The efficacy of routine brain MRI for term neonates admitted to neonatal intensive care unit.

OBJECTIVE: The efficacy of routine brain MRI for term infants admitted to a neonatal intensive care unit (NICU) has not been well studied. This study aimed to investigate the types and frequencies of abnormal findings on routine brain MRI and the predictors of abnormality for term infants in an NICU setting. METHODS: We examined the results of routine brain MRI of 239 term infants who were hospitalized in the NICU. Data on the perinatal factors were also collected, and the association with MRI abnormalities was assessed. RESULTS: Of the 239 MRI scans, we found abnormal findings in 52 (21.8%) patients. Intracranial hemorrhage accounted for 74% of the abnormal findings, including subdural, intraparenchymal, cerebellar, and subependymal hemorrhages. Twenty-six percent of these were ischemic lesions, including cerebral infarction, white matter abnormal intensities, and cystic periventricular leukomalacia (PVL). Five (2.1%) MRI scans required detailed examination or were known to be associated with a poor neurological prognosis. No patient needed treatment for the findings. An Apgar score ≤7 points at 5 min was identified as a perinatal factor significantly associated with abnormal MRI findings (adjusted OR = 3.034, 95% CI: 1.107-8.315, p = .031). CONCLUSION: The efficacy of routine brain MRI for term infants admitted to the NICU was limited. Routine brain MRI is not recommended for this population.

The prenatal causes of slight lateral ventricular enlargement in healthy infants.

OBJECTIVE: The aim of this study was to determine the prenatal causes of slight lateral ventricular enlargement in healthy infants. METHODS: We examined 1089 healthy infants who weighed at least 2000 g and were born at a gestational age of at least 36 weeks. We assessed the presence of ventricular enlargement when an apparent space was observed in the frontal horn or body of the lateral ventricle of the brain by a transfontanel ultrasound scan. We investigated the relationships between slight lateral ventricular enlargement and various prenatal factors. RESULTS: Slight lateral ventricular enlargement was observed in 497 (45.6%) infants. Slight lateral ventricular enlargement was related to maternal anemia (p = .004; odds ratio = 1.630; 95% CI: 1.168-2.276), threatened premature labor (p = .010; odds ratio = 1.441; 95% CI: 1.093-1.900), and diabetes mellitus (p = .022; odds ratio = 2.020; 95% CI: 1.109-3.682) using multiple logistic regression analysis. The birth weight of the infants with slight lateral ventricular enlargement was heavier than that of those without ventricular enlargement at 36-40 weeks of gestation. Forty infants with ventricular enlargement had head circumferences greater than the 90th percentile, while only one infant without ventricular enlargement did (p < .001). In addition, 22 infants with ventricular enlargement had head circumferences less than the 10th percentile, while only 4 infants without ventricular enlargement did (p < .001). In 497 infants with ventricular enlargement, the numbers of infants with left side dominant, equivalent, and right side dominant ventricular enlargement were 289 (58.1%), 110 (22.1), and 98 (19.7%), respectively. CONCLUSIONS: Slight lateral ventricular enlargement could be caused by several pathological conditions in utero, including brain atrophy, ventricular enlargement, the influence of blood flow in the brain, and various pathological changes in different brain regions.

The prognosis of infants with neonatal respiratory inhibition syndrome.

