A survey of the current status of neonatal disseminated intravascular coagulation in neonatal intensive care units in Kyushu, Japan.

BACKGROUND: Neonatal disseminated intravascular coagulation (DIC) is a rare disease with a poor outcome. However, data on the incidence, treatment, and outcome of neonatal DIC are scarce. Thus, this study investigated the status of neonatal DIC in Japan. METHODS: We sent a retrospective questionnaire-based survey regarding the status of diagnosis and treatment of neonatal DIC from January 1, 2016, to December 31, 2018, to 30 hospitals in Kyushu with a neonatal-perinatal medicine division. The data collected by the questionnaire survey included information about the patients diagnosed with neonatal DIC. RESULTS: Among the 13,582 neonates surveyed, 120 (0.9 %) were diagnosed with DIC. Of them, clinical data were available for 105 cases. There were 11 deaths (mortality rate: 10.4 %), with the most common underlying condition being infection (n = 9), followed by neonatal asphyxia and hematologic disease (both, n = 1). Compared with the survival group, the death group had more infections, as well as a higher rate of bleeding symptoms and organ dysfunction. CONCLUSIONS: Neonatal DIC associated with infectious diseases has a poor outcome. Therefore, it is necessary to formulate diagnostic and treatment guidelines for early intervention in such cases.

Early diagnosis of neonatal-onset cyclic vomiting syndrome.

Cyclic vomiting syndrome (CVS) is characterized by recurrent episodes of severe vomiting with a completely asymptomatic interictal interval. Relatively few patients develop CVS in the neonatal period, and an early diagnosis is difficult. We experienced an infant who was diagnosed with neonatal-onset CVS in early infancy. An 8-day-old girl was admitted to our neonatal intensive care unit because of frequent vomiting beginning 12 h after birth and weight loss reaching 84.2% of her birth weight. Despite extensive examinations, no abnormalities to explain the vomiting were found. She continued to vomit, and a cyclical pattern with a vomiting phase lasting for three days followed by a non-vomiting phase lasting for about one to two weeks became obvious. Based on her clinical course, the family history of migraine and the effectiveness of Phenobarbital, she was diagnosed with CVS at three months old. Although CVS is a diagnosis of exclusion, a family history of migraine can aid its early diagnosis. If the illness is suspected in the neonatal period, diagnostic treatment with Phenobarbital may be considered. The case suggests the need to include CVS in the differential diagnosis of neonates with unexplained repetitive vomiting.

Incidence and In-Hospital Mortality of Neonatal Disseminated Intravascular Coagulation in Japan: An Observational Study of a Nationwide Hospital Claims Database.

This study aimed to estimate the incidence and prognosis of neonatal disseminated intravascular coagulation (DIC) in Japan by analyzing data retrieved from a national administrative database. Clinically, the prognosis of DIC in neonates is poor, but there is little epidemiological data in Japan. This retrospective observational study identified patients diagnosed with neonatal DIC and who were registered in the Japanese diagnosis procedure combination (DPC) database between April 1, 2014 and March 31, 2016. The patients, who were diagnosed with neonatal DIC, included those with ICD-10 code D65 or P60 in primary and secondary diagnosis, with comorbid conditions existing at admission, and with complications occurring after admission. Of 78,073 neonates admitted to 1,474 neonatal intensive care units, 1,864 (2.4%) were diagnosed with DIC. There was no difference between sexes in incidence of DIC; the incidence of DIC was higher in extremely low birth weight infants (9.8%), and significantly higher than that in normal birth weight infants. The overall mean length of hospital stay was longer in neonates with DIC (69.5 days) than in those without DIC (32.6 days, P < 0.001). The number of deaths was 1,156 (1.5%). In-hospital mortality was significantly higher in neonates with DIC (14.1%) than in those without DIC (1.2%, P < 0.001), especially in premature babies. This nationwide study was the first report to investigate the incidence and in-hospital mortality of neonatal DIC in Japan. Neonatal DIC has a significant impact on prognosis, and its influence is greater in premature than in term infants.

The evaluation of the appropriate gentamicin use for preterm infants.

