Vitamin A status in full-term and premature infants

Vitamin A status has been assessed by studying plasma vitamin A and retinol binding protein (RBP) levels in premature infants receiving 7,500 IU vitamin A/d (RDA 660-3,300 IU/d) and in control term babies during the 3 first months of life. Sampling was performed within the first week (D0-D7), between the 8th and the 30th day (D8-D30) and during the 2nd and the 3rd month of life (M2-M3). At D0-D7, vitamin A levels of the PTI group (28-32 weeks gestational age), PTII (33-36 weeks GA) and AT (control term newborn) were 242.1 +/- 20.5 (X +/- SEM), 176.1 +/- 12.3 and 213.1 +/- 17.1 micrograms/l respectively (P = 0.005). At D8-D30, these values were 264.2 +/- 26.0, 270.4 +/- 21.6 and 242.6 +/- 24.5 micrograms/l respectively (NS), and at M2-M3 234.2 +/- 21.6, 282.1 +/- 18.5 and 292.1 +/- 31.5 micrograms/l (NS). A significant difference was found between the values of the different dosage periods for PTII and AT groups; no difference in RBP levels was found either between groups or between dosage periods. At birth, our results show that the RBP synthesis is not closely linked to gestational age. The plasma vitamin A levels which rely on foetal stores and therefore on transplacental passage and on peripheral tissue requirements are low at 33-36 weeks gestational age. With a 7,500 IU daily supplement, excessively high vitamin A levels were not observed in premature infants; vitamin A and RBP levels in premature infants receiving supplement are not different from controls despite the 8-12-week term high vitamin A supply.     

Activation of the plasma kallikrein-kinin system in respiratory distress syndrome.

Components of the plasma kallikrein-kinin and fibrinolytic systems together with antithrombin III were measured the first days postpartum in 13 premature babies with severe respiratory distress syndrome (RDS). Seven of the patients received a single dose of porcine surfactant (Curosurf) as rescue treatment. Nine premature babies without lung disease or any other complicating disease served as controls. There were no differences in prekallikrein values between surfactant treated and non-treated RDS babies during the first 4 d postpartum. The controls had, however, significantly higher prekallikrein values than the RDS babies already at the first day of age (mean +/- SD 32 +/- 8% in controls versus 22 +/- 6 and 21.5 +/- 5% in the treated and nontreated RDS groups, respectively). Plasma kallikrein activities did not differ between RDS and control patients. Plasma kallikrein inhibition values, which increased steadily in all groups, were lower in the RDS babies treated with surfactant than in controls at d 2 and 4. The degree of degradation of plasma high molecular weight kininogen was measured in RDS patients treated with surfactant and was significantly higher when compared with controls at d 1, demonstrating an increased proteolysis of kininogen to kinin early in RDS. There were no differences in plasminogen and plasmin values between RDS and control babies. This study shows that the plasma kallikrein-kinin system is activated in RDS. This system as well as the fibrinolytic system does not seem to be influenced by rescue instillation of a single dose of porcine surfactant into the lungs of premature babies with RDS.     

Erythropoietin in the cerebrospinal fluid of neonates who sustained CNS injury.

We previously reported that erythropoietin (Epo) is present in human cerebrospinal fluid (CSF). It is not known whether CSF Epo concentrations change under conditions of CNS injury or, if so, whether this change reflects loss of blood-brain barrier integrity or increased CNS Epo synthesis. We hypothesized that CSF Epo increases in conditions of neural injury including hypoxia, meningitis, and intraventricular hemorrhage (IVH) and that CSF Epo concentrations are independent of plasma Epo concentrations. To test these hypotheses, Epo concentrations were measured in 122 paired CSF and blood samples obtained from neonates and children categorized as follows: 16, asphyxia; 31, meningitis; 11, IVH; 41, controls. Twelve infants treated with recombinant Epo (rEpo) and 11 additional samples from children with miscellaneous neurologic problems were also evaluated. CSF and plasma Epo concentrations were significantly higher in asphyxiated infants than in controls (225.0+/-155.0 versus 4.5+/-0.5 mU/mL; mean +/- SEM, p < 0.05, respectively, in CSF; 1806.7+/-1254 versus 5.2+/-0.5, p < 0.05 in plasma). Neonates with IVH had higher CSF Epo concentrations than controls (p < 0.01) but did not have higher plasma Epo concentrations than controls. Patients with meningitis did not have elevated CSF or plasma Epo concentrations. There was no correlation between CSF and plasma Epo concentrations in infants treated with rEpo. We conclude that Epo is selectively increased in the CSF by hypoxia, less so by IVH, and not at all by meningitis. rEpo treatment does not elevate CSF Epo. These findings suggest that rEpo does not cross the blood-brain barrier and that hypoxia induces increased CNS synthesis of Epo.     

