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Propylene glycol: a natural protection against cold stress at delivery?

Presented at the Neonatal Society 2012 Summer Meeting (programme).

Hyde MJ, Romero MG, Wijeyesekera AD, Perez IG, Jeffries S, Logan K, Andreas N, Gale C, Holmes E, Modi N

Neonatal Medicine, Imperial College London, 369 Fulham Road, London, SW10 9NH, UK

Background: We have previously used 1H NMR to study the hepatic metabolome in 7 day post-partum piglets, delivered vaginally (VD) or by pre-labour Caesarean section (CS) (1). In the present study we aimed to evaluate the urinary metabolome during the first 7 days post-partum in human babies born by VD or CS. The study was conducted with Research Ethics Committee approval (08/H07/11/43).

Methods: A urine sample was collected on cotton wool from 30 infants within 72 hours of birth, at Chelsea & Westminster Hospital, and stored at -80șC until analysis. Samples were analysed using one-dimensional 1H NMR spectroscopy at 300K on a Bruker Avance 600 MHz spectrometer, using standard parameters and pre-processing algorithms, as previously described (2). The spectra were automatically phased; baseline corrected, referenced using an in-house routine written in MATLAB, normalised using probabilistic quotient normalisation to the median profile and aligned; continuous spectral data were used for statistical analysis. Spectra were analysed on the basis of experimental group using principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) to explore the variation between the groups.

Results: Urinary samples were analysed from 15 VD and 15 CS infants (Pre-labour CS = 7; Emergency CS = 8) born between 37-42 weeks gestation. There was a significant difference in the urinary metabolome of infants born by CS and VD when examined using PLS-DA (Fig 1a). One of the metabolites with greatest difference between CS and VD babies was propylene glycol (doublet at 1.14ppm; Fig 1b). As this was unexpected, we reviewed previously analysed data acquired from 15 term baby urine samples. We classified these according to mode of delivery (6 VD and 9 CS) and found a similar difference in propylene glycol between CS and VD babies.

Figure 1: a) PLS-DA scores plot of UV scaled data from 1H NMR spectra of urine collected from term infants born by CS (; n = 15) vs. VD (▲; n = 15) infants. (R2 = 0.831; Q2 = -0.049). b) Representative NMR spectra (red = CS; black = VD) showing the doublet associated with propylene glycol.

Conclusion: In our previous work one of the metabolites which differed strongly between VD and CS delivered piglets was also propane-1,2-diol (propylene glycol), which was increased in the former. We previously attributed propylene glycol in the liver of VD animals to its use as a vehicle for sodium pentobarbital used for euthanasia, and hypothesised that differences between CS and VD piglets reflected altered underlying metabolism. We now show that propylene glycol is also increased in human infants born by VD compared to CS. Upon review of published literature we find reports of propylene glycol in cerebral in vivo 1H NMR spectra in the human neonate following asphyxial injury and also in urine; these authors concluded that the source of the propylene glycol was phenobarbitone vehicle (3,4). The presence of propylene glycol in healthy VD infants suggest an alternative hypothesis, namely that propylene glycol, through its involvement in lactate/pyruvate metabolism, may be produced in VD infants in response to the transient hypoxaemia associated with VD. Propylene glycol is commonly used as antifreeze, and though postulating a role as a natural protection against cold stress at delivery may be implausible, its significance to the physiology of the newborn is intriguing. Our finding is novel and demands further study.

Corresponding author:

1. Hyde, M.J. (2010) Clin Sci (Lond.). 118, 47-59.
2. Beckonert, O. (2007) Nature Protocols. 2, 2692-703.
3. Cady, E.B. (1994) MRM. 32, 764-7.
4. Ma, S. (1995) Appl Biochem and Biotech. 53, 37-51.

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