Temporal Relationship between Serum Levels of Interleukin-6 and C-Reactive Protein in Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy.

Objective C-reactive protein (CRP) is a useful marker of neonatal infection. Recent studies have shown that neonatal therapeutic hypothermia delays an elevation of CRP in infants with hypoxic-ischemic encephalopathy (HIE). This study investigated the time difference of peak levels of serum CRP and other inflammatory responses during therapeutic hypothermia. Study design We prospectively studied the serial serum data of CRP, interleukin-6 (IL-6), procalcitonin (PCT), and complete blood counts during the first week of life in HIE infants receiving therapeutic hypothermia. Results We identified 22 infants who received therapeutic hypothermia between August 2013 and July 2015. No infants developed clinically overt infections. The peak of serum levels of IL-6, PCT, and CRP were postnatal days 1, 2, and 4, respectively. White blood cells, neutrophils, and platelet counts gradually decreased from days 1 to 7. Early postnatal serum levels of IL-6 correlated with CRP on day 4 (IL-6 on day 2; r = 0.78, p < 0.001). Conclusion The peak value of CRP on day 4 might reflect the early production and secretion of IL-6 rather than an actual infection. Serial measurement of IL-6 might help avoid invasive sepsis workup and unnecessary change of antibiotics in infants.

Evaluation of lymphatic dysplasia in patients with congenital pleural effusion and ascites using indocyanine green lymphography.

OBJECTIVES: To investigate the use of indocyanine green (ICG) lymphography in the diagnosis and assessment of the severity of lymphatic dysfunction in infants and neonates with congenital lymphatic pleural effusion and ascites. STUDY DESIGN: We performed ICG lymphography on 10 neonates and infants with congenital lymphatic pleural effusion and ascites. After the subcutaneous injection of ICG, circumferential fluorescent images of lymphatic drainage channels in the extremities and trunk were identified using an infrared camera system. The lymphographic findings were classifiable into 2 patterns-those showing a linear lymphatic pattern, suggesting normal lymphatic flow, and those showing lymphatic channels with retrograde lymphatic flow (dermal backflow pattern), suggesting an abnormal lymphatic flow. We analyzed the severity of the ICG lymphography findings and the clinical outcomes. RESULTS: Based on the ICG lymphography, the severity of lymphatic dysplasia were classified into 4 categories: mild dysplasia, moderate dysplasia, severe dysplasia, and lymphatic hypoplasia. All cases diagnosed with mild (n = 3) or moderate dysplasia (n = 2) survived, and 2 of the 4 cases diagnosed with severe dysplasia died. The duration of endotracheal intubation ranged from 1 to 17 days (median, 7) in the patients with mild or moderate dysplasia and from 25 to 110 days (median, 77) in those with severe dysplasia. CONCLUSIONS: The ICG lymphographic findings were consistent with the clinical conditions. This imaging technique may be important to the future clinical management of lymphatic dysplasia in neonates and infants.

The diameter of the inferior vena cava provides a noninvasive way of calculating central venous pressure in neonates.

AIM: To explore a less invasive way of assessing preload in neonates than fitting catheters to measure central venous pressure (CVP). This study evaluated the relationship between inferior vena cava (IVC) measurements and gestational age (GA) or body weight (BW) in term and premature infants and the correlation between those measurements and CVP in sick infants under mechanical ventilation. METHODS: We studied 57 clinically stable infants, together with 14 sick infants fitted with central venous catheters to measure CVP. Subcostal transverse views were recorded at the level of the left branch of portal vein, and the minimum (DS ) and maximum (DL ) diameters of the IVC were measured. We evaluated the values of DS and DL and the S/L ratio (DS divided by DL ) in the clinically stable infants and the correlation between S/L and CVP in the sick infants with central catheters. RESULTS: DS and DL correlated positively and strongly with both GA and BW, whereas S/L was almost independent of both GA and BW and correlated strongly with CVP. CONCLUSION: At the subcostal transverse views, S/L is much less affected by either GA or BW than DS or DL and correlates strongly with CVP in mechanically ventilated infants.

Tailor-made circulatory management based on the stress-velocity relationship in preterm infants.

