Real-time ultrasonography in the neonate: a systematic study of a high-risk infants population

During a 12-month period a prospective and systematic study was carried out by means of portable real-time ultrasound (US) scanner in order to detect cerebral lesions in a population of high-risk neonates. Newborn infants were allocated into two groups: group A: all premature infants (n = 83) of less than or equal to 34 weeks' gestation or less and group B: neonates (n = 36) of more than 34 weeks' gestation presenting with abnormal neurological signs. Group A: the overall incidence of periventricular haemorrhage (PVH) was 47% (15 grade I, 16 grade II, 3 grade III, 1 Plexus choroid haemorrhage, 1 isolated intraventricular haemorrhage). Infants of 30 weeks or less were at highest risk to develop a PVH. The degree of severity did not depend on gestational age. Repeated scans accurately timed the onset of PVH; 67% developed a PVH within the first 24 hours of life and 31% within the first 6 hours. A post-haemorrhagic ventricular dilatation was noted in 50% of the 28 infants who survived more than 28 days (4 transient, 7 arrested and 3 rapidly progressive). Group B: 15 of 36 infants had US abnormalities. Cerebral lesions were miscellaneous. Diagnosis of PVH, leukomalacia, agenesis of corpus callosum, calcifications in the basal ganglia, hydranencephaly were made and confirmed at autopsy in 9 fatal cases. US has proved useful for the detection of cerebral lesions among high-risk newborn infants in a Neonatal Unit.     

Head size,brain growth,and lateral ventricles in very low birthweight infants.

Ninety eight newborn infants weighing less than 1500 g at birth and with gestational ages from 26 to 32 weeks were followed prospectively. They were grouped according to real time ultrasound scans in the neonatal period: infants in group A (n = 20) had periventricular haemorrhage (PVH) and normal ventricles; infants in group B (n = 26) had PVH and dilated ventricles (none with clinical hydrocephalus); and infants in group C, who formed the control group (n = 52), had no PVH and normal ventricles. At outpatient follow up a static image ultrasound scanner was used to measure the width of the lateral ventricles and brain hemispheres. The three groups of infants showed similar growth in occipitofrontal circumference, biparietal diameter, and brain hemispheres irrespective of a history of PVH or ventricular dilatation. The relation of ventricle size to biparietal diameter was similar in those infants in groups A (PVH alone) and C (controls) who had a good outcome. About a third (n = 8) of the infants in group B had persistent ventricular dilatation in relation to biparietal diameter and a poor outcome associated with developmental delay and cerebral palsy. By contrast, the remaining two thirds (n = 18) of the infants in group B who later had smaller ventricles in relation to biparietal diameter showed fewer neurodevelopmental sequelae. It is suggested that persistent ventricular dilatation in relation to biparietal diameter at follow up carries a bad prognosis, which might be due to brain atrophy.     

Significance of ultrasound appearances in the neurological development and cognitive abilities of preterm infants at 5 years

The developmental outcome at 5 years of age was studied in 93 preterm infants who had been prospectively examined for peri-ventricular leucomalacia (PVL). Standardised neurological examination and developmental assessment, including tests of cognitive function, were carried out. Major sequelae (n=10) could be ascribed in most cases to the presence of large PVL lesions. Children with normal scans (n=51), with isolated haemorrhage (n=15) and with post-haemorrhagic ventricular dilatation (n=3) had a favourable prognosis. Patients with small focal PVL changes (n=16) had lower cognitive abilities on the McCarthy scale and presented more abnormal neuromotor signs and more attention deficits when compared to children with normal scans and isolated haemorrhage. Small focal PVL changes seem therefore to interfere with development at 5 years of age and might represent a morphological marker of a more diffuse brain injury. This study demonstrated also the effect of socioeconomic status on outcome at the age of 5 years.     

