Vitamin K Status of Premature Infants:
Implications for Current Recommendations
Deepak Kumar, MD, MRCP*; Frank R. Greer, MD‡; Dennis M. Super, MD, MPH*; John W. Suttie, PhD§; and John J. Moore, MD*
ABSTRACT. Objective. Newborn infants are vitamin K deficient. Vitamin K status in full-term infants after intramuscular vitamin K supplementation at birth has been described. Similar information in growing prema-ture infants has not been reported. The objective of this study was to assess vitamin K status in premature infants by measuring plasma vitamin K and plasma protein-induced in vitamin K absence (PIVKA II) from birth until 40 weeks’ postconceptional age.
Methods. Premature infants (<36 weeks’ gestation)
were divided at birth into groups by gestational age (group 1, <28 weeks; group 2, 29 –32 weeks; group 3,
33–36 weeks). Supplemental vitamin K (1 mg intramus-cularly) was administered at birth followed by 60g/day (weight<1000 g) or 130g/day (weight>1000 g) via total
parenteral nutrition. After hyperalimentation, most ceived vitamin K–fortified enteral feedings with the re-mainder receiving unfortified breast milk. Blood was obtained for PIVKA II in cord blood and for PIVKA II and vitamin K at 2 weeks and 6 weeks after birth and at 40 weeks’ postconception.
Results. Of the 44 infants enrolled, 10 infants in each gestational age group completed the study. The patient characteristics for groups 1, 2, and 3 were as follows: gestational age, 26.3 ⴞ 1.7, 30.3 ⴞ 1.3, and 33.9 ⴞ 1.1 weeks; birth weight, 876ⴞ176, 1365ⴞ 186, and 1906ⴞ 163 g; and days of hyperalimentation, 28.9ⴞ16, 16.8ⴞ12, and 4.3 ⴞ 4 days, respectively. At 2 weeks of age, the vitamin K intake and plasma levels were highest in group 1 versus group 3 (intake: 71.2ⴞ39.6 vs 13.4ⴞ16.3 g/kg/day; plasma levels: 130.7 ⴞ 125.6 vs 27.2 ⴞ 24.4 ng/mL). By 40 weeks’ postconception, the vitamin K in-take and plasma levels were similar in all 3 groups (group 1, 2, and 3: intake, 11.4ⴞ2.5, 15.4ⴞ6.0, and 10.0ⴞ 7.0g/kg/day; plasma level, 5.4ⴞ3.8, 5.9ⴞ3.9, and 9.3ⴞ 8.5 ng/mL). None of the postnatal plasma samples had any detectable PIVKA II.
Conclusions. Premature infants at 2 weeks of age have high plasma vitamin K levels compared with those at 40 weeks’ postconceptional age secondary to the par-enteral administration of large amounts of vitamin K. By 40 weeks’ postconception, these values are similar to those in term formula-fed infants. Confirming “adequate vitamin K status,” PIVKA II was undetectable by 2 weeks of life in all of the premature infants. With the
potential for unforeseen consequences of high vitamin K levels, consideration should be given to reducing the amount of parenteral vitamin K supplementation in the first few weeks of life in premature infants. Pediatrics
2001;108:1117–1122;vitamin K, PIVKA II, premature, total parenteral nutrition, enteral nutrition.
ABBREVIATIONS. PIVKA II, protein-induced in vitamin K ab-sence or antagonism; IM, intramuscularly; NICU, neonatal inten-sive care unit; TPN, total parenteral nutrition; MBM, maternal breast milk.