Preterm infants frequently experience pulmonary hemorrhage or cerebral intraventricular hemorrhage after birth. The immature myocardium of the left ventricle faces a high afterload after the baby is separated from the placenta. However, the preterm left ventricle has limited ability to respond to such an increase in afterload. This results in depressed cardiac function and a deterioration in hemodynamics. We speculated that the perinatal deterioration in cardiac performance would be closely related to serious hemorrhages. To prove our hypothesis, we studied the interrelationship between the perinatal changes in cardiac performance and the incidences of intraventricular and pulmonary hemorrhage. We obtained the stress-velocity relationship (rate-corrected mean fiber shortening velocity and end-systolic wall stress relationship) by M-mode echocardiography and arterial blood pressure measurement. We found that the incidences of intraventricular and/or pulmonary hemorrhages were higher in infants with an excessive afterload, which resulted in a decrease in the function of the left ventricle. We suggest that careful attention to keep the afterload at an acceptable level by vasodilator therapy and sedation may reduce or prevent these serious complications. In this review, we will discuss our data along with related literature.

Unilateral glomerulocystic kidney disease associated with tuberous sclerosis complex in a neonate.

We report a case of glomerular cystic kidney disease (GCKD) associated with tuberous sclerosis complex (TSC) in a neonate. The patient displayed progressive abdominal enlargement attributed to GCKD associated with TSC. After birth, the right kidney was resected because it compressed his liver and right lung, and possible malignancy could not be excluded. Macroscopically, the resected kidney was markedly enlarged, and histologically the kidney had numerous glomerular cysts accompanied by papillary epithelial growth. Notably, a small area of normal parenchyma was observed at the lower pole. The epithelial cells of the cysts displaying a papillary growth pattern were positive for mTOR, phosphorylated mTOR, and phosphorylated S6 ribosomal protein (p-S6). The morphologically noncystic, normal-looking tubular epithelium was also positive for p-S6. These results imply that one more molecular event might be necessary for cyst formation in GCKD associated with TSC, in addition to the activation of mTOR signaling.

TSH suppression after intravenous glucocorticosteroid administration in preterm infants.

BACKGROUND: Reports have described that, in adults, steroids suppress thyroid-stimulating hormone (TSH) and triiodothyronine (T3) and might suppress thyroxine (T4). No data have been reported for thyroid hormone changes before or after administration of glucocorticoid in preterm infants. AIMS: The aim of this study was to investigate short-term effects of thyroid hormones on preterm infants. INDEX CASES: We measured TSH, free T3 (FT3), and free T4 (FT4) before and after one or two doses of glucocorticoids administered to five infants at 29-37 weeks of corrected gestational age. RESULTS: Comparison of thyroid hormone levels before and 1 day after glucocorticoid administration showed that TSH significantly decreased by 76% (64%-87%), FT3 by 33% (10%-50%), and FT4 by 10% (3%-17%). The decline in TSH and FT3 was followed by an increase around the pretreatment level at 3-15 days after glucocorticoid administration. In two of the five infants, FT4 continued to decrease from 1 day after glucocorticoid administration. CONCLUSIONS: In preterm infants, assessing thyroid hormones after glucocorticoid therapy demands caution because very short-term administration causes marked changes.

Congenital omphalocele and polyhydramnios: a study of 52 cases.

INTRODUCTION: Unlike gastroschisis, congenital omphalocele is often associated with other anomalies and is frequently complicated by polyhydramnios. We examined the relationships between polyhydramnios, pregnancy outcome and fetal prognosis. PATIENTS AND METHODS: Clinical data from cases diagnosed antenatally with congenital omphalocele from 1993 to 2006 were analyzed retrospectively. RESULTS: Fifty-two cases were diagnosed antenatally with congenital omphalocele, and 38 of these pregnancies resulted in delivered infants. Of these 38 pregnancies, 55.3% were preterm births before 37 weeks of gestation. The mean birth weight was 2,148 g (n = 38). Associated anomalies were recognized in 29 cases (76.3%), including 13 cases (34.2%) of chromosomal aberrations. There were 2 cases of trisomy 13, 10 cases of trisomy 18 and 1 case of trisomy 21. Polyhydramnios was detected in 14 cases (36.8%), and other anomalies were present in all of these cases. DISCUSSION: For antenatal evaluation in cases of congenital omphalocele, it is important to examine the fetus for associated anomalies or underlying disease, especially when polyhydramnios is detected.

