DOI: 10.1542/peds.2013-0420; originally published online April 29, 2013; 2013;131;e1676Pediatrics

Steven A. Abrams and the COMMITTEE ON NUTRITIONCalcium and Vitamin D Requirements of Enterally Fed Preterm Infants

  

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CLINICAL REPORT

Calcium and Vitamin D Requirements of Enterally FedPreterm Infants

abstractBone health is a critical concern in managing preterm infants. Keynutrients of importance are calcium, vitamin D, and phosphorus. Al-though human milk is critical for the health of preterm infants, itis low in these nutrients relative to the needs of the infants duringgrowth. Strategies should be in place to fortify human milk for preterminfants with birth weight <1800 to 2000 g and to ensure adequatemineral intake during hospitalization and after hospital discharge.Biochemical monitoring of very low birth weight infants should beperformed during their hospitalization. Vitamin D should be providedat 200 to 400 IU/day both during hospitalization and after dischargefrom the hospital. Infants with radiologic evidence of rickets shouldhave efforts made to maximize calcium and phosphorus intake byusing available commercial products and, if needed, direct supple-mentation with these minerals. Pediatrics 2013;131:e1676–e1683

In 2011, the Institute of Medicine (IOM) released dietary guidelines forcalcium and vitamin D intakes for all age groups.1 However, no intakerecommendations were made specifically for preterm infants, be-cause they were considered a special population and did not fit withinthe guidelines for dietary reference intakes developed by the IOM.Preterm infants have unique bone mineral requirements that may notbe assumed to be similar to those of full-term newborn infants.Previous statements in the United States have limited their recom-mendations to full-term infants.2,3 However, The European Society forPediatric Gastroenterology, Hepatology, and Nutrition has recentlydescribed enteral nutrition recommendations for preterm infants.4,5

Data on in utero bone mineralization rates are limited. Cadaver studies,beginning with the classic work of Widdowson et al,6 generally supportan in utero accretion of calcium during the third trimester of 100 to130 mg/kg per day, peaking between 32 and 36 weeks’ gestation.Phosphorus accretion is approximately half the accretion of calciumthroughout gestation. Remarkably, more recent reevaluation of thesedata by using modern body composition techniques7 provided valuessimilar to those developed by Widdowson et al.6

In full-term infants, there is a strong correlation between maternal andinfant cord blood 25-hydroxyvitamin D (25-OH-D) concentrations, al-though the cord blood concentration is less than the maternal con-centration.8 A substantial proportion of pregnant women, especially

Steven A. Abrams, MD and the COMMITTEE ON NUTRITION

KEY WORDSpreterm infants, human milk, vitamin D, calcium, phosphorous,nutrient intake

ABBREVIATIONS25-OH-D—25-hydroxyvitamin DAPA—alkaline phosphatase activityIOM—Institute of MedicineVLBW—very low birth weight

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authorshave filed conflict of interest statements with the AmericanAcademy of Pediatrics. Any conflicts have been resolved througha process approved by the Board of Directors. The AmericanAcademy of Pediatrics has neither solicited nor accepted anycommercial involvement in the development of the content ofthis publication.

The guidance in this report does not indicate an exclusivecourse of treatment or serve as a standard of medical care.Variations, taking into account individual circumstances, may beappropriate.

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African American and Hispanic wo-men in the United States and Europe,have 25-OH-D concentrations <20 ng/mL (50 nmol/L),9 a value set for thebasis of the Recommended DietaryAllowance.1 However, in utero, skeletalmineralization is primarily indepen-dent of maternal vitamin D status,making the clinical significance of 25-OH-D concentrations during preg-nancy unclear.10,11

EFFECTS OF PRETERM BIRTH ONMINERAL METABOLISM

Population-based studies of ricketsamong preterm infants are lacking;therefore, the frequency is not knownor reliably estimated. Approximately10% to 20% of hospitalized infants withbirth weight <1000 g have radio-graphically defined rickets (meta-physeal changes) despite currentnutritional practices.12 This frequencyis much lower than the 50% incidencein this population described beforefortification of human milk and theuse of preterm high mineral contain-ing formulas were routine.13 Onechallenge in identifying the prevalenceof rickets is the confusion related toterminology. Rickets is defined byradiographic findings, not by anybiochemical findings. Standard radio-graphic definitions of rickets areused. Poorly defined terms, such asosteopenia or biochemical rickets, areoften used in the literature inter-changeably with radiographically de-fined rickets. Rickets is not widelyreported in preterm infants with birthweight >1500 g unless there arehealth issues severely limiting enteralnutrition.