A
ll newborn infants are relatively vitamin K deficient in the first few months of life.1– 4 Prenatal supplementation with vitamin K has little effect on umbilical cord blood vitamin K lev-els.3,5–7 Vitamin K deficiency may cause life-threat-ening bleeding as a result of inadequate activity of vitamin K– dependent coagulation factors (II, VII, IX, and X), correctable by vitamin K replacement. Vita-min K deficiency also results in the secretion of un-dercarboxylated (abnormal) prothrombin into the plasma, called protein-induced in vitamin K absence or antagonism (PIVKA II).8 –10Because breast milk is very low in vitamin K compared with standard for-mulas,4,11vitamin K deficiency is a particular prob-lem in exclusively breastfed infants. Because of the risk of bleeding from vitamin K deficiency, all infants receive vitamin K prophylaxis (0.5–1.0 mg intramus-cularly [IM]) at birth. This is efficacious for term infants, but no studies have provided similar data on preterm infants. The US Recommended Dietary Al-lowances committee recommends a vitamin K intake of 1 g/kg/day for term infants after birth.12 For premature infants, recommendations are arbitrary and range from 5 to 10g/kg/day13to as high as 100 g/kg/day.14 Recently, vitamin K status and ways to improve it have been reported in healthy term infants.8,15Similar data are not available for prema-ture infants. Our aim was to assess vitamin K status of premature infants by measuring plasma vitamin K concentrations and PIVKA II concentrations from birth until 40 weeks’ postconceptional age.METHODS Patient Selection
Premature infants who were born at the MetroHealth Medical Center (MHMC) atⱕ36 weeks’ gestation and whose birth weight was appropriate for gestation were included in the study. Infants with life-threatening congenital anomalies, uncertainty of gesta-tional age, administration of fresh-frozen plasma within the week
From the *Department of Pediatrics, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio; and the Departments of ‡Pediatrics and Nutritional Sciences and §Biochemistry and Nutritional Sciences, University of Wisconsin, Madison, Wisconsin.
Received for publication Nov 29, 2000; accepted Apr 17, 2001.
Reprint requests to (D.K.) Department of Pediatrics, MetroHealth Medical Center, 2500 MetroHealth Dr, Cleveland, OH 44109. E-mail: dkumar@ metrohealth.org
before blood sampling, multiple gestation (⬎2; for twin births, only 1 infant enrolled), or antenatal exposure to anticonvulsants or antituberculosis agents were excluded. Mothers who were admit-ted to the labor and delivery unit for premature delivery were identified and were approached by the principle investigator to participate in the study. When the parents of a premature infant declined to participate in the longitudinal study, all patient iden-tifiers (except gestational age, gender, and race) were removed from the cord blood sample. This study was approved by the Human Subject Committee of the Institutional Review Board at MHMC. Informed written consent was obtained from parents of all of the infants enrolled in the study. Patients were enrolled until 30 premature infants (10 for each of the gestational age groups) completed the study. The gestational age groups were defined a priori as group 1 (ⱕ28 weeks), group 2 (29 –32 weeks), and group 3 (33–36 weeks).
Vitamin K Supplementation
All of the premature infants received 1 mg of vitamin K IM at birth per policy in the neonatal intensive care unit (NICU) at MHMC. Postnatal parenteral vitamin K supplementation was pro-vided through total parenteral nutrition (TPN), using standard multivitamin mixture (MVI-Pediatric, Astra Pharmaceuticals, Westborough, MA) to provide 60g/day to infants who weighed
⬍1000 g and 130g/day to infants who weighed 1000 to 3000 g. Vitamin K content of Intralipid 20% IV Fat Emulsion (Fresenius Kabi Nutrition AB, Clayton, NC) varies from lot to lot and ranges from 200 to 700g/L (Diane Nitzki-George, Clinitec Nutrition Division, Baxter Healthcare Corporation, personal communica-tion, October 2000).16 –19For the purpose of calculating vitamin K intake from the infused standard Intralipid 20% IV Fat Emulsion, we used vitamin K concentration of 300 g/L (Diane Nitzki-George, Clinitec Nutrition Division, Baxter Healthcare Corpora-tion, personal communicaCorpora-tion, October 2000). Enteral vitamin K intake was provided by commercial premature formula (65–100 g/L),20fortified maternal breast milk (MBM; 45– 49g/L),20or unfortified MBM (2g/L).4In the NICU, the amount and type of nutrition for 3 consecutive days before a blood sampling was recorded. After discharge, the parents maintained a feeding record at home for 3 days before the scheduled visit for blood sampling and weight measurement. For breastfed infants, the amount per feeding was calculated from the difference in the infant’s weight before and after a feeding on the day of the blood sampling. This amount was then multiplied by the number of breastfeedings per day to calculate daily breast milk intake. The average daily vita-min K intake for that period was calculated by multiplying the average volume received for those 3 days by the known concen-trations of vitamin K for each type of nutrition.
