloride tubing (Argyle Feeding

Tube, Argyle Laboratories, St Louis). The tubing was filled with formula from the syringe, and excess

formula was discarded so that the final volume in the syringe was 30 mL. The syringe was placed in a horizontal position and by means of a peristaltic pump the formula was infused over a period of

three hours into a plastic collecting beaker covered

with plastic wrap to prevent evaporation. At the

end ofthe infusion period, the formula in the beaker

was stirred and an aliquot (postpump sample) was

taken for determination of calcium and phosphorus. The procedure was repeated three times with each of the three formulas.

Simulated

Bolus Feeding

The barrel of a 30-mL syringe attached to a

40-cm length of 5 French polyvinyl chloride tubing

(Argyle) was fixed in a vertical position with the

tip of the syringe 38 cm above a table. The free end of the tubing was placed in a beaker on the table. Feeding units were shaken by hand for approxi-mately one minute and 10 mL was poured into a

container for analysis (predelivery sample). Thirty milliliters of formula was immediately poured into

the barrel of the syringe and allowed to drain by gravity into the beaker. Delivery time was recorded. When the syringe was empty and formula was present only in the distal portion of tubing, this

formula was flushed with 2 mL of air into the

beaker. The formula in the beaker was then stirred and an aliquot (postdelivery sample) was taken for

determination of calcium and phosphorus.

RESULTS

Formula

Obtained

from Premature

Nursery

Concentrations of calcium and phosphorus in full bottles of ready-to-feed Similac Special Care

ob-tamed from the neonatal intensive care unit were greater than label claims and demonstrated

rela-tively little variability from bottle to bottle (Table 1). Concentrations in the partly full (used) bottles

were considerably greater and much more variable than in the full bottles. When the quantity of calcium remaining in a used bottle was subtracted

from the mean content of the six full bottles and the result was divided by the difference in volume between the full bottle (120 mL) and the used bottle, the concentration in the volume presumed

to have been fed was found to be substantially less

than that of the full bottle or the label declaration.

This observation pertained to phosphorus as well as calcium.

Rate of Settling

of Calcium

As may be seen from Table 2, concentrations of

calcium in formula sampled during stirring were greater than the label declaration. Concentrations

of calcium sampled from the top of a cylinder demonstrated a substantial decrease with time for

Similac Special Care (ten-minute value 70% of

value during stirring) but only a slight decrease

with time for Enfamil Premature and SMA Pree-mie.

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Simulated

Syringe-Pump

Feeding

In the trials with simulated syringe-pump feed-ings, the range of concentrations of calcium (and

phosphorus) in the prepump sample was variable

for Similac Special Care but not for the other two

formulas (Table 3). Concentration of calcium in the postpump sample was 59% of that in the prepump

sample for Similac Special Care, 75% for Enfamil

Premature, and 68% for SMA Preemie. In the case

of phosphorus, the postpump concentrations of the

three formulas were 67%, 94%, and 102%,

respec-tively, of the prepump concentrations. Postpump

TABLE 1. Bottle

Obtained from Pre s of mat

Formula (Similac Special Care) ure Nursery

No. of Mean Concentration

Bottles ± SD (mg/L)

Calcium*

Full 6 1,632

±

29

Used 12 2,452 ± 436

Presumed fedt 850 ± 354

Phosphorus*

Full 6 803 ± 16

Used 12 1,152 ± 163

Presumed fedt 480

±

139

* Label claims 1,440 mg/L for calcium and 720 mg/L for

phosphorus.

t Calculated by subtracting quantity of calcium or phos-phorus in used bottle from corresponding mean value for

quantity in full bottle and dividing result by volume of

formula in full bottle minus volume in used bottle.

concentrations of phosphorus were more variable for Similac Special Care than for the other two

formulas.

Repetition of simulated syringe pump feeding

with the syringe in a vertical position (tip pointing downward), rather than horizontal position, yielded

results similar to those in Table 3 and these results are not presented.

Simulated

Bolus Feeding

Results of simulated bolus feeding are presented

in Table 4. It was of some interest that the flow characteristics of the formulas were different, with shorter delivery times for Similac Special Care and

for SMA Preemie than for Enfamil Premature. In contrast to the observations with simulated syringe pump feeding, postdelivery concentrations

of calcium were not greatly different from predeliv-ery concentrations. The postdelivery concentration was 91% of the predelivery concentration with

Sim-ilac Special Care, 95% with Enfamil Premature,

and 100% with SMA Preemie. Corresponding

val-ues for phosphorus concentrations were 92%, 102%,

and 100%.

