Selenium deficiency and the effects of supplementation on preterm infants

Freitas, Renata Germano B. O. N.; Nogueira, Roberto José N.; Antonio, Maria ngela R. G. M.; Barros-Filho, Antonio de Azevedo; Hessel, Gabriel

doi:10.1590/S0103-05822014000100019

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Revista Paulista de Pediatria

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Review • Rev. paul. pediatr. 32 (01) • Jan-Mar 2014 • https://doi.org/10.1590/S0103-05822014000100019 copy

Selenium deficiency and the effects of supplementation on preterm infants

Deficiencia de selenio y los efectos de la suplementación en prematuros

Authorship SCIMAGO INSTITUTIONS RANKINGS

Objective:

This study aimed to review the literature about blood concentrations of selenium associated with gestational age, feeding, supplementation and related clinical features in preterm infants.

Data sources:

Systematic review in the following databases: MEDLINE, PubMed, Google academics, SciELO. org, ScienceDirect (Elsevier) and CINAHL-Plus with Full Text (EBSCO). Articles published up to January 2013 with the keywords "selenium deficiency", "selenium supplementation", "neonates", "infants", "newborn" and "preterm infants" were selected.

Data synthesis:

The studies reported that low blood selenium levels are associated with increased risk of respiratory diseases. Preterm infants, especially with low birth weight, presented lower selenium levels. Selenium deficiency has also been associated with the use of oral infant formula, enteral and parenteral nutrition (with or without selenium addition). The optimal dose and length of selenium supplementation is not well-established, since they are based only on age group and selenium ingestion by breastfed children. Furthermore, the clinical status of the infant affected by conditions that may increase oxidative stress, and consequently, selenium requirements is not taken into account.

Conclusions:

Prematurity and low birth weight can contribute to low blood selenium in premature infants. Selenium supplementation seems to minimize or prevent clinical complications caused by prematurity.

