Environmental risk factors for sudden infant death syndrome in Japan.

While the prevalence of sudden infant death syndrome (SIDS) has decreased worldwide, this decline has plateaued recently. Strategies are needed to resume the constant decrease of SIDS in Japan. A prospective electrocardiographic screening program for infants was performed between July 2010 and March 2011. Parents of 4319 infants were asked about environmental factors related to SIDS through questionnaires at a one-month medical checkup and one year. Parental awareness of prone position, smoke exposure, and breast feeding as environmental factors were 81.4 %, 69.0 %, and 47.8 %, respectively. The prevalence of laying infants exclusively in a supine position was 96.7 %. At the one-month medical checkup, smoking prevalence was 41.7 % in fathers and 2.1 % in mothers. Maternal smoking prevalence was significantly increased at one year after (p < 0.001). Multivariate regression analysis showed that risk factors for new or continued maternal smoking habits were maternal smoking habits at one month (p < 0.001), paternal smoking habits one year later (p < 0.001), and younger maternal age (p = 0.02). CONCLUSION: Most parents already avoid laying infants in the prone position, and parental smoking is still a SIDS risk concern in Japan. Smoking cessation programs should be further implemented for parents to decrease risks of SIDS in Japan. What is Known: • The prevalence of sudden infant death syndrome (SIDS) has decreased worldwide, however, this decline has plateaued recently. What is New: • Most infants were laid sleeping in the supine position (96.7 %) and were fed breast milk or a mix of expressed milk and formula (92.7 %), and 2.1 % of mothers smoked at the one-month medical checkup. • Maternal smoking prevalence significantly increased from the one-month medical checkup to one year later, and smoking mothers were more likely to feed infants by formula rather than breast milk. • Independent risk factors for new or continued maternal smoking habits included younger maternal age, maternal smoking habits at one month, and paternal smoking habits one year later.

6q21-22 deletion syndrome with interrupted aortic arch.

Interstitial deletion of 6q21-22 has been previously reported in 11 individuals, who presented with intellectual disability, facial dysmorphism, cardiac abnormality, cerebellar hypoplasia and dysplasia of the corpus callosum. Here, we report the first instance of a patient with 6q21-22 deletion presenting with interrupted aortic arch in addition to the previously described clinical signs. Array analysis using Agilent Human genome CGH 180K identified a 13.3-Mb deletion at 6q21-q22.31 (nt. 109885195-123209593).

Electrocardiographic screening of 1-month-old infants for identifying prolonged QT intervals.

BACKGROUND: Neonatal electrocardiographic screening is used to screen infants with prolonged QT intervals, as previously shown in whites. However, this procedure needs to be confirmed in other ethnic groups. METHODS AND RESULTS: In 8 areas in Japan, an ECG was recorded in 4285 infants at 1-month medical checkup. A prospective study showed that a provisional criterion of QTc≥470 ms was appropriate for infants. To assess the validity of the criterion, all infants with a QTc between 460 and 470 ms were followed up. Five infants had a QTc≥470 ms. Four infants were diagnosed with prolonged QT intervals from follow-up ECGs. Four infants showed no symptoms and did not have a family history of long-QT syndrome. Two infants showed progressive prolongation of QT intervals, and medication was started. Genetic testing was performed in 3 of 4 infants with prolonged QT intervals, and it revealed a KCNH2 mutation (3065 delT, L1021fs+34X) in 1 infant. One infant with a QTc≥470 ms and 2 infants with a QTc between 460 and 470 ms showed a decline in their QTc values during follow-up. The study screened another infant with Wolff-Parkinson-White syndrome who was diagnosed with noncompaction before symptoms appeared. CONCLUSIONS: Neonatal electrocardiographic screening can identify infants likely to be affected by long-QT syndrome in the Japanese population, as already shown in whites. This screening may also be useful in identifying other important cardiac diseases.

[Cardiac papillary fibroelastoma on the Chiari's network of a 3-month-old baby; report of a case].

A 3-month-old boy was transferred to our hospital because of a cardiac tumor in the right heart, which had been prenatally diagnosed by fetal echocardiography. During the operation, the tumor was found on the Chiari's network in the right atrium. The tumor was excised and the ventricular septal defect was repaired. Postoperative histological examination revealed that the tumor was a papillary fibroelastoma. He was transferred to a pediatric unit for postoperative care.