Blood Collection
Blood (2 mL) was obtained in lithium heparin containers at birth (cord), 2 weeks (⫾2 days), 6 weeks (⫾4 days), and at term (40⫾2 weeks’ postconceptional age). As the infants in group 3 would be term at 6 weeks of age, the results from their 6-week phlebotomy are reported as 40 weeks’ postconceptional age rather than 6 weeks of age. The blood samples were centrifuged for 5 minutes at 2100 ⫻g at 4°C. The plasma was then split into 2 aliquots and stored at⫺70°C.
Vitamin K Assay
Vitamin K was assayed in plasma by a modification of a pre-viously described multistage procedure.21After extraction of 0.5
mL of plasma with hexane, the lipid extract was purified by normal-phase high-performance liquid chromatography and ana-lyzed with reversed-phase high-performance liquid chromatogra-phy using electrochemical detection in the redox mode. Menaqui-none-6 was used as the internal standard. The lower limit of detection was 0.05 ng/mL. The mean plasma vitamin K concen-tration of healthy fasting adults is 0.5 ng/mL.15,22Individuals who conducted the vitamin K assays were blinded to the gestational age and type of nutrition that the infants were receiving.
PIVKA II Assay
The PIVKA II assay was performed on plasma using a murine monoclonal antibody available in an enzyme immunoassay kit (Asserachrom PIVKA-II; Diagnostica-Stago, Asnieres Sur Seine, France). The normal value for PIVKA II in adults is⬍2 ng/mL with this method.23 Individuals who conducted the PIVKA II assays were blinded to the gestational age and type of nutrition that the infants were receiving.
Statistics
Interval data are reported as mean ⫾ standard deviation. Kruskal-Wallis 1-way analysis of variance was used to determine the differences among the 3 groups for interval data. When theP
value was⬍.05, posthoc Mann-WhitneyUtest was performed with the Bonferroni adjustment for reducing test-wise error. The Wilcoxon matched-pairs signed-ranks test was used for paired interval level data. Statistical significance was defined a priori as aP⬍.05 (2-tail). Data were analyzed with SPSS for Windows V9.0 (SPSS Inc, Chicago, IL).
RESULTS Patient Characteristics
Between December 1997 and June 1999, 71 infants were identified as eligible candidates for the study. Forty-four infants were enrolled, 30 of whom com-pleted the study. One infant who was born at 33 weeks’ gestation died at 2 weeks of age in the NICU. The remaining 13 infants were lost to follow-up. Two of these infants had blood drawn at 2 and 6 weeks of age but not at 40 weeks’ postconceptional age. Hence, they were excluded from the study. One (34 weeks’ gestation) was readmitted to the pediatric intensive care unit with respiratory syncytial virus infection at 2 weeks of age, and parents refused blood draw. Ten infants (33–36 weeks’ gestation) did not show for appointment despite reminders 3 days before scheduled visits. Patients in each of the 3 groups were similar with regard to race and gender. However, the infants in groups 1 and 2 versus 3 had more days of TPN (Table 1).