Utility of breath ethane as a noninvasive biomarker of vitamin E status in children.

The purpose of our study was to determine if the ethane content of expired air could be a useful index of vitamin E status in children. Eight children with vitamin E deficiency secondary to chronic severe liver disease were studied: six of these children were treated with parenteral vitamin E (2-5 mg/kg/dose every 4-7 d). Measures of vitamin E status pre- and posttherapy were: serum vitamin E, 2 +/- 1 versus 7 +/- 1 micrograms/mL (p less than 0.001); serum vitamin E:total lipids, 0.3 +/- 0.1 versus 1.0 +/- 0.1 mg/g (p less than 0.001); and erythrocyte peroxide hemolysis test, 80 +/- 10 versus 6 +/- 12% (p less than 0.001). Fasting breath ethane in the patients pre- and posttherapy was 78 +/- 10 versus 31 +/- 11 pmol/kg/min (p less than 0.001). Breath ethane correlated negatively with serum vitamin E (p less than 0.042) and serum E:total lipids (p less than 0.004) and positively with the erythrocyte peroxide hemolysis test (p less than 0.003). Values for treated patients did not differ from those for fasted sibling controls (34 +/- 12 pmol/kg/min), postprandial sibling controls (31 +/- 12 pmol/kg/min), and healthy children sampled randomly, in the nonfasted state (21 +/- 14 pmol/kg/min). Breath ethane production in one patient (up to 168 pmol/kg/min) did not normalize after treatment of vitamin E deficiency until her selenium deficiency was corrected as well. We conclude that this noninvasive test can be useful as a screen for vitamin E deficiency in children and for ascertaining response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin D nutritional status of premature infants supplemented with 500 IU vitamin D2 per day

The vitamin D nutritional status of premature infants was assessed by determining plasma 25-hydroxyvitamin D concentrations before and during supplementation with 500 IU vitamin D2 per day. Fifty-one samples were collected from 25 healthy infants fed breast milk and a vitamin D3 fortified formula. Gestational age was 32.2 +/- 2.4 weeks (mean +/- 1 SD). 25-hydroxyvitamin D levels before supplementation correlated well with maternal values (r = 0.81). The infants' mean plasma concentration increased from 30.6 +/- 13.7 nmol/l (mean +/- 1 SD) after birth to 46.3 +/- 10.5 nmol/l after 9 +/- 1 days (p less than 0.0025), and to 65.3 +/- 16.6 nmol/l after 37 +/- 10 days of vitamin D2 treatment (p less than 0.0005). 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were determined separately, and it appeared that the rise was accounted for by the D2 fraction while 25-hydroxyvitamin D3 concentrations were unchanged. The results demonstrate that vitamin D2 is well absorbed and hydroxylated in the 25 position by premature infants free of associated disease, and that a supplementation of 500 IU per day in addition to breast milk and a regular vitamin D fortified formula is adequate to rapidly establish 25-hydroxyvitamin D levels within the normal adult range.     

Serum concentrations of vitamin E in healthy infants fed commercial milks

Serum vitamin E concentrations were determined in 60 term and 26 premature infants during the first 2 months of life. All infants received commercial milk formula containing vitamin E. In addition, premature infants older than 10 days were given vitamin E orally as a multivitamin preparation. Thus, daily intake of vitamin E was nearly 1.2 mg/kg body weight in term infants and 2–3 mg/kg body weight in premature infants.In term infants serum levels of vitamin E rose from 2.6 mg/l (cord blood) to 7.0 mg/l (3rd–13th day) and 9.1 mg/l (16th–25th day) and remained at 10 mg/l (in the second month of life). Hemoglobin concentration and red cell number decreased continuously due to physiological anemia of infancy. In premature infants mean values of vitamin E were the same as in term infants. Vitamin E deficiency with hemolytic anemia could be demonstrated in a 2 months old infant suffering from cystic fibrosis.Dedicated to Prof. Dr. H.-R. Wiedemann on the occasion of his 65th birthday     

Cerebrospinal fluid immunoglobulins in children.

