Effects of supplemental oxygen on urinary 8-hydroxy-2'-deoxyguanosine levels in extremely low birth weight infants.

As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 ± 6.9 vs. 5.6 ± 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.

Radiographic findings of diaphragmatic hernia and hypoplastic lung.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) has a poor prognosis, despite intensive management. The prognosis of CDH is correlated with hypoplastic lung, but it is difficult to measure the degree of hypoplasia. The aims of this study were, therefore, to examine the relationship between chest X-ray and prognosis, and to assess whether the radiographic findings were a good indicator of hypoplastic lungs in patients with CDH. STUDY DESIGN: Fifty neonates with CDH were classified radiographically into apex and hilar types. To assess the differences in clinical course between these two groups, gestational age, birth weight, prenatal diagnosis, survival rate, requirement of extracorporeal membrane oxygenation (ECMO) therapy and lung area on X-rays were analyzed. RESULTS: In all, 32 cases were of the apex type and 18 were hilar. The survival rate of the hilar group (33%) was significantly worse than that of the apex group (81%) (P<0.001). The hilar group required ECMO therapy more frequently than did the apex group. CONCLUSIONS: The present results show a significant correlation between survival rate and the findings of chest X-rays in CDH. Radiographic findings are thus a good clinical indicator of the prognosis of CDH in neonates.

[Fungal keratitis in a daily disposable soft contact lens wearer]. / Kératite fongique et lentilles cornéennes jetables Journalières.

A case of fungal keratitis was diagnosed in a young female who had been wearing daily disposable soft contact lenses for 2 Years. No risk factor was demonstrated and specific treatment was effective. This case emphasizes that patients must be aware of the importance of hygiene as daily disposable contact lenses must be discarded daily.

Variation of des-gamma-carboxyprothrombin (PIVKA-II) levels in cord blood throughout gestation.

The variation of des-gamma-carboxyprothrombin (PIVKA-II, protein induced by vitamin K absence) levels in umbilical cord blood throughout gestation was examined using a highly sensitive method, electrochemiluminescence immunoassay (ECLIA). PIVKA-II levels in infants without any complications were low, but modestly high, exceeding the normal range of healthy adults during the preterm period, followed by a remarkable increase after the 37th week of gestation. Among infants complicated with severe preeclampsia a marked increase of PIVKA-II levels was observed in preterm infants, showing a good correlation with the existence ofinfarctions on the placenta. On the other hand, among infants complicated with preterm premature rupture of the membranes (PROM) in which antibiotics were administered during the prenatal period, a moderate elevation of PIVKA-II levels was observed. These data suggest that the normal range of PIVKA-II in fetuses is modestly high compared with adults and any deficient status of vitamin K would not exist throughout the preterm period. Nevertheless, the vitamin K status might readily fall into a deficient condition in term infants. Furthermore, it is notable that vitamin K deficiency would be induced in complicated gestation with severe preeclampsia and medication with antibiotics.

Cervico-mediastinal bronchogenic cyst occurring in the prenatal period: report of a case.

We experienced a case of cervico-mediastinal bronchogenic cyst in which a cervical cystic mass was detected by prenatal ultrasonography. On prenatal ultrasound, a unilocular, well-defined and hypoechoic mass was detected in the fetal neck. The baby was born by a normal vaginal delivery at 40 weeks of gestation, and had no respiratory distress. Radiological investigations demonstrated a cyst in the cervico-mediastinal region, which displaced the trachea to the left. At the age of 32 days, an elective resection was easily performed through a right inferior collar incision after first aspirating the contents of the cyst. Prenatal sonography showing abnormal findings is effective for identifying cysts in the perinatal period and allows for the timely resection of such cysts before respiratory distress occurs.

Intrauterine infection, magnesium sulfate exposure and cerebral palsy in infants born between 26 and 30 weeks of gestation.

OBJECTIVE: To identify prenatal events associated with cerebral palsy (CP) in infants born between 26 and 30 weeks of gestation. STUDY DESIGN: Case (n=22)-control (n=170) study was performed using a logistic regression model. RESULTS: Significant association of intrauterine infection with increased risk of CP was found in a logistic regression model that controlled for abnormal FHR patterns, placental infection, fetal acidosis at birth (umbilical artery pH<7. 1), and low Apgar score (<7) (odds ratio (OR) 5.47, 95% confidence interval (CI) 1.46-20.4). Magnesium sulfate exposure was associated with decreased risk (OR 0.13, CI 0.03-0.66) after exclusion of premature rupture of the membranes and abruptio placentae. In the magnesium exposure group, cases were infants born less than 28 weeks of gestation (3/21 vs. 0/61, P=0.015). CONCLUSION: In this case-control study, both intrauterine infection and magnesium sulfate exposure were significant factors related to the occurrence of cerebral palsy.