Limited long-term studies of bonemineralization exist in former preterminfants. In general, these studies donot demonstrate significant long-termnegative effects on bone health inpreterm infants who demonstratecatch-up growth occurring during the

first 2 years after birth.14 A singlestudy demonstrated a small decreasein young adolescent height when thealkaline phosphatase concentrationexceeded 1200 IU/L.15 That study waslimited because of the use of formulascontaining relatively low amounts ofenergy and protein. The preterminfants had reduced adult height andlow lumbar spine bone mineral den-sity compared with population refer-ence data, and the deficits weregreatest in those with birth weight<1200 g and those born small forgestational age.16

One study indicated a significant de-crease in height during the prepubertalyears of former very low birth weight(VLBW) infants exposed to dexametha-sone for the treatment of broncho-pulmonary dysplasia.17 In addition, Dalzielet al18 demonstrated that prenatalsteroid use did not affect peak bonemass. It appeared that slower fetalgrowth, rather than preterm birth,predicted lower peak bone mass. Thelower peak bone mass in those bornsmall for gestational age was ap-propriate for their adult height.

IN-HOSPITAL ASSESSMENT ANDMANAGEMENT

A summary of high-risk factors for thedevelopment of rickets is shown in Ta-ble 1. It is common medical practice toassess VLBW infants biochemically forevidence of abnormalities of bone-related parameters, especially the se-rum alkaline phosphatase activity (APA)and serum phosphorus concentration,and subsequently to evaluate them

radiographically if these evaluationssuggest a high risk of developing rick-ets. No absolute values for a low serumphosphorus concentration exist, withvalues below ∼4 mg/dL often, but notalways, being considered associatedwith low phosphorus status. On theother hand, there is little, if any, evi-dence supporting measuring bonemineral-related laboratory values ininfants with birth weight >1500 g un-less infants are unable to achieve fullfeeds or have other conditions, such assevere cholestasis or renal disease,placing them at risk for bone loss.

Typically, a very high serum APA(>1000 IU/L) is suggestive, but notproof, of rickets. In 1 study, values>1000 IU/L were associated with anincidence of radiologic rickets of∼50% to 60%,12 although some caseswere also seen with serum APA in therange of 800 to 1000 IU/L. Elevations ofserum APA and clinical rickets areuncommon in the first 4 weeks afterbirth at any gestational age. There-fore, screening the serum APA andserum phosphorus at 4 to 6 weeksafter birth in VLBW infants followed bybiweekly monitoring is appropriate.Typically, the APA will peak at 400 to800 IU/L and then decrease in VLBWinfants who do not develop rickets. Inthis circumstance, clinical experienceindicates that if the infant has APAvalues in this range and has achievedfull feeds of human milk with a min-eral-containing fortifier or formuladesigned for preterm infants, there isminimal, if any, risk of developingrickets, and measurement of APA canusually be stopped.

TABLE 1 High-Risk Criteria for Rickets in Preterm Infants

Born at <27 weeks’ gestationBirth weight <1000 gLong-term parenteral nutrition (eg, >4 to 5 weeks)Severe bronchopulmonary dysplasia with use of loop diuretics (eg, furosemide) and fluid restrictionLong-term steroid useHistory of necrotizing enterocolitisFailure to tolerate formulas or human milk fortifiers with high mineral content

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Other markers of bone status includeserum osteocalcin concentration andbone-specific APA; the latter has beenconsidered of value in cases of cho-lestasis to help identify the bone-related fraction from total APA. Atpresent, there are no data demon-strating clinical utility of measuringserum osteocalcin concentration andbone-specific APA in neonates, andnormal values do not exist for preterminfants. Backstrom et al19 found noadditional information gained frommeasurement of bone-specific APAcompared with total APA in preterminfants. It is, therefore, unlikely thatthese laboratory values, which arepoorly standardized in neonates andexpensive to obtain, will be a sub-stantial aspect of clinical decision-making in an individual infant.