Postnatal Vitamin K Supplementation
At 2 weeks of age, the vitamin K supplementation was higher in the more premature infants (group 1 vs 3;P⬍.05). By 40 weeks’ postconceptional age, it was similar among all groups (Table 2). At 2 weeks, the
TABLE 1. Patient Characteristics
Group 1 ⱕ28 Weeks
(n⫽10)
Group 2 29–32 Weeks
(n⫽10)
Group 3 33–36 Weeks
(n⫽10) Gestational age (wk) (mean⫾SD) 26.3⫾1.7 30.3⫾1.3 33.9⫾1.2 Birth weight (g) (mean⫾SD) 875.8⫾176.4 1365.3⫾185.9 1906.0⫾162.8
Race (% white) 40 30 60
Gender (% male) 40 40 60
TPN (d) (mean⫾SD) 28.9⫾16.2* 16.8⫾12.2† 4.3⫾4.6*† SD indicates standard deviation.
higher vitamin K supplementation in the more pre-mature infants was secondary to more of these in-fants receiving TPN (group 1: 80%; group 3: 12.5%). By 40 weeks’ postconceptional age, all infants were fed enterally (Table 3).
Plasma Vitamin K Concentrations
At 2 weeks of age, the vitamin K levels were high-est in group 1 (Table 4). In each of the 3 groups, the vitamin K levels decreased significantly (P ⬍ .05) from 2 weeks to 40 weeks’ postconceptional age. By 40 weeks’ postconceptional age, the vitamin K levels were similar among all groups (Table 4). The lowest individual vitamin K concentration obtained in our study was 0.8 ng/mL. Hence, all infants exceeded 0.5 ng/mL, the mean normal vitamin K concentration in healthy fasting adults.
Plasma Vitamin K Concentration in Relation to Nutrition
At 2 weeks of age, parenteral nutrition resulted in higher plasma vitamin K levels than enteral nutrition (Table 5). By 40 weeks’ postconception, all of the infants who had initially received TPN were exclu-sively enterally fed. At term, their plasma vitamin K levels were similar to those who received enteral feedings only at 2 weeks.
Only 4 infants (group 3) received unfortified MBM for any significant duration (mean vitamin K intake: 0.4 g/kg/day). One infant received TPN for the first 8 days of life followed by only unfortified MBM until term. This infant had plasma vitamin K levels of 16.9 ng/mL and 0.8 ng/mL at 2 weeks and term, respectively. The second received unfortified MBM until 2 weeks of age followed by vitamin K–fortified MBM and formula. This infant had a plasma vitamin K level of 8.8 ng/mL at term. The third infant had a vitamin K level of 1.31 ng/mL at term after 5 weeks of unfortified MBM. The fourth infant (born at 36 weeks), who was fed unfortified MBM exclusively since birth, had a vitamin K level of 1.4 ng/mL 2 weeks after birth.
PIVKA II
PIVKA II was detectable in 19 (27.5%) of 69 cord blood samples that were available for assay. If PIVKA II of ⬍10 ng/mL is considered normal for newborn infants, then 14 (20.3%) of 69 had values
ⱖ10 ng/mL. There was no difference in the incidence of detectable PIVKA II in cord blood for gender, race, and gestational age. Of the 30 infants who were followed longitudinally, 9 of the available 28 cord blood samples had detectable PIVKA II. With vita-min K supplementation, none of their postnatal sam-ples at 2, 6, and 40 weeks had any detectable PIVKA II.
DISCUSSION
Published guidelines for vitamin K supplementa-tion are specific for all ages except for premature infants.12There are no published data regarding the appropriateness and adequacy of current recommen-dations for vitamin K supplementation of premature infants. Our study begins to address these issues.
