Journal of Pediatric Ophthalmology and Strabismus

Relationship Between Serum Inositol Concentration and Development of Retinopathy of Prematurity: A Prospective Study

Charles A Friedman, MD; John McVey, MD; Michael J Borne, MD; Maurice James, MD; Warren L May, PhD; David M Temple, MD; Kenny K Robbins, MD; C Jason Miller, MD; John E Rawson, MD

Abstract

ABSTRACT

Purpose: To examine the relationship between the intake of sugar inositol, serum inositol levels, and ROP in three groups of low birthweight infants receiving feedings containing various concentrations of inositol.

Methods: Infants with a birthweight <1 500 g, with severe lung disease, were eligible for the study when they began enteral feedings. Infant formulas contained three different inositol concentrations: 2500, 710, and 242 pmol/L Serum inositol concentrations were averaged over specific time intervals. A logistic regression model was used to investigate the confounding effect of duration of mechanical ventilation and oxygen therapy, birthweight, Apgar score, and serum inositol concentration on development of ROP.

Results: Infants receiving high inositol formula and with higher serum inositol concentrations at birth and after 30 days had a statistically significant lower incidence of severe ROP than those receiving the lower inositol formula and with lower serum concentrations (P<.05). The effective serum inositol concentration (EC90) associated with lesser disease was >215 pmol/L By logistic regression, the odds of developing severe ROP were greater among infants with low serum inositol concentration (odds ratio=4.7, 95% confidence interval 0.90-24.8, P=.01 7).

Conclusion: Inositol supplementation may help prevent the most severe form of ROP.

Journal of Pediatric Ophthalmology and Strabismus 2000;37:79-86.

Abstract

ABSTRACT

Purpose: To examine the relationship between the intake of sugar inositol, serum inositol levels, and ROP in three groups of low birthweight infants receiving feedings containing various concentrations of inositol.

Methods: Infants with a birthweight <1 500 g, with severe lung disease, were eligible for the study when they began enteral feedings. Infant formulas contained three different inositol concentrations: 2500, 710, and 242 pmol/L Serum inositol concentrations were averaged over specific time intervals. A logistic regression model was used to investigate the confounding effect of duration of mechanical ventilation and oxygen therapy, birthweight, Apgar score, and serum inositol concentration on development of ROP.

Results: Infants receiving high inositol formula and with higher serum inositol concentrations at birth and after 30 days had a statistically significant lower incidence of severe ROP than those receiving the lower inositol formula and with lower serum concentrations (P<.05). The effective serum inositol concentration (EC90) associated with lesser disease was >215 pmol/L By logistic regression, the odds of developing severe ROP were greater among infants with low serum inositol concentration (odds ratio=4.7, 95% confidence interval 0.90-24.8, P=.01 7).

Conclusion: Inositol supplementation may help prevent the most severe form of ROP.

Journal of Pediatric Ophthalmology and Strabismus 2000;37:79-86.

INTRODUCTION

Retinopathy of prematurity (ROP) condnues to be a major complication for low-birthweight infants with severe eye disease, defined as stage 3 or 4 ROP, occurring in 15%-20% of surviving infants.1,2 The incidence of the disease is inversely related to gestational age and birthweight, and correlates with the severity of underlying conditions such as respiratory failure due to hyaline membrane disease.3

Although the benefit of treatment of threshold ROP with cryotherapy4 and laser photocoagulation has been established,5 only meticulous attention to arterial blood gas values and continuous monitoring of peripheral oxygen saturation can help prevent ROP from developing in infants receiving oxygen therapy. Hallman et al6 noted that a group of lowbirthweight infants given the sugar inositol (hexahydroxycyclohexane) had a lower incidence of severe ROP than a control group (.#=.014), but no follow-up study of the relationship between inositol intake or serum inositol concentration and the development of ROP has been published.

This study examined the relationship between inositol intake or serum inositol concentration and the development of ROP in a group of low birthweight infants receiving feedings containing various concentrations of inositol. If an inverse relationship does in fact exist between inositol concentration and ROP severity, we may be able to protect highrisk infants against ROP by supplementing with this sugar.

MATERIALS AND METHODS

This study was conducted at two referral hospital neonatal intensive care units between October 1994 and June 1998. The study protocol was reviewed and approved by the institutional review board of each institution. Infants who met the criteria were entered into the study after informed parental consent was obtained.

