A Neonatal Patient Diagnosed with a COL4A1 Mutation Presenting with Hemorrhagic Infarction and Severe Jaundice.

We report a patient diagnosed with a COL4A1 mutation in the early postnatal period. Patients with early postnatal jaundice, intracranial lesions that are negative for TORCH syndrome, and recurrent hemolytic anemia should be suspected of having a COL4A1/COL4A2 gene mutation.

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 infants treated in a neonatal intensive care unit.

OBJECTIVE: The aim of this study was to determine the prenatal causes of slight lateral ventricular enlargement in infants treated in a neonatal intensive care unit. METHODS: We examined 318 infants with a gestational age of at least 28 weeks who were treated in a neonatal intensive care unit. We investigated the relationships between slight lateral ventricular enlargement and prenatal factors. Also, we investigated the relationships between the laterality of lateral ventricular enlargement and arm growth to verify our proposed mechanism of lateral ventricular enlargement. RESULTS: Slight lateral ventricular enlargement was observed in 97 (30.5%) infants. Slight lateral ventricular enlargement was related to gestational age (p < .001), maternal anemia (p = .025), diabetes mellitus (p = .048), threatened premature labor (p = .027), and premature rupture of the membrane (p = .049). In 97 infants with ventricular enlargement, the numbers of infants with left-side dominant, equivalent, and right-side dominant laterality were 60 (61.9%), 27 (27.8%), and 10 (10.3%), respectively. Maternal anemia and diabetes mellitus were related to left-side dominant ventricular enlargement. Threatened premature labor and premature rupture of the membrane were related to right-side dominance. The laterality of lateral ventricular enlargement was not relate to that of the arm growth. CONCLUSIONS: We propose that the main cause of slight lateral ventricular enlargement may not be malnutrition but instead may be hypoxic stress in utero.

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.

Respiratory inhibition after crying and feeding hypoxemia in infants.

OBJECTIVE: To determine the incidence, risk factors and natural history of respiratory inhibition after crying (RIAC) and feeding hypoxemia. METHODS: We screened for RIAC and feeding hypoxemia among 393 infants with a gestational age ≥ 36 weeks using pulse oximetry. Twenty-seven infants were treated in the neonatal intensive care unit. RESULTS: RIAC and feeding hypoxemia were observed in 95 (24.2%) and 124 (31.6%) infants, respectively. RIAC correlated with feeding hypoxemia (p < 0.001), grade II increased echogenicity in the ganglionic eminence (p = 0.005), dilation of the lateral ventricle (p = 0.044), threatened premature labor (p = 0.033) and twin gestation (p = 0.089). Feeding hypoxemia correlated with RIAC (p < 0.001), abnormal cranial ultrasound findings (p < 0.001), maternal smoking during pregnancy (p = 0.083), asymmetric intrauterine growth restriction (p = 0.012) and twin gestation (p = 0.067). All infants recovered from RIAC in an average of 4.5 (2.0-7.0) d. Fifteen infants recovered from feeding hypoxemia, but 10 infants needed additional assistance and monitoring by nursing until the day of discharge. The day of discharge was day 8.0 (5.0-12.4). CONCLUSIONS: RIAC and feeding hypoxemia are observed among healthy infants, and these infants experience repeated events of prolonged hypoxemia.

Asymmetric intrauterine growth restriction is a risk factor for respiratory inhibition after crying in infants.

OBJECTIVE: We investigated whether intrauterine growth restriction (IUGR) correlated with respiratory inhibition after crying (RIAC) and feeding hypoxemia. METHODS: We screened for RIAC among 1248 infants with a gestational age ≥36 weeks using our established method with cranial ultrasound, SpO2 monitoring, and polygraphy. We classified the infants into three groups: symmetric IUGR, asymmetric IUGR, and control. We compared the perinatal factors with the incidence of RIAC and feeding hypoxemia among the three groups. RESULTS: Overall, 26 infants had symmetric IUGR, 143 infants had asymmetric IUGR, and 1079 infants were in the control group. RIAC was observed in 10 (6.9%) infants in the asymmetric IUGR group and in 37 (3.4%) infants in the control group. Feeding hypoxemia was observed in 15 (10.5%) infants in the asymmetric IUGR group and in 52 (4.8%) infants in the control group. The incidence of RIAC and feeding hypoxemia in the asymmetric IUGR group was significantly more than that in the control group. None of the infants with symmetric IUGR exhibited RIAC or feeding hypoxemia. CONCLUSIONS: The results indicate that asymmetric IUGR is a risk factor for RIAC and feeding hypoxemia. These infants should be aggressively screened for RIAC.

Polygraphic findings of 47 cases with respiratory inhibition after crying.

OBJECTIVE: To report the polygraphic findings of infants with respiratory inhibition after crying (RIAC). METHODS: We screened for RIAC among infants with a gestational age ≥36 weeks using our established method with cranial ultrasonography, SpO(2) monitoring and polygraphy. RIAC is defined as central apnea that occurred immediately after crying with a decrease in SpO(2) to <60%, followed by repeated irregular respiration and apnea as the respiration gradually recovered. The subjects were infants with RIAC for whom we could study the polygraphic findings in detail. RESULTS: Forty-seven RIAC cases were included in the present analysis. The frequency of RIAC was 2.1 (1.2-7.0) times per 24 h. The maximum duration of respiratory inhibition was 78.0 (52.6-109.0) s. The maximum duration of SpO(2) <60% during RIAC was 39.0 (9.8-93.2) s. The minimum SpO(2) value during RIAC was 53.0% (42.2-58.0%). The minimum heart rate during RIAC was 103.0 (79.1-127.1) bpm. CONCLUSIONS: RIAC is observed among healthy infants, and they experience repeated prolonged hypoxemia.