Etiology of childhood hypothyroidism

This study prospective without any selection bias included 80 of the 152 hypothyroid infants and children seen over the past six years. The clinical diagnosis was confirmed by TSH and thyroid hormone (T3, T4) studies. Scanning for thyroid with TC99m pertechnetate was carried out in all except seven older children with grade II and III goiters where 131I uptake studies were done. Serum thyroglobulin (RIA) was estimated and antithyroglobulin and antimicrosomal antibodies were tested. Based on thyroid 131I scan or 131I uptake, 52.5% had no demonstrable thyroid tissue except one with hypoplasia (Group I, n = 42), 25% had ectopic thyroid (Group II, n = 20), and 22.5% had normal or enlarged thyroid gland (Group III, n = 18). One hypothyroid patient of Group III had thyroiditis with high antibody titre and one was proved to have iodine deficiency). The mean age at time of diagnosis was lowest in Group I (age in months--30.3 +/- 36.2; 60.6 +/- 53.9; 106.2 +/- 69.3 in Groups I, II and III respectively. The intergroup differences in age were significant. The mean serum Tg levels increased progressively from Groups I to III. In the present series thyroid dysgenesis led to hypothyroidism in 77.5%, with athyreosis in 52.5% and ectopia in 25%. Dyshormonogenesis was noted in 20% and thyroiditis in 1.5%.     

Outcome of intrauterine periventricular haemorrhage and leukomalacia

This case study reports five very low birthweight infants with ultrasound evidence of intrauterine insult to the brain. Intrauterine periventricular haemorrhage (PVH) accompanied by ventricular dilatation occurred in two preterm infants both of whom survived and were severely handicapped at follow-up. Three preterm infants had intrauterine periventricular leukomalacia (PVL); one survived and is severely handicapped at one year of age. Our experience and rare case reports in the literature indicate that intrauterine PVH and PVL carry a high risk of death in the neonatal period and severe neurological sequelae in survivors.     

Biliary atresia with a “cyst at porta”: management and outcome as per the cholangiographic anatomy

The purpose of this study is to classify biliary atresia (BA) with a "cyst at porta" according to the cholangiographic anatomy and to define management strategy and outcome in each group. A cyst at porta was identified in 13 of 58 babies (22.4%) with BA at first presentation. The cholangiographic anatomy was classified as; Group A (n = 7), type III BA with extrahepatic cyst; Group B (n = 2), type I or II BA with extrahepatic biliary cyst; and Group C (n = 4), type I or II BA with both extrahepatic and intrahepatic biliary cysts. The remaining 45 patients were comprised of type III BA without a cyst. A Kasai's portoenterostomy (PE) was performed for all Group A patients. Groups B and C were treated by hepaticojejunostomy (n = 5) or portoenterostomy (n = 1). All 45 patients with type III BA without a cyst were treated by a Kasai's PE. The median age at surgery was 92 days (ranges 28-342 days). There were three early post-operative deaths, all in patients with type III BA without cyst. Overall 18/55 (32.7%) patients achieved a jaundice free state. In Group A, 5/7 (71.4%) patients had bile flow, 2/7 (28.6%) are anicteric and 2/7(28.6%) had 1-2 episodes of post-operative cholangitis. In Group B, both patients are anicteric and none had post-operative cholangitis. In Group C, all four babies had bile flow but, significant morbidity because of recurrent severe cholangitis. Only one patient reached a jaundice free state. Of the remaining 42 patients with type III BA without a cyst, 27 (64.3%) had bile flow, 13 (31%) became jaundice free and 14 (33.3%) have had 1-2 episodes of post-operative cholangitis. In conclusion, thirteen of 58 (22.4%) babies with BA had a "cyst at porta" at first presentation in this series. The outcome was most satisfactory in type I BA without intrahepatic cystic dilatation (Group B) in terms of achieving a jaundice free state and freedom from recurrent cholangitis. However, intrahepatic biliary cysts (Group C) were associated with recurrent severe cholangitis and a poor eventual outcome despite a good initial bile flow. The outcome in type III BA with extrahepatic cyst was comparable to type III BA without cyst.     

Developmental and neurological progress of preterm infants with intraventricular haemorrhage and ventricular dilatation.