Increased α1-antitrypsin levels in acute-phase Kawasaki disease as shown by SELDI-TOF MS analysis.

Various agents have been suggested as causal or associated factors in the pathogenesis of Kawasaki disease (KD); however, the underlying factors of KD remain unknown. Plasma exchange is one of the most effective treatments for the acute phase of KD. This indicates that plasma may contain factors associated with the pathogenesis of KD. To search for proteins that may be involved in KD pathogenesis, we analyzed serum proteins with surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS). Serum samples were obtained from 17 KD patients. Serum from six of the patients was collected during acute phase before acetylsalicylic acid (ASA) and intravenous immunoglobulin administration (phase A1), during remission with ASA (phase A2), and during remission without any medication (phase A3). Serum from the remaining 11 patients was collected for phases A1 and A2 only. There were two age- and sex-matched control groups comprising 8 afebrile healthy children (group B) and 8 febrile children with several infectious diseases (group C). There were no statistical differences in laboratory examination between phase A1 and group C except for albumin level, alanine aminotransferase, or sodium level. Serum samples were analyzed by SELDI-TOF MS after purification. We detected five peaks, i.e., those were specifically increased or decreased during phase A1, and identified 1 of these as α1-antitrypsin (α1-AT). α1-AT can inhibit neutrophil elastase activity. This elastase is thought to play a role in coronary artery damage. Our findings present an interesting starting point for further investigations into the pathophysiology of KD.

Elevated serum interleukin-7 level in idiopathic steroid-sensitive nephrotic syndrome.

BACKGROUND: Several cytokines have a pathological association with idiopathic steroid-sensitive nephrotic syndrome (ISSNS) in inducing proteinuria or regulating T cells. Because interleukin (IL)-7 plays important roles in regulating T-cell proliferation and sustaining naïve or memory T cells, IL-7 is one of the candidate cytokines in the pathogenesis of ISSNS. Very little is known, however, about the association of IL-7 with ISSNS. To clarify the IL-7 dynamics in children with ISSNS, serum IL-7 level was investigated, from the nephrotic phase before steroid treatment (STx; group A1) to the remission phase with STx (group A2) and without STx (group A3). METHODS: Eighteen children with ISSNS were included in the present study. A total of 25 paired samples were analyzed for groups A1 and A2, and a total of 10 paired samples for groups A1, A2, and A3 due to recurrence. Two control groups (with normal urinalysis, group B; or with nephrotic syndrome other than ISSNS, group C), matched for age and gender, were also included. Serum cytokine level was measured on bead-based assay. RESULTS: Each serum IL-7 level in groups A1 and A3 was higher than each serum IL-7 level of groups C and B, respectively. The group A2 serum IL-7 level was higher than that of group A1. There was no statistical significance of serum IL-7 level between group A1 and group A3. CONCLUSION: Serum IL-7 level was elevated in children with ISSNS regardless of the status of the disease. This brings us one step closer to a better understanding of the pathophysiology of ISSNS in children.

Tissue Doppler combined with pulsed-wave Doppler echocardiography for evaluating ventricular diastolic function in normal children.

BACKGROUND: The ratio of the peak transmitral velocity during early diastole (E) to the peak mitral valve annular velocity during early diastole (E') obtained by tissue Doppler imaging correlates with the left ventricular end-diastolic pressure in adults. However, the E/E' ratio has not been established in normal children. The purpose of this study was to assess the effect of age on the various tissue Doppler indices of ventricular diastolic function. METHODS: The subjects in this study included 174 children with normal cardiac function. The left and right ventricular inflow velocities were recorded, and the peak of late diastolic flow velocities (A), E, and the ratio of E/A were determined. The following tissue Doppler indices were obtained: peak velocities of early and late diastolic mitral annulus in the left ventricular lateral wall (E'l and A'l) and in the interventricular septum (E'se and A'se) and those of the lateral tricuspid annulus in the right ventricle, E'r and A'r. RESULTS: The E'l and the E'se increased with age up to 5 years after birth, after which they became constant. The E'r was constant after birth. The E'l/A'l and E'se/A'se increased with age up to 5 years after birth, after which they became constant. The E'r/A'r was constant after birth. The Em/E'se and Em/E'l decreased with age up to 5 years after birth, after which they became constant. The Et/E'r was constant after birth. CONCLUSION: The age-related changes suggest age-related alterations in left ventricular diastolic function. Right ventricular diastolic function is constant after birth.