Objective: The goal of this study was to investigate the prognosis of infants with neonatal respiratory inhibition syndrome (NRIS).Methods: Infants with a gestational age of at least 36 weeks and a birth weight of at least 2000 g who were born at Nara Prefecture General Medical Center, in Nara, Japan, between March 2013 and June 2016 were screened for NRIS using our established method. NRIS was defined as severe hypoxemia caused by respiratory inhibition immediately after crying (RIAC) or gastroesophageal reflux (RIGER) or as a respiratory pause during feeding (feeding hypoxemia), accompanied clinically by central cyanosis and a decrease in SpO2 to less than 70%. All infants were monitored using pulse oximetry immediately after birth. Diagnosis of RIAC, feeding hypoxemia, and RIGER are based on observation by both parents and medical staff as well as on on-screen computer analysis using specific software. All infants were examined at a one-month check-up. Parents of the infants who experienced one or more episodes of NRIS accompanied by a decrease in SpO2 to less than 70% for more than approximately 60 s received a questionnaire by mail about their child's development. We conducted a logistic regression analysis with developmental problems as the dependent variable.Results: NRIS was observed in 362 (28.5%) infants; 216 (17.0%) infants showed RIAC, 254 (20.0%) infants showed feeding hypoxemia, and 54 (4.2%) infants showed RIGER. Although all infants were monitored in the maternity ward nursery, 184 (85.2%) infants with RIAC and 111 (43.7%) infants with feeding hypoxemia were overlooked. All infants with NRIS were found to have successfully recovered at one month after birth. Sixty-two cases were examined in the follow-up study by the mailed questionnaire. The median age of the subjects at time of study was 22 months. Fourteen cases (22.6%) exhibited developmental problems including delayed speech development, stereotyped interests and behaviors, sensory disturbance, hyperactivity, delayed motor development, and short stature. Developmental problems tended to relate to shorter gestational age (odds ratio, 0.622; p = .068; 95% CI, 0.373-1.036), smaller birth weight (odds ratio, 0.998; p = .069; 95% CI, 0.997-1.000), and maximum duration of SpO2 to less than 70% by RIAC (odds ratio, 1.009; p = .086; 95% CI, 0.999-1.020). All cases had experienced severe hypoxemia accompanied by a decrease in SpO2 to less than 60%. Seven cases had experienced prolonged hypoxemia accompanied by a decrease in SpO2 to less than 70% for at least 2 min. Among the subjects, 19 infants were examined closely, and their natural course of NRIS was observed in the neonatal intensive care unit. No cases demonstrated abnormal findings with blood examinations, chest-abdominal X-ray, echocardiogram, laryngoendoscopy, hearing loss screening, or mass screening. Only one case had a small intracranial hemorrhage as evidenced in a magnetic resonance imaging of the head.Conclusions: The infants with severe NRIS tended to have developmental problems. Spreading knowledge about NRIS worldwide is thought to be very important.

A simple and feasible antimicrobial stewardship program in a neonatal intensive care unit of a Japanese community hospital.

BACKGROUND: Although tertiary hospitals have successfully introduced ASPs by antimicrobial stewardship teams, lots of community hospitals without pediatric infectious disease specialists have difficulty implementing ASP. We present a successful implementation of simple and feasible NICU antimicrobial stewardship program in a Japanese community hospital. METHOD: We developed a protocol of antimicrobial treatment in our NICU department and have implemented the protocol from September 2017. The protocol consists of start and stop of criteria antimicrobial treatment, weekend report of blood culture result from microbiology department and stopping ordering antimicrobials beforehand for the next day. We compared days of therapy (DOT) during the post-implementation period (September 2017 to August 2018) with that of pre-implementation period (March 2013 to August 2017). RESULT: In pre- and post-ASP implementation periods, 913 and 194 patients were analyzed. DOT was 175.1 and 41.6/1000 patient-days, respectively (p < 0.001) with 76.2% reduction. The percentage of neonates who had any antimicrobials and the percentage of prolonged antimicrobial treatments among neonates who had any antimicrobials decreased significantly (55.3% vs 20.6%, p < 0.001 and 65.0% vs 32.5%, p < 0.001). The protocol compliance rates were also significantly different (55.4% vs 95.4%; p < 0.001). The methicillin-resistant rate of S.aureus rates were significantly reduced in post-ASP period (31.1% vs 12.9%; p = 0.002). CONCLUSION: This ASP program was easily implemented in a NICU department of a community hospital and significantly reduced antimicrobial prescription. This kind of simple protocol may be successfully scaled-up in resource limited community hospitals without no pediatric infectious disease specialists or antimicrobial stewardship team.