A prospective neurological and developmental assessment was completed at ages 6, 9, and 12 months on 39 preterm infants under 34 weeks'' gestation. In the newborn period each infant had an assessment of gestation and sequential neurological and ultrasound examinations and was placed in one of three groups: intraventricular haemorrhage (IVH) (n = 14), IVH followed by ventricular dilatation (n = 11), and control infants with no evidence of IVH (n = 14). When corrected for prematurity the Griffiths''s developmental quotients (DQs) were normal at 6, 9, and 12 months for every infant except one aged 12 months. In contrast, the uncorrected DQs at 12 months were under 80 in only one of the 14 preterm infants without haemorrhage, compared with 2 of the 14 with IVH, and with 7 of the 9 with IVH and dilatation. There was also a higher incidence of neurological abnormality at each follow-up age in the infants with IVH plus ventricular dilatation, compared with those with IVH alone, or with infants without IVH. Similar differences were also demonstrated in 5 milestones reflecting gross motor, fine motor, and social or verbal development in the three groups at 6, 9, and 12 months. The neurological and developmental deficits seemed to relate more closely to the presence of post-haemorrhagic ventricular dilatation than to the size of the initial haemorrhage itself. These results may have important implications for therapeutic intervention in the management of newborn infants with IVH and ventricular dilatation.     

A study of periventricular haemorrhage, post-haemorrhagic ventricular dilatation and periventricular leucomalacia in Chinese preterm infants

Serial cranial ultrasound scans were performed in 178 preterm Chinese infants (gestation less than 35 weeks, birthweight less than 2000 g) to study the incidence, age of onset and associating risk factors of periventricular haemorrhage (PVH), and also the occurrence of post-haemorrhagic ventricular dilatation and periventricular leucomalacia (PVL). Sixty-four infants developed haemorrhage, giving an incidence of 36%. Among infants of birthweight less than 1500 and less than 1000 g the respective incidence was 52 and 69%. Seventy-two per cent (46 of 64) of haemorrhages were initially detected within the first 3 days of life, but delayed haemorrhage occurring after 1 week of age occurred in nine infants. In eight of these infants PVH had been shortly preceded by a major clinical disaster. Eleven perinatal factors were found to be significantly associated with PVH but only systemic hypotension showed a significant independent association. Post-haemorrhagic ventricular dilatation developed in 17 (46%) of the 37 infants who survived for more than 1 month after PVH. This was transient in 41%, persistent but stable in 29% and progressive in 29%. PVL was detected in eight infants who survived the initial period following PVH.     

Hemorrhagic and hypoxic-ischemic intracranial lesions in neonates diagnosed by realtime sonography: incidence and short-term outcome

887 neonates at risk, referred to our neonatal unit underwent serial cranial ultrasound examinations and neurological follow-up over a period of 2 years. Our study focused on the prognosis of hemorrhagic and hypoxic-ischemic intracranial lesions. 194 patients with hemorrhages (subependymal hemorrhages [SEH] I degree-IV degrees according to Papile, hemorrhages of the choroid plexus [CPH], primarily intraparenchymal hemorrhages [PIH]) and/or hypoxic-ischemic lesions (infarcts of the major intracranial arteries and lesions of the periventricular white matter) were neurologically followed-up 12 to 24 months postnatally. A group of 266 patients with normal ultrasound scans out of the same population was equally followed-up and served as a control group. At the age of 12 months a preliminary neurodevelopmental diagnosis was made and the patients were divided into 3 groups. Group N (normal) had a normal neuromotor outcome, group S (suspect) showed minor neurological abnormalities without evidence of cerebral palsy and/or a developmental quotient between 80 and 90. Group A (abnormal) included patients with any degree of cerebral palsy (CP) and/or a development quotient below 80. A normal neurological outcome was seen in 88.3% of patients without intracranial lesion and in a comparable proportion of patients with SEH I degree (88.9%), SEH II degrees (84.8%) and CPH (81.3%). Patients with SEH III degrees developed normally in 72.7%, whereas only 25% of patients with SEH IV degrees and PIH were neurological normal at 12 months of age. For detailed statistical evaluation only preterm neonates (birthweight below 2500 grms) with and without hemorrhagic lesions were compared. Concerning the neurological short-term outcome our analysis revealed no statistically significant difference between patients with SEH I degrees, II degrees, III degrees, CPH and the control group. SEH IV degrees and PIH showed a unfavourable outcome. Only 2/8 surviving patients had a normal development, but small numbers of patients made a statistical analysis impossible. Two children with infarcts of the middle cerebral artery developed spastic hemiplegia of the contralateral body side. One child with an infarct of the posterior cerebral artery developed normally until the age of 1 year, but could not be followed-up further. Patients with periventricular lesions showed a normal neuromotor development in 88.9% and 75% when they had solitary periventricular cysts or wedge-shaped periventricular lesions, whereas none of 9 children who suffered from extensive cystic periventricular leucomalacia was neurologically normal at the age of 1 year.(ABSTRACT TRUNCATED AT 400 WORDS)     