Resumption of sinus rhythm from fetal complete atrioventricular block after maternally administered ritodrine.

Reports have indicated that maternal administration of ritodrine increased the ventricular rate and thus ameliorated signs of heart failure in a fetus with complete atrioventricular block (CAVB). A fetus from a mother without the anti-SS-A/SS-B antibody had CAVB, with atrial rate 148-154 bpm and ventricular rate 53-57 bpm. After maternal administration of ritodrine, the ventricular rate increased to 60-65 bpm, and then sinus rhythm resumed. Ritodrine may not only increase the ventricular rate but also induce sinus rhythm in a fetus with CAVB.

Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome.

BACKGROUND: Various studies reported a higher incidence of allergic disorders, with an overreactivity of type 2 helper T-cell (Th2) immune mechanisms, in children with idiopathic steroid-sensitive nephrotic syndrome (ISSNS). However, Th2 predominance in ISSNS has not been definitively identified. To determine whether Th2 was predominant in children with ISSNS, we used paired samples to measure the type 1 helper T-cell (Th1)/Th2 ratios and serum cytokine levels secreted by Th1 and Th2. METHODS: We measured the Th1/Th2 ratios and levels of Th1- or Th2-secreted cytokines in paired samples. Fourteen children met the inclusion criteria: (1) ISSNS; (2) selectivity index < 0.1; (3) sera obtained in at least two disease phases; (4) no infection; (5) no immunosuppressants. Two control groups (group B, normal urinalysis; group C, nephrotic syndrome other than ISSNS) were included for cytokine level comparisons. Th1 and Th2 numbers were counted by three-color flow cytometry. Cytokine levels were measured by bead-based assay. RESULTS: The Th1/Th2 ratio was lower in group A-1 [nephrotic-phase before steroid treatment (STx)] than in groups A-2 (remission-phase with STx) and A-3 (remission-phase without STx). Th2-secreted interleukin-5 (IL-5) levels were higher in group A-1 than in groups A-2 and A-3. There were no differences in IL-5 levels between groups A-1 and C and between groups A-3 and B. CONCLUSION: Our results suggest that Th2 played a predominant role both in the Th1/Th2 ratio and in the serum IL-5 level in children with ISSNS in the nephrotic phase.

Grown-up Kawasaki disease patients who have giant coronary aneurysms.

BACKGROUND: Many Kawasaki disease (KD) patients have reached adulthood in Japan. The current status of adult patients who have giant coronary aneurysms with KD is not well understood. METHODS: Medical records of 48 KD patients (33 males and 15 females) with giant coronary aneurysms (maximum coronary artery internal diameter >8 mm) aged 20 years or over were retrospectively reviewed. RESULTS: The age of the patients at the diagnosis of KD ranged from 0.3 to 12.8 years (median 2.9 years) and the age of the patients in this review ranged from 20.0 to 33.1 years (median 25.2 years). During the follow-up period, the maximum coronary artery internal diameter ranged from 8.2 to 30.0 mm (median 10 mm). Giant coronary aneurysms progressed to coronary artery stenosis and/or complete occlusion in 34 (74%) of 46 patients. Coronary artery bypass graft surgery was performed in 9 (19%) of 48 patients. Myocardial infarction occurred in 14 (31%) of 45 patients. Other complications or problems occurred in 5 patients with angina pectoris, low left ventricular ejection fraction, ventricular tachycardia, hemorrhagic cerebral infarction, or thyroid carcinoma respectively. In the patients followed up, 4 dropped out. In addition, 1 patient succeeded in pregnancy and delivered a baby. CONCLUSIONS: Close attention should be paid to ventricular tachycardia in adult KD patients with giant coronary aneurysms, especially for those who have low left ventricular ejection fraction. To reduce the number of dropped out patients, it is important that the patients should be referred to a new doctor when they change their place of residence.