Study Population

Infants with birthweights ≤1500 g and with lung disease severe enough to require intubation, mechanical ventilation, and surfactant replacement therapy were eligible for entry when they began enteral feedings. Beginning on die third day after birrh, all infants received parenteral alimentation consisting of glucose, amino acid, and lipid infusions and were gradually weaned to full enteral feedings of 150 mL/kg per day. Intravenous solutions contained 1 mL/dL of a multivitamin preparation (MVI Pediatric, Astra Pharmaceutical, Westborough, Mass). All infants also received 0.25 mL/day of a multivitamin oral supplementation (Poh/ViSol, Mead Johnson and Co, Evansville, Ind) after achieving full-strength feedings.

Infant formulas at die study institutions contained different inositol concentrations: a high-density 30-calorie/oz formula containing 2500 umol/L inositol (high-inositol) and a 24-calorie/oz formula containing 242 pmol/L inositol concentration (lowinositol). The high-inositol formula also had a higher concentration of fat-soluble vitamins than the low-inositol formula (A, 8024 versus 5397 IU/L; D, 1410 versus 1200 IU/L; E, 45 versus 32 IU/L). Mothers who elected to breast feed dieir preterm infants provided a basis for a third formula that consisted of expressed breast milk supplemented with calories and minerals; it contained 24 cal/oz and a per patient mean (±SD) inositol concentration of 710±536 pmol/L, range 225-1400 pmol/L (medium-inositol).

The formula for the first 48 nonbreast-fed infants entered into the study was assigned by sequential random card selection; randomization ended when the high-inositol formula was no longer available. The study was then extended to include an additional 23 low-inositol infants.

Assignment to expressed breast milk was by maternal election to breast feed. Ross Products Division of Abbott Laboratories (Columbus, Ohio) provided the high- and low-inositol formulas and the feeding supplement for expressed breast milk. The three feeding groups were compared by demographic and clinical risk variables.

Primary outcome variables were the incidence and maximum severity of ROP and die need for laser surgery, as determined by ophthalmologists who used standard ROP classification criteria7 and who were unaware of which feeding die infants were receiving. Retinopathy of prematurity was classified as no, moderate (stage 1-2 disease), or severe (stage 3-4 disease with or without die need for laser surgery). Approximately 50 pL of blood was obtained at least twice weekly during hospitalization and the serum frozen at - 200C until analyzed. In most cases, the serum remaining after standard laboratory tests was adequate for inositol analysis; additional blood samples were taken as necessary. Serum inositol concentrations during hospitalization were related to die presence and stage of ROP by standard statistical analyses. Inositol concentrations in serum were averaged over specific time intervals, eg, 0-3 days, 4-7 days, 7-30 days, and mondih/ thereafter.

Mean inositol concentrations were compared for the feeding groups from birth to discharge. Secondary outcome variables were duration of mechanical ventilation and oxygen therapy, incidence of radiographically documented necrotizing enterocolitis and culture-documented bacteremias, the use of glucocorticoids to ameliorate chronic lung disease, and death. Clinical data and feedings were recorded in a computerized database. The results of ophthalmologic examinations were recorded on standard forms.7

Table

TABLE 1PATIENT BIRTH CHARACTERISTICS COMPARED BY FORMULA INOSITOL CONCENTRATION*

TABLE 1

PATIENT BIRTH CHARACTERISTICS COMPARED BY FORMULA INOSITOL CONCENTRATION*

Ten microliters of a 1 :20 dilution of serum in water containing mannitol as an internal standard were injected into a high-pressure liquid Chromatograph. The analysis used a Carbopac MAl carbohydrate column (Dionex Corp, Houston, Tex) with a mobile phase of 480 mM NaOH at 0.4 mL/min flow rate, a pulsed amperometric gold electrode detector, and computerized data analysis referencing an inositol standardization curve.8 Samples were analyzed in duplicate. The assay was linear ±10% in the range 50-1000 pmol/L inositol.

Statistical Analysis

Categorical data were analyzed using chi-square or Fisher's exact tests where appropriate. Continuous variables were analyzed using analysis of variance (ANOVA) or nonparametric tests when parametric assumptions were in question. Statistical significance was defined as a .P value <.05. A logistic regression model was used to investigate the confounding effect of duration of mechanical ventilation and oxygen therapy, birthweight, 5-minute Apgar score, and serum inositol concentration on development of ROP. The demographic and clinical variables of each feeding group were compared to detect whether differences in these parameters existed. Effect measures were reported as odds ratios (OR) with 95% confidence interval (CI).