Elevated C-reactive protein in umbilical cord blood: Neonatal case review.

BACKGROUND: C-reactive protein (CRP) has limited placental transportability. Relying on CRP level in umbilical cord blood alone is an inaccurate way to predict early onset neonatal sepsis, and we retrospectively reviewed the clinical courses of neonates with elevated CRP in umbilical cord blood. METHODS: This study was a retrospective case review of neonates with elevated CRP in umbilical cord blood (>0.5 mg/dL) in the Nara Prefecture General Medical Center, Nara, Japan between February 2013 and August 2017. We investigated the association of maternal and neonatal factors with neonatal clinical course. Then, we compared the cases of neonates with and without elevated CRP in umbilical cord blood. RESULTS: The subjects consisted of a total of 22 neonates with elevated CRP in umbilical cord blood and 344 neonates without elevated CRP in umbilical cord blood. Of the 22 neonates with elevated CRP, 18 had some symptoms of sepsis at birth, but the symptoms of 85% of the symptomatic patients resolved ≤24 h after birth. Two neonates with elevated CRP in umbilical cord blood had bacteremia, and they had poor prognoses. Elevated CRP in umbilical cord blood was associated with length of antimicrobials (P = 0.021), immature/total neutrophil ratio (P = 0.017), and pathological chorioamnionitis (CAM; P = 0.028) on multivariable logistic regression analysis. CONCLUSION: Elevated CRP in umbilical cord blood was associated with pathological CAM. Most symptoms of sepsis resolved <24 h after birth.

Prenatal predictors of neonatal intensive care unit admission due to respiratory distress.

BACKGROUND: Admission to the neonatal intensive care unit (NICU) due to respiratory distress is determined according to subjective clinician judgement. We investigated prenatal factors predictive of NICU admission in neonates with respiratory distress. METHODS: This case-control study was conducted at Nara Prefecture General Medical Center, Nara, Japan, from February 2013 to April 2017 and included neonates with birthweight ≥2,000 g, ≥36 weeks of gestational age, who required oxygen due to respiratory distress at birth. The cases consisted of neonates admitted to the NICU, and the control group consisted of neonates who did not require NICU admission. Perinatal factors between the groups were compared, and multivariate logistic regression analysis carried out to evaluate predictive factors. RESULTS: The NICU group consisted of 94 neonates, and the control group, 417 neonates during the period reviewed. On multivariate analysis, maternal anemia (OR, 2.97; 95%CI: 1.42-6.21), infertility treatment (OR, 2.79; 95%CI: 1.36-5.71), threatened preterm labor (OR, 2.16; 95%CI: 1.10-4.23), premature rupture of membranes (OR, 5.30, 95%CI: 2.52-11.17), fibroids (OR, 6.06; 95%CI: 1.57-23.41), history of uterine surgery (OR, 3.53, 95%CI: 1.13-11.06), abruptio placentae (OR, 10.21; 95%CI: 1.83-57.17), intrauterine growth restriction (OR, 6.69; 95%CI: 1.96-22.85), and having twins (OR, 0.23; 95%CI: 0.09-0.58) were significant prenatal predictors of NICU admission. CONCLUSION: Factors that potentially predict NICU admission were identified. Clinicians may wish to consider these factors when treating neonates with respiratory distress.

Efficacy of routine catheter tip culture in a neonatal intensive care unit.