Timing of injury in utero causing respiratory inhibition after crying.

BACKGROUND: The aim of this study was to clarify the timing of injuries in utero that cause respiratory inhibition after crying (RIAC). We evaluated infants with cranial ultrasound abnormalities diagnosed during hospitalization. METHODS: We retrospectively examined the medical records of preterm infants who were treated in the neonatal intensive care unit at Nara Prefectural Hospital in Nara, Japan from January 2006 through December 2010. Inclusion criterion was gestational age less than 34 weeks. We evaluated the perinatal factors and cranial ultrasound abnormalities associated with RIAC, feeding hypoxemia, and prolonged apnea. We also evaluated the timing of appearance of cranial ultrasound abnormalities. RESULTS: A total of 125 infants were examined. Mean gestational age was 30.6 ± 2.4 weeks and mean birthweight was 1465 ± 454 g. The numbers of infants who showed RIAC, feeding hypoxemia, and prolonged apnea were 44, 48, and 63, respectively. Among 91 infants who showed cranial ultrasound abnormalities, 67 had increased echogenicity in the ganglionic eminence (GE). There was a significant correlation between increased echogenicity and RIAC (P < 0.001). Of the infants who showed increased echogenicity in the GE, 19 had this finding during the course of hospitalization. In these 19 infants, however, gestational age of those with RIAC was less than 31 weeks. CONCLUSION: We speculate that the timing of intrauterine injury resulting in RIAC in infants is less than 31 gestational weeks.

Normal values for KL-6 in cord venous plasma of neonates.

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.

Respiratory inhibition after crying in infants.

BACKGROUND: Among full-term neonates, the authors discovered infants who showed respiratory inhibition after crying which involved a marked decrease in SpO2. The infants were found to present increased echogenicity or a cyst in a cranial region termed the ganglionic eminence, or to have a subependymal cyst. The authors prospectively examined the relationship between respiratory inhibition after crying and these changes to examine the prevention and treatment of the episode. METHODS: The authors conducted cranial ultrasonography to screen 381 full-term neonates who showed no abnormalities at birth and whose parents requested ultrasonographic screening of the head, followed by polygraphy of infants who showed increased echogenicity or a cyst in ganglionic eminence, or had a subependymal cyst. The authors similarly conducted polygraphy for 50 neonates without cranial ultrasound abnormalities; the former constituted the control group. Respiratory inhibition was defined to be central apnea immediately after crying with a decrease in SpO2 to <60%. RESULTS: Among 381 neonates examined, 104 showed cranial ultrasound abnormalities; 60 of the 104 neonates indicated respiratory inhibition after crying. Oxygenation failed to improve the episode in 17 neonates with severe respiratory inhibition. However, theophylline alleviated the episode, and SpO2 no longer decreased to <60%. Theophylline was discontinued successfully by 6 months after birth, while 50 neonates in the control group showed no respiratory inhibition after crying. CONCLUSION: Respiratory inhibition after crying which involved a marked decrease in SpO2 was observed in full-term neonates who showed no abnormalities after birth. These neonates could be screened by cranial ultrasonography.

Dosage regimen of arbekacin for methicillin-resistant Staphylococcus aureus infection in newborns and infants.

BACKGROUND: Arbekacin (ABK) is an aminoglycoside antibiotic that has a dose-dependent bactericidal action. Because it inhibits the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus (MRSA), it has attracted attention as a therapeutic drug for MRSA infection. In this study, the authors investigated the pharmacokinetics of ABK based on therapeutic drug monitoring (TDM), in order to establish an effective dosage regimen with minimal adverse reactions in MRSA infected newborns and infants. METHODS: Arbekacin was administered to nine MRSA infected newborns and infants between October 2000 and March 2002. Following the initial ABK administration, blood was collected and the blood concentration of ABK was measured. The blood concentrations of ABK were analyzed by the two-compartment model or by a model-independent method in order to elucidate the pharmacokinetics of ABK. Pharmacokinetic analysis was performed using WinNonlin Professional V3.1. RESULTS: The mean age at initial ABK administration was 24.0 +/- 26.0 days (postconceptional age: 39.2 +/- 3.9 weeks). The increase in the peak blood concentration of ABK was 2.40 +/- 0.20 microg/mL per mg ABK per kg bodyweight, showing great consistency among cases. The elimination half-life of ABK was 0.22-3.52 h in the alpha phase (T(1/2alpha)) and 2.42-33.44 h in the beta phase (T(1/2beta)), showing great variation among cases. The distribution volume was 0.75 +/- 0.13 L/kg, and systemic clearance was 0.054 +/- 0.012 L/h/kg. ABK alleviated clinical symptoms and inflammations in all cases. CONCLUSION: Nine newborns and infants with MRSA infection and various underlying diseases were successfully treated with TDM-based administration of ABK with no severe adverse reactions.