Cerebrospinal fluid (CSF) immunoglobulins were measured in 62 normal children, in 9 children with purulent meningitis, and in 10 children with presumptive viral meningitis. The mean values in normal children were IgA 0, IgM 0, and IgG 0.84 +/- 1.4 mg/100 ml (+/- SD). The mean levels of all CSF immunoglobulins were raised in acute bacterial meningitis and were significantly greater than the levels found in viral meningitis. CSF IgM was 0.16 +/- 0.5 mg/100 ml in viral meningitis compared with 2.64 +/- 2.06 mg/100 ml in bacterial meningitis (P less than 0.01). However, these values overlapped to a considerable extent and, generally, measurement of CSF immunoglobulins did not enhance diagnostic accuracy in this group of children.     

Cerebrospinal fluid immunoglobulins in children

Cerebrospinal fluid (CSF) immunoglobulins were measured in 62 normal children, in 9 children with purulent meningitis, and in 10 children with presumptive viral meningitis. The mean values in normal children were IgA 0, IgM 0, and IgG 0.84 +/- 1.4 mg/100 ml (+/- SD). The mean levels of all CSF immunoglobulins were raised in acute bacterial meningitis and were significantly greater than the levels found in viral meningitis. CSF IgM was 0.16 +/- 0.5 mg/100 ml in viral meningitis compared with 2.64 +/- 2.06 mg/100 ml in bacterial meningitis (P less than 0.01). However, these values overlapped to a considerable extent and, generally, measurement of CSF immunoglobulins did not enhance diagnostic accuracy in this group of children.     

Vitamin B6 Intake and Plasma Pyridoxal Phosphate Concentrations in the First 2 Weeks of Life

ABSTRACT. Plasma pyridoxal phosphate concentrations were measured in 178 hospitalised neonates. A reference interval for neonates less than 7 day old, of 25 to 78 nmol/l has been established. Vitamin B₆ intakes did not correlate well with plasma pyridoxal concentrations despite 26 neonates receiving less than the Recommended Allowance (0.3 mg/d) and 19 receiving amounts below which convulsions have been associated (0.1 mg/d). Ten percent of those infants fed breast milk had plasma pyridoxal phosphate levels below the reference interval compared with only 4 % of those fed milk formulae. Breast milk from mothers with babies less than 14 days old had a total vitamin B₆ contents reference interval of 5 to 40 μg/l. Twenty percent of breast milk samples had virtually no vitamin B₆ detected.     

Comparative study of oral versus injectable vitamin K in neonates.

One hundred term exclusively breast fed babies weighing more than 2.5 kg were evaluated to determine the efficacy of various modes and doses of Vitamin K to prevent hemorrhagic disease of newborn (HDN). The babies were grouped into four categories of 25 each: Group A--1 mg Vitamin K intramuscular (Menadione sodium disulphite) at birth; Group B--0.5 mg Vitamin K intramuscular; Group C--1 mg Vitamin K orally, and group D--no Vitamin K. The prothrombin index was estimated in all babies between 36-72 hours of age. The results revealed a prothrombin index in Groups A, B, C and D as 94.98 +/- 7.64%, 95.08 +/- 9.91%, 92.51 +/- 10.10% and 80.39 +/- 15.90%, respectively. The differences between Groups A, B and C were insignificant. However, Group D, prothrombin index was significantly reduced as compared with the other three groups. It is, therefore, concluded that oral Vitamin K is as effective as injectable Vitamin K and its usage is recommended in our country to reduce complications and costs of parenteral therapy.     

Plasma hypoxanthine and xanthine levels in the early newborn period in problem-free preterm babies and those with idiopathic respiratory distress syndrome

The use of hypoxanthine measurements for quantitative monitoring of intrauterine asphyxia is generally accepted. A high level in blood or in CSF is a consequence of tissue hypoxia. Hypoxanthine and xanthine were measured by selective high pressure liquid chromatography in mature newborns, in healthy, symptom-free preterm babies, and in preterm babies affected by idiopathic respiratory distress syndrome. The measurements were carried out from peripheral venous blood within three hours after birth and at the age of 48-72 hours. In mature newborns the mean hypoxanthine level was 11.10 mumol/l in the early determinations, and 8.45 mumol/l in the second set of measurements. In unaffected prematures there were significantly higher levels, and the highest values (44.22 +/- 15.13 mumol/l) were encountered in premature babies subsequently dying of severe hypoxia. Xanthine showed a similar course. In addition to establishing normal values for prematures we desired to clarify the changes in the levels of purine metabolites during idiopathic respiratory distress and their prognostic value. Hypoxanthine and xanthine levels were found to be informative in postnatal hypoxia, especially together with other parameters.     

