Sustained lower bilirubin-binding affinity of albumin in extremely preterm infants.

BACKGROUND: Elevated albumin-free or unbound bilirubin (UB) levels beyond the first week of life have been associated with the development of bilirubin encephalopathy in preterm infants. However, the mechanism(s) that induces this prolonged unbound bilirubinemia has remained unknown. We hypothesized that it may due to a sustained lower bilirubin-binding affinity of albumin in extremely premature infants. METHODS: Twenty-two very preterm infants born at 28-31 weeks' gestational age (GA) (VPT Group) and 21 extremely preterm infants born at 22-27 weeks' GA (EPT Group) were retrospectively studied. On days 14, 21, and 28, bilirubin-binding affinity of albumin was assessed by calculating of the UB/total bilirubin ratio, bilirubin-albumin molar ratio (BAMR), and binding affinity (Ka). RESULTS: On days 14, 21, and 28, significantly higher UB/total bilirubin ratios were found in the EPT than in the VPT Group. Although BAMRs were comparable, significantly lower Ka values on days 14, 21, and 28 were observed in the EPT than those in the VPT Group (56.1 vs. 70.9 L/µmol, p < 0.001; 55.2 vs. 74.7 L/µmol, p < 0.001; 53.0 vs. 86.5 L/µmol, p < 0.001, respectively). CONCLUSIONS: EPT infants have a sustained lower bilirubin-binding affinity of albumin beyond the first week of life. IMPACT: Bilirubin encephalopathy is still reported in extremely preterm (EPT) infants. EPT infants often have prolonged unbound bilirubinemia beyond the first week of life. Sustained lower bilirubin-binding affinity of albumin, regardless of the bilirubin-albumin molar ratio (BAMR), is observed in EPT infants. BAMRs should not be used as a surrogate marker of unbound bilirubinemia, especially in EPT infants at a later postnatal period.

Time-Fixed Glucose Oxidase-Peroxidase Method for Measurement of Serum Unbound Bilirubin Levels.

BACKGROUND: In the original glucose oxidase-peroxidase (GOD-POD) protocol, the time required to decrease the initial total bilirubin (TB) level by 20% is used for unbound bilirubin (UB) calculation. However, it needs to continuously monitor the TB levels by spectrometry. METHODS: Here, we hypothesized that the TB decrease during fixed time periods can also be used to extrapolate UB values (fixed-time protocol). Serum UB levels measured by the different protocols were compared using 10 newborn serum samples. RESULTS: Serum UB levels determined using the fixed-time protocol, especially using periods of 10 - 40 seconds, were strongly correlated with those determined using the original protocol (coefficient of determination > 0.9). The fixed-time protocol, using periods of 20 - 60 seconds, showed the high measurement precision (coefficient of variation < 5%). CONCLUSIONS: The fixed-time protocol, using periods of 20 - 40 seconds, can help determine serum UB levels as effectively as the original protocol.

Improving survival in patients with trisomy 18.

The effects of medical and surgical interventions on the survival of patients with trisomy 18 have been reported, leading to changes in perinatal management and decision-making. However, few studies have fully reported the recent changes in survival and treatment of trisomy 18. We examined how treatment and survival of patients with trisomy 18 have changed over a decade in a Japanese pediatric tertiary referral center. This retrospective cohort study included patients with trisomy 18 who were admitted within the first 7 days of life at the Hyogo Prefectural Kobe Children's Hospital between 2008 and 2017. The patients were divided into early period (EP) and late period (LP) groups based on the birth year of 2008-2012 and 2013-2017, respectively. Changes in treatment and survival rates were compared between the two groups. A total of 56 patients were studied (29 in the EP group and 27 in the LP group). One-year survival rates were 34.5% and 59.3% in the EP and LP groups, respectively. The survival to discharge rate significantly increased from 27.6% in the EP group to 81.5% in the LP group (p < 0.001). The proportion of patients receiving surgery, especially for congenital heart defects, significantly increased from 59% in the EP group to 96% in the LP group (p = 0.001). In our single-center study, survival and survival to discharge were significantly improved in patients with trisomy 18, probably because of increased rate of surgical interventions. These findings may facilitate better decision-making by patients' families and healthcare providers.

Chemical characterization of milk oligosaccharides of the tiger quoll (Dasyurus maculatus), a marsupial.

