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Lumirubin is the most prevalently excreted hydrophilic bilirubin photoisomer in phototherapy for neonatal jaundice caused by excess hydrophobic unconjugated bilirubin (ZZ-bilirubin). We developed a simple method to estimate the amount of lumirubin by monitoring the reverse photoisomerization of lumirubin to ZZ-bilirubin. Although lumirubin formation was long considered irreversible, exposure to blue light in the presence of the fluorescent protein UnaG, which binds specifically and tightly to ZZ-bilirubin, enables the reverse photoisomerization of lumirubin. This reaction was first detected using a fluorescence assay of neonatal urine sampled during phototherapy and purified lumirubin. The phenomenon of reverse photoisomerization of lumirubin was validated using liquid chromatography–mass spectrometry, which confirmed that lumirubin is reconverted to ZZ-bilirubin in the presence of UnaG. Analyses of 20 urine samples from 17 neonates revealed a significant correlation (correlation coefficient [r] = 0.978; 95% confidence interval 0.867–0.979; P

Chronic lung disease (CLD) is a major neonatal pulmonary disorder associated with inflammation. Recent studies have shown that protein C anticoagulant pathways, such as those for protein C (PC), protein S (PS), and thrombomodulin (TM), could be useful indices for reflecting pulmonary injury. However, the involvement of these factors in preterm infants with very low birthweight (VLBW) who have developed CLD remains to be investigated. Here, we investigated whether PC pathway-related factors could predict the development of CLD in preterm infants with VLBW.We collected plasma samples from 26 preterm infants with VLBW (13 each from those with and without CLD) at the time of birth and measured TM, PC, and PS levels in their plasmas. We analyzed prospectively the relationship between these factors in infants with and without CLD.There were significant differences in gestational age, birthweight, Apgar score (5 min), and duration of mechanical ventilation between the CLD and non-CLD groups. No significant differences in the PC and PS levels at birth were observed between the two groups, whereas the TM levels in the CLD group were significantly higher than those in the non-CLD group (P = 0.013). The TM levels correlated with gestational age and duration of mechanical ventilation. However, covariance analysis demonstrated that gestational age was significantly associated with TM levels, and consequently, development of CLD was not associated with TM level at birth.Thrombomodulin, PC, and PS levels at birth could not predict the development of CLD in preterm infants with VLBW.

To clarify the incidence and genetic risk of neonatal-thromboembolism, we conducted a nationwide study exploring the impact of thrombophilia on neonatal-thromboembolism in Japan.A questionnaire survey was conducted for perinatal centers in Japan, focusing on the clinical expression, genotype, treatment, and outcome of patients who developed thromboembolism within 28 days of birth from 2014 to 2018.The estimated incidence of neonatal-thromboembolism was 0.39 cases per 10 000 live births. Intracranial lesions and purpura fulminans occurred in 66 and 5 of 77 patients, respectively. Fifty-eight (75.3%) infants presented within 3 days after birth. Four (5.2%) died, and 14 (18.2%) survived with disability. At the diagnosis,20% plasma activity of protein C was noted in 16 infants, protein S (in 2), and antithrombin (in 1). Thirteen genetic tests identified 4 biallelic and 5 monoallelic protein C-variants but no protein S- or antithrombin-variants. Protein C-variants had purpura fulminans (P .01), ocular bleeding (P .01), positive-family history (P = .01), and death or disability (P = .03) more frequently than others. Protein C-variants were independently associated with disability (OR 5.74, 95% CI 1.16-28.4, P = .03) but not death. Four biallelic variants had serious thrombotic complications of neurologic disability, blindness, and/or amputation. Three monoallelic variants survived without complications. The only protein C-variant death was an extremely preterm heterozygote infant.Monoallelic protein C-variants had a higher incidence of neonatal-thromboembolism than biallelic variants. Thrombophilia genetic testing should be performed in the setting of neonatal-thromboembolism and low protein C to identify the underlying genetic defect.

