Cord blood glutathione depletion in preterm infants: correlation with maternal cysteine depletion

Abstract

Background: Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants.

Objective: Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH.

Methodology: Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry.

Principal findings: Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants.

Conclusion: The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates.

Figure 1. Glutathione concentration [GSH] in erythrocytes from maternal blood (A), venous umbilical cord blood (B) and arterial umbilical cord blood (C) of preterm and full-term subjects.

The boxplot shows the median (central horizontal line) and includes the 25^th (lower box border) to 75 ^th percentile (upper box border) of [GSH] (µmol/L). Preterm (n = 16) were compared with full-term (n = 16) subjects. Significant differences were observed between the two groups (p<0.05), as assessed with the Mann-Whitney U test.

Figure 2. Correlation between glutathione concentration [GSH] (A) or cysteine concentration [cys] (B) in venous umbilical cord of preterm and full-term subjects and their maternal blood.

[GSH] or [cys] in venous umbilical cord blood are positively and significantly correlated with those in maternal blood (R² = 0.65; p<0.05 for GSH and R² = 0.62; p<0.05 for cysteine) as assessed with the Mann-Whitney U test.

Figure 3. Cysteine concentration [cys] in erythrocytes from maternal blood (A), venous umbilical cord blood (B) and arterial umbilical cord blood (C) of preterm and full-term subjects.

The boxplot shows the median (central horizontal line) and includes the 25^th (lower box border) to 75^th percentile (upper box border) of cysteine concentration (µmol/L). Preterm (n = 8) were compared with full-term (n = 8) subjects. Significant differences were observed between the groups (p<0.05) as assessed with the Mann-Whitney U test.