The ultimate diagnosis of ricketsrequires a radiographic evaluation, usu-ally of either the wrist or the knee.Chest radiographs revealing abnor-malities of the ribs may be suggestiveof rickets, but a confirmatory long-bone film of the wrist or knee shouldbe obtained to confirm the diagnosis.The radiologist should categorize theinfant as likely having or not havingrickets. Nonspecific terms, such as“osteopenia” or “washed out bones,”have little clinical meaning. Ricketsin preterm infants appears radio-graphically similar to rickets in olderinfants and should be characterizedas such. The use of either bone ul-trasonography or, before discharge,dual energy radiographic absorpti-ometry to evaluate bone status maybe considered. However, the lack ofdata related to normal values in former

preterm infants indicate that theseare performed primarily for researchpurposes. Current data do not sup-port routine use of any of thesetechniques for preterm infants, in-cluding those with abnormal radio-graphic findings.

CALCIUM AND PHOSPHORUSINTAKE AND ABSORPTION

Rickets in preterm infants is almostalways attributable to decreased totalabsorbed calcium and phosphorus.Decreases in absorption can resultfrom either low intake or low absorp-tion efficiency.20 Several studies haverevealed that, in healthy preterminfants, calcium absorption averages∼50% to 60% of intake,21–24 which issimilar to that of breastfed full-terminfants.1 In contrast, phosphorus ab-sorption is typically 80% to 90% ofdietary intake.23

Unfortified human milk, parenteralnutrition, and infant formulas designedfor full-term infants, including aminoacid-based and soy-based formulas,do not contain enough calcium andphosphorus to fully meet the needs forbone mineralization in preterm infants.Even at very high rates of absorption(eg, 80% or more), the calcium andphosphorus intakes from unfortifiedhuman milk or formulas not intendedfor preterm infants would be a limitingfactor in bone growth.20 Table 2 pro-vides sample numbers for the intake,absorption, and retention of calcium ina VLBW infant fed fortified human milkor a formula for preterm infants typi-cally used in the United States com-pared with unfortified human milk.

Although most attention is focused oncalcium intake, the very high urinarycalcium concentrations found inpreterm infants fed unfortified humanmilk suggests that phosphorus de-ficiency is at least as important, if notmore important, than calcium defi-ciency in the etiology of this disease.4,25,26

Some cases of hypercalcemia havebeen reported in preterm infants fedunfortified human milk as a resultof the very low phosphorus contentand resultant relative excess ofcalcium.27

VITAMIN D IN PRETERM INFANTS

Vitamin D enhances the absorption ofcalcium, and in general, calcium ab-sorption efficiency is greater in peoplewhose calcium intake is low and inwhom vitamin D-dependent absorp-tion increases. However, in preterminfants, the calcium absorption frac-tion appears to be relatively constantacross a wide range of intakes. It hasbeen suggested21 that most calciumabsorption may not be vitamin D de-pendent in preterm infants in the firstmonth after birth but rather occursprimarily via a passive, paracellularabsorption. This hypothesis is unproven,however, and the exact timing andproportion of vitamin D-dependent ab-sorption of calcium and phosphorusin preterm infants is unknown. Someolder data suggest an effect of high-dose vitamin D on calcium absorp-tion, but these data have not beenverified by using isotopic techniquesnor performed on groups of infantsusing currently available high mineral-containing diets.5

TABLE 2 Approximate Calcium Balance in a Typical Infant Receiving 120 kcal/kg Per Day Intake

Calcium Concentration(mg/dL)

Intake (mg/kg perday)

Absorption % Total Absorption (mg/kg perday)

Approximate Retention(mg/kg per day)

Human milka 25 38 60 25 15–20Preterm formula/fortified human milk 145 220 50–60 120–130 100–120a Human milk assumed to be 20 kcal/oz, and preterm formula and fortified human milk assumed to be 24 kcal/oz.

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It is accepted that the best availablemarker of vitamin D exposure and vi-tamin D status is the serum 25-OH-Dconcentration.1 Although the active formof vitamin D is 1,25 dihydroxyvitaminD, its serum value is not closely as-sociated with overall outcomes or vi-tamin D exposure.1 Therefore, excludingrare cases of severe renal diseaseor suspicion of vitamin D-resistantrickets, vitamin D status in preterminfants as well as older infantsshould be monitored exclusively bymeasuring the serum 25-OH-D con-centration, not the 1,25 dihydrox-yvitamin D concentration.