RESULTS

Ninety-three infants were entered into the study. Two died prior to ophthalmic examination, and insufficient serum samples were available for 3 infants, leaving 88 infants for analysis. Half of the first 48 infants were randomized to receive highinositol and half to receive low-inositol formula. An additional 23 nonbreast-fed infants were not randomized and received low-inositol formula. Seventeen infants whose mothers elected breast feedings were classified as receiving medium-inositol. There were no statistically significant differences (P>.10) in the birth characteristics and clinical outcomes of the three feeding groups (Tables 1 and 2). There also were no statistically significant differences in patient demographics and clinical outcomes for the 23 low-inositol formula-fed infants who were not in the initial randomization process when compared to the 24 low-inositol formula-fed infants who were randomized (Table 3); therefore, all 47 low-inositol formula-fed infants were subsequendy considered as one group.

The relationship between serum inositol concentration, postnatal age, and ROP is shown in Table 4. Serum inositol concentration declined progressively in all study patients, with the patients who ultimately developed any stage ROP having lower concentrations just after birth (days 0-3) (P=.04), and declining to lower values after 30 days (P=.02), than patients with no ROP. By plotting die apparent relationship between increasing serum inositol concentrations after 30 days postnatal age against the decreasing probability of severe ROP, the effective concentration at the 90% level (EC90) associated with no or lesser disease was ≥215 µmol/L (Figure).

Table

TABLE 2PATIENT CLINICAL OUTCOME COMPARED BY FORMULA INOSITOL CONCENTRATION

TABLE 2

PATIENT CLINICAL OUTCOME COMPARED BY FORMULA INOSITOL CONCENTRATION

Table

TABLE 3COMPARISON OF CLINICAL OUTCOME FOR LOW-INOSITOL FORMULA CONCENTRATION FOR RANDOMIZED AND NONRANDOMIZED PATIENTS

TABLE 3

COMPARISON OF CLINICAL OUTCOME FOR LOW-INOSITOL FORMULA CONCENTRATION FOR RANDOMIZED AND NONRANDOMIZED PATIENTS

This analysis suggested diat infants >30 days old with high serum levels of inositol have a lower risk of severe ROP. However, because of possible confounding effects such as differences in Apgar scores, duration of mechanical ventilation and oxygen therapy, gestational age, and birthweight, each of diese variables was examined individually. As expected, there was a statistically significant association between duration of mechanical ventilation, duration of oxygen therapy, and ROP (P<.001) (Table 5), and between infants of die lowest gestational age and birthweight and the development of severe ROP (P<.001) (Table 6). Infants receiving the low-inositol formula had a higher incidence of severe ROP (P=M) (Table 7) and a lower mean serum inositol concentration after 30 postnatal days than infants receiving die medium- or high-inositol formula (P=.04). Furthermore, when only patients with lower birdiweights (<1250 grams) were considered, the distribution of patients with severe ROP among the high-, medium-, and low-inositol feeding groups was not statistically significantly different compared to the distribution of patients of all birthweights (ie, <1500 g) with severe ROP among the three feeding groups (0%, 25%, and 75% compared to 7%, 21%, and 72%, respectively [P>.10] for high-, medium-, and low-inositol feedings).

Table

TABLE 4MEAN SERUM INOSITOL CONCENTRATIONS IN STUDY INFANTS BY POSTNATAL ACE AND RETINOPATHY OF PREMATURITY (ROP) STAGE

TABLE 4

MEAN SERUM INOSITOL CONCENTRATIONS IN STUDY INFANTS BY POSTNATAL ACE AND RETINOPATHY OF PREMATURITY (ROP) STAGE

In a logistic regression model that adjusted for formula, duration of oxygen therapy, and birthweight as continuous variables, each decrease of 100 pmol/L in serum inositol concentration produced nearly a 4.3-fold increase in the odds of developing severe ROP. This analysis demonstrated that after adjusting for weight, feeding type, and duration of oxygen therapy, those with low serum inositol concentrations (EC90 <215 pmol/L) beyond 30 days postnatal age and low inositol intake are four to nearly six times more likely to develop severe ROP rhan infants with higher inositol intake and higher serum inositol concentration (Table 8).

