Cord blood retinol and retinol-binding protein in preterm and term neonates

Nutrition Research, Vol. 16, No. 2, pp. 191-196.1996 Copyright 8 1996 Elwier Science Inc. Rimed in the USA. All rights reserved 0271-5317/96 $15.00 + .OO

PII SO271-5317(%)00002-8

ELSEVIER

CORD BLOOD RETINOL AND RETINOL-BINDING IN PRETERM AND TERM NEONATES

PROTEIN

Arturo Cardona-P&es, MD*, Roxana Valdds-Ramos, MSc**, Blanca Topete-Lezama, BSc**, Carlos Meza-Camacho, BSc**, Enrique UdaetaMora, MD*** * Division de Neonatologia. Instituto Nacionalde Perinatologia. ** Departamento de Investigacidn en Nutrition. Instituto National de Perinatologla. *** Departamento de Neonatolog1a. Hospital Infantil de Mexico.

ABSTRACT Vitamin A deficiency causes abnormalities in cellular replication, affecting the functional and structural integrity of epithelial cells. Based on the fact that vitamin A is transferred to the fetus in the last trimester of pregnancy, and the preterm baby may have low concentrations of this nutrient, we decided to study two groups their serum of newborns during a six month period, evaluating retinol and retinol-binding protein concentrations from cord blood samples. Group I consisted of 41 neonates with gestational age 2 37 weeks and group II of 58 newborns with gestational age at birth 5 36.6 weeks. Results showed suboptimal concentrations of retinol in protein the preterm group ( < 40 ug/dL) and retinal-binding suggestive of a relative concentrations ( < 3 mg/dL) hypovitaminosis A in the same group of patients. It is important to undertake follow-up studies during the first month of life of the preterm babies in order to evaluate the need of vitamin A supplementation therapy in this group of patients. Key words: Prematurity,

Retinol, Retinol-binding

protein, Neonates.

INTRODUCTION Vitamin A in its different forms, carotenoids and retinoids, is necessary for cellular reproduction and is considered a vital substance for preserving functional and structural integrity of epithelial cells, as it promotes normal proliferation of mucous leads to secretory cells in different organs. Its deficiency epithelial autolysis and abnormalities in cellular replication. Roxana Valdes-Ramos, MSc. author: Address of Corresponding Instituto National de Perinatologia. Departamento de Investigation 11000, en Nutrition. Montes Urales 800, Cal. Lomas Virreyes. Mexico, D.F. MEXICO. 191

192

A. CARDONA-PfkREZ

etal.

It has been reported that the accumulation of vitamin A stores in the fetus takes place during the last trimester of pregnancy (l), which means that preterm children have a higher risk to have lower various levels of this vitamin than term children, causing epithelial tissue alterations. There are some diseases, such as Bronchopulmonary Dysplasia (BPD) that are frequent in preterm babies where their recuperation is their influenced among other factors by epithelial cell regeneration and differentiation capacity, these processes may be directly associated to vitamin A levels (2). Circulating vitamin A depends on its adequate intake and the amount of retinol-binding protein (RBP). Vitamin A is kept in the liver, being liberated joined to RBP, which is synthesized in the liver. If hypoproteinemia exists, hypovitaminosis A may occur, secondary to a decreased synthesis of RBP, even if there are adequate levels of this vitamin (3). Reports on serum concentrations of Vitamin A in term newborns, indicate that these vary between 13 and 46 ug/dL while in preterm babies they are of 13 to 16 ug/dL (4,5). Recent studies in motherchild pairs report a maternal/fetal ratio of 2/l in terms of vitamin A levels (6,7). Normal values of Retinol-Binding protein are above 3 mg/dL (4). These data have led us to evaluate levels of vitamin A of preterm infants, in comparison to term neonates, in order to determine the levels of this vitamin and its transport protein at different gestational ages, based on the hypothesis that retinol and retinol binding protein would be lower in preterm than in term neonates. MATERIAL

AND METHODS

A longitudinal follow-up study was designed to study two groups of neonates: I. with gestational age 2 37 weeks, and II. gestational age 5 36.6 weeks. Gestational age was based on Capurro or last menstrual date in case of a difference of more than two weeks. Inclusion criteria were: born healthy at the Instituto National de Prinatologla, with an adequate weight for gestational age. The present study was evaluated and accepted by the Institute's ethic's committee. A 3ml blood sample was obtained from placental cord with heparin, and kept from the light, serum was kept frozen at -70C by High with nitrogen until analyzed. Vitamin A was determined Performance Liquid Chromatography according to Driskell et al radial was determined by (8).Retinol Binding Protein Diagnostics. Variation according to Behring immunodiffusion coefficients were less than 5% for both techniques and a 5% sensibility. Conversion factors for calculating molar ratios were: 286.44 g/mol for retinol and 21 kd/mol for RBP. Maternal status was not considered for selection of patients and was not evaluated. Statistical analysis was descriptive and differences between groups were determined by Student's T test for independent samples.