The plasma vitamin K concentrations were high in premature infants at 2 weeks of age, especially in those who were receiving multivitamins in TPN so-lutions. This reflects high amounts of vitamin K given IM at birth and subsequently through paren-teral nutrition. Premature infants (24 –36 weeks) in our study had much higher vitamin K plasma con-centrations at 2 and 6 weeks of age than that docu-mented in the literature in healthy, term, formula-fed infants (4 – 6 ng/mL).4By 40 weeks, when all infants were enterally fed, the mean plasma vitamin K con-centrations in all groups were similar to those of
TABLE 2. Vitamin K Supplementation in Postnatal Period Group 1 (ⱕ28 Weeks)
Group 2 (29–32 Weeks)
Group 3 (33–36 Weeks)
2 Weeks of age
Weight (kg; mean⫾SD) 0.84⫾0.18* 1.39⫾0.21* 2.01⫾0.18* Vitamin K (g/kg/day; mean⫾SD) 71.2⫾39.6† 51.6⫾39.7 13.42⫾16.3† 6 Weeks of age
Weight (kg; mean⫾SD) 1.32⫾0.42* 2.01⫾0.36* ‡ Vitamin K (g/kg/day; mean⫾SD) 23.1⫾25.0 19.2⫾18.5 ‡ 40 Weeks (postconceptional age)
Weight (kg; mean⫾SD) 2.58⫾0.62* 2.89⫾0.28 3.40⫾0.59* Vitamin K (g/kg/day; mean⫾SD) 11.4⫾2.5 15.4⫾6.0 10.0⫾7.0 SD indicates standard deviation.
*P⬍.05. †P⬍.05.
‡ By 6 weeks of age, infants were 40 weeks (postconceptional age).
TABLE 3. Type of Nutrition % of Total Intake Group 1
(ⱕ28 Weeks)
Group 2 (29–32 Weeks)
Group 3 (33–36 Weeks)
2 Weeks of age
TPN (%) 80 60 12.5
Formula (%) 0 20 37.5
FBM (%) 20 20 25
MBM (%) 0 0 25
6 Weeks of age
TPN (%) 30 14.3 *
Formula (%) 20 57.1
FBM (%) 50 28.6
MBM (%) 0 0
40 Weeks’ postconception
TPN (%) 0 0 0
Formula (%) 70 90 70
FBM (%) 30 10 0
MBM (%) 0 0 30
healthy, term, formula-fed infants during the first 6 months of life.4 Sann et al24 documented a plasma vitamin K concentration of 310 ng/mL in 10 low-birth-weight infants with mean gestation of 35 to 36 weeks at 24 hours of age after 2 mg of vitamin K orally. In term infants, Greer et al3 documented plasma vitamin K concentrations of 21 ng/mL in healthy breastfed infants and 27.5 ng/mL in healthy formula-fed infants at day of life 5 after 1 mg of vitamin K IM at birth. In both of these studies, the vitamin K levels reflect the amounts of vitamin K given at birth. At all times, plasma vitamin K con-centrations in our preterm infants, irrespective of their gestation and route of vitamin K supplementa-tion, were higher than that of healthy fasting adults (0.5 ng/mL). The unfortified MBM–fed infants with plasma vitamin K concentrations ofⱖ1.4 ng/mL at 2 weeks of age reflect the persisting high vitamin K levels after large dose of vitamin K (1 mg IM) at birth.
Our study confirmed the high reported incidence of detectable PIVKA II (10%–50%) in cord blood.22,25 PIVKA II was detected in 27.5% of the premature (69) cord blood samples assayed. There was no relation-ship between PIVKA II concentrations in cord blood and gestation, race, or gender. If⬍10 ng/mL is con-sidered normal, then 14 (20.28%) premature cord blood samples were abnormally elevated for PIVKA II. The only other published study of PIVKA II mea-surements in premature cord blood included 13 pre-mature (27–36 weeks) and 46 term (37– 41 weeks) cord blood samples. The presence of elevated cord PIVKA II (ⱖ10 ng/mL) in 31 of their 57 (52%) infants was unrelated to their gestational age.26 Although
cord blood samples have almost undetectable vita-min K levels at birth, it is uncertain why only 20% of our premature infants had elevated PIVKA II levels. Reassuring is that all measurements done in the 30 premature infants postnatally at 2 and 6 weeks of age and 40 weeks’ postconception contained no detect-able PIVKA II, confirming adequate vitamin K status also confirmed by the vitamin K concentrations in their plasma.