Correlation between magnetic resonance imaging and clinical profiles of periventricular leukomalacia.

Magnetic resonance imaging (MRI) findings of 70 children with periventricular leukomalacia (PVL), examined between 1 year 2 months and 8 years of age (mean: 2 years 4 months of age), were analysed. Neurological assessments were made between 1 year 3 months and 15 years (mean: 4 years 9 months). The possible correlations between MRI findings and clinical profiles of PVL were investigated using three parameters of the MRI findings. The grade of ventriculomegaly correlated well with the severity of cerebral palsy (CP) but not with the severity of mental impairment. The grade of reduction of periventricular white matter correlated well with the severity of CP and mental impairment, and is the most reliable parameter for neurological prognosis. The degree of periventricular hyperintensity on T2-weighted images did not correlate well with severity of CP, but correlated to some degree with mental impairment. There was a significantly lower degree of periventricular hyperintensity in children at less than 28 weeks of gestation than at 28 or more weeks of gestation, but no significant difference in other parameters. The periventricular hyperintensity should be evaluated in view of the gestational age.

Neonatal 24-hour urinary C-peptide and birth weight in infants of diabetic mothers.

OBJECTIVE: Our purpose was to investigate the relationship between the birth weights and 24-h urinary C-peptide in infants of diabetic mothers. METHODS: Sixty pregnancies with gestational diabetes mellitus (DM) were enrolled. Neonatal urine was collected for the first and second 24 h for measuring C-peptide. Birth weights were classified into 3 categories according to the Japanese standard curves; heavy-for-date (HFD), appropriate-for-date (AFD), and light-for-date (LFD). Unpaired t-test was used for comparison of 24-h urinary C-peptide in the 3 birth weight categories, with P-value <0.05. There were 7 HFD, 47 AFD, and 6 LFD infants. Birth weight averaged 3.9+/-0.7, 3.0+/-0.4, and 2.3+/-0.3 kg, respectively. RESULTS: Insulin concentrations of the umbilical artery were significantly higher in HFD than in AFD, and significantly higher in AFD than in LFD (49.5+/-45.1, 16.8+/-15.2, and 6.3+/-6.1 microU/ml). During the first 24 h, urinary C-peptide was significantly higher in HFD than in AFD (2.73+/-1.52 vs. 0.76+/-0.81 microg/day), and significantly higher in AFD than in LFD (0.27+/-0.27). On the second day, there was no longer statistical significance. CONCLUSIONS: Measurement of 24-h urinary C-peptide revealed that, among infants of diabetic mothers, HFD infants continue to secrete more insulin than AFD and LFD infants for the first 24 h.

Echocardiographic findings of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum in utero.

BACKGROUND: Neonates with right ventricular outflow obstruction and intact ventricular septum show serious hemodynamic problems, such as severe hypoxemia, congestive heart failure due to massive tricuspid regurgitation, respiratory distress related to huge pulmonary hypoplasia or ventricular dysfunction due to right ventricle-coronary communication. Recent advances in fetal diagnosis include many cases of in utero diagnosis of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum. METHOD: Among the fetuses examined from April 1994 to March 1998, five fetuses were found with pulmonary atresia (PA) or critical pulmonary stenosis (CPS). Fetal echocardiograms were reviewed to elucidate the accuracy of fetal information and the efficacy of fetal diagnosis in the perinatal management of patient with CPS or PA and intact ventricular septum. RESULTS: The five cases were divided into two groups: two with a very small right ventricle (group 1) and three with a tripartite right ventricle (group 2). Fetal cardiomegaly and right atrial dilatation were prominent in group 2, whereas cardiac sizes were normal in group 1. Serial fetal examination in one group 2 fetus revealed developing right ventricular hypertrophy in utero. All group 2 cases showed massive tricuspid regurgitation (TR). Estimated right ventricular pressures from TR always exceeded the systemic blood pressures of gestational age-matched neonates. Reversed flow through the ductus arteriosus was recorded in both groups and ductus-dependent pulmonary circulation after birth was anticipated. Patency of both tricuspid and pulmonary valves was difficult to recognize in utero, as was right ventricle-coronary artery communication. Four of the five cases were maternally transported and survived palliative and/or definitive intervention. One fetus with chromosomal abnormality was observed without intervention during infancy and received palliative surgery when she was two years old. CONCLUSION: Fetal hemodynamic information was useful for making decisions not only after birth, but also in utero, and may eventually result in improving the prognosis of babies with PA/CPS. Serial observation of the fetuses with PA/CPS may also suggest the possible pathogenesis of PA/CPS in utero.