Intestinal absorption of vitamin E in low birth weight infants

Intestinal absorption of dl-alpha-tocopheryl acetate was studied in low birth weight infants. Vitamin E was given from the first day of life, either as a water-soluble (Ephynal) or as a lipid-soluble preparation (E-vitamin). Serum-alpha-tocopherol concentrations were determined before treatment and on days three and seven. Treatment with both vitamin E preparations increased serum-alpha-tocopherol on day three and seven. The mean serum-alpha-tocopherol +/- SD on day seven were 41.4 +/- 10.7 mumol/l for the Ephynal group and 26.7 +/- 12.5 mumol/l for the E-vitamin group, this difference being statistically significant (p less than 0.025). Oral feeding seems to influence the absorption of tocopherol from E-vitamin, as the infants with the highest serum-alpha-tocopherol concentrations were those with the highest oral/total feeding ratios. In infants with birth weight less than 1 000 g treatment with 25 mg Ephynal/day was found to increase serum-alpha-tocopherol on day seven to 46.9 +/- 12.3 mumol/l (mean +/- SD). This concentration is comparable to those reported by others using higher doses of oral vitamin E.     

Erythrocyte lipid abnormalities in Reye's syndrome

Previous studies have demonstrated alterations in plasma free fatty acid content in Reye's syndrome (RS). We have therefore studied erythrocyte membrane lipids to determine if there are concomitant structural and functional modifications attributable to RS. Erythrocyte lipids were measured in children with RS and in critically ill children also requiring intensive care (ICU). In comatose RS patients erythrocyte phospholipid arachidonate was increased 2-fold relative to control ICU patients: 20.46 +/- 2.14 versus 10.41 +/- 2.32% of total erythrocyte phospholipid, p less than 0.05. RS coma patients also demonstrated an increased ratio of erythrocyte phospholipid polyunsaturated/saturated fatty acids (0.76 +/- 0.10) compared to ICU controls (0.48 +/- 0.08, p less than 0.05). Erythrocyte cholesterol was higher in RS patients (79.00 +/- 6.61 micrograms/mg protein) than in ICU controls (59.74 +/- 6.09, p less than 0.05). Erythrocyte malondialdehyde generation was decreased in comatose RS patients (404 +/- 28 nmol malondialdehyde/g hemoglobin) versus ICU (517 +/- 29, p less than 0.05). Although plasma vitamin E was depressed in RS patients, the erythrocyte vitamin E concentrations were no different in RS patients than in ICU patients. All RS patients had a typical viral prodrome and either a history of aspirin intake and/or measurable serum salicylate on admission. All of the biochemical abnormalities in RS patients listed above returned to values comparable to those of healthy RS siblings on recovery. The transient nature of these phenomena suggests that they were related to viral infection and/or aspirin rather than to intrinsic differences in lipid metabolism between RS patients and controls.     

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 in girls with premature thelarche

Premature thelarche (PT) is characterised by precocious breast development without any other sign of puberty, normal height velocity (HV) and normal bone maturation, while girls with central precocious puberty (CPP) show increased HV, bone maturation and increased serum IGF-I and IGFBP-3 levels. This prompted us to study serum IGF-I and IGFBP-3 concentrations in girls with PT. Thirty-nine girls with premature breast development were studied and classified as PT or CPP according to clinical and laboratory evaluation. Normal prepubertal and pubertal girls were studied as controls. Serum IGF-I and IGFBP-3 were determined in all girls by IRMA. IGF-I levels in PT (155 +/- 61 microg/l) were lower than in CPP (337 +/- 149 microg/l) or late-pubertal controls (355 +/- 84 microg/l) and similar to those found in prepubertal (113 +/- 72 microg/l) and early-pubertal (222 +/- 81 microg/l) girls. Considering the SDS of IGF-I for chronological age (CA), the values observed in PT were in an intermediate position between CPP and prepubertal controls and statistically similar to those observed in CPP and prepubertal girls. IGFBP-3 levels in PT (2.1 +/- 0.5 mg/l) were similar to those found in CPP (2.5 +/- 0.8 mg/l), but only the latter were higher than in prepubertal girls (1.9 +/- 0.9 mg/l). IGF-I/IGFBP-3 molar ratios in PT were in an intermediate position between CPP and prepubertal controls. In conclusion, IGF-I and IGF-I/IGFBP-3 values in PT are intermediate between those observed in prepubertal children and in CPP, suggesting that PT could be a very early stage of puberty with slight but real changes in the GH-IGF axis.     

