The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group. Randomised clinical trial of parenteral selenium supplementation in preterm infants. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and child outcomes.
Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease.
                A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency.
                No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity.
                Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted. To determine whether selenium supplementation of parenteral nutrition with 3 micrograms/kg/day of selenious acid is safe and effective in improving the selenium status of preterm infants.
                Thirty eight preterm infants with mean (SEM) birthweight of 1171 (38) g and gestational age 29 (0.3) weeks were randomly allocated to a non-supplemented (PN-selenium, n = 19) or supplemented (PN+selenium, n = 19) group. The study began at 2.8 (0.2) (range 1-5) days of age. Term breastfed (n = 23) and formula fed (n = 8) infants were used as a reference group.
                Initially there was no difference between the preterm groups in plasma or erythrocyte selenium or glutathione peroxidase activity. Plasma selenium declined by a mean (SEM) of -13.3 (3.2) micrograms/l from 28 (4) to 16 (3) micrograms/l over the first three weeks in the PN-selenium group, but there was no fall in the supplemented infants and no net change in either group over six weeks. Over six weeks, there was a net decline in erythrocyte selenium of -106 (27) ng/g haemoglobin in the PN-selenium group, but no change in the PN+selenium group, such that at week 6 erythrocyte selenium was lower in the PN-selenium group (401 (17) ng/g haemoglobin) than the PN+selenium group (493 (25) ng/g haemoglobin). Urinary selenium was substantially higher in the PN+selenium group at each week. Initially term and preterm plasma selenium concentrations were similar, but they increased in term breastfed infants (+17 (2) micrograms/l), with both groups of preterm infants having lower plasma selenium concentrations at week 6 compared with term breastfed infants (PN-selenium 22 (3) micrograms/l; PN+selenium 23 (4) micrograms/l and term breastfed 49 (2) micrograms/l).
                Selenium supplementation of PN at 3 g/kg/day prevented depletion in newborns, but was inadequate to achieve selenium concentrations equivalent to those of breastfed term infants. Whether higher doses are more effective remains to be determined, particularly in light of the high urinary selenium secretion in supplemented infants. Selenium supplementation of both parenteral nutrition and formulas is recommended, but the optimal form and dose remain unclear. In observational studies, adequate selenium status has been associated with better pregnancy outcomes and slowed HIV disease progression.
                We investigated the effects of daily selenium supplements on CD4 cell counts, viral load, pregnancy outcomes, and maternal and infant mortality among 913 HIV-infected pregnant women.
                In this randomized, double-blind, placebo-controlled trial, eligible women between 12 and 27 wk of gestation were given daily selenium (200 mug as selenomethionine) or placebo as supplements from recruitment until 6 mo after delivery. All women received prenatal iron, folic acid, and multivitamin supplements irrespective of experimental assignment.
                The selenium regimen had no significant effect on maternal CD4 cell counts or viral load. Selenium was marginally associated with a reduced risk of low birth weight [relative risk (RR) = 0.71; 95% CI: 0.49, 1.05; P = 0.09] and increased risk of fetal death (RR = 1.58; 95% CI = 0.95, 2.63; P = 0.08), but had no effect on risk of prematurity or small-for-gestational age birth. The regimen had no significant effect on maternal mortality (RR = 1.02; 95% CI = 0.51, 2.04; P = 0.96). There was no significant effect on neonatal or overall child mortality, but selenium reduced the risk of child mortality after 6 wk (RR = 0.43; 95% CI = 0.19, 0.99; P = 0.048).
                Among HIV-infected women from Dar es Salaam, Tanzania, selenium supplements given during and after pregnancy did not improve HIV disease progression or pregnancy outcomes, but may improve child survival. This trial was registered at clinicaltrials.gov as NCT00197561.
Supplementing very preterm infants with selenium is associated with benefit in terms of a reduction in one or more episodes of sepsis. Supplementation was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. Supplemental doses of selenium for infants on parenteral nutrition higher than those currently recommended may be beneficial. The data are dominated by one large trial from a country with low selenium concentrations and may not be readily translated to other populations.