Prenatal management of the fetus with lethal malformation: from a study of oligohydramnios sequence.

47 cases of oligohydramnios sequence (OS) diagnosed at Kanagawa Children's Medical Center from 1992 to 2008 were studied retrospectively. Early termination of pregnancy was chosen in 9 cases, observed natural labor was chosen in 23 cases, and 18 cases resulted in natural deliveries. Fetal demise occurred during labor in 44.4% of terminated cases, while it occurred in 5.6% of observed cases. Preterm labors and breech presentations occurred most frequently. Most infants died within 18 hours after their births. There were 3 familial cases. These results provide important information for planning the perinatal care when fetuses are diagnosed with OS.

Blood potassium and urine aldosterone after doxapram therapy for preterm infants.

OBJECTIVE: We often encounter infants who developed hypokalaemia following low-dose doxapram for apnea of prematurity (AOP). AIMS: To determine changes in blood potassium (K+) levels after doxapram administration. STUDY DESIGN: We studied infants born before 30 weeks gestation. Doxapram (0.1-0.3 mg/kg/h) in addition to methylxanthines was used to treat AOP refractory to methylxanthines. RESULTS: Twenty-five infants received doxapram were studied. Fifty-two percent developed hypokalemia (<3.0 mEq/L) during doxapram administration. Time after starting doxapram to nadir blood K+ (<3.0 mEq/L) level was 11 days. Blood K+ levels normalized after 5 days of stopping doxapram administration. Data at 10 days before and after and at the time of doxapram administration were, respectively: lowest blood K+ level: 3.9, 3.0, and 3.6 mEq/L; urine aldosterone: 90, 206, and 146 pg/µg creatinine. Blood pH, blood pressure and urine volume were similar. CONCLUSIONS: Doxapram-induced hypokalemia may be due to an inappropriate increase in aldosterone levels.

Effectiveness of Corticosteroid Therapy for Acute Neurological Symptoms in Incontinentia Pigmenti.

BACKGROUND: Incontinentia pigmenti is a rare neurocutaneous disorder that may result in neurological symptoms in addition to its characteristic skin rashes. The pathogenesis of central nervous system disorders in incontinentia pigmenti remains unclear, but it has been suggested that vascular abnormalities and inflammatory processes may play important roles. Notably, there is no established treatment for central nervous system disorders in incontinentia pigmenti. We report a neonate with acute neurological symptoms of incontinentia pigmenti who was effectively treated with corticosteroid therapy. We review the literature and discuss the pathophysiology, diagnosis, and treatment of acute central nervous system disorders in incontinentia pigmenti. PATIENT DESCRIPTION: A 15-day-old girl with incontinentia pigmenti experienced neurological symptoms such as decreased level of consciousness and a weak sucking reflex. Magnetic resonance imaging revealed multiple cerebral infarctions. We administered corticosteroid therapy, and the symptoms improved immediately and significantly. CONCLUSION: We suggest that corticosteroid therapy may be an effective treatment during the acute phase of central nervous system dysfunction due to incontinentia pigmenti. It is important to determine the existence of acute phase lesions on magnetic resonance imaging when neurological symptoms occur or worsen.

Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center.

To investigate the pregnancy outcome of the fetuses with trisomy 18, we studied 123 cases of trisomy 18 who were born at our hospital from 1993 to 2009. Among them, 95.9% were diagnosed with trisomy 18 prenatally. Prenatal ultrasound findings showed fetal growth restriction in 77.2%, polyhydramnios in 63.4% and congenital heart defects in 95.1%. For 18 cases, cesarean section (C-section) was chosen, and for 75 cases, transvaginal delivery was chosen. Premature delivery occurred in 35.5%. Stillbirths occurred in 50 cases (40.7%). Fetal demise before onset of labor occurred in 30 cases and fetal demise during labor occurred in 20 cases which was 26.7% of vaginal deliveries. Among the 73 live-born infants, the survival rate for 24 h, 1 week, 1 month and 1 year were 63%, 43%, 33% and 3%. The median survival time was 3.5 days. There was no significant difference between the survival time of C-section and that of vaginal delivery. However, for the births involving breech presentation, the survival time of C-section was significantly longer than that of vaginal delivery. When the fetus is diagnosed with trisomy 18, the parents have to make many choices. These findings constitute critical information in prenatal counseling to the couples whose fetuses have been found to have trisomy 18, especially when they choose palliative approaches in the perinatal management.