Prevalence of vitamin K deficiency in children with mild to moderate chronic liver disease

OBJECTIVES: Children with chronic liver disease are at risk for vitamin K deficiency because of fat malabsorption and inadequate dietary intake. The objective of this study was to determine the prevalence of vitamin K deficiency in children with mild to moderate chronic cholestatic and noncholestatic liver disease. METHODS: Vitamin K status was examined in 43 children (0.25-15.9 years) with mild to moderate chronic cholestatic liver disease, 29 children (0.9-16.9 years) with chronic mild to moderate noncholestatic liver disease, and in 44 healthy children (1-18 years). Vitamin K status was assessed by the plasma PIVKA-II (protein induced in vitamin K absence) assay (enzyme-linked immunosorbent assay). Plasma PIVKA-II values greater than 3 ng/mL are indicative of vitamin K deficiency. RESULTS: The mean plasma PIVKA-II (+/-SD) in cholestatic, noncholestatic, and healthy children was 61.9 +/-144, 1.2 +/- 3, and 2.1 +/- ng/mL, respectively (P < 0.002). Fifty-four percent of the children supplemented with vitamin K had plasma PIVKA-II greater than 3 ng/mL. Plasma conjugated bilirubin, total bile acids, and severity of liver disease were positively correlated with plasma PIVKA-II levels (P < 0.05). CONCLUSIONS: Vitamin K deficiency is prevalent in children with mild to moderate chronic cholestatic liver disease, even with vitamin K supplementation. Elevated PIVKA-II levels occurred in children with a normal prothrombin, indicating that more sensitive markers of vitamin K status should be used in children with chronic liver disease. Vitamin K deficiency was related to degree of cholestasis and severity of liver disease in children. Children without cholestasis did not exhibit vitamin K deficiency.     

Pharmacokinetics of nelfinavir and its active metabolite,hydroxy-tert-butylamide,in infants perinatally infected with human immunodeficiency virus type 1

BACKGROUND: In children younger than 2 years of age vertically infected with HIV-1, the recommended pediatric dosing regimen for nelfinavir (20 to 30 mg/kg three times a day) provides insufficient drug exposure. This study was conducted to determine the steady state pharmacokinetics of nelfinavir and its active metabolite, M8, in this population. METHODS: Fourteen infants (2.3 to 8.5 months) underwent 18 intensive pharmacokinetic studies of nelfinavir and M8 at steady state. Nelfinavir and M8 concentrations were measured by high performance liquid chromatography coupled with mass spectrometry, and individual pharmacokinetic values were determined. RESULTS: A mean nelfinavir daily dose of 135.7 +/- 18.8 mg/kg (twice or three times a day) resulted in median C(min), C(max), area under the plasma concentration-time curve (AUC(0-24 h)) and CL/ for nelfinavir of 0.627 mg/l, 2.39 mg/l, 30.6 mg*h/l and 4.2 liters/h/kg, respectively. When normalized for a daily dose of nelfinavir of 150 mg/kg/day, 16.7% of C(max) and 27.8% of AUC(0-24 h) values were below the tenth percentile for adult values. CONCLUSIONS: During the first year of life, nelfinavir requirement is much higher than in older children and adults to obtain similar drug exposure. The mechanisms underlying such differences may involve higher first past metabolism and/or drug interactions or might be related to feeding conditions.     

Est-il légitime d'administrer des vitamines liposolubles (A,E et D) chez le prématuré pendant 6 mois ?

Information on the vitamin A and E nutritional status in preterm infants is scarce. POPULATION AND METHODS: In the present prospective and longitudinal study, we measured the plasma concentrations of vitamins A, E, D and of retinol binding protein (RBP) in preterm infants (32-34 weeks of gestation) at birth, and verified whether oral supplementation with these 3 vitamins for 1, 3 and 6 months affected their plasma concentrations. The 17 consecutively recruited premature infants received daily 3000 IU of vitamin A, 5 mg of vitamin E and 1000 IU of vitamin D. RESULTS: At birth, premature infants exhibited a low plasma concentrations of vitamin A (0.66 [0.41-0.96]) micromol/l, vitamin E (8.1 [4.2-16.9] micromol/l), RBP (0.45 [0.22-0.71] micromol/l) and 25 hydroxyvitamine D (25 OHD) (20 [20-40] nmol/l). Plasma vitamin A, E , D and RBP concentrations increased with time, but vitamin A at 1, 3 and 6 months did not attain values considered normal in term infants or adolescents. At 6 months, the plasma 25 OHD was at 92 (71-116) nmol/l, a concentration considered normal and non-toxic. CONCLUSION: We recommend to increase oral administration of vitamin A to 5000 IU/day, at least for the first month of life and, thereafter to administer 3000 IU for 5 months. As for vitamin E and vitamin D, the doses used in this study are sufficient but should be administered for 6 months.     