Cerebral hemorrhage associated with sildenafil (Revatio) in an infant.

A case of cerebral hemorrhage associated with sildenafil (Revatio) use in an infant is presented. Sildenafil is increasingly used in the treatment of primary and secondary pulmonary arterial hypertension and pulmonary arteriovenous fistula. In the reported case, sildenafil used to treat pulmonary arteriovenous fistula improved right-to-left shunting across the pulmonary fistula but resulted in cerebral hemorrhage. Cerebral hemorrhage, a previously reported complication of sildenafil, developed in an infant after a rapid increase in dose, to 4.7 mg/kg/day. Therefore, sildenafil doses must be increased only with care, and cerebral hemorrhage must be considered a potential complication.

Prediction of responsiveness or non-responsiveness to treatment of acute Kawasaki disease using 1 gram per kilogram of immunoglobulin--an effective and cost-saving schedule of therapy.

Standard treatment of acute Kawasaki disease involves giving 2 grams per kilogram of immunoglobulin intravenously along with aspirin. More than half of the patients with acute Kawasaki disease, nonetheless, can be cured by giving only 1 gram per kilogram of immunoglobulin, thus reducing this aspect of the cost of treatment by half. Our purpose was to predict those patients with acute Kawasaki disease who would respond to treatment with 1 gram per kilogram of immunoglobulin given intravenously on the basis of their clinical profiles and laboratory findings prior to the initial treatment. We performed a retrospective review of the clinical records of consecutive patients with acute Kawasaki disease treated in our hospital with intravenous immunoglobulin from January, 2001, to December, 2005.During this period, we treated in this fashion 98 patients with acute Kawasaki disease. 65% of these needing immunoglobulin therapy were cured by giving 1 gram per kilogram. The neutrophil count and the percentage of white blood cells representing neutrophils, along with aspirate aminotransferase, alanine aminotransferase, bilirubin and C reactive protein, were all significantly lower, and sodium was significantly higher, in those responding to 1 gram per kilogram of immunoglobulin when compared to those who did not respond. The days of illness at the first intravenous treatment was later in those responding than in those failing to respond. We generated a score for prediction, assigning a point for each of C reactive protein equal to or greater than 10 mg/dl, sodium equal to or lower than 133 meq/l, alanine aminotransferase equal to or greater than 110 IU/l, and 2 points for the percentage of white blood cells representing neutrophils equal to or greater than 70%. Using a cut-off point of a score less than 2, we were able to identify those responding with 60% sensitivity, and 91% specificity.Thus, we are now able to predict those patients with acute Kawasaki disease who will respond to immunoglobulin given intravenously at 1 gram per kilogram using laboratory data, with a potential saving in medical costs.

Fetus with heart failure due to congenital atrioventricular block treated by maternally administered ritodrine.

BACKGROUND: The efficacy of maternal administration of ritodrine in cases of congenital atrioventricular block (CAVB), especially with fetal heart failure, is not yet determined. CASE: At 21 2/7 weeks of gestation, isolated CAVB with a ventricular/atrial rate of 55-70/130-140 bpm was found in a fetus from a 30-year-old Japanese nulliparous woman with anti-SSA antibody. Cardiothoracic area ratio (CTAR) was 40% and no fetal hydrops was observed. At 30 2/7 weeks, the ventricular rate decreased to 49 bpm with an atrial rate of 125 bpm. CTAR increased to 53.8% and ascites appeared. Maternal continuous ritodrine infusion was started with rapid improvement of fetal cardiac function; increment in the ventricular rate to 57 bpm and atrial rate to 137 bpm, with a decrement in CTAR to 44.6%. Ascites also gradually decreased and by the fourth day, it had completely disappeared with CTAR of 40.2%. On the 12th day after ritodrine treatment (32 1/7), amniotic fluid volume decreased and fetal weight gain stopped, which led us to assume a worsening intrauterine environment, and cesarean section was performed. A 1,178 g male infant was born with a 5-min Apgar score of 8. Continuous isoproterenol infusion was started, increasing the ventricular rate from 71 to 80 bpm. Pacemaker implantation is under consideration to treat this infant. CONCLUSION: Maternal administration of ritodrine not only increased the fetal heart rate but also ameliorated the signs of fetal heart failure, and thus is considered one treatment of choice in CAVB.