DISCUSSION

Although the etiology of ROP is multifactorial,2,3 this study suggests, by statistical inference, that inositol supplementation helped prevent the severest form of the disease. As reported by other authors,1'2 prolonged mechanical ventilation and oxygen treatment along with birthweight <1000 g were significant risk factors. Infants who ultimately developed any stage ROP had lower mean serum inositol concentration shortly after birth than those who did not (280±177 pmol/L versus 415±243 pmol/L; P=.04) and after 30 postnatal days (151±52 pmol/L versus 233±121 µmol/L; P=.02) for rhose with severe ROP compared to those with no ROP. Prolonged oxygen exposure, birthweight <1000 g, and low serum inositol concentration (EC90 <215 pmol/L) after the first postnatal month were further associated with poor eye outcome (OR= 4.7, CI: 0.90-24.8, P=.017).

Figure: Probability of stage 3 or 4 ROP versus inositol concentration.

Figure: Probability of stage 3 or 4 ROP versus inositol concentration.

Table

TABLE 5RELATIONSHIP OF THE DURATION OF MECHANICAL VENTILATION AND OXYGEN THERAPY TO RETINOPATHY OF PREMATURITY (ROP) STAGE

TABLE 5

RELATIONSHIP OF THE DURATION OF MECHANICAL VENTILATION AND OXYGEN THERAPY TO RETINOPATHY OF PREMATURITY (ROP) STAGE

Table

TABLE 6RELATIONSHIP OF 5-MINUTE APGAR SCORE, GESTATIONAL AGE, AND BIRTHWEIGHT TO RETINOPATHY OF PREMATURITY (ROP) STAGE

TABLE 6

RELATIONSHIP OF 5-MINUTE APGAR SCORE, GESTATIONAL AGE, AND BIRTHWEIGHT TO RETINOPATHY OF PREMATURITY (ROP) STAGE

Table

TABLE 7RELATIONSHIP OF FORMULA INOSITOL CONCENTRATION TO SERUM INOSITOL CONCENTRATION AND RETINOPATHY OF PREMATURITY (ROP)

TABLE 7

RELATIONSHIP OF FORMULA INOSITOL CONCENTRATION TO SERUM INOSITOL CONCENTRATION AND RETINOPATHY OF PREMATURITY (ROP)

This prospective investigation differs from two recent reports on the role of inositol in eye disease. First, the Hallman et al6 study, while concluding that high intravenous inositol supplementation during the first 7-10 postnatal days decreased the expected incidence of severe ROP, was not designed as a prospective evaluation of inositol and ROP, but rather was a secondary finding in a study of the role of inositol in ameliorating lung disease in infants. That study, which included infants with somewhat greater birthweight (<2000 g) than our patients, noted that newborns whose serum inositol concentrations maintained >380 pmol/L for the first two postnatal weeks had a decreased incidence of poor eye outcome compared to patients receiving no supplementation (P=.0l4). A more recent study9 failed to find any association between inositol serum concentrations and ROP in groups of infants fed formula supplemented to 1110 umol/L compared to controls; however, no formula in that report contained as much inositol as in our highest supplemented group (2500 pmol/L), and most infants' serum inositol concentrations after 30 days postnatal age averaged < 1 50 umol/L.

Table

TABLE 8PREDICTIVE VALUE FOR SEVERE RETINOPATHY OF PREMATURITY (STAGES 3-4) OF LOW-INOSITOL SERUM CONCENTRATION, LOW-INOSITOL FORMULA, PROLONGED OXYGEN THERAPY, AND LOW BIRTHWEIGHT COVARIATES IN HIGHEST RLSK INFANTS

TABLE 8

PREDICTIVE VALUE FOR SEVERE RETINOPATHY OF PREMATURITY (STAGES 3-4) OF LOW-INOSITOL SERUM CONCENTRATION, LOW-INOSITOL FORMULA, PROLONGED OXYGEN THERAPY, AND LOW BIRTHWEIGHT COVARIATES IN HIGHEST RLSK INFANTS

Inositol is synthesized in the placenta from glucose10 and is present in high concentrations in breast milk, including the colostrum of mothers delivering prematurely,11 although we found that the inositol concentration in breast milk varied considerably during the prolonged feeding times of our breast-fed preterm infants, as indicated by the large standard deviation and wide range of breast milk inositol concentrations.