Data on the relationship between vi-tamin D intake and serum 25-OH-D inpreterm infants are extremely limited.Backstrom et al28 found that an intakeof 200 IU/kg in the first 6 weeks afterbirth led to mean 25-OH-D concen-trations of ∼50 nmol/L and 80 nmol/Lby 12 weeks of age (to convert fromnmol/L to ng/mL, divide by 2.5). Simi-lar results were found by Koo et al.29

Most full-term infants achieve 25-OH-Dconcentrations of more than 50 nmol/Lwith vitamin D intakes of 400 IU/day.1

However, it is difficult to extrapolatedata from full-term infants to pre-term infants, especially those whoare hospitalized, in whom UV B-mediatedvitamin D formation is likely to beminimal and in whom fat mass, inwhich vitamin D and its metabolitesare stored, is minimal. A recent studyrevealed a high incidence of verylow 25-OH-D concentrations in thecord blood of Arab preterm infantsin the Middle East, likely attribut-able to very low maternal vitamin Dstatus.30

CARE OF VLBW INFANTS RELATEDTO BONE HEALTH

Calcium, Phosphorus, and Vitamin D

The basic approach to prevention ofrickets in preterm infants is the useof diets containing high amounts ofminerals. In almost all infants withbirth weight <1800 to 2000 g, re-gardless of gestational age, it is rec-ommended to use formulas designedfor preterm infants or human milksupplemented with fortifiers designedfor use in this population. Bone min-eral content is low in infants who aresmall for gestational age, leading tothe recommendation to use these pro-ducts on the basis of weight ratherthan gestational age.31 Further re-search is needed, however, to clarifywhether this is appropriate practicefor all preterm infants with birthweight <2000 g.

In the United States, fortified humanmilk and formulas designed for pre-term infants provide calcium intakesof ∼180 to 220 mg/kg per day andapproximately half that amount ofphosphorus (Table 3). Two widely usedsets of recommendations in theUnited States from Tsang et al32 andKlein et al33 (Table 4) are consistentwith these intakes, and for calcium, it

is reasonable to adopt the lower valueand the higher value of the 2 asa range for recommended intakes (ie,150 to 220 mg/kg per day). For phos-phorus, the lower value of 60 mg/kgper day would lead to a 2:1 ratio orhigher with the recommended cal-cium intakes, and thus, a minimumlower intake level of 75 mg/kg per dayis recommended to provide a calcium-to-phosphorous ratio less than 2:1. Althoughno optimal calcium-to-phosphorous ratiois identified, generally a 1.5 to 1.7:1ratio may be optimal for preterminfants.34 For an upper intake recom-mendation for phosphorous, the highervalue of 140 mg/kg per day is sug-gested. As noted later, phosphorus de-ficiency may occur in some preterminfants, and thus, a higher upper levelrecommendation is provided.

Pending further research, using thefull-term infant vitamin D intake rec-ommendation of 400 IU/day is appro-priate for preterm infants born withbirth weight >1500 g. Potential risksrelated to high 25-OH-D concentrationsare unknown, and the establishedupper tolerable intake of 1000 IU/dayfor healthy full-term infants may beconsidered an upper intake for pre-term infants as well.

TABLE 3 Intakes of Calcium, Phosphorus, and Vitamin D From Various Enteral Nutrition Feedings at 160 mL/kg Per Day Used in the United States

Unfortified Human Milka (20 kcal/oz) Fortified Human Milka (24 kcal/oz) Preterm Formula (24 kcal/oz) Transitional Formula (22 kcal/oz)

Calcium (mg/kg) 37 184–218 210–234 125–144Phosphorus (mg/kg) 21 102–125 107–130 74–80Vitamin D (IU/day)b 2.4 283–379 290–468 125–127a Human milk data based on mature human milk.38b Based on an infant weighing 1500 g.

TABLE 4 Recommendations for Enteral Nutrition for VLBW Infants

Calcium, mg/kgper day

Phosphorus, mg/kg per day Vitamin D, IU/day

Tsang et al (2005)32 100–220 60–140 150–400a

Klein (2002)33 150–220 100–130 135–338b

Agostonic (2010)5 120–140 65–90 800–1000This AAP clinical report 150–220 75–140 200–400a Text says “aim to deliver 400 IU/daily.”b 90–125 IU/kg (total amount shown is for 1.5-kg infant).c Reflects European recommendations.