Milk oligosaccharides were separated from the carbohydrate fraction of milk of the tiger quoll a species of marsupial that is closely related to the eastern quoll, Dasyurus viverrinus. They were characterized by (1)H - nuclear magnetic resonance spectroscopy and matrix - assisted laser desorption/ionization time-of-flight mass spectrometry. The following oligosaccharides were identified; Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Neu5Ac(α2-3) Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc with an α(2-3)Neu5Ac linked to ß(1-4)Gal residue of either branch of Gal(ß1-4)GlcNAc(ß1-6) units, and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc with a ß(1-3) linked Gal and an α(2-3) linked Neu5Ac. In addition, larger oligosaccharides were characterized as follows; Gal(ß1-3){Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)GlcNAc(ß1-6)}Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3){Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)GlcNAc(ß1-6)}Gal(ß1-4)Glc and their α(2-3) linked Neu5Ac derivatives.

Characterization of two novel sialyl N-acetyllactosaminyl nucleotides separated from ovine colostrum.

The milk/colostrum of some mammalian species is known to contain sugar nucleotides including uridine diphosphate (UDP) oligosaccharides in addition to lactose and milk oligosaccharides, but the detailed structures of these UDP oligosaccharides have not so far been clarified. In this study we isolated two UDP-sialyl N-acetyllactosamines from ovine colostrum and characterized them using (1)H-NMR and MALDI-TOFMS spectroscopies. Their structures were found to be Neu5Gc(α2-3)Gal(ß1-4)GlcNAcα1-UDP and Neu5Gc(α2-6)Gal(ß1-4)GlcNAcα1-UDP.

Chemical characterization of milk oligosaccharides of the common wombat (Vombatus ursinus).

Previous structural characterizations of marsupial milk oligosaccharides have been performed in the tammar wallaby, red kangaroo, koala, common brushtail possum and the eastern quoll. To clarify the homology and heterogeneity of milk oligosaccharides among marsupial species, which could provide information on their evolution, the oligosaccharides of wombat milk carbohydrate were characterized in this study. Neutral and acidic oligosaccharides were isolated from the carbohydrate fractions of two samples of milk of the common wombat and characterized by (1) H-nuclear magnetic resonance spectroscopy. The structures of six neutral saccharides were found to be Gal(ß1-4)Glc (lactose), Gal(ß1-3)Gal(ß1-4)Glc (3'-galactosyllactose), Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc (3',3"-digalactosyllactose), Gal(ß1-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose I) and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novooctaose), while those of six acidic saccharides were Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-4)Glc. (sialyl 3'-galactosyllactose), Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc (sialyl 3',3"-digalactosyllactose), Neu5Ac(α2-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose a), Gal(ß1-3)[Neu5Ac(α2-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose c), Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc,, Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc and Gal(ß1-3)Gal(ß1-3)[Neu5Ac(α2-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc. In addition, small amounts of sulfated oligosaccharides but no oligosaccharides containing Neu5Gc or α(2-6) linked Neu5Ac were detected.

Chemical characterization of milk oligosaccharides of the eastern quoll (Dasyurus viverrinus).

Structural characterizations of marsupial milk oligosaccharides have been performed in four species to date: the tammar wallaby (Macropus eugenii), the red kangaroo (Macropus rufus), the koala (Phascolarctos cinereus) and the common brushtail possum (Trichosurus vulpecula). To clarify the homology and heterogeneity of milk oligosaccharides among marsupials, the oligosaccharides in the carbohydrate fraction of eastern quoll milk were characterized in this study. Neutral and acidic oligosaccharides were separated and characterized by (1)H-nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The structures of the neutral oligosaccharides were Gal(ß1-3)Gal(ß1-4)Glc (3'-galactosyllactose), Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc (3",3'-digalactosyllactose), Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novopentaose I), Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose I), Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose II), Gal(ß1-3)[Gal(ß1-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose III) and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novooctaose). The structures of the acidic oligosaccharides detected are Neu5Ac(α2-3)Gal(ß1-4)Glc (3'-sialyllactose), Gal(ß1-3)(O-3-sulfate)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novopentaose I sulfate a), Gal(ß1-3)[Gal(ß1-4)(O-3-sulfate)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novopentaose I sulfate b), Neu5Ac(α2-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose a), Gal(ß1-3)[Neu5Ac(α2-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose c), Neu5Ac(α2-3) Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc with an α(2-3) Neu5Ac linked to ß(1-4)Gal residue of either branch of Gal(ß1-4)GlcNAc(ß1-6) units. The most predominant oligosaccharides in the carbohydrate fraction of mid-lactation milk were found to be lacto-N-novopentaose I and lacto-N-novooctaose, i.e., branched oligosaccharides that contain N-acetylglucosamine. The predominance of these branched oligosaccharides, rather than of a series of linear ß(1-3) linked galacto oligosaccharides, appears to be the main feature of the eastern quoll milk oligosaccharides that differentiates them from those of the tammar wallaby and the brushtail possum.