Procalcitonin-Based Antibiotic Use for Neonatal Early-Onset Bacterial Infections: Pre- and Post-Intervention Clinical Study.

We previously reported the 95th percentile cutoff value of the serum procalcitonin (PCT) reference curve for diagnosing early-onset bacterial infection. We aimed to verify the effectivity of these novel diagnostic criteria by comparing antibiotic use and incidence of early-onset bacterial infection between pre- and post-introduction periods. We included newborns admitted to our neonatal intensive care unit who underwent blood tests within 72 h after birth between 2018 and 2022. The neonates were divided into the pre-intervention (admitted before the introduction, n = 737) or post-intervention (admitted after the introduction, n = 686) group. The days of antibiotics therapy (DOT) per 1000 patient days up to 6 days after birth, percentage of antibiotic use, and incidence of early-onset bacterial infection were compared between the groups. The post-intervention group had significantly lower DOT per 1000 patient days (82.0 days vs. 211.3 days, p < 0.01) and percentage of newborns receiving antibiotics compared with the pre-intervention group (79 (12%) vs. 280 (38%), respectively, p < 0.01). The incidence of early-onset bacterial infections did not differ between the groups (2% each, p = 0.99). In conclusion, our diagnostic criteria using the 95th percentile cutoff value of the serum PCT reference curve for early-onset bacterial infection were proven safe and effective, promoting appropriate use of antibiotics.

Body Fat-Reducing Effects of Whey Protein Diet in Male Mice.

This study investigated the mechanism of reducing body fat via whey protein diet. Pregnant mice were fed whey or casein, and their offspring were fed by birth mothers. After weaning at 4 weeks, male pups received the diets administered to their birth mothers (n = 6 per group). At 12 weeks of age, body weight, fat mass, fasting blood glucose (FBG), insulin (IRI), homeostatic model assessment of insulin resistance (HOMA-IR), cholesterol (Cho), triglyceride (TG), the expression levels of lipid metabolism-related genes in liver tissues and metabolomic data of fat tissues were measured and compared between the groups. The birth weights of pups born were similar in the two groups. Compared to the pups in the casein group, at 12 weeks of age, pups in the whey group weighed less, had significantly lower fat mass, HOMA-IR and TG levels (p < 0.01, p = 0.02, p = 0.01, respectively), and significantly higher levels of the antioxidant glutathione and the anti-inflammatory 1-methylnicotinamide in fat tissues (p < 0.01, p = 0.04, respectively). No differences were observed in FBG, IRI, Cho levels (p = 0.75, p = 0.07, p = 0.63, respectively) and expression levels of lipid metabolism-related genes. Whey protein has more antioxidant and anti-inflammatory properties than casein protein, which may be its mechanism for reducing body fat.

Association of umbilical cord insulin-like growth factor 1 levels with severe retinopathy in extremely preterm infants.

BACKGROUND: The association between umbilical cord blood insulin-like growth factor 1 (IGF-1) levels and retinopathy of prematurity (ROP) remains unclear. This study aimed to investigate whether umbilical cord blood IGF-1 levels can predict the development of severe ROP in extremely preterm infants. METHODS: This hospital-based retrospective cohort study included infants born at <37 weeks gestational age (GA) between 2019 and 2021 and then classified them into the two GA groups: extremely preterm, <28 weeks and preterm infants, 28-36 weeks. Extremely preterm infants were further subclassified into two groups according to the laser treatment as follows: the severe ROP (ROP-Tx) and ROP (No ROP-Tx) groups. Median umbilical cord blood IGF-1 values were compared between the groups. Perinatal risk factors were identified by univariate and multivariate analyses. Finally, umbilical cord IGF-1 cut-off values requiring ROP treatment with laser were determined by receiver operating characteristic (ROC) curve analyses. RESULTS: A total of 205 infants were enrolled, with 32 being extremely preterm (ROP-Tx: n = 11; No ROP-Tx: n = 21) and 173 being preterm. IGF-1 levels were significantly lower in extremely preterm (13.5 ng/mL) than preterm infants (36 ng/mL, p < 0.001). In extremely preterm infants, IGF-1 levels were significantly lower in the ROP-Tx group than the No ROP-Tx group (10 vs. 19 ng/mL, respectively, p = 0.024). Only GA, umbilical cord blood IGF-1 levels, birth head circumference, and birth chest circumference were identified as risk factors by univariate analysis (p < 0.05). Multivariate analysis showed that only umbilical cord blood IGF-1 was an independent risk factor (odds ratio: 1.26, p = 0.021). ROC curves revealed an IGF-1 cut-off value of 14 ng/mL. CONCLUSION: The need of laser treatment for ROP was found to be associated with low umbilical cord blood IGF-1 levels in extremely preterm infants. Umbilical cord blood IGF-1 can be used as a biomarker for the risk of developing severe ROP.