review; selenium; supplementation; infant, newborn; infant, premature

Author/year	Type of study	Country	Population	Feeding
Amin et al, 1980⁽²⁸⁾	Study 1: Cross- sectional Study 2: Longitudinal	USA	Study 1: 68 preterm infants (GA 28–36wks.), 18 term infants, 50 normal children. Study 2: 8 preterm infants with severe respiratory insufficiency. Assessment until the 6^th wk of age.	PN and F
Lockitch et al, 1989⁽²¹⁾	Prospective observational longitudinal	Canada	Baseline: 56 healthy term newborns and 39 LBW infants with a mean (SD) BW of 1940±257g and 35 VLBW infants of 1064±264g with <37wks. of gestation. Assessment until the 7^th wk of life in 16 preterm infants.	PN (without Se) with or without oral intake.
Huston et al, 1991⁽⁴⁷⁾	Prospective Randomized Clinical Trial	USA	20 preterm infants (BW<1000 g). The mean (SD) GA in G1=26.7±1.5 and G2=26.5±1.2 wks. Assessment until the 60th day.	PN and EN. G1 (n = 10; 1.34µg/kg/day of selenious acid) and G2 (without Se).
Smith et al, 1991⁽²⁹⁾	Prospective Clinical Trial	USA	46 preterm infants (BW<1700 g). The mean GA was 29.3 weeks. Assessment until the 3th wk of life.	BF (n=21; 24ng Se/mL), F (n=13; 7.8 ng Se/mL), and F (n=12; 34.8 ng Se/mL).
Mask et al, 1993⁽²⁷⁾	Cross-sectional	USA	13 preterm newborns (Mean (SD) BW and GA was 1869±449g and 33.5±1.8wks.), 15 term newborns and their mothers and 15 women who were not pregnant.	(Not differentiated)
Darlow et al, 1995⁽³²⁾	Prospective observational longitudinal	New Zealand	79 preterm newborns with a mean (SD) GA of 28.3±2.5wks. And BW of 1164±254g. Assessment until the 28^th day of life.	PN (without Se), EN and BF or F.
Daniels et al, 1996⁽¹⁸⁾	Prospective Randomized Clinical Trial	Australia	Preterm newborns (G1: 19 and G2: 19) healthy term newborns (RG=32). The mean (SD) BW and GA were 1171±38g and 29±0.3wks. Assessment until the 6th wk of life.	G1:PN (without Se), G2:PN (3µg/kg/day of selenious acid) and RG (F and BF).
Bogye et al, 1998⁽⁵¹⁾	Randomized Clinical Trial	Hungary	36 preterm newborns with VLBW. BW of 975±122g and GA 27±1wk. Supplementation for 14 days.	G1 (n=18): (nasogastric EN by drip) with 4.8mg yeast (5µg of Se) G2 (n=18): not supplied
Bogye et al, 1998⁽³⁸⁾	Randomized Clinical Trial	Hungary	28 preterm newborns with birth weight and GA of 962±129g and 27±1wk. Supplementation for 14 days.	G1 (n=14): (nasograstric EN by drip) with 4.8mg of yeast (5µg of Se). G2 (n=14): not supplied
Merz et al, 1998⁽⁴⁰⁾	Prospective	Germany	34 VLBW infants with GA and BW 28.6±2.5wks. and 1075±249g respectively. Assessment until 4^th wk of life.	Mainly PN and were not specifically supplied with Se.
Klinger et al, 1999⁽³⁹⁾	Cross-sectional	Israel	29 VLBW infants with mean (SD) age and weight 26±1.7wks and 809±129g	Se: 2µg/kg/d selenious acid.
Darlow et al, 2000⁽²⁴⁾	Double-blind placebo-controlled randomized Trial	New Zealand	534 infants with BW<1500g Assessment until 36wks of life.	PN: 7µg/kg/d and F: 5µg/kg/day sodium selenite.
Winterbourn et al, 2000⁽⁴⁸⁾	Randomized controlled Trial	New Zealand	173 newborns with weight <1500g. Assessment until 36wks of life.	PN: 7µg/kg/d and F: 5µg/kg/day sodium selenite.
Sievers et al, 2001⁽⁴⁵⁾	Prospective observational longitudinal	Germany	16 preterm newborns (GA 25–32wk and BW 595–1495g), 14 term newborns with F and 17 term newborns with BF. Assessment until 1^st year of life.	BF, F and complementary feeding.
Makhoul et al, 2004⁽⁸⁾	Cross-sectional	Israel	165 preterm newborns and term newborns (24–42wks.) and their mothers.	(Not differentiated)
Mentro et al, 2004⁽⁹⁾	Prospective observational longitudinal	14 Caucasians, 3 Hispanics and 1 Asian-American	18 preterm newborns with BW of 1013g (650–1370g) and risk of BPD. Mean GA was 27 weeks. Assessment until 4^th week of life.	BF, PN, EN and F. Mean ingestion of Se in the 1^st wk was 0.82µg/kg/day and 1.7µg/kg/day in the 4^th wk.
Galinier et al, 2005⁽³⁰⁾	Cross-sectional	France	248 preterm newborns and 262 term newborns. The mean GA and BW (SD) for preterm newborns was 32.4±2.52wks. and 1845±489g.	(Not differentiated)
Nassi et al, 2009⁽¹⁰⁾	Prospective observational longitudinal	Italy	30 preterm infants with mean (SD) BW and GA of 1605±122 g and 34.5±0.5 wk. The control group included 30 term infants. Assessment until the 100^th day of life.	BF