National survey of periventricular leukomalacia in Japan.

BACKGROUND: Clarification of the present status of periventricular leukomalacia (PVL) in Japan. METHODS: Questionnaires were mailed to the leading neonatal intensive care units (NICU) and rehabilitation centers for children. RESULTS: The incidence of PVL in the group of surviving preterm infants of gestational ages less than 33 weeks was 4.8-4.9% on ultrasound and 7.7-7.9% on magnetic resonance imaging and/or computed tomography. The incidence of PVL did not decrease between 1990 and 1994. The incidence of PVL in the NICU varied from 0 to 47.1%. Infants from multiple pregnancies had a higher incidence (9.1%) of PVL than those from single pregnancies (6.2%). The proportion of PVL in all patients in rehabilitation centers with cerebral palsy (CP) has increased recently. CONCLUSIONS: It was roughly calculated that about 750 cases of CP with PVL occurred annually in Japan, thus accounting for about one-third of the total number of cases of CP.

Fetal glioblastoma: rapid growth during the third trimester.

We present a case of fetal glioblastoma which appeared after 28 weeks' gestation. The first ultrasonographic finding was an enlarged fetal head with right shifted falx cerebri at 31 weeks' gestation. At 33 weeks, a large and high echogenic mass in the left hemisphere and right enlarged ventricle was identified. Magnetic resonance imaging showed that the tumor was localized in the left hemisphere and a margin of the tumor was defined. Because fetal well-being judging from biophysical parameters was good and we considered that the tumor was resectable, a male fetus weighing 2,670 g was delivered at 34 weeks' gestation by cesarean section. However, he was inoperable due to consumptive coagulopathy and rapid growth of the tumor, and died on the 41st day of life.

Effect of arginine vasopressin on breathing movements of chronically instrumented fetal lambs.

BACKGROUND: In hypoxic conditions, fetal breathing movements (FBM) are reportedly inhibited with simultaneous elevation of the plasma level of catecholamines and arginine vasopressin (AVP). Although some kinds of catecholamines are reported to inhibit FBM, the effects of AVP on FBM are still unknown. The present study was undertaken to elucidate whether or not AVP has an inhibitory effect on FBM and electrocortical activities in chronically instrumented fetal lambs. METHODS: Arginine vasopressin was injected slowly into the fetal external jugular vein via a catheter over a 30 minute period at an infusion rate of 4.9 approximately 10.0 mIU/minute/body. In 15 fetuses (36 estimations) the mean fetal age, mean estimated fetal body weight, and mean infusion dose were 132.4 +/- 4.5 days, 3.4 +/- 0.3 kg and 1.7 +/- 0.3 mIU/kg/min. RESULTS: The infusion caused a persistent decrease in the fetal heart rate and an increase in the fetal arterial pressure during the 30 minute period. The infusion of AVP resulted in a significant decrease in the incidence of FBM from 36.1 +/- 14.8% to 12.4 +/- 14.9% (p <0.01). However, there were no significant differences in the incidence of the low voltage fast (LVF) activity before and during infusion of AVP. CONCLUSION: AVP has an inhibitory effect on FBM. The mechanism of this inhibition was not a direct suppression of the CNS as there was a dissociation between FBM and the electrocortical activity during infusion of AVP.

Comparison of circulatory effects between arginine vasopressin (AVP) and dopamine in conscious newborn goats.

By using conscious chronically instrumented newborn goats, the circulatory effect of arginine vasopressin (AVP) (20 mIU/kg/ min) was studied, assuming a potential use for AVP to treat circulatory failure in the newborn, and the results were compared with those of dopamine (20 micrograms/kg/min). The AVP infusion decreased heart rate (HR) and cardiac output (CO) significantly, and increased systemic arterial pressure (SAP) and pulmonary arterial wedge pressure (PAWP) significantly, but did not change pulmonary arterial pressure (PAP) appreciably. The dopamine infusion did not change HR, SAP, and PAWP but increased CO and PAP significantly. Right atrial pressure (RAP) increased significantly in both groups. The pulmonary vascular resistance (PVR) increased significantly in both groups. The systemic vascular resistance (SVR) increased significantly in the AVP group, but did not change during experiments in the dopamine group. The calculated PVR/SVR ratios decreased significantly from the baseline value after initiation of the AVP infusion. In contrast, the dopamine infusion increased PVR/SVR ratios significantly throughout the experiments. Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome characterized by right-to-left shunting of blood at the level of the foramen ovale and ductus arteriosus. AVP may reduce the shunting of blood by elevating only SAP selectively.