Congenital Candida glabrata infection without specific nodules on the placenta and umbilical cord.

Two extremely premature infants died as a result of congenital Candida glabrata infection, and their placentas and umbilical cords were free of macroscopic Candida nodules. Because non-Candida albicans Candida infections are less likely to produce necrotic foci, we should not exclude Candida infections in the absence of macroscopic nodules on the placenta and umbilical cord.

Re-evaluation of chorioamnionitis and funisitis with a special reference to subacute chorioamnionitis.

Our purpose is to prove that prolonged inflammation of the chorionic plate, which we have termed subacute chorioamnionitis (SCAM), is a distinctive entity and should be differentiated from acute chorioamnionitis (ACAM) because it is an excellent prognostic indicator of chronic lung disease (CLD), including Wilson-Mikity syndrome (WMS). Ninety singleton placentas with stage-3 chorioamnionitis were delivered at 23 to 32 weeks of gestation during 1993 to 1996, and the infants survived more than 28 days. There were 49 placentas with stage 3 SCAM, 33 placentas with stage 3 ACAM, and 8 placentas with subacute necrotizing funisitis (SNF) and without inflammation of the chorionic plate. Fifty-three of gestation- and birthweight-matched placentas without chorioamnionitis were selected as control. To determine the risk factors for CLD, 27 clinical and 6 histological variables were analyzed. Logistic regression analysis showed that amniotic necrosis (AN) (P =.0168) and low birthweight (P =.0341) were the major contributing risk factors for CLD. SNF was not significantly related to CLD. Patients with SCAM (AN+, SNF-) were highly susceptible to CLD. In conclusion, SCAM, especially when associated with AN, seems to be a unique prognostic indicator of CLD.

Familial severe congenital diaphragmatic hernia: left herniation in one sibling and bilateral herniation in another.

Familial congenital diaphragmatic hernia (CDH) is extremely rare; it comprises about 2% of all CDH cases. The empirical risk is about 2%, increasing to 10% in a family with two affected children. This report describes severe CDH in two siblings who had been diagnosed prenatally. The female newborn diagnosed with left CDH prenatally was born at 38 weeks of gestation. Despite surgical repair and intensive treatment, she died 10 days after birth. Her younger brother was born at 39 weeks of gestation after being diagnosed with bilateral CDH prenatally, and died 75 min after birth. Both infants had neither other congenital anomaly nor chromosomal abnormalities. Their parents are healthy without consanguinity. Their first daughter and the fourth child have no congenital anomalies.

Mortality rates for extremely low birth weight infants born in Japan in 2005.

OBJECTIVE: Our goal was to investigate the neonatal mortality rate and the mortality rate during the NICU stay for extremely low birth weight infants born in Japan in 2005. METHODS: The Committee of Neonatal Medicine of the Japan Pediatric Society retrospectively surveyed the deaths of extremely low birth weight infants born and hospitalized between January 1 and December 31, 2005. From 297 institutions in Japan, data on 3065 extremely low birth weight infants, which represented 98.4% of those reported in the maternal and health statistics of Japan in 2005, were collected. RESULTS: The neonatal mortality rate and the mortality rate during the NICU stay were 13.0% and 17.0%, respectively, which were lower than 17.7% and 21.5% in the survey in 2000. The neonatal mortality rates and the mortality rates during the NICU stay were 53.3% and 67.7% in the <400-g birth weight group (n = 62), 42.1% and 53.5% in the 400- to 499-g birth weight group (n = 159), 22.2% and 27.7% in the 500- to 599-g birth weight group (n = 387), 16.8% and 22.2% in the 600- to 699-g birth weight group (n = 537), 9.4% and 12.7% in the 700- to 799-g birth weight group (n = 574), 6.3% and 9.1% in the 800- to 899-g birth weight group (n = 649), and 3.9% and 5.3% in the 900- to 999-g birth weight group (n = 697), respectively. The factors involved in the deaths of extremely low birth weight infants included lower gestational age, lower birth weight, male gender, multiple birth, institutions in which <10 extremely low birth weight infants were admitted per year, and no prenatal maternal transfer. CONCLUSION: The mortality rates of extremely low birth weight infants who were born in 2005 demonstrated definite improvement.