Introduction We analyzed the frequency spectrum of two neonatal sleep stages, namely active sleep and quiet sleep, and the relationship between these sleep stages and autonomic nervous activity in 74 newborns and 16 adults as a comparison. Method Active and quiet sleep were differentiated by electroencephalogram (EEG) patterns, eye movements, and respiratory wave patterns; autonomic activity was analyzed using the RR interval of simultaneously recorded electrocardiogram (ECG) signals. Power values (LFa, absolute low frequency; HFa, absolute high frequency), LFa/HFa ratio, and the values of LFn (normalized low frequency) and HFn (normalized high frequency) were obtained. Synchronicity between the power value of HFa and the LFa/HFa ratio during active and quiet sleep was also examined by a new method of chronological demonstration of the power values of HFa and LFa/HFa. Results We found that LFa, HFa and the LFa/HFa ratio during active sleep were significantly higher than those during quiet sleep in newborns; in adults, on the other hand, the LFa/HFa ratio during rapid eye movement (REM) sleep, considered as active sleep, was significantly higher than that during non-REM sleep, considered as quiet sleep, and HFa values during REM sleep were significantly lower than those during non-REM sleep. LFn during quiet sleep in newborns was significantly lower than that during active sleep. Conversely, HFn during quiet sleep was significantly higher than that during active sleep. Analysis of the four classes of gestational age groups at birth indicated that autonomic nervous activity in a few preterm newborns did not reach the level seen in full-term newborns. Furthermore, the power value of HFa and the LFa/HFa ratio exhibited reverse synchronicity. Conclusion These results indicate that the autonomic patterns in active and quiet sleep of newborns are different from those in REM and non-REM sleep of adults and may be develop to the autonomic patterns in adults, and that parasympathetic activity is dominant during quiet sleep as compared to active sleep from the results of LFn and HFn in newborns. In addition, in some preterm infants, delayed development of the autonomic nervous system can be determined by classifying the autonomic nervous activity pattern of sleep stages.

We describe herein the case of a 3-day-old male neonate with umbilical arteriovenous malformation showing umbilical hemorrhage. The patient was born after 38 weeks and 3 days of gestation with a birth weight of 2784 g. Sudden massive umbilical hemorrhage occurred on day 3. Cardiopulmonary arrest developed, but the patient was successfully rescued by immediate cardiopulmonary resuscitation. An umbilical venous catheter was inserted for blood access. However, umbilical hemorrhage continued and hemostasis was difficult. Congenital bleeding disorders were excluded based on laboratory findings. Ultrasonography on day 15 revealed a mass with rich blood supply directly under the umbilicus. Umbilical arteriovenous malformation was suspected from abdominal contrast-enhanced computed tomography on day 17. Excision of the arteriovenous malformation was performed on day 29. The mass was connected to three arteries including the umbilical arteries, with the umbilical vein flowing out from the mass. Umbilical arteriovenous malformation was diagnosed from evidence during the operation and pathological findings. Umbilical arteriovenous malformations are rare and often discovered by heart failure symptoms, but rare cases present with umbilical bleeding, as in this report. Umbilical arteriovenous malformation must be taken into consideration as along with congenital bleeding disorders when massive umbilical hemorrhage is identified.

Background: Although clinical experience in neonates with candidiasis exists for amphotericin B and fluconazole, these standard treatments are often hindered by drug-associated toxicity or development of resistant strains. The aim of the present study was therefore to investigate the efficacy and tolerability of a new antifungal agent, micafungin (MCFG), for treating Candida infections in premature infants. Methods: This was a retrospective cohort study. Premature infants diagnosed with Candida infections from October 2003 to July 2004 were brought to the neonatal intensive care unit at the Center of Perinatal Medicine, Nara Medical University Hospital. Four newborns were given 0.5–1.0 mg/kg per day micafungin. Results: Four premature infants (mean ± SD gestational age, 24.1 ± 0.9 weeks; mean ± SD birthweight, 579.3 ± 80.5 g) experienced complications from Candida infection; two cases of the fungal infection were caused by Candida glabrata and two cases were caused by Candida albicans. MCFG was administered at 0.5 or 1.0 mg/kg per day (mean dosage days, 9.8 ± 3.1 days) and it decreased β-d-glucan levels while improving clinical symptoms in all cases. Additionally, there were no apparent side-effects. Conclusion: MCFG is both effective and tolerable for use in premature infants suffering from Candida infections.