Cardiac oxygenation by extracorporeal membrane oxygenation in exteriorized fetal lambs.

OBJECTIVE: The purpose of this study was to determine the degree of cardiac oxygenation produced by different routes of extracorporeal membrane oxygenation in fetal lambs submerged in warm saline solution. STUDY DESIGN: Seven fetal lambs ranging in age from 113 to 133 days of gestation were delivered by cesarean section and oxygenated with extracorporeal membrane oxygenation. To maintain the patency of the ductus arteriosus, prostaglandin E1 was continuously infused intravenously to the fetus. Initially the extracorporeal membrane oxygenation route was from the right atrium to the carotid artery. Then the extracorporeal membrane oxygenation route was changed to flow from the right atrium to the umbilical vein. The fetus was kept in a warm saline solution bath, and the fetal circulation was maintained. Extracorporeal membrane oxygenation flow ranged between 100 and 200 ml/min throughout the experiment. Simultaneous blood samples were taken during both types of extracorporeal membrane oxygenation from the following points in the fetal circulation: premembrane (least oxygenated blood leaving the fetus from the right atrium), postmembrane (oxygenated blood returning to the fetus), the carotid artery, and the left ventricle. The respiratory gases and pH of each sample were measured. Six fetuses received nonradioactive colored microspheres injected into the oxygenated blood returning to the fetus flow before returning to the fetuses during both types of extracorporeal membrane oxygenation. After the animals were killed, microspheres were counted in the myocardium separately taken from the right and left atria and the right and left ventricles to determine cardiac blood flow. RESULTS: During right atrium to carotid artery extracorporeal membrane oxygenation, left ventricle PO2 remained low as postmembrane PO2 increased; these values were not significantly correlated (r = 0.234, p = 0.61). During right atrium to umbilical vein extracorporeal membrane oxygenation, left ventricle and postmembrane PO2 exhibited a significant positive correlation (r = 0.855, p = 0.014). When the extracorporeal membrane oxygenation route was switched from the right atrium to carotid artery to the right atrium to umbilical vein, there was a significant increase in left ventricle PO2 and a decrease in left ventricle PCO2, whereas the respiratory gases and pH remained unchanged at other sites in the circulation. Microsphere counts were consistently higher during right atrium to umbilical vein extracorporeal membrane oxygenation than during right atrium to carotid artery extracorporeal membrane oxygenation in all four samples from different parts of myocardium (p < 0.001 by paired t test). CONCLUSION: More effective cardiac oxygenation is provided by right atrium to umbilical vein extracorporeal membrane oxygenation than by right atrium to carotid artery extracorporeal membrane oxygenation.

[The perinatal risk factors and periventricular leukomalacia (PVL) in premature infants--relationship between fetal heart rate decelerations and PVL].

Periventricular leukomalacia (PVL) has recently been recognized as an important risk factor of neurological impairment in premature infants. We studied 29 PVL cases on perinatal risk factors comparing with a non-PVL matched control group retrospectively. Variable decelerations were more frequently observed with statistical significance in the PVL group in the intrapartum period. Then another study was conducted to evaluate the relationship between fetal heart rate (FHR) decelerations and cystic PVL prospectively. Since January 1993 through December 1994 we studied 209 low birth weight infants (31.1 +/- 3.2 weeks, 1,424 +/- 419 g) who had been subjected to intrapartum FHR monitoring and postnatal sonographic intracranial examinations sequentially every 7 days until discharge. Cystic PVL was detected in 6 of 209 cases (2.9%) and occurred only in infants who had revealed severe variable deceleration or prolonged deceleration (6/37, 16%) in intrapartum FHR monitoring. We conclude that in low birth weight infants intrapartum severe variable deceleration or prolonged deceleration might play a causal role in cystic PVL.

Oxygenation in fetal lambs supported by extrauterine right atrium to artery extracorporeal membrane oxygenation.

