Concentration of Twelve Plasma Proteins at Birth in Very Low Birthweight and in Term Infants

ABSTRACT. Plasma samples obtained at birth from 70 very low birth weight (VLBW) infants (gestational age 24 to 34 weeks) and from 20 term infants were analysed for concentrations of 12 different proteins. The plasma concentrations of albumin, transthyretin (TTR), retinol-binding protein (RBP), vitamin D-binding protein, apolipoprotein A I, fibronectin, orosomucoid and α₁-antichymotrypsin were significantly lower in the VLBW infants than in the term infants, whereas the values of α-fetoprotein (AFP) were significantly higher in the VLBW infants. No differences were found between the two groups for apolipoprotein A II, apolipoprotein B and transferrin. Birth asphyxia and sex had no influence on the measured plasma protein concentrations. The plasma concentrations of apolipoprotein A I and A II were significantly lower in small-forgestational age (SGA), VLBW infants compared with appropriate-for-gestational age (AGA), VLBW infants. Possible acute inflammation (defined as raised concentrations of orosomucoid or α₁-antichymotrypsin) was associated with significantly higher values of vitamin D-binding protein in both VLBW and term infants, suggesting that this protein may act as an acute phase protein in newborn infants.     

Eleven plasma proteins as indicators of protein nutritional status in very low birth weight infants

Concentrations of 11 plasma proteins were measured in 28 healthy, growing, very low birth weight, appropriate-for-gestational-age infants fed varying levels of human milk protein intake (range 1.7 to 3.9 g/kg per day). Significant positive correlations were found between mean protein intake and concentrations of 7 of the plasma proteins studied (transthyretin, retinol-binding protein, and transferrin: P less than .001; vitamin D-binding protein and apolipoprotein B: P less than .01; albumin and apolipoprotein A I: P less than .05). A weak negative correlation with mean protein intake was seen for the plasma level of orosomucoid, whereas no significant correlations were found for the plasma concentrations of fibronectin and alpha 1-antichymotrypsin. Protein intake, not energy intake, constituted the main contribution to the changes in the concentrations of transthyretin, retinol-binding protein, and transferrin. The levels of plasma transthyretin and transferrin were also strongly correlated with weight and length growth of the infants during the study as well as with other indicators of protein nutritional status such as preprandial concentrations of plasma amino acids and serum and urine urea. These data indicate that of the 11 plasma proteins studied, transthyretin, transferrin, and retinol-binding protein are the most suitable to evaluate protein nutritional status in very low birth weight infants.     

Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia

We conducted a randomized, double-blind, controlled trial to determine whether vitamin A supplementation from early postnatal life could reduce the morbidity associated with bronchopulmonary dysplasia in very low birth weight (VLBW) neonates. Forty VLBW neonates (700 to 1300 g birth weight, 26 to 30 weeks gestational age), who were oxygen dependent and required mechanical ventilation for at least 72 hours after birth, were given by the intramuscular route either supplemental vitamin A (retinyl palmitate 2000 IU) or 0.9% saline solution on postnatal day 4 and every other day thereafter for a total of 14 injections over 28 days. The study groups were comparable in gestational maturity, clinical characteristics, initial lung disease, and vitamin A status at entry into the trial. Vitamin A administration resulted in significantly higher mean plasma concentrations of vitamin A and retinol-binding protein in treated infants compared with controls. Bronchopulmonary dysplasia was diagnosed in nine of 20 infants given vitamin A supplement and in 17 of 20 control infants (P less than 0.008). Four of 19 infants in the vitamin A group and 11 of 20 in the control group required mechanical ventilation on study day 28 (P less than 0.029). The need for supplemental oxygen, mechanical ventilation, and intensive care was reduced in infants given vitamin A supplement compared with controls. Airway infection and retinopathy of prematurity were less frequent in the vitamin A group. We conclude that vitamin A supplementation at the dosage used in this trial in VLBW neonates not only improves their vitamin A status but also appears to promote regenerative healing from lung injury, as evidenced by a decrease in the morbidity associated with bronchopulmonary dysplasia.     