Left ventricular systolic and diastolic functions in children living in a moderate-severe iodine deficiency area

Although the effects of impaired thyroid functions on the cardiovascular system is well known, there is no report investigating left ventricular functions in children with iodine deficiency. We evaluated left ventricular functions in children living in a moderate-severe iodine deficient area of northern Turkey. Of 40 children, 13 had stage I, 19 had stage II and eight had stage III goiter. None of the children had clinical signs of hypothyroidism, hyperthyroidism or cardiac dysfunction. Urinary iodine concentration decreased significantly from mild (Group 1) to moderate (Group 2) and severe (Group 3) iodine deficient groups (p <0.05). Mean serum free T3 levels did not differ significantly between the groups. However, a significant difference in mean serum free T4 level was found between Groups 1 and 2 (p <0.05), but remained in the normal range. Although the mean serum TSH level differed significantly between Group 1 and Group 3 and Group 2 and Group 3 (p <0.05), mean values were in the normal range. Mean left ventricular ejection fraction, shortening fraction and diastolic filling parameters did not differ significantly between groups. In conclusion, in case of preserved thyroid hormone levels, a moderate-severe iodine deficiency does not seem to affect left ventricular functions.     

Follow-up of infants receiving cranial ultrasound for intracranial hemorrhage

Intracranial hemorrhage (ICH) was detected in 38 preterm neonates, using cranial ultrasonic (US) scanning. Forty-three preterm neonates examined during the same period but who had no cranial US evidence of ICH were also identified. Neurodevelopmental follow-up was performed at a mean age of 22.3 months on these 81 children. As a group, children with ICH demonstrated developmental indexes in the normal range but about ten points lower than children without ICH. The outcome in survivors of grade III ICH was quite similar to the outcome in survivors of grades I and II ICH. Survivors of grade IV (intraparenchymal) hemorrhage had a worse outcome. Cerebral palsy was significantly more prevalent in children with ICH. Only two thirds of children without ICH had a completely normal outcome, reinforcing the concept that factors other than ICH alone contribute to neurodevelopmental morbidity in this population.     

Risk factors associated with the development of peri-intraventricular haemorrhage and periventricular leukomalacia

81 preterm infants of 34 weeks' gestation or less were prospectively and sequentially examined by means of real-time ultrasound in order to identify which clinical risk factors might be associated with the development of peri-intraventricular haemorrhage (PVH) and periventricular leukomalacia (PVL). Infants were allocated in three groups: group A (n = 44): with normal scans; group B (n = 24): with isolated PVH, and group C (n = 13): with PVL. 28 obstetrical and neonatal factors were compared within the three groups using two methods of statistical analysis (2 x 2 chi 2 analysis and multivariate logistic regression analysis). Hyaline membrane disease, acidosis, pneumothorax and Apgar score at 10 min were statistically associated with PVH. The multivariate logistic regression analysis showed that need for resuscitation, hyaline membrane disease, acidosis and gestational age were the most important factors. Gestational age, seizures, hyaline membrane disease, apnoea with hypoxaemia and bradycardia were strongly associated with PVL. These results suggest that a low gestational age, the need for resuscitation and a respiratory distress syndrome with its consequences might lead to PVH, whereas a low gestational age, hypoxaemia and cardiocirculatory disturbances might decrease cerebral perfusion and result into PVL.     