COMMENT

In recent years a great deal of effort has been devoted to devising formulas that will meet the

nutritional needs of small premature infants. Thus

TABLE 2. Concentration ofCalcium in Formula Sampled from Top of Cylinder

Formula Concentrati on of Cal cium (mg/L)

Label Claim

During Stirring

Time in Cylinder .

1 mm 5 mm. 10 mm.

Similac Special Care

Enfamil Premature SMA Preemie

1,440

950

750

1,613

995

907

1,405

946

907

1,164

936

906

1,126

940

895

TABLE 3. Calcium and Phosphorus Concentrations in Formulas Delivered by

Syringe-Pump

Similac Special Care Enfamil Premature SMA Preemie

Calcium (mg/L) Prepump

Mean 1,261 1,046 990

Range* 1,041-1,511 1,023-1,058 984-995

Postpump

Mean 749 786 676

Range 707-802 779-793 672-682

Phosphorus (mg/L)

Prepump

Mean 672 537 411

Range 652-773 524-545 418-437

Postpump

Mean 449 503 419

Range 427-474 497-508 414-423

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40 FORMULAS FOR PREMATURE INFANTS

TABLE 4. Calcium and Phosphorus Concentrations in Formulas After Bolus Delivery*

Similac Special Care Enfamil Premature SMA Preemie Calcium (mg/L)

Predelivery

Mean

Range Postdelivery Mean Range

Phosphorus (mg/L) Predelivery

Mean Range

Postdelivery

Mean Range

1,427 1,389-1,500

1,018 1,015-1,023

953 948-963

1,296 1,248-1,369

972 960-982

951

939-960

749

721-764

525

520-536

422

419-423

688

658-721

538 520-559

420 412-428

aDelivery time for three formulas was: Similac Special Care, 8, 9, and 9 minutes; Enfamil

Premature, 18, 18, and 19 minutes; SMA Preemie, 11, 11, and 12 minutes.

far, most of the attention seems to have been given to matching formula composition with the

pre-sumed nutrient requirements of the infant. Less attention has been paid to delivery of these

nu-trients to the infant under practical circumstances

of feeding.

Although label instructions for Similac Special

Care and Enfamil Premature formulas indicate that they should be shaken before use, in our neonatal

intensive care unit concentrations of calcium and phosphorus in Similac Special Care were apprecia-bly less in formula withdrawn from the bottle for

delivery to the infant than in the full bottles (Table

1). Enfamil Premature and SMA Preemie appear to be more stable in this respect than is Similac Special Care (Table 2).

Although we have restricted our report to consid-eration of concentrations of calcium and

phospho-rus, it is evident that other formula components may also be involved in discrepancies between what

is

present in the bottle

and

what is delivered to the infant.

The loss ofcalcium during syringe-pump delivery

of premature infant formulas is appreciable (Table 3), and the advisability of this method of delivery

is questionable. Simulated gavage bolus feeding with delivery of formula by gravity does not appear to be associated with major losses of calcium or phosphorus.

The problems identified here must be considered in proper perspective. Nutritional management of

small premature infants is a new field. It has placed

new demands on formula manufacturers and it can be anticipated that there will be problems that will need to be solved. Testing of infant formulas is clearly a responsibility of the manufacturers, but it is also a responsibility of pediatricians. It is not enough to know what is in the bottle; we must know what is delivered to the infant. Vigorous shaking of the bottle immediately before withdrawing the amount to be fed to the infant appears to be essen-tial, at least with some formulas. We must develop methods of supervision that will assure consistent feeding procedures in our nurseries so that concen-trations of nutrients delivered to the infant

are

at least predictable. Meanwhile, the manufacturers

must continue their efforts to produce formulas in

which the suspension of nutrients will be stable

regardless of the method chosen for delivery of

formula to the infant.

ACKNOWLEDGMENT

This work was supported in part by US Public Health

Service grant 1PO1HD 07578.

REFERENCES

1. Ross Laboratories: Similac Special Care Infant Formula. Columbus, OH, Ross Laboratories, 1980, p 35

2. Antonson DL, Smith JL, Nelson RD Jr, et al: Vitamin and mineral content of a low-birth-weight infant formula during continuous enthral feeding, abstracted. JPEN 1981; 5:563 3. Fiske CH, Subbarow Y: The colorimetric determination of

phosphorus. J Biol Chem 1925; 66:375

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1983;72;37

Pediatrics

Jatinder Bhatia and Samuel J. Fomon