Calcium-regulating hormones and minerals from birth to 18 months of age: a cross-sectional study. I. Effects of sex, race, age, season, and diet on vitamin D status

The influence of sex, race, age, season, and diet (cow's milk formula v human milk) on the vitamin D and vitamin D-binding protein status in infants less than 18 months of age was investigated in this cross-sectional, prospective study of 198 infants. No differences by sex were observed in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, or vitamin D-binding protein concentrations. By race, black infants had significantly elevated serum 1,25-dihydroxyvitamin D levels relative to white infants. By age, vitamin D-binding protein concentrations increased with increasing age. By season, serum 25-hydroxyvitamin D concentrations were low in winter, whereas 1,25-dihydroxyvitamin D and vitamin D-binding protein were high in winter compared with summer. By diet, formula-fed infants had higher serum concentrations of all measured vitamin D metabolites and vitamin D-binding protein than human milk-fed infants. Thus, race, age, season, and diet exert, individually or in combination, different and significant effects on vitamin D metabolites; these should be considered in assessing infant vitamin D status.     

A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants

INTRODUCTION: Very-low-birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. METHODS: Preterm infants with birth weight < or =1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, chi, and analysis of variance. RESULTS: The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 +/- 29 g and 25.5 +/- 0.3 weeks (mean +/- SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 +/- 0.009 mg/kg/day), 35% more vitamin A (318.3 +/- 11.4 microg/kg/day), and 14% more vitamin E (3.17 +/- 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 +/- 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 +/- 0.022 microg/mL) and vitamin E (22.26 +/- 1.61 /mL) concentrations were greater in the modified group. CONCLUSIONS: The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.     

Transthyretin levels are not related to Apgar score in low birth weight and very low birth weight infants

BACKGROUND: Previous studies have reported an increased incidence of thyroid dysfunction in premature/low birth weight infants. The cord blood concentrations of transthyretin (TTR), a thyroid hormone binding protein, have also been found to be decreased in preterm infants. While thyroid hormone concentrations are decreased in sick infants, it is not known if physical condition influences TTR levels. Serial concentrations of TTR following birth have not previously been reported. AIMS: To measure serial serum concentrations of TTR in premature infants following birth, and determine whether TTR levels are related to physical condition. METHODS: A cohort of 65 premature very low birth weight (VLBW) and LBW infants were studied. Serum samples were obtained on the day of birth, and for 8 weeks following birth. Apgar scores at birth as well as the incidence of respiratory distress syndrome (RDS) were noted. RESULTS: Baseline serum T4 concentrations and Apgar scores were significantly lower in VLBW infants, while the severity of RDS was significantly higher in the VLBW group. Multivariate analyses revealed that T4 levels were negatively associated with RDS, while TSH concentrations were positively related to gestational age. TTR concentrations were not related to gestational age at birth, Apgar score, or RDS, and did not change markedly over 8 weeks. CONCLUSIONS: These findings suggest that serum TTR concentrations are not related to birth weight/gestational age and are not associated with either clinical condition at birth (as assessed by Apgar score) or the occurrence of RDS. Reference values for TTR concentrations in VLBW and LBW infants are provided from birth to 8 weeks of age.     

Visual development in very low birth weight infants

Extremely preterm infants are at risk for neurodevelopmental problems and the visual system is particularly vulnerable. However, development of visual function in preterm infants with little or no retinal or neurologic injury has not been well defined. This study compared development of visual function in preterm infants without severe retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) to that of term infants at 5-7 mo corrected age. Twenty-one very low birth weight (VLBW) preterm infants (24-32 wk gestational age, weighing < 1500 g), and 22 healthy term infants were tested at 5-7 mo corrected age. Infants with any IVH/PVL and > Stage II ROP or Plus disease were excluded. Contrast sensitivity, grating acuity, and vernier acuity were measured using swept-parameter visual evoked potentials. Thresholds and maximum amplitudes were compared between groups. VLBW and term infants showed no differences in sensitivity for contrast (67.5 versus 63.8), grating resolution (12.4 versus 12.5 cpd) or vernier acuity (1.2 versus 1.0 arcmin). However, the amplitudes for swept contrast (p < 0.03) and swept vernier offset (p < 0.04) stimuli were higher in VLBW infants. Visual thresholds in VLBW infants without serious retinal or neurologic abnormalities were not significantly different from those of term infants, suggesting that increased visual experience does not influence visual sensitivity. The higher amplitudes in VLBW infants, suggests that visual experience may affect responses to suprathreshold stimuli.     