Neurodevelopmental outcome at 6 years of age after intrauterine laser therapy for twin-twin transfusion syndrome

This study was undertaken to evaluate neurodevelopmental outcome of children at 6 years of age after intrauterine laser therapy for Twin-twin transfusion syndrome (TTTS). This is part of a longitudinal study in children after intrauterine laser therapy for TTTS; 190 of 254 (74.8%) children, previously investigated at a median age of 2 years 10 months, were re-evaluated at 6 years 5 months (range 4 years 11 months –10 years 4 months). Sixty-four patients were not examined due to loss of contact. The median gestational age at birth was 34 + 3 weeks. The study included a physical/neurological examination, a standardized neurodevelopmental test (Kaufman-ABC) and/or results from the national screening programme for children as well as questionnaires. Patients were grouped in three outcome categories: group I: normal examination and test result; group II: minor neurological deficiencies and normal test results; group III: major neurological deficiencies and/or test results below minus two standard deviations. The following results were obtained at 6 years 5 months (for comparison, results of the same patients at 2 years 10 months in brackets). Group I: 79.5% (84.2%); group II: 11.6% (8.9%); group III: 8.9% (6.8%). Twenty-one (11%) patients had a worse and 8 (4.2%) an improved classification at 6 years 5 months as compared to 2 years 10 months. Overall, the results with 6 years did not significantly differ from the results with 2 years. Neurodevelopmental outcome at 6 years 5 months was not statistically, significantly different from outcome at 2 years 10 months.     

Clinical risk factors and periventricular leucomalacia.

Two hundred infants of below 1501 g at birth were regularly examined with real time ultrasound using a 7.5 MHz transducer. Abnormalities were categorized as periventricular haemorrhage (PVH) (n = 107) or periventricular leucomalacia (PVL), with or without PVH (n = 52). Of the group with PVL, 25 had the appearances of prolonged flare without cavitation. Prospective assessments of up to 50 potential clinical risk factors were made wherever possible on each infant including stratification of all blood gas and systolic blood pressure data. Multivariate logistic regression analyses confirmed a strong correlation between immaturity and PVH but this was not found in cases of PVL. Independent variables associated with PVL included pneumothorax, maximum bilirubin concentration, surgery, and the proportion of time the infant''s PaCO2 remained above 7 kPa. There was a very strong inverse correlation between anaemia and PVL. Systolic blood pressure data were carefully analysed and there was no relation between either hypotension or antepartum haemorrhage and the development of PVL.     

Outcome of intrauterine periventricular haemorrhage and leukomalacia

This case study reports five very low birthweight infants with ultrasound evidence of intrauterine insult to the brain. Intrauterine periventricular haemorrhage (PVH) accompanied by ventricular dilation occurred in two preterm infants both of whom survived and were severely handicapped at follow-up. Three preterm infants had intrauterine periventricular leukomalacia (PVL); one survived and is severely handicapped at one year of age. Our experience and rare case reports in the literature indicate that intrauterine PVH and PVL carry a high risk of death in neonatal period and severe neurological sequelae in survivors.     