In this population of premature infants who were ⱕ36 weeks’ gestation, the vitamin K intakes were comparable to the current recommendations. Recom-mended vitamin K intakes of parenterally fed pre-mature infants vary (2–100 g/day14 to 80 g/ day27). Infants who received any parenteral nutrition at 2 weeks of age had a vitamin K intake (84.2 g/ day) similar to that recommended (80 g/day) by the American Academy of PediatricsPediatric Nutri-tion Handbook.27Infants exclusively enterally fed had intakes similar to those recommended by the Amer-ican Academy of Pediatrics (6 –9 g/kg/day) for growing preterm infants.13,27 This is also similar to vitamin K intakes of term formula-fed infants during the first 6 months of life.4 For most patients, the vitamin K intake was higher at 2 weeks secondary to supplementation with parenteral nutrition. In fact, the premature infants who received the highest in-takes of intravenous nutrition received the largest intake of vitamin K. By 40 weeks, when all infants were exclusively enterally fed, vitamin K intake was similar in all groups. Exclusively MBM-fed infants received significantly less vitamin K, 0.41 g/kg/ day, which is less than the US Recommended Di-etary Allowances Committee recommendation (1
TABLE 4. Plasma Vitamin K Concentrations Group 1 (ⱕ28 Weeks)
Group 2 (29–32 Weeks)
Group 3 (33–36 Weeks)
Vitamin K (2 wk) (ng/mL)
130.7⫾125.6*‡§ 60.8⫾52.9‡ 27.2⫾24.4*‡
Vitamin K (6 wk) (ng/mL)
13.8⫾10.7§ 14.0⫾19.5 †
Vitamin K (40 wk) (ng/mL)
5.4⫾3.8‡ 5.9⫾3.9‡ 9.3⫾8.5‡
*P⬍.05 (group 1 vs 3).
† By 6 weeks of age, infants were 40 weeks (postconceptional age). ‡P⬍.05, intragroup differences from 2 to 40 weeks (postconceptional age). §P⬍.05, intragroup difference from 2 to 6 weeks (postconceptional age).
TABLE 5. Plasma Vitamin K Concentration in Relation to Nutrition at 2 Weeks Type of Nutrition at 2 Weeks
Any TPN (n⫽15)
Only Enteral Feeds (n⫽13)†
2 Weeks
Vitamin K supplement
(g/kg/day) 81.4⫾24.1* 8.7⫾5.2*
Plasma vitamin K (ng/mL) 124.4⫾101.1* 20.6⫾19.9* Term (38–42 wk)‡
Vitamin K supplement
(g/kg/day) 12.7⫾3.9 12.4⫾7.2
Plasma vitamin K (ng/mL) 6.0⫾4.7 6.8⫾4.7 *P⬍.01 (any TPN vs enteral feed).
g/kg/day) for all ages but similar to vitamin K intakes of term, healthy, breastfed infants through the first 6 months of life.4
One limitation of our study, which started in 1997, is that all study infants received 1 mg of vitamin K IM at birth according to our NICU policy, which is the upper limit of the current recommendation (0.5– 1.0 mg).27This dose was concurrent with the former recommendations of the American Academy of Pe-diatrics.28 Revised recommendations for premature infants with birth weight of⬍1000 g are 0.3 mg/kg IM and became available in 1998.27 Only 8 of 30 premature infants in our study had a birth weight of ⬍1000 g. Data from our unfortified MBM–fed infants suggest that 1 mg of vitamin K IM at birth is ade-quate at 2 weeks of age, even in MBM-fed infants. For the infants who received large amounts of vita-min K through TPN (81 g/kg/day; Table 5), the plasma vitamin K levels are high (124 ng/mL). It is of note that children and adults on parenteral nutrition may maintain adequate vitamin K status from 20% Intralipid infusion alone because it contains a signif-icant amount of vitamin K (200 –700 g/L; Diane Nitzki-George, Clinitec Nutrition Division, Baxter Healthcare Corporation, personal communication, October 2000).16 –19,29Accordingly, premature infants may receive a significant (1–3.5g/kg/day) portion of total daily recommended vitamin K from 1 g/kg of 20% Intralipid infusion. It has been suggested that 10 g/kg/day vitamin K via TPN would be more than adequate for premature infants.13This amount would approximate the vitamin K intake of formula-fed infants, which is known to prevent vitamin K deficiency bleeding.13 Presently, an appropriate in-travenous multivitamin parenteral preparation that could provide the suggested reduced amount (10 g/kg/day) of vitamin K is not available.