Autonomic function in adolescents with orthostatic dysregulation measured by heart rate variability.

We evaluated the responses of autonomic nervous system to transient positional changes and daily changes in orthostatic dysregulation (OD) patients in order to clarify the mechanisms underlying the appearance of symptoms. The control group consisted of 16 healthy adolescents (8 males and 8 females), and the OD group consisted of 25 adolescents (13 males and 12 females). Each subject underwent continuous electrocardiographic monitoring during the head-up tilt test, followed by electrocardiographic monitoring for 24 h. Low frequency power (LF) and high frequency power (HF) were calculated as indices of autonomic function. During 0-5 min in the standing position in the tilt test, HF was higher in the OD group than in the control group (180+/-110 ms(2) vs. 42.6+/-54.1 ms(2); p<0.05). The LF/HF ratio during standing for 15-20 min was higher in OD patients than in the controls (4.75+/-3.45 vs. 1.67+/-1.21; p<0.05). The 24 h analysis showed that HF during sleep was significantly lower in the OD patients than in the controls (516+/-290 ms(2) vs. 1,290+/-429 ms(2); p<0.05); the LF/HF ratios were consistently higher in the OD patients than in the controls (4.13+/-3.41 and 2.92+/-2.00 vs. 2.46+/-0.89 and 1.35+/-1.54 in waking and sleeping states, respectively; p<0.05). This study showed that OD patients have less variability of the parasympathetic nervous system as well as hyperactivity of the sympathetic nervous system. This autonomic dysfunction is responsible for the symptoms of OD.

Volume measurement of the left ventricle in children using real-time three-dimensional echocardiography: comparison with ventriculography.

OBJECTIVES: Recently, a real-time three-dimensional echocardiography (RT3DE) volume scanning technique was developed and used clinically. For precise ventricular volumetry, independent of mathematical assumptions, imaging techniques such as three-dimensional echocardiography are required in children with heart disease. This study evaluated whether RT3DE is suitable for left ventricular volumetry in children, and whether left ventricular volumes measured by RT3DE correlate sufficiently well with those measured by left ventriculography (LVG). METHODS: Twenty-five children with heart disease, 17 boys and 8 girls aged from 8 months to 18 years (mean age 5.9 +/- 5.3 years), underwent cardiac catheterization at our institution. RT3DE was performed within 30 min after LVG using the Philips SONOS 7500 ultrasound system with an electronic sector probe consisting of a X 4 matrix phased array transducer (center frequency of 2-4 MHz). Ultrasound images of the ventricle were calculated offline using TomTec 4D Cardio-View RT 1.2 software. Left ventricular volumes by LVG were calculated using Siemens Hicor T.O.P. Finally, the left ventricular volumes by RT3DE and LVG were compared. RESULTS: Left ventricular volumes measured by RT3DE correlated and agreed well with those measured by LVG(r = 0.996, Y = 0.566 + 0.964 X, mean difference -0.29 +/- 1.90ml; left ventricular end-systolic volume, r = 0.979, Y=-0.187 + 0.897 X, mean difference -6.76 +/- 10.58ml; left ventricular end-diastolic volume). CONCLUSIONS: RT3DE is suitable for left ventricular volumetry in children. There was a good correlation between RT3DE and LVG, but the volume of left ventricular end-diastolic volume estimated by RT3DE was smaller than that by LVG.

Volume measurement of a pediatric ventricular phantom model using three-dimensional echocardiography.