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For VLBW infants, few data are avail-able. Their smaller size may lead toa lower need for vitamin D to achieveadequate 25-OH-D concentrations,28,29

but further data are needed on thisrelationship. On the basis of limiteddata, a vitamin D intake of 200 to 400IU/day for VLBW infants is recom-mended. This intake should be in-creased to 400 IU/day when weightexceeds ∼1500 g and the infant istolerating full enteral nutrition. Be-cause this would require supple-mental vitamins being added inaddition to available human milkfortifiers, some may wish to wait untilweight is closer to 2000 g to providea full 400 IU/day because of concernabout the osmolarity of vitamin sup-plements. These intake recommenda-tions should be subject to clinical trialswith rickets and fractures as clinicaloutcomes.

Comparisons With OtherRecommendations

In Europe, a considerably lower targetfor calcium and phosphorus intake iscommon (Table 4). European guide-lines generally suggest higher intakesof vitamin D of 800 to 1000 IU/day,4,5

but there is no direct comparison ofthis approach compared with the ap-proach used in the United States. Al-though this vitamin D intake is likelysafe and is within the tolerable upperintake limit of the IOM for full-terminfants,1 no data are available forgroups of VLBW infants and especiallyinfants with birth weight <1000 g toassess the safety of providing thesevitamin D intakes, which, on a body-weight basis may be 5 to 10 times theamount recommended for full-termneonates.

As noted by the IOM report,1 thereare no clinical outcome data to sup-port routine measurement of vi-tamin D concentrations in preterminfants. Infants with cholestasis, other

malabsorptive disorders, or renaldisease should be considered for as-sessment, targeting a 25-OH-D con-centration >50 ng/mL.1,3 Preterminfants with radiologic evidence ofrickets or high APA (>800 IU/L) areoften provided the tolerable upperintake total of 1000 IU/day of vitaminD; however, no evidence-based dataare available to support any specificbenefit to this practice.

Research in a small number of pre-term infants has suggested improve-ment in bone mineral content with anexercise or physical therapy programfor preterm infants. No studies havedemonstrated a decrease in rickets orfractures with such a program. Carewould need to be taken because of thefragile nature of the preterm infants’bones. At present, this therapy re-quires further clinical investigationbefore it can be recommended forroutine use.35

OTHER MANAGEMENT ISSUES

Despite the use of feedings with highmineral content, some infants maydevelop rickets. The management ofinfants who have rickets and remaindependent on intravenous nutrition isbeyond the scope of this review, butin general, maximizing calcium andphosphorus intake from intravenousnutrition while minimizing factors thatlead to mineral loss (steroids, some

diuretics) is advised. Managementapproaches for infants who are fedenterally are described in Table 5.These principles have not been testedin controlled trials but reflect expertopinion related to mineral intake andmetabolism.

Whether minerals should be addeddirectly to human milk separate fromthe use of human milk fortifiers iscontroversial. This practice has beenadvocated, combined with monitoringof urinary calcium and phosphorus.36

Although shown to be effective insome small studies, adding mineralsdirectly to human milk, especially inthe absence of using human milkfortifiers, is not widely performed inthe United States for routine man-agement of VLWB infants, becauseindividually supplementing these min-erals does not also provide the extraprotein and other nutrients neededfor growth.

However, in some infants who haveevidence of rickets, the need for fluidrestriction or inability to tolerate for-mula designed for preterm infants orhuman milk fortifier may lead to theneed to directly supplement calciumand phosphorus. Optimal or safestforms and doses of calcium andphosphorus to add directly to the dietof preterm infants are unknown. Ingeneral, most widely used is calciumglubionate, a liquid form of calcium

TABLE 5 Management Approach for Enterally Fed Preterm Infants With Radiologic Evidence ofRickets

1. Maximize nutrient intake. Consider increasing human milk fortifier and/or feeding volume of pretermformula, as clinically indicated. If unable to tolerate human milk fortifier or preterm formula, then willlikely need elemental minerals added as described below.

2. If no further increases in these can be made, add elemental calcium and phosphorus as tolerated.Usually beginning at 20 mg/kg per day of elemental calcium and 10–20 mg/kg per day elementalphosphorus and increasing, as tolerated, usually to a maximum of 70–80 mg/kg per day of elementalcalcium and 40–50 mg/kg per day elemental phosphorus.

3. Evaluate cholestasis and vitamin D status. May consider measuring 25-OH-D concentration, targetingserum 25-OH-D concentration of >20 ng/mL (50 nmol/L).