Plasma and erythrocyte vitamin E levels in children with insulin dependent diabetes mellitus.

Vitamin E is considered to be one of the most important antioxidants. There is a trend today to supply diabetic children with vitamin E in order to prevent microvascular complications. In this study, our objective was to demonstrate validity of plasma and erythrocyte vitamin E levels in diabetic children. This study was conducted on twenty-five diabetic patients aged from 7-16 years and ten non-diabetic, age-matched healthy subjects as the control group. Vitamin E levels were measured by high-performance liquid chromatography. There was no significant difference between the mean plasma vitamin E levels of diabetic and control groups, 870.80 +/- 220.51 micrograms/dl and 891 +/- 221.21 micrograms/dl, respectively (p > 0.05). The mean erythrocyte vitamin E levels of diabetic and control groups were significantly different: 183.12 +/- 62.58 micrograms/dl and 246.90 +/- 68.26 micrograms/dl, respectively (p < 0.05). Erythrocyte vitamin E levels were significantly lower than plasma vitamin E levels in both groups. We further investigated whether a correlation exists between plasma and erythrocyte vitamin E levels and duration of diabetes, insulin dose and HbA1c measurements. However no correlation was found. In conclusion, measurement of erythrocyte vitamin E levels may be considered to be more valuable than plasma vitamin E levels in diabetic children and supplementation may be provided according to erythrocyte levels rather than plasma levels.     

Vitamin A and E supplementation in breast-fed newborns

BACKGROUND: Vitamins A and E are two potent antioxidant nutrients that play a significant role in immune function. In contrast to the numerous studies of vitamin A and E status in children, adolescents, and adults, information on term infants, particularly breast-fed infants, is scarce. The goals of the present investigation were to examine the vitamins A and E nutritional status of term breast-fed infants at birth and to assess retinol and tocopherol plasma levels during a 3-month supplementation trial. METHODS: The study was a prospective, blinded comparison of a supplementation protocol with a placebo in a group of consecutively recruited term newborns. The supplemented group received 3000 IU vitamin A and 5 IU vitamin E orally. The placebo group received a solution of similar viscosity and organoleptic characteristics. Vitamin A and E were separated by reverse-phase high-performance liquid chromatography on a C18 Spectrasyl column and quantified by ultraviolet spectrophotometry. RESULTS: Vitamin A and E levels steadily increased with age in both groups of infants. However, levels at 3 months were higher in the supplemented than in the control group. CONCLUSION: The data show that supplementation with 3000 IU vitamin A and 5 IU vitamin E for 3 months increases circulating vitamin levels in newborn term babies compared with those in nonsupplemented infants.     

Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants

We conducted a prospective study to determine (1) the maternal-fetal vitamin K1 transport in premature infants after vitamin K1 was given to the mothers antenatally and (2) the vitamin K1 effects on blood coagulation in the babies. Women in labor at less than or equal to 34 weeks of gestation were randomly selected to receive antenatal vitamin K1, 5 mg given intramuscularly (vitamin K1 group), or no vitamin K1 (control group). Eight infants, including one set of twins, were in the vitamin K1 group and six in the control group. Vitamin K1 concentrations were higher in the vitamin K1 group than in the control group (p = 0.06). Activated partial thromboplastin time was prolonged, and factor II coagulation activity and factor II antigen were proportionately decreased in cord plasma in both groups. The average ratio of factor II coagulation activity to antigen was not decreased in either group. Protein induced by vitamin K absence-II (PIVKA-II) was not detectable in any cord plasma sample in either group. These findings support previous reports that the decreased vitamin K-dependent coagulation activity in premature infants is the result of reduced synthesis of precursor proteins, rather than the result of vitamin K deficiency, and suggest that additional vitamin K1 is not likely to improve coagulation activity. Among those infants who underwent cranial ultrasonography, all four in the vitamin K1 group and one of five in the control group had mild intraventricular hemorrhage. Studies of a larger number of patients are necessary before it can be established that maternal antenatal administration of vitamin K1 results in improvement of coagulation and the prevention of intraventricular hemorrhage in premature infants.