PURPOSE: Volume measurement of the ventricle is necessary to evaluate cardiac function. Accurate volume measurement of the ventricle by three-dimensional (3D) echocardiography will mark a new step in pediatric cardiovascular diagnosis and treatment. We studied volume measurement of a pediatric ventricular model using 3D echocardiography. METHODS: The ultrasonic diagnostic setup used in this study comprised a Philips Sonos 7500 ultrasound system with an electronic sector probe of a ×4 matrix phased array transducer. The ventricular model was made from a latex surgical glove. The tip of the third finger of the glove was cut off and fixed to a manifold. The ventricular model was gently placed in a reservoir filled with water. Volumes of physiological saline solution ranging from 2 ml to 50 ml in 2-ml increments were injected into the ventricular model and examined. Twenty-five ultrasound images of the ventricular model were obtained using 4D Cardio View RT 1.2 software. RESULTS: There was excellent correlation and agreement between the injected volumes and the calculated volumes (Y = -0.539 + 1.005X, r = 0.997, four cut plane; Y = -0.191 + 1.006X, r = 0.997, eight cut plane). Thus, accurate volume measurement of the ventricular model by 3D echocardiography was confirmed. CONCLUSIONS: Our study demonstrated that 3D echocardiography is highly accurate for volume measurement in a pediatric ventricular model (for volumes of 2 to 50 ml) under static conditions.

Efficacy of iodine-123-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid single photon emission computed tomography imaging in detecting myocardial ischemia in children with Kawasaki disease.

To evaluate its efficacy in detecting myocardial ischemia in children, iodine-123-labeled 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) imaging was performed in 16 pediatric patients with Kawasaki disease (KD, 11 male, 5 female; mean age and range: 13 years 8 months and 8 years 11 months to 17 years 7 months). Five children with chest pain and no cardiac disease were studied as controls (2 male, 3 female; mean age and range: 13 years 4 months and 9 years 4 months to 17 years 11 months). Selective coronary angiography was also performed in the 16 patients to evaluate the location of coronary stenosis and coronary aneurysms. The SPECT images were expressed as polar maps (Bull's eye maps) and the 'defect' area was defined as where the uptake of BMIPP was less than the standardized BMIPP images of the 5 control children. In the 16 patients, 33 segments had coronary aneurysms and 10 (10/33: 30.3%) had significant coronary stenosis on selective coronary angiography. Nine of the 10 (90%) segments with significant coronary stenosis showed a defect on the BMIPP image whereas only 6 of the 23 (26.1%) segments without coronary stenosis showed a defect on BMIPP imaging. The sensitivity of BMIPP SPECT imaging for detection of coronary stenosis was 90% (9/10) and its specificity was 73.9% (17/23), whereas the sensitivity of (201)Tl SPECT imaging was 80% (8/10) and its specificity was 60% (14/23). There was no significant difference between the BMIPP and 201Tl SPECT images in either the sensitivity or specificity for the detection of coronary stenosis. In the present series, only one case had discordant BMIPP uptake (BMIPP uptake < (201)Tl uptake) in which there was a large coronary aneurysm and re-canalization after complete obstruction at segment 1 of the right coronary artery. This discordant BMIPP uptake reflects the possibility of ischemic but viable myocardium after re-canalization of a large aneurysm in KD. In conclusion, BMIPP SPECT imaging is useful for detecting the areas of ischemic myocardium caused by coronary artery stenosis in children with KD.

Autonomic function in Kawasaki disease with myocardial infarction: usefulness of monitoring heart rate variability.

BACKGROUND: Despite anticoagulant therapy, many patients with Kawasaki disease and giant coronary artery aneurysm develop myocardial infarction. These patients have a high risk of sudden death, but the etiology is not clear. We studied autonomic function and the possibility of malignant ventricular arrhythmia through heart rate variability. METHODS: We studied six Kawasaki disease patients with myocardial infarction and 16 normal controls. Heart rate variability was investigated using a 24 h electrocardiogram. We assessed the standard deviation from the mean of the normal R-R intervals (SDNN), the proportion of adjacent R-R intervals with a difference greater than 50 msec (pNN50) and the root-mean square of successive R-R differences as time-domain analysis (rMSSD). We assessed very low-frequency power, low-frequency power (LF), high-frequency power (HF) and the LF/HF ratio in frequency-domain analysis. RESULTS: There was no significant difference in SDNN, but there was a significant difference in pNN50 and rMSSD. Patients with Kawasaki disease showed lower HF and higher LF/HF than normal controls. CONCLUSION: Our findings suggest that patients with Kawasaki disease and myocardial infarction show decreased vagal activity, which could cause malignant arrhythmia.