OBJECTIVE: Our purpose was to determine the adequacy of oxygenation, particularly cranial and cardiac oxygenation, in exteriorized fetal lambs on right atrium to artery extracorporeal membrane oxygenation. STUDY DESIGN: Thirteen fetal lambs were placed on right atrium to artery extracorporeal membrane oxygenation between the gestational ages of 113 and 133 days. Various PO2 and oxygen saturation (SO2) values were obtained by varying the oxygen concentrations at the oxygenator membrane. Blood gases, pH, and SO2 were observed on samples taken before and after membrane oxygenation from the left ventricle and through the cranial carotid arterial catheter. These were compared with control values obtained before the cessation of umbilical circulation. Fetal coronary oxygenation was represented by left ventricle PO2 and SO2 and cranial oxygen by carotid artery PO2 and SO2. RESULTS: We classified oxygen saturation as low, medium, and high on the basis of the level of postmembrane SO2. Carotid artery cranial oxygenation in the low SO2 group was equivalent to control values, but that in the medium and high SO2 groups was significantly higher than in the control group. Left ventricle oxygenation was consistently lower than cranial oxygenation in any SO2 group. In the low group left ventricle oxygenation was significantly lower than the control values. CONCLUSIONS: Right atrium to artery extracorporeal membrane oxygenation appears sufficient to oxygenate the fetal cranial circulation but may be inadequate for the efficient distribution of oxygenated blood into the left ventricle and thus the coronary circulation.

[The perinatal risk factors of periventricular leukomalacia (PVL) in premature infants].

Periventricular leukomalacia (PVL) has recently been recognized as an important risk factor in neurological impairment of the premature infant. We studied 29 PVL cases concerning perinatal risk factors retrospectively comparing them with a non-PVL matched control group. Variable decelerations were more frequently observed with statistical significance in the PVL group in the intrapartum period. There was no significant difference between the two groups in the appearance of late deceleration. A lower incidence of RDS, a higher incidence of low Apgar score, a longer period of ventilation and oxygen inhalation and a more persistent presence of apneic spells were documented in the PVL group with statistical significance. Our study suggests the significance of variable deceleration as a risk factor in the occurrence of PVL in premature infants as well as other previously documented risk factors.

Management of meconium aspiration syndrome by tracheobronchial lavage and replacement of Surfactant-TA.

Meconium aspiration syndrome creates mechanical airway obstruction with air trapping and atelectasis. Tracheobronchial saline lavage to dislodge meconium may precipitate respiratory distress, a wet lung appearance and respiratory failure. Two case studies are reported in which meconium aspiration resulted in mechanical obstruction and displacement of surfactant and in whom tracheobronchial saline lavage and artificial surfactant replacement reversed respiratory failure.

Histologic observation of the ductus arteriosus in premature infants with intrauterine growth retardation.

The ductus arteriosus of 19 premature infants with intrauterine growth retardation (IUGR) (study group) was compared histologically with that of 22 infants without IUGR (control group). The two groups exhibited no significant differences in gestational age, age at death, and frequency of disseminated intravascular coagulation. Maternal complications, that is, pregnancy-induced hypertension, cesarean section, and low umbilical artery oxygen tension values, were seen more frequently (p < 0.01) in the study group than in the control group. The histologic changes of ductus arteriosus, such as fragmentation, coagulation necrosis of the intimal elastic lamina, hemorrhage with necrosis, and loosening of elastic fibers and muscles in the tunica media, were seen more frequently in the study group. These findings are suggestive of both the maturation process and the prenatal hypoxic response of premature IUGR fetuses with chronic hypoxia. These changes may have produced subsequent patent ductus arteriosus, which in turn may have induced pulmonary hemorrhage.

[The efficacy of prophylactic antibiotic and tocolytic therapy for premature rupture of the membranes--a prospective randomized study].

A comparative study in patients with premature rupture of the membranes (PROM) from 25 to 34 weeks of gestation was carried out, prospectively. Group 1 (34 patients) was given aggressively intrauterine therapy including the administration of tocolytic agents (ritodrine and/or magnesium sulfate) and prophylactic antibiotics (AB-PC 2g/day). Group 2 (41 patients) was managed conservatively with bed rest only. At the time of admission to the study, there were no clinical signs of infection, fetal distress, or active labor in either group. All patients were delivered if the pregnancy had reached 35 weeks of gestation or later, had established labor, or developed evidence of chorioamnionitis or fetal distress. Prolongation for more than 72 hours was greater in group 1 than in group 2. There was no difference in the incidence of chorioamnionitis, postpartum endometritis, or placental infection in the groups. However, the incidence of a low Apgar score (7 < at 5 min), requiring artificial ventilation, and infection was more common in group 1. It is concluded that the use of antibiotics and tocolytics might make the management of PROM more complicated.