Cerebrospinal fluid C-reactive protein measurement--a bedside test in the rapid diagnosis of bacterial meningitis

C-reactive protein (C-RP) determinations were performed by the Latex agglutination method on the cerebrospinal fluid (CSF) samples of 212 patients with clinical features suggestive of meningitis. Patients were grouped as follows Group I: bacterial meningitis and partially treated bacterial meningitis (n = 22). Group II: viral encephalitis (n = 11). Group III: tuberculous meningitis (n = 18). Group IV: (i) febrile convulsions (n = 87); (ii) epileptic seizures (n = 70); (iii) intracranial haemorrhage (n = 4). C-RP was a better indicator of bacterial meningitis (sensitivity 91 per cent) than the Gram's stain (sensitivity 46 per cent). C-RP was positive in 91 per cent of patients in Group I, none in Groups II and III and 0.6 per cent in Group IV. C-RP determination in CSF proved to be a useful indicator of bacterial meningitis and served to distinguish it from viral encephalitis, tuberculous meningitis, febrile convulsions and other central nervous system disorders.     

Serum IgG antibodies to gliadin in children with celiac disease as measured by an immunofluorescence method

Antigliadin antibodies (AGAs) were studied in sera from 190 patients divided into five clinical groups. Group I included 28 sera from children with newly diagnosed celiac disease on a normal diet. Group II consisted of 43 sera from children with celiac disease who were fed a gluten-free diet (GFD). Group III included 25 sera from children with celiac disease who had been in remission but exposed to a gluten-containing diet (GCD). Group IV consisted of 46 sera from children with chronic diarrheal disorders other than celiac disease. Group V included 43 sera from healthy children. The observed p values proved that (a) mean titer levels of AGAs in Groups I and III were significantly higher than the mean values for all other groups (p less than 0.001), and (b) the mean titer level of AGAs in Group II was significantly higher than the mean values for Groups IV and V. A good correlation between the AGA titers and the morphology of the duodenal mucosa was found in children with celiac disease. The examination of IgG AGAs by the immunofluorescence technique used in our study appears to be a useful tool in the follow-up of individual patients to determine adherence to a GFD.     

Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia

AIMS: To compare the ultrasound (US) evolution and neurodevelopmental outcome of infants with localised (grade II) and extensive (grade III) cystic periventricular leucomalacia (c-PVL). METHODS: Over a nine year period, c-PVL was diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were excluded from the study. Thirty nine infants with grade II PVL were compared with 39 infants with grade III PVL. RESULTS: The two populations were comparable for gestational age and birth weight. In infants with grade II PVL, cysts were noted to develop more often after the first month of life (53%) in contrast with grade III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to 12.63)). Cysts were also more often unilateral in grade II (54%) than in grade III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with grade II PVL, with ventriculomegaly being the only visible sequel in nine cases. In grade III PVL, cysts were still present in 25 of the 27 surviving infants. Nine infants with grade II PVL were free of motor sequelae at follow up compared with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two out of 29 children with grade II PVL who developed cerebral palsy achieved independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to 662)). CONCLUSIONS: In the cohort studied, 50% of the infants with c-PVL had a more localised form (grade II). In grade II PVL, the cysts developed beyond the first month of life in more than half of the cases and were often no longer visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential US should also be performed beyond the first month of life. Mild ventriculomegaly noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly less common and tended to be less severe in infants with grade II PVL than in those with grade III PVL.     

Periventricular leucomalacia and neurodevelopmental outcome in preterm infants.

During an 18 month period, 120 preterm infants of 34 weeks'' gestation or less were prospectively examined for periventricular leucomalacia (PVL) by cerebral ultrasound. Neurological and developmental assessment was carried out at 18 months of age corrected for prematurity in 82 surviving neonates. The developmental outcome (Griffiths development quotient) was above 80 and similar in infants with normal scans (n = 41), isolated periventricular-intraventricular haemorrhage (n = 13), and post-haemorrhagic hydrocephalus (n = 4), and no major handicap was diagnosed in these groups. By contrast, the prognosis was variable and poorer in infants with PVL (n = 24) and depended on the extent and site of the lesion. Infants with frontal PVL (n = 13) developed normally. Major sequelae (n = 8) were closely related to frontal-parietal PVL and frontal-parietal-occipital PVL and could be ascribed to the presence of cysts as well as to a persistent hyperechogenic ultrasonographic PVL appearance. A relation between size and site of the lesion and type and severity of the handicap was established.