Correction: Go et al. Diagnostic Accuracy of Biomarkers for Early-Onset Neonatal Bacterial Infections: Evaluation of Serum Procalcitonin Reference Curves. Diagnostics 2020, 10, 839.

In the original publication [...].

A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight.

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.

Percentile-Based Reference Values of Umbilical Cord Blood Insulin-like Growth Factor 1 in Japanese Newborns.

We aimed to create percentile-based reference values of the umbilical cord blood insulin-like growth factor-1 (IGF-1) levels in Japanese newborns, as these values have not yet been established. A total of 259 newborns were classified into four gestational-age-at-birth (GA) groups: extremely preterm (<28 weeks); early preterm (28−33 weeks); late preterm (34−36 weeks); and term (≥37 weeks). They were further subclassified as small-for-gestational-age (SGA) or non-SGA. The 10th, 25th, 50th, 75th, and 90th percentiles of the umbilical cord blood IGF-1 levels were calculated and compared between the groups by using reference values of 9, 18, 33, 52, and 71 ng/mL, respectively. In the extremely preterm group, the IGF-1 levels were significantly lower than those in the early preterm, late preterm, and term groups (13.5, 24.0, 44.5, and 47.5 ng/mL, respectively; p < 0.001). The umbilical cord blood IGF-1 levels in the SGA newborns were significantly lower than those in the non-SGA newborns in all subgroups. In multivariate analyses, the GA and birth weight standard deviation scores were independent determinant factors for the umbilical cord blood IGF-1 levels. Thus, we established percentile-based reference values of umbilical cord blood IGF-1 in Japanese newborns; these reference values can be applied on the basis of the extent of prematurity and the SGA status.

Successful Treatment of Hyperbilirubinemia by Monitoring Serum Unbound Bilirubin in an Extremely Preterm Infant with Bacterial Infection.

BACKGROUND: Bacterial infections and some antibiotics show displacer effects on bilirubin-albumin binding and increase unbound bilirubin (UB) but not total bilirubin (TB) in serum. METHODS: A case study was conducted to show a successful treatment of hyperbilirubinemia by monitoring UB. RESULTS: In an extremely preterm infant with bloodstream bacterial infection caused by methicillin-resistant coagulase-negative staphylococci, 2 days after high-dose ampicillin and regular-dose amikacin were initiated, UB markedly increased, but TB did not. After vancomycin was substituted, UB decreased immediately with phototherapy and intravenous albumin infusion. CONCLUSIONS: When using antibiotics, the clinicians should be mindful regarding the displacer effect on bilirubin-albumin binding.

Diagnostic Accuracy of Biomarkers for Early-Onset Neonatal Bacterial Infections: Evaluation of Serum Procalcitonin Reference Curves.

To date, no clinical studies have compared the accuracy of serum procalcitonin (PCT) reference curves. We aimed to validate the diagnostic accuracy of previously reported serum PCT reference curves and to determine which biomarkers among a cut-off value over the 95th percentile in the serum PCT reference curve, white blood cell (WBC) count, and C-reactive protein (CRP) and immunoglobulin M (IgM) levels, have the highest diagnostic accuracy for early-onset neonatal bacterial infections. This retrospective cohort study assessed 16 preterm and 23 term infants with suspected bacterial infections within 72 h after birth. Each infant group was divided into two subgroups: confirmed- and non-infection. The diagnostic accuracy was determined using the Youden index. The reference curves by Fukuzumi et al. in preterm and term infants had the highest Youden indexes: 1.000 and 0.324, respectively. Among preterm infants, the Youden index for PCT was 1.000. Among term infants, the Youden index for a combination of PCT, CRP, and WBC and/or IgM was 1.000. In conclusion, a serum PCT level over the 95th percentile on the reference curve for preterm infants and a combination of PCT and CRP levels with WBC count and/or IgM levels for term infants provided sufficient diagnostic accuracy.