The role of inositol in the development of die eye is unknown, as is die mechanism by which it could ameliorate ROP. Retinopathy of prematurity is a neovascularizing disease. In the first phase, hyperoxia causes intense vasoconstriction, resulting in retinal ischemia. The next phase is characterized by vascular proliferation, which is caused by release of excessive angiogenic factor (vascular endothelial growth factor) elaborated by the ischemic retina.12,13 Vascular endothelial growth factor is a potent mitogen that acts on vascular endothelial growth factor receptors in endodielial membranes, resulting in tyrosine kinase activation of an intracellular phosphorylation cascade, including activation of phospholipase C and phosphatidylinositol-3 kinase.14 This leads to endothelial proliferation, in part through stimulation of Ras-dependent cellular processes15 and mobilization of intracellular calcium.16

No published study has investigated whether exogenous inositol could prevent the initial hyperoxia-induced retinal vasoconstriction in ROP or block VEGR upregulation in the second phase of retinal vessel proliferation. In a mouse model for folate-resistant neural tube defects, however, oral inositol (250-400 mg/kg) prevented neural tube defects at serum inositol concentrations as low as 50 pg/mL (280 pmol/L).17 The neural protective effect was initiated by increased flux through the inositol phospholipid cycle mediated by protein kinase C, which upregulated retinole acid receptor beta RAR-beta). We speculate that the ameliorating effects of inositol supplementation on ROP also may involve an increased flux through inositol phospholipid pathways, perhaps also requiring vitamin A.

The formulas fed to die three infant groups differed not only in inositol concentration but also in calories and vitamin A and E content. However, as Table 2 shows, die differences in calorie content had no statistically significant effect on mean weight gain. Since the excess absolute amount of those vitamins in die high-inositol diet compared to the low-inositol diet (540 IU vitamin A and 1.9 IU vitamin E, per kg) are small in comparison to therapeutic doses of A, 2000 IU,1819 and E, 100 IU,20 they are unlikely to be significant confounding factors. There were no statistically significant differences in known risk factors, including birthweight, duration of mechanical ventilation, oxygen therapy, gender, and 5-minute Apgar score among the three feeding groups.

No statistically significant deleterious effects direcdy attributable to the high inositol formula feeding were found, but, as with any high density feeding, caution regarding necrotizing enterocolitis must be exercised. There were three deaths in die high-inositol group, one related to chronic pulmonary disease and two attributed to necrotizing enterocolitis, compared to rwo deaths in the lowinositol group, one due to necrotizing enterocolitis and one to sepsis, and no deaths in the mediuminositol group. There was no statistically significant difference in the distribution of ROP among die deaths. In addition, the high-inositol formula-fed infants' mean birthweight was 100 g more than that of die low-inositol formula-fed infants in whom severe ROP was more common. This birthweight discrepancy was less (838 ± 1 13 g versus 771 ± 120 g; P>A0) when only infants of the lowest birthweight (<1000 g) and consequently at highest risk for ROP are compared for inositol intake. Nevertheless, the birthweight discrepancy, while not statistically significantly different, could have prejudiced our ROP data against the low-inositol formula-fed group.

CONCLUSION

Formula supplementation with high inositol concentration for infants at risk for ROP may reduce the incidence of severe ROP. Higher serum inositol concentrations, particularly after 30 postnatal days, predicted a decreased incidence of severe ROP even in the presence of prolonged oxygen dierapy and birthweight <1000 g. Although most of our patients were in the highest risk categories for severe ROP (eg, birthweight <1000 g and oxygen therapy >30 days), our conclusions about the role of inositol in preventing severe ROP are limited by the small total numbers of at risk patients. However, these results may help in the design of larger studies directed at the use of inositol supplementation for prevention of severe ROP.

References

1. Gibson DL, Sheps SB, Uh SH, Schechter MT, McCormick AQ. Retinopathy of prematurity-induced blindness: birth weight-specific survival and the new epidemic. Pediatrics. 1990;86:405-412.

2. Keith CG, Doyle LW. Retinopathy of prematurity in extremely low birth weight infants. Pediatrics. 1995;95:42-45.

3. Avery GB, Glass P. Retinopathy of prematurity: what causes it? Clin PerinatoL 1988;15:917-928.

4. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicentcr trial of cryotherapy for retinopathy of prematurity: 1 year outcome. Structure and function. Arch Ophthalmol 1990;108:1408-1416.