Improved vitamin A supplementation regimen for breastfed very low birth weight infants

OBJECTIVE: Preterm infants usually have low retinol status at birth and at discharge from hospital. We have evaluated a new protocol designed to improve plasma retinol in very low birth weight infants (VLBW, birth weight < 1500 g). DESIGN: An open intervention trial was conducted in which vitamin A was given in a human milk fortifier. The daily dose of vitamin A varied according to bodyweight and was given mixed with human milk instead of as a bolus. Blood samples were collected at inclusion and at discharge from hospital. Plasma was analyzed for retinol using high-performance liquid chromatography. The daily intake of vitamin A and plasma retinol concentration was compared with the vitamin protocol normally used in Norwegian hospitals. RESULTS: Sixty VLBW infants were included and 53 completed the study. At discharge from hospital, the reference group had lower median plasma retinol concentrations compared to the modified group (0.30 microM vs. 0.49 microM, p = 0.008). Fewer infants in the modified group had plasma retinol levels below 0.35 microM (indicating reduced hepatic stores) compared to infants in the reference group (44% vs. 69%, p = 0.04). CONCLUSION: The modified protocol improved plasma retinol levels at discharge compared to the reference protocol.     

Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants

Aim: To examined the changes in basal plasma concentrations of glicentin in developing children and the postnatal and postprandial changes in plasma glicentin levels in infants. Methods: Glicentin, an active component of enteroglucagon, is considered to have a significant trophic action on the intestinal mucosa. Fasting plasma concentrations of glicentin in healthy children and in term and preterm infants were measured before and 30 min after feeding during the first 14 d of life. Results: Plasma basal concentrations of glicentin in children under 1 y of age were significantly higher than those in children aged 1 to 15 y. Plasma basal concentrations of glicentin at 5 or 6 d (2496 and 2190 pg/ml) and at 14 d (2987 and 2817 pg/ml) after birth were significantly higher than those at 1 or 2 d (1098 and 1240 pg/ml) after birth in normal birthweight (NBW) and low-birthweight (LBW) infants. There was no significant difference in the glicentin level between infants at 1 or 2 d (1864 pg/ml) and at 5 or 6 d (1910 pg/ml) after birth in very-low birthweight (VLBW) infants, but the levels at 14 d (3310 pg/ml) after birth were significantly higher than either of those levels. Plasma glicentin concentrations after feeding were significantly higher than those before feeding at 1 or 2 d and at 5 or 6 d after birth in NBW and LBW infants, but a significant increase in the plasma glicentin level after feeding was first observed at 14 d after birth in VLBW infants. There were no significant differences in the basal plasma (2401 and 2718 pg/ml) and postprandial (3007 and 3912 pg/ml) glicentin levels between breastfed and formula-fed infants.

Conclusion: The results of the study suggest that glicentin may play an important role in intestinal mucosal growth in the early period of life, although its role in VLBW infants should be further investigated.     

Plasma and urine riboflavin during riboflavin-free nutrition in very-low-birth-weight infants

BACKGROUND: Very-low-birth-weight (VLBW; birth weight <1500 g) infants receive enteral and parenteral nutriture that provides greater daily riboflavin (vitamin B2) than does term infant nutriture, and elevated plasma riboflavin develops in these infants after birth. The purpose of this study was to measure plasma and urine riboflavin concentrations in VLBW infants during riboflavin-free nutrition. Our hypothesis was that elevated plasma riboflavin develops in VLBW infants because of high daily intake and immature renal riboflavin elimination. METHODS: Eighteen clinically healthy VLBW infants received parenteral nutrition and preterm infant formula during the first postnatal month. On postnatal days 10 and 28, the infants received specially prepared riboflavin-free enteral and parenteral nutrition for the 24-hour study period. Serial collections of plasma were made at time 0 and at 12 and 24 hours. Urine was collected continuously for the 24-hour period in 4-hour aliquots. Samples were analyzed for riboflavin concentration. RESULTS: During the 24-hour riboflavin-free study period on postnatal day 10, plasma riboflavin decreased 56% from 185 +/- 37 ng/mL (mean +/- SEM), and urine riboflavin decreased 75% from 3112 +/- 960 mg/mL. Similarly, on postnatal day 28, plasma riboflavin decreased 79% from 184 +/- 32 ng/mL, and urine riboflavin concentration decreased 91% from 5092 +/- 743 ng/mL during the 24-hour riboflavin-free study period. Riboflavin half-life (t(1/2)) was 18.5 hours on postnatal day 10 and decreased 48% by postnatal day 28. Riboflavin elimination was 145.1 +/- 20.6 mg/kg per day on postnatal day 10 and increased 40% by postnatal day 28. CONCLUSION: The VLBW infants who received parenteral nutrition and preterm infant formula had elevated plasma riboflavin on postnatal days 10 and 28. Plasma riboflavin t(1,2) was shorter and renal riboflavin elimination was greater on postnatal day 28 than on postnatal day 10. Plasma riboflavin was normal after 24 hours of riboflavin-free nutrition. The pattern of plasma and urine riboflavin in VLBW infants suggests a lower daily intake would maintain plasma riboflavin close to normal.     