4. Follow serum phosphorus concentration and serum APA weekly or biweekly.5. Recheck radiographs for evidence of rickets at 5- to 6-week intervals until resolved.6. Advise caregiving team to be cautious in handling of infant.7. Limit use of steroids and furosemide, as clinically feasible.

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containing 23 mg/mL of elemental cal-cium for oral supplementation. Whenneeded, starting doses of 20 mg/kg perday of elemental calcium may be used,increasing slowly to a maximum ofapproximately 60 to 70 mg/kg per dayof elemental calcium. Data specific tothe use of calcium carbonate are notavailable, but the high pH of the neo-natal intestine may make calciumcarbonate less than ideal. Calciumgluconate (9.3 mg/mL elemental cal-cium) may also be used. Salts thatcontain both calcium and phosphorusare also used.23 For example, calciumtribasic phosphate contains 0.39 mgcalcium and 0.28 mg of phosphorusper milligram of powder, althoughcalcium tribasic phosphate must becompounded as a liquid for adminis-tration to infants.

A special population is older preterminfants who develop a low serumphosphorus concentration, often in con-junction with a serum APA <500 IU/L.The specific cause of this low serumphosphorus concentration is unknown,but it is likely partly related to the useof phosphorus in nonbone tissue, suchas muscle. The exact serum phospho-rus concentration for which evidencedemonstrates a need to supplementphosphorus without calcium is notknown, but a serum concentration be-low ∼4.0 mg/dL, especially if presentfor more than 1 to 2 weeks, suggestsconsideration of adding phosphorusdirectly.

An ideal oral form of phosphorus foruse in preterm infants does not exist.Administering the intravenous pre-parations orally can be considered,because they are lower in osmolar-ity than are commercially availablephosphorus-containing liquids. Forexample, potassium phosphate pro-vides 31 mg of elemental phosphorusper millimole, and a dose of 10 to 20mg/kg per day of elemental phos-phorus is reasonable and will likely

resolve hypophosphatemia in mostpreterm infants.

Transitioning Off High-MineralContaining Products

Decreasing mineral intake, by eitherusing less human milk fortifier ordiscontinuing the use of formulas forpreterm infants, is often begun ata body weight of ∼2000 g. Delayingthe switch to transitional formulasand continuing the use of formuladesigned for preterm infants or hu-man milk fortifier should be consid-ered for infants on fluid restriction,especially <150 mL/kg per day, or forinfants with a prolonged course ofparenteral nutrition and a persistentelevation of serum APA (ie, >800 IU/L).Use of formula designed for preterminfants would likely be safe until bodyweight of at least 3000 g is reached,after which some concern might bepresent about vitamins or minerals(especially vitamin A) exceeding theestablished tolerable upper intakelevels.37 No clinical evidence of vitaminA toxicity exists, although for intakesslightly above the upper level, a risk-benefit assessment may need to beperformed regarding use of formulasdesigned for preterm infants in somelarger infants.

Preterm infants who do not toleratecow milk protein or lactose-containingproducts represent a special circum-stance. Amino acid-based, soy-based,and other specialized infant formulasgenerally have higher levels of min-erals than do routine infant formulas,but the bioavailability of these miner-als, especially in high-risk infants suchas those with a history of feedingintolerance or intestinal failure, isuncertain. As such, biochemical mon-itoring may need to be continued foran extended period of time, and insome cases, direct supplementationwith added minerals should be con-sidered.

POSTDISCHARGE MANAGEMENT OFPRETERM INFANTS

VLBW infants who are discharged ex-clusively breastfeeding will often dowell from a bone mineral perspective;however, they may be at risk for a veryhigh serum APA after discharge. Nospecific research or clinical studieshave addressed this issue. A mea-surement of serum APA 2 to 4 weeksafter discharge is appropriate in ex-clusively breastfed former VLBW in-fants, with careful follow-up for values>800 IU/L and consideration of directmineral supplementation if serum APAexceeds 1000 IU/L. Parents may alsochoose to provide some feedings perday of a higher mineral-containingformula (such as transitional formu-las at 22 kcal/oz) to infants with birthweight <1500 g after hospital dis-charge. Transitional formulas contain22 kcal/oz, and their nutrient contentsare between those used for full-terminfants and those used for preterminfants.