Author	Results
Amin et al, 1980⁽²⁸⁾	The mean serum concentration in term infants (0.098±0.025μg/mL) was slightly higher than preterm infants (0.032 μg/ml), but there was not difference significant.
Lockitch et al, 1989⁽²¹⁾	The mean concentration decreased from 0.74±0.13 to 0.63±0.15μmol/L at day 7 (p=0.01) and at day 14 decreased to 0.51±0.19μmol/L (p<0.001). Se values decreased in all 16 preterm infants followed over the first 50 days. In 11 infants, levels dropped to <0.22μmol/L (17μ/L).
Smith et al,1991⁽²⁹⁾	After 3^th week there were no significant differences of Se concentration between groups (preterm infants with F and BF).
Mask et al, 1993⁽²⁷⁾	The plasma Se was lower in preterm newborns (0.08±0.02μg/mL) than term newborns (0.10±0.02μg/ml), p=0.052.
Darlow et al, 1995⁽³²⁾	There was no significant correlation between gestational period and plasma Se. The correlations among GPx and plasma Se was weak at birth (0.39) and at 28 days (0.17).
Merz et al, 1998⁽⁴⁰⁾	After birth the value of plasma Se was 34.2μg/L and reduced to 16.1μg/L after 4 weeks (p<0.001).
Klinger et al, 1999⁽³⁹⁾	No correlation was observed between the plasma Se and gestational age (r=0.27, p=0.16). There was significant correlation between gestational age and the level of T4 (r=0.45; p=0.02).
Winterbourn et al, 2000⁽⁴⁸⁾	There was no statistically significant difference in GA between the group with and without Se.
Sievers et al, 2001⁽⁴⁵⁾	Plasma Se concentrations in preterm newborns were 11.7 (6.5–20.8)μg/L (assessment in the hospital). At 4 months: preterm newborns = 11.6 (8.8–16.7)μg/L, term newborns fed with IF=31.3 (24.3–47.5)μg/L and term newborns BF=45.6 (27.1–65.1)μg/L.
Makhoul et al, 2004⁽⁸⁾	Linear relationship between umbilical cord blood concentrations and GA (r =0.341, p<0.0001).
Mentro, Smith, Moyer-Mileur, 2004⁽⁹⁾	Se concentrations decreased from the 1^st to 4^thwk of life. Plasma Se (SD)=0.97±0.21μmol/L in the 1^st wk and 0.72±0.27 μmol/L in the 4^th wk (p=0.001). There was not change in plasma GPx among week 1 and 4. The erythrocyte GPx increased along the time period (t =-3.38; p=0.004) and was associated to the GA.
Galinier et al, 2005⁽³⁰⁾	Se concentration increased with GA from 0.4±0.1μmol/L (26^thto 33^rd week) to 0.5±0.1μmol/L (from the 33^rd to the 37^th week) and 0.6±0.1μmol/L (>37^th weeks) (p<0.001, r=0.593).
Nassi et al, 2009⁽¹⁰⁾	Up until 20 days postnatal, the GPx was lower in the preterm infants than in the term infants.

Author/year	Results
Darlow et al, 1995⁽³²⁾	Between 48h and 28 days of life, it was observed that each 0.1µmol/L decrease in plasma Se was associated with a 28% increase in the number of days the infants received O₂ (95%CI -0.5–64; p= 0.06). In the 28th day, plasma Se was significantly lower in preterm newborns with CLD (p<0.001). Mean plasma Se was lower in preterm newborns with BPD. And each 0.1 µmol/L decrease in plasma Se was associated with a 58% increase in days of O₂ dependency.
Daniels et al, 1996⁽¹⁸⁾	When boys were analyzed separately, it was noticed that the incidence of CLD is similar between groups (60% in BW without supplementation and 63% in BW with supplementation).
Merz et al, 1998⁽⁴⁰⁾	Se values were not significantly different among the preterm infants with and without BPD.
Klinger et al, 1999⁽³⁹⁾	26 infants was diagnosed with Se deficiency (serum levels were <0.72µM). Low values of T4 were found in 10 of the 26 children who also had low levels of Se, but it was not observed low levels of TSH. No correlation was observed between the plasma Se and T4 (r=0.36; p=0.06) or TSH (r =0.06; p=0.76).
Darlow et al, 2000⁽²⁴⁾	Before randomization the mean plasma Se was 0.33 µmol/l in both groups. In 28 days it had increased to 0.56μmol/L in the supplemented infants, but had dropped to 0.29μmol/L in the infants without Se (p<0.0001). The lower plasma Se found before randomization was associated with increased respiratory morbidity. After the first week, the infants with lower supplementation had an episode of sepsis (p<0.038).
Winterbourn et al, 2000⁽⁴⁸⁾	There was a weak negative correlation with GPx in the 36^thweek (correlation coefficient, -0.23, p=0.01). Regarding MDA, there was no correlation with plasma Se and GPx at any given moment. Therefore, Se supplementation did not influence the levels of these markers.
Mentro et al, 2004⁽⁹⁾	Se ingestion in the 1^st week was associated with a reduction in O₂ dependency in the 28^th day.