Serum orosomucoid concentration in newborn infants

Serum orosomucoid concentration was measured by laser nephelometry in 1970 serum samples collected from 1170 full term and preterm infants. The determinations were carried out in 1 h. Reference values are given: they show that the low levels at birth are influenced by gestational age. The concentrations increase rapidly during the first week in all infants, the adult values being reached by 10 months of age. High levels of orosomucoid concentration were detected in 85% of the infants with severe bacterial infections. Serum orosomucoid concentration proved less valuable in viral and parasitic infection. Twenty-six per cent of the sick infants without infection had a slightly elevated orosomucoid level which decreased rapidly. In the bacterial infections the evolution of serum orosomucoid concentration followed the clinical course. Thus serum orosomucoid concentration was a useful parameter for diagnosis and monitoring of bacterial infection in neonates.     

Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants.

A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month.     

Urinary S-100B concentrations in term and preterm infants at risk for brain damage

BACKGROUND: Elevated serum concentrations of S-100B, a 21-kDa protein expressed in astroglial cells, has been used to assess cerebral damage after head trauma, infection, ischemia, and perinatal asphyxia. OBJECTIVE: As S-100B is eliminated by the kidneys, we investigated the feasibility of measuring S-100B in urine of newborns with severe perinatal asphyxia, and in very low birth weight (VLBW) preterm infants at risk for neurodevelopmental impairment. METHODS: We first analyzed urine samples of 8 term or near-term newborns without major medical problems, followed by urine samples of 2 term newborns with severe birth asphyxia, and finally urine samples of 8 VLBW (gestational age 24-28 weeks) infants collected every 4 h for up to 10 days. RESULTS: Urinary S-100B concentrations in 8 term or near-term newborns without major medical problems were consistently <1 microg/l. In 2 term newborns with severe asphyxia (Apgar 0/0/0 and 0/2/4) who subsequently had widespread cerebral damage on magnetic resonance imaging, peak urinary S-100B concentrations on the first day of life were 28.1 and 28.4 microg/l, respectively. In 5/8 VLBW infants, urinary S-100B was> microg/l in samples obtained on the first day of life (range 1.2-44.9 microg/l, median 6.8 microg/l). Peak S-100B in urine samples collected during the first 12 h of life were negatively related to gestational age (R(s)=-0.882, p=0.009). Three of the 8 preterm infants had peak urinary concentrations>0 microg/l but neither ultrasound signs of brain damage nor neurodevelopmental delay at 1 year corrected age. CONCLUSIONS: The determination of urinary S-100B concentrations might be helpful in term infants with severe asphyxia, while high urinary S-100B concentrations in preterm infants are to be attributed to immaturity.     