Gentamicin (GM) is used for neonates as the initial treatment for neonatal bacterial infection. An association between high trough GM levels and the elevation of the serum creatinine (sCr) level and hearing loss has been reported, although there have been no reports investigating the serial changes in the sCr level in preterm neonates treated with GM. The present study evaluated the serial changes in the sCr level and the incidence of hearing loss in preterm neonates treated with GM. This study included 56 neonates born at a gestational age of 32-36 weeks. Fifteen (group 1) and 20 (group 2) neonates were treated with 2.5 mg/kg of GM every 12 h and 4 mg/kg of GM every 36 h, respectively. Group 3 included 21 neonates without GM therapy. Serum GM levels, serial changes in the sCr levels, and the incidence of hearing loss were then compared among the three groups. The serum trough GM level in group 2 was significantly lower than that in group 1 (P < 0.001), whereas the serum peak GM levels in these groups were almost the same. The ratio of the sCr level at birth to that at the 5th day of life in group 1 was the lowest among the 3 groups. No neonates had hearing loss. GM therapy worsened the sCr level in late preterm neonates, especially those with multiple doses per day. The appropriate use of GM is needed in order to prevent the occurrence of nephrotoxicity.

Impact of High Flow Nasal Cannula Therapy on Oral Feeding in Very Low Birth Weight Infants with Chronic Lung Disease.

Previous studies on high-flow nasal cannula (HFNC) in very-low-birth-weight infants (VLBWIs) focused on comparing HFNC with nasal continuous positive airway pressure (nCPAP) to determine the usefulness of HFNC as a backup in the case of extubation failure and nasal trauma; however, the studies did not consider oral feeding. This retrospective case-control study aimed at elucidating whether HFNC could prevent the delay in feeding and achievement of full oral feeding in VLBWIs with chronic lung disease (CLD). Forty five VLBWIs were enrolled in this study: an HFNC group (n = 11) that was supported by HFNC at oral feeding initiation, and a non-HFNC group (n = 34) that could start oral feeding without HFNC. The gestational age and birth weight of the HFNC group were lower than those in the non-HFNC group. The median duration of exposure to oxygen and neonatal intensive care unit stay were comparable in both groups. The timings of oral feeding initiation and full oral feeding achievement in both groups were not significantly different: 35.3 (33.0 - 38.1) vs. 35.5 (33.7 - 42.4) weeks (P = 0.91) for the HFNC and 38.6 (34.4 - 42.3) vs. 36.7 (34.6 - 44.4) weeks postmenstrual age (P = 0.29) for the non-HFNC. Clinically significant aspiration pneumonia during the period of oral feeding was not observed in the HFNC group. Respiratory support by HFNC in VLBWIs with CLD might prevent oral feeding delay. Initiation of oral feeding of VLBWIs on HFNC might be safe and might accelerate the achievement of oral feeding milestones.

The Physiological Variation in Plasma Presepsin Levels During the Early Neonatal Period.

Neonatal sepsis continues to be a global problem with significant morbidity and mortality, because of the difficulty in predicting its onset with clinical symptoms alone. Thus, the presence of biomarkers is useful for the diagnosis of neonatal sepsis. Presepsin is a 13-kDa truncated form of soluble CD14 that is produced through proteolytic cleavage on activated monocytes. Presepsin, consisting of 64 amino acid residues, has been proposed as a reliable biomarker for the early diagnosis of sepsis in neonates. However, some biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variation, whereas such variation in presepsin levels is uncertain. The objective of this study is to investigate the physiological variation in plasma presepsin levels during the early neonatal period. This prospective study included 30 full-term healthy neonates, including 15 neonates delivered by cesarean section. Plasma presepsin levels were examined at birth and on the first day and the fifth day of life in neonates, and the levels on the 5th day of life were lower than those at any other points (P < 0.001). Moreover, there was no significant difference of plasma presepsin levels between neonates delivered vaginally and by cesarean section. The physiological variation in plasma presepsin levels was observed during the early neonatal period. Attention needs to be paid when measuring plasma presespsin levels for the screening of sepsis during the early neonatal period.

An infant case with hydrocephalus as the initial manifestation of Mycoplasma hominis-associated meningitis.