193

RETINOL AND RBP IN NEONATES

TABLE General

Data of Preterm

Characteristics Birth weight Gestational Length

(weeks)*

(cm) *

Head circumference Ponderal Index * p < .OOl

and Term Neonates TERM

(g) * age

1

PRETERM

3022 + 329

1736 + 554

39.4 + 1.1

33.2 + 2.3

48.4 + 1.3 (cm)

Evaluated

412

4

34.2 + .93

35 + .37

2.66 + .27

2.36 + .3

RESULTS Table 1 shows the general data, where group I consisted of 41 newborns with a mean gestational age of 39.5 + 1.05 weeks, while group II consisted of 58 newborns with a mean gestational age of 33+ 2.3 weeks. Mean weight for group I was 3022 + 329.5 g and 1736 Protein + 514.1 g for group II. Vitamin A and Retinol-Binding concentrations are shown in table 2. Mean vitamin A levels in group I were 33.87+ 7.9 ug/dL and in group II was of 29.8 + 8.26 ug/dL. Retinol-Binding Protein was 2.1 + .54 mg/dL for group I and 1.18 + .55 mg/dL in group II. Retinol/RBP molar ratio was 1.21 +0.3 and I and II respectively 1.27+ 0.39 for groups (Table 2). A statistically significant difference (p < 0.001) was found between both groups in terms of retinol and its transport protein, however, there were no differences in retinol/RBP molar ratio. DISCUSSION Cord blood studies are useful to determine the newborn's vitamin A status, before any possible changes caused by external nutritional management appear. Studies in various animal species have shown that vitamin A placental transfer occurs mainly in the last trimester of pregnancy (9-13). The exact mechanism of this process is yet unknown, it seems that maternal vitamin A associated with RBP is the main source of vitamin A for the fetus during gestation. During the last phases of pregnancy, fetal liver begins to synthesize RBP, becoming more important in the utilization of this vitamin from placental circulation. Paired maternal-fetal samples at different gestational ages have shown that the relation in healthy pregnancies is 2 to 1. If maternal vitamin A status is deficient or marginal, fetal plasma concentrations remain within normal limits or could be higher than the mother's (14-16). On the other hand, studies where the mothers have been supplemented with vitamin A, have shown that their babies' vitamin A levels are similar to those of non-supplemented

A. CARDONA-PEREZ

194

patients important

etal.

status is indicating that maternal (14,17,18) to a certain point for fetal and neonatal status.

not

TABLE 2 Retinol,

Retinol-Binding Protein and their molar in preterm and term neonates.

Indicator Retinol RBP

(ug/dL)*

(mg/dL)*

Retinol/RBP * p < .OOl

ratio

TERM

PRETERM

33.87 + 7.9

29.86 + 8.26

2.1 + .54

1.8 + .54

1.21 + .32

1.27 + .39

Comparative studies of retinol levels in cord blood of term and preterm neonates have shown that premature babies have significantly lower values of both indicators (16.0 f. 6.2 vs 23.9 + 10.2; p< 0.001) (4,5). The results of the present study also indicate a significant difference between preterm and term newborns (pcO.001) (Table 2), however, retinol levels were always around 30 in ug/dL, which is usually considered indicative of deficiency adults. The values of RBP in both groups of neonates studied (table 2), were below the cut-off point for deficiency of 3 mg/dL. In this sense, Shenai (4) observed a mean value of RBP for preterms of 2.8 + 1.2 mg/dL and 3.6 + 1.1 mg/dL for term neonates, which are well above the values found in the present study. Under normal conditions, RBP is found almost totally saturated with retinol; thus the molar ratio of retinol/RBP should be 1. While the mean of this ratio for adults is 0.82, the observed relation in studies of term neonates is of 0.51 and for preterms is of 0.39 (5). In the present study, the molar ratio was of 1.2 + 0.3 in group I and 1.26+ 0.39 in group II (table 2). Other researchers have reported molar ratios varying from 0.94 + 0.47 and 1.02 + 0.37 (7). This represents an abnormal saturation of RBP with a free plasma excess of vitamin A. This may be due to a low synthesis of RBP probably caused by hypoproteinemia, which would decrease transport and utilization of free retinol (3). We do not know the cause of this phenomenon, which leads to a more careful search for associations with other nutrients such as vitamin E, zinc and total proteins. The results of the present study, show that the premature as well as term patients evaluated have suboptimal concentrations of vitamin A (~40 ug/dL) with RBP concentrations indicative Of a is necessary to do neonatal relative deficiency (< 3mg/dL). It studies in order to establish the evolution patterns of this vitamin and its transport protein during the first months of life and establish if there is a need for supplemental therapy.

RETINOL AND RBP IN NEONATES

195

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