Cognitive outcome at 2 years of age in Finnish infants with very low birth weight born between 2001 and 2006

Aim: To study cognitive outcome of premature, very low birth weight (VLBW) infants in relation to parental education and neonatal data. Methods: A regional cohort of 182 VLBW infants born between 2001 and 2006 was followed up. Brain ultrasounds (US) were examined serially until term age and brain magnetic resonance imaging at term age. Neurological status was examined systematically. Cognitive development was assessed using the Mental Developmental Index (MDI) of Bayley Scales at 2 years of corrected age. A total of 192 healthy full‐term (FT) controls were assessed with the MDI at 2 years of age. Results: The mean MDI in VLBW infants was 101.7 (SD 15.4), which was lower compared with FT controls (109.8, SD 11.7, p < 0.001). In regression analysis of the demographic and medical data of VLBW infants, postnatal corticosteroids (p = 0.04), intestinal perforation (p = 0.03) and major brain pathology (p = 0.02) were negatively associated with the MDI. In VLBW infants, the prevalence of neurodevelopmental impairment was 9.9% (3.3% MDI below 70, 7.1% cerebral palsy, 2.2% hearing aid, no blind infants). Conclusion: Cognitive development of VLBW infants seemed to have improved in comparison with earlier publications, but it differed from the FT controls. Neonatal factors affected cognitive development. Therefore, updated regional follow‐up data are important for clinicians.     

Oral vitamin A, E and D supplementation of pre-term newborns either breast-fed or formula-fed: a 3-month longitudinal study

BACKGROUND: In contrast to the studies of vitamin A and E status in children, adolescents and adults, information on preterm infants is scarce. In the present investigation we examined the vitamin A, D and E status of pre-term infants at birth, and verified whether, at 1 and 3 months, breast or formula feeding affected the plasma concentration of those vitamins while being supplemented with Uvesterol ADEC. PATIENTS AND METHODS: In this prospective study, 2 groups of consecutively recruited preterm newborns fed either breast milk or formula received 3000 IU of vitamin A, 5 IU of vitamin E and 1000 IU of vitamin D daily. Vitamin A and E were measured by high performance liquid chromatography and spectrophotometry. 25-hydroxyvitamin D, a surrogate marker for vitamin D status, was measured by radioimmunoassay, and retinol binding-protein concentration was measured by immunonephelometry. RESULTS: At birth, formula-fed and breast-milk fed infants had similar plasma concentrations of vitamin A (0.75 +/- 0.20 and 0.64 +/- 0.21 micromol/L, ns), 25-hydroxyvitamin D (34.4 +/- 25.6 and 47.5 +/- 26.7 nmol/L, ns) and vitamin E (9.5 +/- 3.2 and 8.4 +/- 3.3 micromol/L, ns). Vitamins A and E, and retinol binding-protein concentrations steadily increased with time in both groups of infants without attaining, at 3 months, values considered normal in term infants and in young children. At 3 months of age, concentrations of 25-hydroxyvitamin D reached values comparable to those observed in term infants. CONCLUSION: Plasma concentrations of vitamins A and E and of retinol binding-protein steadily increased during the the study without reaching full repletion values. At the conclusion of the study, the type of nutrition did not affect plasma vitamin concentrations.     

Growth and neurodevelopmental outcome of VLBW infants at 1 year corrected age

Objectives

To evaluate growth and neurodevelopmental outcome of very low birth weight infants (VLBW) and compare with term normal birth weight infants (NBW) till 12 months corrected age.

Design

A prospective cohort study

Setting

Tertiary care neonatal unit in northern India

Subjects

37 VLBW infants and 35 NBW infants born between January 2007 and December 2007.

Interventions

Anthropometric measurements were recorded and Z-scores were computed serially at birth, discharge, 40 weeks post menstrual age (PMA), and at 1, 3, 6 and 12 months of corrected age. Developmental quotient (DQ) at 12 months corrected age was assessed.

Results

Z-scores for weight, length and head circumference (HC) at birth were ?1.21(±0.92), ?0.98(±1.32) and ?0.70(±1.14), respectively for VLBW infants and ?0.37(±0.72), ?0.11(±0.96) and 0.05(±0.73) respectively for NBW infants. VLBW infants had a significant drop in all Z-scores by discharge (P<0.001). There was a catch up to birth scores by 12 month age. VLBW infants had significantly lower Z-scores for weight, length and HC at one year corrected age as compared to NBW infants (P =0.01, 0.04 and 0.001, respectively). DQ at 12 months was significantly lower in VLBW infants (91.5+7.8) than NBW infants (97.5±5.3) (P <0.001). DQ of small for gestational age (SGA) and appropriate for gestational age (AGA) VLBW infants was comparable.