No data are available to define thelength of time exclusively breastfedinfants receiving such formula sup-plements or transitional formula needto continue them. This decision is oftendriven by growth in weight, head cir-cumference, and length, not by bonemineral concerns. Infants consumingless than ∼800 mL of currently mar-keted transitional formula daily afterdischarge from the hospital will re-ceive <400 IU/day of vitamin D forseveral weeks to several months. It isreasonable to supplement these in-fants with a small amount of vitamin D(often 200 to 400 IU/day) to ensurea total intake of at least 400 IU/day.

From a bone mineral perspective,infants with birth weight 1500 to 2000g will generally do well with exclusivebreastfeeding or routine infant for-mula after discharge from the hospi-tal. Some pediatricians choose to usea transitional infant formula after

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infants reach ∼34 weeks’ postmen-strual age or ∼1800 to 2000 g bodyweight.

There are no specific studies related tothe bone mineral needs of infants whoare “late preterm” (ie, 34–36 weeks’gestation and >2000 g at birth).However, there are no clinical reportsof mineral deficiency or rickets in thispopulation whether breastfed exclu-sively or fed formula designed forpreterm infants, as long as long-termvitamin D status is adequate. There-fore, it is likely that late preterminfants do not generally need specialmanagement related to bone mineralsafter discharge from the hospital.Breastfed preterm infants who are athome should receive 400 IU/day of vi-tamin D. Formula-fed preterm infantsreceiving formulas designed for full-term infants would generally not ach-ieve an intake of 400 IU/day of vitaminD until consuming ∼800 mL of formuladaily, depending on the formula. Pro-viding these infants with an additional200 to 400 IU/day may be considered,but there are no data indicating anyclinical benefit to this practice.

Small-for-gestational-age infants at ornear term, such as is common in manyglobal settings, may usually be pro-vided minerals in the same way aslarger infants of the same gestationalage. Such infants should be monitoredcarefully for growth, and an adequateintake of vitamin D should be ensured.

SUMMARY

1. Preterm infants, especially those<27 weeks’ gestation or with birthweight <1000 g with a history ofmultiple medical problems, are athigh-risk of rickets.

2. Routine evaluation of bone mineralstatus by using biochemical testingis indicated for infants with birthweight <1500 g but not those withbirth weight >1500 g. Biochemicaltesting should usually be started 4to 5 weeks after birth.

3. Serum APA >800 to 1000 IU/L orclinical evidence of fractures shouldlead to a radiographic evaluationfor rickets and management fo-cusing on maximizing calcium andphosphorus intake and minimizingfactors leading to bone mineralloss.

4. A persistent serum phosphorusconcentration less than ∼4.0 mg/dLshould be followed, and consider-ation should be given for phospho-rus supplementation.

5. Routine management of preterminfants, especially those with birthweight <1800 to 2000 g, should in-clude human milk fortified withminerals or formulas designedfor preterm infants (see Table 4for details).

6. At the time of discharge from thehospital, VLBW infants will often be

provided higher intakes of miner-als than are provided by hu-man milk or formulas intendedfor term infants through the useof transitional formulas. If exclu-sively breastfed, a follow-up serumAPA at 2 to 4 weeks after dischargefrom the hospital may be consid-ered.

7. When infants reach a body weight>1500 g and tolerate full enteralfeeds, vitamin D intake should gen-erally be ∼400 IU/day, up to a max-imum of 1000 IU/day.

LEAD AUTHORSteven A. Abrams, MD

COMMITTEE ON NUTRITION,2011–2012Jatinder J. S. Bhatia, MD, ChairpersonSteven A. Abrams, MDMark R. Corkins, MDSarah D. de Ferranti, MDNeville H. Golden, MDJanet Silverstein, MD

LIAISONSLaurence Grummer-Strawn, PhD – Centers forDisease Control and PreventionRear Admiral Van S. Hubbard, MD, PhD – NationalInstitutes of HealthValerie Marchand, MD – Canadian PediatricSocietyBenson M. Silverman, MD – Food and DrugAdministrationValery Soto, MS, RD, LD – US Department ofAgriculture

STAFFDebra L. Burrowes, MHA

REFERENCES

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DOI: 10.1542/peds.2013-0420; originally published online April 29, 2013; 2013;131;e1676Pediatrics

Steven A. Abrams and the COMMITTEE ON NUTRITIONCalcium and Vitamin D Requirements of Enterally Fed Preterm Infants

  

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