We report an infant with hydrocephalus as the initial manifestation of Mycoplasma hominis-associated meningitis, who recovered without appropriate antimicrobial treatment. The analysis of the 16S rRNA gene by polymerase chain reaction amplification using universal primers and pathogen-specific primers was useful for the diagnosis and the investigation of serial detection status of the pathogen. This method may be helpful for the assessment of the frequency and the prediction of severity in M. hominis-associated central nervous system infection in infants, and investigating the association between M. hominis and the development of hydrocephalus.

Efficacy of periodic surveillance culture in a neonatal intensive care unit in the presumption of causative pathogens of late-onset bacterial infection.

BACKGROUND: Surveillance cultures have been recommended for infection control of resistant bacteria in neonatal intensive care units (NICUs). However, the utility of surveillance cultures in the presumption of causative bacteria in late-onset bacterial infection has been controversial. The aim of the present study was to investigate the relationship between the causative pathogens of late-onset bacterial infection and the results of periodic surveillance cultures in a NICU. METHODS: A retrospective study was performed on 600 patients hospitalized in the NICU of a large metropolitan hospital from 2010-2013. The correspondence of the results of surveillance cultures with causative pathogens was analyzed in patients who developed late-onset bacterial infection. RESULTS: Staphylococcus species and enterobacterium were the most prevalent in the samples obtained from the oropharynx and rectum, respectively, during the investigation period. Twenty patients (3.3%) developed late-onset bacterial infection. The causative pathogens in 15 patients (75%) were also detected from the final surveillance cultures; these patients tended to be older than the other 5 patients (P = .003). CONCLUSIONS: Surveillance cultures might be useful for the presumption of causative pathogens of late-onset bacterial infection in patients with risk factors for the development of nosocomial bacterial infection.

Analysis of the Physiological Variation in Neutrophil CD64 Expression during the Early Neonatal Period.

Background Several biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variations. The aim of this study was to investigate the physiological variation in neutrophil CD64 (nCD64) expression during the early neonatal period and the change in nCD64 expression in neonates with noninfectious diseases. Methods Of 71 neonates enrolled in this prospective study, 5 and 51 were diagnosed as having bacteremia and noninfectious diseases, respectively. Fifteen healthy neonates were enrolled as normal controls. Peripheral white blood cell counts, serum C-reactive protein and procalcitonin levels, and nCD64 expression were examined at birth and on the first and fifth day of life in neonates with noninfectious diseases and healthy neonates. In neonates with bacteremia, these markers were measured at onset. Results nCD64 expression was significantly higher in neonates with bacteremia (median, 1,992) than in those with noninfectious diseases (1,823, p < 0.001) and healthy neonates (1,848, p = 0.002). Unlike other biomarkers, no differences in nCD64 expression were observed on the same days between neonates with noninfectious diseases and healthy neonates. Conclusion nCD64 expression may be a useful marker for the diagnosis of bacterial infection in the early neonatal period, because it does not show any physiological variations.

Circulating PCSK9 levels correlate with the serum LDL cholesterol level in newborn infants.

BACKGROUND AND AIMS: Protein convertase subtilisin/Kexin type-9 (PCSK9) is a substantial player in lipoprotein metabolism. This study was designed to elucidate the role of PCSK9 in the regulation of lipoprotein during the fetal period. STUDY DESIGN AND SUBJECTS: This study was a cross-sectional study. Eighty-one neonates (45 males, 36 females) who were admitted to the neonatal intensive care unit were enrolled in the study. The median age in gestational weeks and weight at birth were 37.1 weeks and 2493 g, respectively. There were no gender differences, but the proportion of infants who were small-for-gestational age (SGA) was significantly higher among females than males. The prefed serum PCSK9 level was assayed with ELISA kits. RESULTS: The median PCSK9 concentration in male newborns was significantly lower than that in females (148.2 ng/ml vs. 171.4 ng/ml, respectively, p<0.001). Circulating serum PCSK9 levels were positively correlated with total cholesterol (r=0.281, p<0.05) and low-density lipoprotein cholesterol (LDL-C; r=0.272, p<0.05). However, there were no correlations between PCSK9 levels and birth weight, gestational age or SGA. Multivariate forward stepwise linear regression analysis revealed that gestational age and circulating PCSK9 levels were independent predictors of the serum LDL-C levels in newborn infants. CONCLUSION: Our first quantitative analysis of neonatal serum PCSK9 levels at birth showed that circulating PCSK9 levels show gender-based differences and are significantly correlated with LDL-C. These results suggest that PCSK9 could play an important role in regulating LDL-C levels during the fetal period.