Author/year	Results
Amin et al, 1980⁽²⁸⁾	Premature infants without Se supplemented had low Se levels the 2^nd week (0.063μg/ml). But when the preterm infants were fed with formula (with Se), the concentrations increased to 0.079μg/ml the 4^th-6^th week of age.
Huston et al, 1991⁽⁴⁷⁾	Se concentrations dropped in infants with and without added Se when PN was discontinued, but were significantly higher in the preterm infants supplemented with EN. GPx demonstrated a significant increase in supplemented group with EN and then tended to fall. In preterm without Se, GPx tended to increase; then dropped significantly when PN was discontinued.
Smith et al, 1991⁽²⁹⁾	At the 3^rd week, the plasma Se was greater in preterm infants BF than the preterm infants fed with F (p<0.05). There were no differences between groups for GPx concentrations.
Darlow et al, 1995⁽³²⁾	A reduction in plasma Se concentration was not significantly correlated with the 28^th day of PN.
Daniels et al, 1996⁽¹⁸⁾	Along the 3 weeks, while all newborns received a mean 82% of daily energy by PN, Se plasma decreased in the PN group without Se (p=0.001; n=17) and maintained the levels in PN with Se. Therefore, in infants without Se, plasma Se levels were significantly lower in the 3^rd week (p=0.026). Se plasma concentration was ≤10μg/L and associated with deficiency symptoms in 24% of the PN group without Se and 13% in the PN group with Se. 3^rd to 6^th week: Among the RG, plasma Se increased in newborns BF (p=0.001; n=23) and decreased in newborns with F (p=0.039; n=8). Among preterm newborns, there was no significant change. 6^th week: preterm newborns (with PN) and term newborns (with F) showed a reduction in Se plasma concentration compared to term newborns (with BF) (p<0.001). The GPx activity increased in supplemented infants (p=0.042) and there was no change in unsupplemented infants (p=0.264).There was no difference in GPx among the groups at week 3 and 6.
Bogye et al, 1998⁽⁵¹⁾	In the EN group without supplementation, mean serum Se concentration decreased significantly in 2 weeks from 34.4±20.4μg/L to 26.1±16.6μg/L (p<0.005). In the supplemented group, it increased from 36.1±12.8μg/L to 43.5±7.9μg/L (p<0.01).
Bogye et al, 1998⁽³⁸⁾	In the EN group without supplementation, the mean serum Se concentration decreased significantly in 2 weeks from 25.9±6.8 to 18.2±6.4μg/L (p<0.004). In the supplemented group, it increased significantly from 32.1±8.5 to 41.5±6.5μg/L (p<0.004).
Winterbourn et al, 2000⁽⁴⁸⁾	Supplementation resulted in a significant increase in plasma Se, virtually doubling the value compared to values observed before supplementation, with the major part increasing in the first week. Supplementation also prevented a decrease in GPx, already showing a statistically significant difference in the 1^st week between groups. There was no significant difference in carbonyl protein concentrations and MDA between the supplemented group and the non-supplemented group.

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