Acta Paediatr 81: 864-7. 1992

Macromolecular absorption in small-for-gestational-age infants G Boehm, I Jakobsson', M Miinsson' and NCR Raiha' Department of Paediatrics. University of Leipzig. Germany and Department of Paediatrics and Experimental Research' University of Lund, Malmo, Sweden I

Boehm G, Jakobsson I, Mansson M, Raiha NCR. Macromolecular absorption in small-forgestational-age infants. Acta Paediatr 1992;81 :864-7. Stockholm. ISSN 0803-5253 Using human a-lactalbumin as a marker protein, macromolecular absorption was studied in 40 preterm infants, appropriate for gestational age (AGA), in 12 AGA term infants and in 18 preterm infants, small for gestational age (SGA). The absorption of a-lactalbumin was measured as concentration in serum after a human milk feed and expressed as pg a-lactalbumin/l serum/l human milk/kg body weight on day 7, 14,21 and 42 after delivery. The serum concentration of a-lactalbumin was correlated negatively with maturity and postnatal age. In the SGA infants, the concentration of alactalbumin was significantly higher than in the AGA infants of similar gestational age. The data show that intrauterine growth retardation causes a delayed postnatal decrease in macromolecular absorption. This may indicate delayed intestinal maturation. 0 Human a-lactalbumin, infants small for gestational age. macromolecular absorption, preterm infants I Jakobsson. Department of Paediatries, University of Lund, Malmo General Hospital, S-214 01 Malmo, Sweden

In human neonates, antigenic macromolecules can penetrate the small intestinal wall membranes in quantities which may be of immunological importance ( I , 2). The absorbed amounts of macromolecules have been found to be increased in preterm infants compared with term infants (2). There is a decrease in the serum concentrations of macromolecules with increasing postnatal age. This reduced transmission is considered to represent intestinal maturation (3, 4). Human a-lactalbumin (aLA), the dominant whey protein in human milk, is a suitable marker for investigation of macromolecular absorption in human neonates (4). Many metabolic and physiologic processes have been found to be delayed in infants small for gestational age (SGA) (5-7). In the light of these findings the present study was designed to determine possible differences in the absorption of aLA between AGA and SGA infants fed human milk exclusively.

Patients and methods Seventy infants were recruited into this prospective study: 22 A G A preterm infants with a gestational age < 30 weeks (group 1); 18 A G A preterm infants with a gestational age of 34-36 weeks (group 2); 12 A G A term infants (group 3); and 18 SGA preterm infants with a gestational age of 34-36 weeks (group 4) (Table 1). Gestational age was determined by menstrual history and clinical assessment according to Dubowitz 8t Dubowitz (8). Infants were classified as SGA if the birth weight was below the 10 percentile of the intrauterine growth charts of Lubchenco et al. (9). All infants were without malformations, signs of intrauterine infections or major postnatal clinical problems and enteral feeding was started during the first 48 h of life in infants in group 1 and on the first day of life in all other infants. No infant required total parental

Table 1. Characteristics of the infants.

Group I

Group 2

Group 3

Group 4

Classification

AGA

AGA

AGA

SGA

n

22 10/12 28.5 (27-29) I 150 (870-1430)

18 I 0/8 34.9 (34-36) 2095 (1860-2230)

12 616 40.2 (3841) 3480 (2860-3750)

18 1117 35.7 (34-36) 1640 (1250-1910)

65.4 (37.5-100) 2.6

82.9 (65.6-100)

100

1.1

0

79.7 (68.2-92.8) 2.2

Sex (male/female)

Gestational age (weeks) (mean range) Birth weight (g) (mean range) Percentage ofenteral nutrition during the first week of life" (mean range) Mean duration of supplementary iv infusions (days) a

Calculated as percentage of volume.

Macromolecular absorpLon

ACTA PRDIATR 81 (1992)

nutrition. Supplementary iv infusions were necessary for at least four days in group 1, for two days in group 2 and for four days in group 4 infants (Table 1). The infants in group 1 were fed with human milk fortified with 6 g freeze-dried human milk per 100 ml from the second week of life (10). All other infants were fed with fresh human milk during the time of the study. Enteral feeding was given as nasogastric bolus feeding via a tube: in group 1, until the 34th week of postconceptional age, and in groups 2 and 4, only during the first days of life. No tube feeding was used in group 3. The characteristics of the infants studied are shown in Table 1. To limit the number of investigations for the lowbirth-weight infants they were randomized separately in each group, to be investigated either on day 7 and 21 or on day 14 and 42 after delivery. The term infants were studied on day 7, 14 and 21. On each study day, 0.5 ml of venous blood was obtained 60 min postprandially, the serum was separated and stored at - 20 "Cuntil analysed. A competitive radioimmunoassay was used for analysis of aLA in the serum samples (4). The serum concentration of ULAwas

15 000

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m

cn

5

10 000

865

expressed in relation to the amount of human milk given per meal as pg/l serum/l human milk/kg birth weight (4). In the infants fed fortified human milk, the feeding volume was corrected by a factor of 1.5, according to the protein content of 6 g of freeze-dried human milk (1 1). For statistical analysis, Student's t-test and Spearman's rank order correlation coefficient were performed. A value o f p < 0.05 was taken as significant. The study was approved by the Ethics Committee of the Department of Paediatrics, University of Leipzig.

Results The highest concentrations of aLA were observed in all study groups on day 7 of life. In the AGA infants, the highest serum concentrations of crLA were found in the infants born most prematurely (Figs 1 and 2). On day 7 of life, group 1 had a mean concentration of 12 514 (SD 2463) pg/l serum/l human milk/kg, group 2 3926 (744) pg/l serum/l human milk/kg and group 3 112.5 (31) pg/l serum/l human milk/kg. In all three groups of AGA

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Fig. 1. Concentration of human a-lactalbumin in serum in 22 AGA

AGA38-41 w e e k s

AGA preterm infants with a gestational age of 34-36 weeks (group 2)

Fig. 2. Concentration of human a-lactalbumin in serum in 18 AGA preterm infants (group 2) and 12 term infants (group 3) in relation to

in relation to postnatal age.

postnatal age.

preterm infants with a gestational age < 30 weeks (group I ) and in 18

G Boehm er al.

ACTA PRDlATR 81 (1992)

* *

p < 0.01) (Fig. 3), but concentrations were significantly higher than those found in AGA infants of similar gestational and postnatal age (group 2 versus group 4) on all study days (Table 2).

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Fig. 3. Concentration of human a-lactalbumin in serum in 18 AGA preterm infants (group 2) and 18 SGA preterm infants (group 4) in relation to postnatal age.

Tuhk 2. Serum concentrations (mean _+ SD) of human a-lactalbumin (pg/l serum/l human milk/kg body weight) in preterm infants appropriate for gestational age (group 2) ( n = 18) and small for

gestational age (group 4) ( n = 18) fed human milk exclusively. Postnatal age (days) 7 14 21 42

Group 2

Group 4

3926 k 907 1912 k 749 553+403 93+41

6288 1296 4366k 1061 2614k 956 814_+357

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infants the serum concentrations of aLA decreased significantly with postnatal age (group 1 : r2 = 0.694, p < O . O O I ; group 2: r2=654, p