BACKGROUND: Routine catheter tip cultures are not recommended because some cases of colonization, such as with Staphylococcus aureus, can lead to subsequent bacteremia. To evaluate the safety of colonization without antimicrobial treatment, as well as the effectiveness of routine catheter tip cultures in the neonatal intensive care unit (NICU), we performed a retrospective data analysis in a Japanese community hospital. METHODS: We reviewed all peripherally inserted central venous catheter tip culture results from the NICU ward between April 2012 and June 2017 and noted outcome (i.e. antimicrobial treatment or subsequent infection). We then performed a cost analysis for routine catheter tip culturing on patients who were symptom free during the study period. RESULTS: Of the 93 positive cases in 80 patients from 1,051 catheter tip cultures, seven patients had suspected infection and were treated with antimicrobials. The other 73 symptom-free, positive patients had no subsequent or exacerbated symptoms indicative of an infection, and did not have antimicrobial treatment. The total cost for catheter tip culturing during the study period was ¥548 731. After excluding patients with symptoms of infection at the time of culture, the efficacy of routine catheter tip cultures on symptom-free patients was estimated to be zero. CONCLUSION: Symptom-free colonization did not affect clinician management in this study, and all colonized patients without suspected infection were safely managed without antimicrobials. Furthermore, routine catheter tip culturing was not cost-effective; therefore, this practice may be no longer recommended in the NICU.

A speculated cause of respiratory inhibition in infants.

OBJECTIVE: In our previous studies, we documented that threatened premature labor and asymmetrical intrauterine growth restriction were risk factors for respiratory inhibition. The goal of this study was to determine the cause of respiratory inhibition by considering perinatal risk factors. METHODS: We examined 1497 infants with a gestational age of 36 weeks or greater. All infants were monitored using pulse oximetry and examined via cranial sonography. Respiratory inhibition was defined as severe hypoxemia caused by respiratory inhibition immediately after crying or gastroesophageal reflux or as a respiratory pause during feeding. We examined the relationships between respiratory inhibition and perinatal factors and speculated on the cause of respiratory inhibition. RESULTS: The median gestational age, birth weight, Apgar score at 1 min, and Apgar score at 5 min of the subjects were 38.9 weeks, 2930 g, 8.0 points, and 9.0 points, respectively. Respiratory inhibition was observed in 422 infants. Lateral ventricle enlargement and increased echogenicity in the ganglionic eminence were observed in 417 and 516 infants, respectively. Respiratory inhibition was significantly correlated with shorter gestational periods, twin pregnancies, lateral ventricle enlargement, and increased echogenicity in the ganglionic eminence. CONCLUSIONS: We speculate that umbilical cord compression is a major cause of respiratory inhibition.

Clinical significance of slightly lateral ventricular enlargement in healthy infants.

OBJECTIVE: The aim of this study was to determine the clinical significance of slightly lateral ventricular enlargement. METHODS: We examined 1151 infants with a gestational age of 36 weeks or greater. We assessed for the presence of ventricular enlargement when apparent space was observed in the frontal horn or body of lateral ventricle by a transfontanel ultrasound scan. RESULTS: Two hundred and forty-eight infants had ventricular enlargement. The atrial widths in most infants were less than 10 mm. Ventricular enlargement correlated with Cesarean delivery, gestational age, birth weight, respiratory disturbance at delivery and respiratory inhibition after crying (RIAC). Ventricular enlargement could be divided into three types by ultrasound findings. Forty-five infants showed only enlargement of the anterior horn (Type A), 97 infants showed enlargement from the body to the posterior horn (Type B), and 108 infants showed whole enlargement from the anterior to the posterior horn (Type C). The infants with Type A correlated with intrauterine growth restriction, placenta previa, male gender and birth weight. The infants with Type B correlated with cesarean delivery. The infants with Type C correlated with diabetes mellitus, respiratory disturbance at delivery, RIAC and feeding hypoxemia. CONCLUSIONS: Slightly lateral ventricular enlargement should be considered clinically significant.

Gastroesophageal reflux related to respiratory inhibition after crying and feeding hypoxemia in infants.