We encountered a male infant with infantile Alexander disease presenting with megalencephaly and hydrocephalus as a neonate and subtle seizures at 3 months of age. At 6 months of age, bulbar paralysis appeared. Brain magnetic resonance imaging (MRI) showed abnormal findings with white matter involvement and a characteristic periventricular rim, satisfying the diagnostic criteria proposed by van der Knaap, except for MRI contrast. R239H mutation of glial fibrillary acidic protein gene was identified, representing a common cause of infantile-type Alexander disease.

Background: KL-6 in umbilical cord blood, including from premature infants, and perinatal factors that may affect these values have not yet been adequately discussed. The authors investigated factors affecting cord venous plasma levels of KL-6 in neonates, and to establish a normal range of values for KL-6 in neonatal cord blood. Methods: Cord plasma levels of KL-6 were measured in 75 neonates, and statistical analysis of factors affecting these levels was performed. A normal range for cord plasma KL-6 levels was calculated by statistical analysis methods based on guidelines by the National Committee for Clinical Laboratory Standards. Results: Data from a total of 75 neonates was analyzed. Gestational age ranged from 25 to 40 weeks (median, 33.4 weeks), and birthweight ranged from 776 to 3760 g (median, 1944 g). There was no statistically significant correlation between cord plasma KL-6 levels with gender, gestational age, birthweight, method of delivery, Apgar score 1 min, and postnatal respiratory distress. The normal range of values for cord plasma KL-6 was 44.3–148.2 U/mL (median, 73.0 U/mL). Conclusion: The cord plasma levels of KL-6 were about half the normal values reported in children and healthy adults and were not affected by various perinatal factors. The authors’ findings suggest that plasma KL-6 levels rise when respiratory function is established after birth and tend to further increase with age.

Background: The aim of the present study was to examine the presence of motilin in the duodenal epithelial cells of premature infants of

To investigate the functional maturity of the lungs of infants with pulmonary hypoplasia, we measured the expression of surfactant apoprotein-A (SP-A) in the autopsied lungs. Autopsied lungs were taken from 16 infants who died at birth or soon after. A lung-to-body weight ratio of less than 1.2% was defined as pulmonary hypoplasia. Eight infants were classified as belonging to the normal group, and eight as belonging to the pulmonary hypoplasia group. Many of the pulmonary hypoplasia group were complicated not only by pulmonary hypoplasia, but also by amniotic fluid volume abnormalities or an anatomical malformation. We measured the expression of SP-A immunologically using murine anti-human SP-A MAb in the autopsied lung tissue, and subjected the tissue to SP-A staining by the direct staining method. The expression of SP-A was assessed as one of four grades: -, +/-, 1+, 2+. The staining intensity of SP-A was high at 1+ or stronger in five infants of the normal group. SP-A expression was significantly reduced, however, in all infants of the pulmonary hypoplasia group except for one infant with normal amniotic fluid volume and relatively mild pulmonary hypoplasia. There was a significant negative correlation between the staining intensity of SP-A and two factors: pulmonary hypoplasia and abnormal amniotic fluid volume (p = 0.039 and p = 0.0063, respectively). In the present study, we demonstrated that SP-A expression was significantly reduced in infants with pulmonary hypoplasia. We speculate that the functional maturity of the lungs of infants with pulmonary hypoplasia is also suppressed.