5. Iverson DA, Trese MT, Orgel IK, Williams GA. Laser photocoagulation for threshold retinopathy of prematurity. Arch Ophthalmol 1991;109:1342-1343.

6. Hallman M, Bry K, Hoppu K, Lappi M, Pohjavouri M. Inositol supplementation in premature infants with respiratory distress syndrome. N Engl J Med 1992;326:1233-1239.

7. Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol 1 984; 1 02: 1 1 30-1 1 34.

8. Lauro PN, Craven PA, DeRubertis FR Two-step high-performance liquid chromatography method for determination of myoinositol and sorbitol. Anal Biochem. 1 989; 1 78:33 1 -335.

9. Carver JD, Strongquist CI, Benford VJ, Minevini G, Benford SA, Bamess LA. Postnatal inositol levels in preterm infants. / PerinatoL 1997;17:389-392.

10. Quirk JG, Bleasdale JE. Myo-inositol homeostasis in the human fetus. Obstet Gynecol 1983;62:41-44.

11. Holub BJ. The nutritional importance of inositol and the phosphoinositides. NEnglJMed. 1992;326:1285-1286.

12. Alon T, Hemo 1, hin A, Peer J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1995;1:1024-1028.

13. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. NEnglJMed 1994;331:480-487.

14. Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992:258:607614.

15. Hu Q, Klippel A, Muslin AJ, Fand WJ, Williams LT. Ras-dependent induction of cellular responses by consetutively activated phosphatidyUnositol-3 kinase. Science. 1995:268:100-102.

16. Divecha N, Irvine RF. Phospholipid signaling. Cell 1995:80:269278.

17. Greene NDE, Copp AJ. Inositol prevents folate-resisrant neural tube defects in the mouse. Nat Med 1997;3:60-66.

18. Kennedy KA, Stoll BJ, Ehrenkranz RA, et al. Vitamin A to prevent bronchopulmonary dysplasia in very low birth weight infants: has rhe dose been too low? The NlCHD Neonatal Research Network. Early Hum Dev. 1997;49:19-31.

19. Verma RP, McCulloch KM. Worrell L, Vidyasagar D. Vitamin A deficiency and severe bronchopulmonary dysplasia in very low birth weight infants. Am J Perinatol 1 996; 1 3:389-393.

20. Johnson L, Quinn GE, Abassi S, et al. Severe retinopathy of prematurity in infants wirh birth weights less than 1250 grams: incidence and outcome of treatment wirh pharmacologic serum levels of vitamin E in addition to cryotherapy from 1985-1991. Pediatr. 1995;27:632-639.

TABLE 1

PATIENT BIRTH CHARACTERISTICS COMPARED BY FORMULA INOSITOL CONCENTRATION*

TABLE 2

PATIENT CLINICAL OUTCOME COMPARED BY FORMULA INOSITOL CONCENTRATION

TABLE 3

COMPARISON OF CLINICAL OUTCOME FOR LOW-INOSITOL FORMULA CONCENTRATION FOR RANDOMIZED AND NONRANDOMIZED PATIENTS

TABLE 4

MEAN SERUM INOSITOL CONCENTRATIONS IN STUDY INFANTS BY POSTNATAL ACE AND RETINOPATHY OF PREMATURITY (ROP) STAGE

TABLE 5

RELATIONSHIP OF THE DURATION OF MECHANICAL VENTILATION AND OXYGEN THERAPY TO RETINOPATHY OF PREMATURITY (ROP) STAGE

TABLE 6

RELATIONSHIP OF 5-MINUTE APGAR SCORE, GESTATIONAL AGE, AND BIRTHWEIGHT TO RETINOPATHY OF PREMATURITY (ROP) STAGE

TABLE 7

RELATIONSHIP OF FORMULA INOSITOL CONCENTRATION TO SERUM INOSITOL CONCENTRATION AND RETINOPATHY OF PREMATURITY (ROP)

TABLE 8

PREDICTIVE VALUE FOR SEVERE RETINOPATHY OF PREMATURITY (STAGES 3-4) OF LOW-INOSITOL SERUM CONCENTRATION, LOW-INOSITOL FORMULA, PROLONGED OXYGEN THERAPY, AND LOW BIRTHWEIGHT COVARIATES IN HIGHEST RLSK INFANTS

10.3928/0191-3913-20000301-06

Sign up to receive

Journal E-contents