Magnetic resonance imaging regional T1 abnormalities at term accurately predict motor outcome in preterm infants.

OBJECTIVE: The aim of this study was to assess whether periventricular leukomalacia findings are sufficiently sensitive for predicting the severity of motor prognosis by conventional MRI in the near term. METHODS: Preterm infants with T1 hyperintensity or cysts in the periventricular regions on term MRI were selected, and their gross motor functions were evaluated at the age of 3 to 5 years. Sixty-two infants had findings of T1 hyperintensity or cysts, and except for infants with these findings, none were diagnosed later as periventricular leukomalacia. RESULTS: All 37 patients with cerebral palsy had periventricular lesions with T1 hyperintensity or cysts in the corona radiata above the posterior limb of the internal capsule on coronal sections. Small T1 hyperintensity lesions were seen on coronal slices and were often difficult to detect on axial slices. All of the 17 infants with T1 hyperintensity findings sparing the corona radiata above the posterior limb of the internal capsule showed normal motor development, irrespective of findings of ventriculomegaly. There was a tendency for the presence of widespread lesions in corona radiata above the posterior limb of the internal capsule to be correlated with the severity of motor handicap. CONCLUSIONS: Lesions in the corona radiata above the posterior limb of the internal capsule on a coronal view by term MRI were useful for predicting motor prognosis in preterm infants with periventricular leukomalacia.

Pregnancy outcome of fetuses with trisomy 18 identified by prenatal sonography and chromosomal analysis in a perinatal center.

To investigate the pregnancy outcome of fetuses affected with trisomy 18, we analyzed 63 cases diagnosed at our hospital from January 1993 to December 2004. Twenty-nine were males and 34 were females. Fifty-eight were prenatally diagnosed, and in 16 (27.6%) of them intrauterine fetal death (IUFD) occurred between 28 weeks and 41 weeks gestation (34.6 +/- 3.9 weeks, Mean +/- SD). Ten (17.2%) fetuses died during labor and their age ranged from 30 weeks to 40 weeks of gestation. The total number of cases ending in fetal demise was 26 (44.8%) and the mean gestational age at the time of fetal demise was 35.0 +/- 3.6 weeks (Mean +/- SD). All liveborn infants (n = 36) were born after 31 weeks gestation. In our study the preterm birth ratio for trisomy 18 is 34.8%, which is much higher than the ratio for the general population. Females are more likely than males to be long-term survivors. These data are helpful in the counseling of parents faced with the difficult decision of whether or not to continue a pregnancy with a fetus affected with trisomy 18.

Morbidity and mortality of infants with very low birth weight in Japan: center variation.

OBJECTIVES: The objectives of this study were to describe the characteristics and morbidity of very low birth weight infants, to identify the medical intervention for these infants, and to evaluate the factors affecting the mortality of these infants among the participating hospitals. METHODS: A large multicenter neonatal research network that included level III NICUs from throughout Japan was established. A standardized mortality rate was formulated by giving a ratio of the observed deaths and the predicted deaths based on a 100-g birth weight interval mortality. A regression model was used to predict the factors that affect neonatal mortality. RESULTS: The network included 37 centers and 2145 infants weighing < or = 1500 g, born or admitted to the centers in 2003. Gestational age and birth weight of studied infants were 28.6 +/- 3.6 gestational weeks (mean +/- SD) and 1025 +/- 302 g, respectively. Overall, 11% of the infants died before being discharged from hospitals (range: 0%-21%). The standardized mortality rate varied among the facilities (range: 0%-30%). No association between the annual number of patients admitted and standardized mortality rate was found. Among all of the very low birth weight infants, 14% were outborn infants, 72% were delivered by cesarean sections, 27% had patent ductus arteriosus, 3% had gastrointestinal perforation, 8% had bacterial sepsis, and 13% had intraventricular hemorrhage. Medical interventions involved were: 41% antenatal corticosteroids, 54% surfactant therapy, 18% postnatal steroids for chronic lung disease, and 29% high-frequency oscillatory ventilation. We found variations in the medical interventions and the clinical outcomes among the centers. CONCLUSIONS: The overall survival rate for very low birth weight infants among neonatal centers in Japan was approximately 90%. However, differences in the morbidity and mortality were observed among these centers.