A report is presented of a patient with neonatal erythema infectiosum who developed petechiae, transient thrombocytopenia and transient cardiac failure due to transplacental transmission of human parvovirus B19 (HPV B19) infection. It is suggested that the thrombocytopenia was caused by platelet-associated IgG produced by the patient, and that the cardiac failure may have been caused by direct entry of HPV B19 into the cardiac tissue.

Three cases of neonatal renal insufficiency in very low birthweight (VLBW) infants following repeated antenatal administration of indomethacin to prevent premature labor are reported. Three pregnant women received indomethacin (total doses of 150-850 mg) for 3-14 days from admission until delivery. The gestational ages and birthweights of the infants ranged from 24 to 28 weeks and 612 to 1432 g, respectively. Oliguria, early onset of hyperkalemia and prolonged renal dysfunction occurred after birth. Renal failure did not improve in one infant. Despite the efficacy of indomethacin for tocolysis in premature labor, VLBW infants born after repeated maternal administration near the time of delivery may have developed impairment of the premature kidney.

Propionic acidemia (PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase. This enzyme is composed of two non-identical subunits, α and β, which are encoded by the PCCA and PCCB genes, respectively. An enzyme deficiency can result from mutations in either PCCA or PCCB. To elucidate the mutation spectrum in Japanese patients, we have performed a mutation analysis of 30 patients with PA, which included nine previously reported patients. The study revealed that 15 patients were α-subunit deficient and 15 patients were β-subunit deficient. Seven novel mutations were found (IVS18 − 6C > G, 1746G > A, C398R, G197E and IVS18 + 1G > A in the PCCA; A153P and IVS9 + 1G > T in the PCCB). Among these Japanese patients with α-subunit deficiencies, 923–924insT, IVS18 − 6C > G, and R399Q mutations were frequent and the total allelic frequency of these three mutations combined was 56% (17/30). This is in sharp contrast to the mutation spectrum found in Caucasian patients, where no prevalent mutations have been identified. Among the β-subunit deficiencies, there were three frequent mutations; R410W, T428I, and A153P, whose allelic frequencies were 30, 26.7, and 13.3%, respectively. In conclusion, a limited number of mutations are predominant in both PCCA and PCCB genes among Japanese patients with propionic acidemia.

Background: This study was undertaken to determine the efficacy of low-dose intravenous erythromycin (EM) administration in infants with feeding intolerance. Methods: The subjects were 26 infants who would not accept enteral feeding within 5 days after birth. Fourteen infants (gestational age: 30.6 ′ 5.4 weeks and birthweight: 1466 ′ 825 g) were given EM intravenously at a dose of 1 mg/kg, three times daily (EM group). Doses were increased to 2 mg/kg in five infants who showed a poor response. Twelve infants (gestational age: 30.5 ′ 5.0 weeks and birthweight: 1317 ′ 672 g) were observed without EM administration (non-EM group). Blood concentrations of EM at 2 h after administration were measured on 8 (′ 2) days after the start of EM administration in the EM group. Results: Digestive perturbations and intestinal gasless and/or atonic shadows on X-ray findings markedly improved in the EM group soon after the treatment. Comparing the EM group and non-EM group, the postnatal ages at the start of successful enteral feeding were 9.1 ′ 3.2 days and 14.0 ′ 4.1 days, respectively (P < 0.01). The postnatal ages at feeding of 100 mL/kg per day were 15.2 ′ 4.0 days and 23.4 ′ 6.2 days, respectively (P < 0.01). The blood EM concentrations of 1 mg/kg and 2 mg/kg were 0.29 ′ 0.28 μg/mL and 0.57 ′ 0.20 μg/mL, respectively (P < 0.05). No adverse effect on cardiac status or in blood examinations was observed in any infant in the EM group. Conclusion: These results suggest that intravenous low-dose EM administration is a useful and safe treatment of feeding intolerance in infants including extremely low-birthweight infants.