We are unsure of the risks to premature infants resulting from the supraphysiologic levels of vitamin K. In the past, high doses of a water-soluble vitamin K (menadione) preparation were associated with red cell hemolysis and hyperbilirubinemia, leading to kernicterus in the premature infants.30 Fat-soluble vitamin K (phylloquinone) preparation has been used for the past 4 decades without any associated hemolysis even when given in large doses. In 1992, Golding et al31questioned the safety of prophylactic intramuscular vitamin K at birth and reported an associated increased rate of childhood cancer. This study had several limitations. Several large popula-tion studies refute these findings.32– 40 Limited basic science data implicating vitamin K in causing in-creased sister chromatid exchanges in human and animal lymphocytes is contradictory.41,42 Both the American and the Canadian pediatric societies have reaffirmed their confidence in intramuscular vitamin K prophylaxis.28,43
CONCLUSION
Vitamin K levels in premature infants directly re-flect vitamin K intakes. With current vitamin K sup-plementation, premature infants at 2 weeks of age have high levels of plasma vitamin K secondary to 1 mg of intramuscular vitamin K administration at
birth and the high amount of vitamin K in parenteral nutrition multivitamins. These levels decline by 40 weeks’ postconceptional age, when infants are enter-ally fed, at which time they are comparable to term, formula-fed infants. Confirming adequate vitamin K status and vitamin K supplementation, PIVKA II is undetectable by 2 weeks of life. In our population of premature infants of⬍37 weeks’ gestation, the vita-min K intakes were consistent with the current rec-ommended wide range of guidelines (from 5–100 g/kg/day) for premature infants. However, cur-rent vitamin K supplementation of premature in-fants, particularly at 2 weeks, provides excessive amounts of vitamin K. Although not apparent in this study, this has a potential for unforeseen side effects. Optimal vitamin K requirements of premature in-fants are undefined, but present evidence suggests that parenteral vitamin K supplementation in the first few weeks of life should be reduced.
ACKNOWLEDGMENTS
This study was funded in part by the General Clinical Research Center (GCRC) Grant from NIH (MO1RR00080) awarded to MetroHealth Medical Center and the American Bioproducts Com-pany/Stago, which kindly provided PIVKA II kits.
Presented in part at the Pediatric Academic Societies and Amer-ican Academy of Pediatrics Joint Meeting in Boston, Massachu-setts, May 12–16, 2000.
We thank Susan Hochevar, Sara Gagnon, and other nurses in the GCRC and the NICU for their diligence, patience, and assis-tance with this project. We are also grateful to the parents and their premature infants for participating in the study.
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SOUTH AFRICA’S FAILURE ON AIDS
“. . . Reservations about treating AIDS cannot explain why South Africa is . . . stalling on simple and cheap programs to cut mother-to-child transmission. The cabinet has withheld approval, preferring to study the programs endlessly . . . A 15-year-old in South Africa now has a better than even chance of dying of AIDS. Antiretrovirals are being used successfully in African nations less developed than South Africa to extend the life and health of AIDS patients . . . South Africa cannot remain a viable nation if half its young people are doomed to an early, protracted, and expensive death.”
New York Times. June 21, 2001
DOI: 10.1542/peds.108.5.1117
2001;108;1117
Pediatrics
Deepak Kumar, Frank R. Greer, Dennis M. Super, John W. Suttie and John J. Moore
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Vitamin K Status of Premature Infants: Implications for Current
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2001;108;1117
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Deepak Kumar, Frank R. Greer, Dennis M. Super, John W. Suttie and John J. Moore
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