High conductivity of the new supramolecular copper complex with oxidized pyrazinoselenathiafulvalene (=pyra-STF) as the ligand, [Cu(I)Cl(1.5)(pyra-STF)(0.5+)].

A new supramolecular copper complex with pyrazinoselenathiafulvalene (=pyra-STF) as the ligand, [CuCl(1.5)(pyra-STF)], has been synthesized. This complex forms a peculiar crystal structure; Cu(I) and Cl(-) construct 1D supramolecular chains with coordination of the oxidized donor molecules, pyra-STF(0.5+), as ligands. The pseudo-1D donor-ligand columns afford high conductivity, 25 S cm(-1), at 298 K and are prohibited to be a complete singlet state below 190 K by the linked, rigid 1D [CuCl(1.5)](n) chains.

Intrinsic carrier doping in antiferromagnetically interacted supramolecular copper complexes with (pyrazino)tetrathiafulvalene (pyra-TTF) as the ligand, [CuIICl2(pyra-TTF)] and (pyra-TTF)2[CuI3Cl4(pyra-TTF)].

New supramolecular copper complexes with pyrazinotetrathiafulvalene (pyra-TTF) as the ligand, [Cu(II)Cl2(pyra-TTF)] (1) and (pyra-TTF) 2[Cu(I)3Cl4(pyra-TTF)] (2), have been synthesized by the diffusion method. Complex 1 is a black block crystal with a three-dimensional (3-D) supramolecular network; the linear chain [-Cu(II)Cl2-(pyra-TTF)-] n extends along the b axis, where the coordinated pyra-TTF donors are stacked in a head-to-tail and ring-over-bond configuration to construct two-dimensional (2-D) sheets, and between the sheets, there are C...Cl(-) or H...Cl(-) contacts. Even though the electron spin resonance (ESR) measurement reveals the nearly Cu(II) state, complex 1 is a semiconductor with sigmaRT=1.0 x 10(-4) S cm(-1) and Ea=0.33 eV. The high-frequency conductivity measurement also confirmed the intrinsic slight carrier doping from Cu(II) to the pyra-TTF donor. This slight doping enhances not only the real and imaginary dielectric constants but also the antiferromagnetic interaction between Cu(II) spins following the 2-D Heisenberg model with 2J=-20 K. In contrast, complex 2 is a very thin black needle. This needle crystal has two crystallographically independent pyra-TTF molecules, which are coordinated and noncoordinated donors. The coordinated donors composed a supramolecular chain [Cu(I)3Cl4(pyra-TTF)(0)]n , whereas the noncoordinated donors formed conducting alpha''-type pyra-TTF(+0.5) sheets. This complex is semiconducting with sigmaRT=0.1 S cm(-1) and Ea=0.15 eV. Both complexes 1 and 2 demonstrate that the pyra-TTF molecule works not only as an oxidized donor by Cu(II) to construct conducting sheets but also as a ligand coordinated to a Cu cation to form supramolecuar chains.

Antiferromagnetic interaction achieved by a 3-D supramolecular CuII complex with pyrazino-fused TTF as the ligand, [CuCl2(BP-TTF)].

The diffusion reaction of TBA2Cu(II)Cl4 (TBA = tetrabutylammonium) and a N-containing organic donor, BP-TTF [=bis(pyrazino)tetrathiafulvalene], yielded a 3-D supramolecular Cu complex, [CuCl2(BP-TTF)] (1). The magnetic measurement of 1 exhibits an antiferromagnetic interaction by fitting a Bonner-Fisher model from 2 to 300 K with S = 1/2 and J = -3.5 K between Cu(IotaIota) mediated by self-assembling donor columns.