OBJECTIVE: To determine the relationships between gastroesophageal reflux (GER) and both respiratory inhibition after crying (RIAC) and feeding hypoxemia in infants. METHODS: We screened for RIAC and feeding hypoxemia among infants with a gestational age of 36 weeks or greater using pulse oximetry. We investigated the infants who showed hypoxemia with a decrease in SpO2 to less than 70% and bradycardia with a heart rate of less than 100 beats per minute caused by GER. We then evaluated the relationships between these events and both RIAC and feeding hypoxemia. RESULTS: We examined 250 infants in the present study. RIAC and feeding hypoxemia were observed in 35 (14.0%), and 30 (12.0%) infants, respectively. Ten infants showed hypoxemia and bradycardia caused by GER. These events were correlated with RIAC (p = 0.006) and feeding hypoxemia (p = 0.031). CONCLUSIONS: In the infants with RIAC and feeding hypoxemia, some show severe hypoxemia and bradycardia caused by GER. Medical staff caring for infants should note the presence of RIAC and feeding hypoxemia.

Phototherapy with blue and green mixed-light is as effective against unconjugated jaundice as blue light and reduces oxidative stress in the Gunn rat model.

OBJECTIVE: Phototherapy using blue light-emitting diodes (LED) is effective against neonatal jaundice. However, green light phototherapy also reduces unconjugated jaundice. We aimed to determine whether mixed blue and green light can relieve jaundice with minimal oxidative stress as effectively as either blue or green light alone in a rat model. METHODS: Gunn rats were exposed to phototherapy with blue (420-520 nm), filtered blue (FB; 440-520 nm without<440-nm wavelengths, FB50 (half the irradiance of filtered blue), mixed (filtered 50% blue and 50% green), and green (490-590 nm) LED irradiation for 24h. The effects of phototherapy are expressed as ratios of serum total (TB) and unbound (UB) bilirubin before and after exposure to each LED. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by HPLC before and after exposure to each LED to determine photo-oxidative stress. RESULTS: Values < 1.00 indicate effective phototherapy. The ratios of TB and UB were decreased to 0.85, 0.89, 1.07, 0.90, and 1.04, and 0.85, 0.94, 0.93, 0.89, and 1.09 after exposure to blue, filtered blue, FB50, and filtered blue mixed with green LED, respectively. In contrast, urinary 8-OHdG increased to 2.03, 1.25, 0.96, 1.36, 1.31, and 1.23 after exposure to blue, filtered blue, FB50, mixed, green LED, and control, indicating side-effects (> 1.00), respectively. CONCLUSIONS: Blue plus green phototherapy is as effective as blue phototherapy and it attenuates irradiation-induced oxidative stress. PRACTICE IMPLICATIONS: Combined blue and green spectra might be effective against neonatal hyperbilirubinemia.

Immunohistochemical analysis of the role of hemocytin in nodule formation in the larvae of the silkworm, Bombyx mori.

Hemocytin, a multidomain protein from Bombyx mori L. (Lepidoptera: Bombycidae), is an ortholog of von Willebrand factor and is expected to be a major mediator of hemocyte aggregation. Antiserum was generated against hemocytin, and immune staining of hemocytes, hemolymph, and nodules was performed. Hemocytin was observed in steady-state hemocytes but not in plasma, even after bacterial injection. When hemolymph was smeared on glass slides, hemocytin-containing fibrous structures formed a cellular network mainly consisting of granulocytes and oenocytoids. Hemocytin was stained only in the granules of the granulocytes. When nodule-like aggregates formed 30 sec after bacterial injection, both granulocytes and bacterial cells were observed binding to hemocytin-containing fibrous structures. When nodule sections were stained with antiserum, hemocytin was seen in the matrix of the nodules surrounding the hemocytes. These data suggest that hemocytin plays a major role in nodule formation as a component of the sticky fibrous structure exocytosed from granulocytes.

Efficacy of micafungin in treating four premature infants with candidiasis.

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 beta-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.

A neonate with umbilical arteriovenous malformation showing hemorrhagic shock from massive umbilical hemorrhage.

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.