Conclusion

VLBW infants falter in their growth during NICU stay with a catch-up later during infancy. In comparison to NBW infants, they continue to lag in their physical growth and neurodevelopment at 1 year of corrected age.     

Postnatal Left Ventricular Contractility in Very Low Birth Weight Infants

The objective of the study was to evaluate postnatal changes in left ventricular (LV) contractility in very low birth weight (VLBW) infants. An echocardiographic study comparing 18 VLBW infants without significant complications and 16 normal term infants was carried out at the Neonatal Intensive Care Unit in Akita University Medical Hospital, Japan. The echocardiographic examinations were performed within 6 hours of birth and on day 5. We obtained the relations between rate-corrected mean velocity of circumferential fiber shortening (mVcfc) and end-systolic wall stress (ESS), which were calculated from two-dimensional LV short-axis views to compensate for the distorted LV shape, and we compared these relations statistically. In both VLBW and term infants there were inverse linear correlations between mVcfc and ESS for each study period (p < 0.05). The regression line of VLBW infants had a lower y-intercept and a steeper slope than that of term infants at 6 hours of age but almost corresponded on day 5. It is concluded that the left ventricle of VLBW infants adapts to postnatal hemodynamic alterations with low contractility but operates with a contractile state similar to that of term infants on day 5.     

Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia.

We performed a randomized, double-blind, controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to receive either 2000 IU retinyl palmitate (n = 27) or saline placebo (n = 22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48%, placebo group 55%; p = 0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 micrograms/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease.     

Estimation of Digoxin Dosage in VLBW Infants Using Serum Creatinine Concentrations

ABSTRACT. Digoxin steady state plasma concentrations (C_ss) and the corresponding serum creatinine concentrations were studied in 17 VLBW infants. Birth weight was in the range of 760-1500 g (mean 1068 g), gestational age ranged from 26 to 32 weeks (mean 28.7 weeks). Digoxin steady state plasma concentrations were found in the range of 0.5-6.5 μg/ml (mean 1.88 μg/ ml) during maintenance therapy with 1.6-8.4 μg/kg BW/24 h (mean 4.4 μg/kg BW724 h) given in two divided doses intravenously. No digoxin-like immunoreactive substance could be detected in the plasma of 18 infants (10 patients with a birth weight <1500 g, 8 patients with a birth weight of 2100-4 730 g) that were not treated with digoxin. The calculated digoxin clearance ranged from 0.38-4.03 ml/min/kg BW. Serum creatinine concentrations were found in the range of 35-274 μmol/l (0.4-3.1 mg/100 ml). A hyperbolic correlation may be derived from the digoxin clearance and the corresponding serum creatinine concentration. A linear relationship was observed between the dose normalized digoxin concentrations (y=C_ss/dose in 24 h) and the respective creatinine concentrations x (v=0.52x-0.05; n=17; 5=0.24; r=0.86; p<0.01). According to this equation we suggest a dosing schedule for digoxin in VLBW infants with impaired renal function. Digoxin maintenance dose is derived from the digoxin target and the creatinine serum concentration. This dose recommendation proved reliable on four VLBW infants (birth weight 770-1260 g) with decreased renal function.     

Effects of infant risk status and maternal psychological distress on maternal-infant interactions during the first year of life

The associations of infant medical risk, prematurity, and maternal psychological distress with the quality of maternal-infant interactions during the first year of life were evaluated in a prospective, longitudinal follow-up from birth. A total of 103 high-risk very low birth weight (VLBW) infants with bronchopulmonary dysplasia, 68 low-risk VLBW infants without bronchopulmonary dysplasia, and 117 healthy term infants were seen at 1, 8, and 12 months of age. Videotaped feedings at each age were rated using the Nursing Child Assessment Feeding Scale, and mothers completed the Brief Symptom Inventory as a measure of psychological distress. VLBW infant status was related to both maternal and infant behaviors as well as to maternal distress, and these relationships varied with infant age. Overall, VLBW infants displayed fewer responsive, clear interactions, with differences from term infants increasing over time. Maternal distress was related to less cognitive growth fostering for all mothers. Because maternal distress is more prevalent in mothers of VLBW infants postpartum, intervention efforts should focus on assessment of maternal distress and the challenges posed by the interactive behaviors of VLBW infants.