Neurologic status and intracranial hemorrhage in very-low-birth-weight preterm infants. Outcome at 1 year and 5 years.

Twenty-six very-low-birth-weight preterm infants with and without intracranial hemorrhage (ICH) were followed up prospectively from birth to school age to determine the relationship between ICH and subsequent neurologic and cognitive outcomes. All children had sequential cranial ultrasound examinations at birth and neurologic assessments at 3-month intervals during the first year, at 1 year of age, and at 5 to 6 years; psychometric assessments were done at 5 to 6 years. Seventeen children had no ICH, 3 had grade 1 ICH, 1 had grade 3 ICH, and 5 had grade 4 ICH. The 1-year Amiel-Tison neurologic assessment in 25 infants demonstrated that 14 were normal, 3 were suspect, and 8 were abnormal. By 5 to 6 years of age, 5 of 8 children neurologically abnormal at 1 year remained abnormal, 2 of 3 children neurologically suspect at 1 year remained suspect; while 9 of 15 children neurologically normal at 1 year remained normal, the remaining 6 had become suspect. The predominant neurologic abnormality at 5 to 6 years was subtle neurologic dysfunctioning. The Wechsler Preschool and Primary Scale of Intelligence at 5 to 6 years revealed a mean group IQ score of 92.1. The Beery Visual Motor Integration Test results demonstrated that 18 of 26 children had mild to severe visual motor perceptual difficulties. Severe ICH (grades 3 and 4) correlated with abnormal neurologic performances at 1 and 5 to 6 years. Mild ICH (grade 1) and no ICH did not correlate with any one of the 1-year neurologic classifications. The 1-year status correlated with the 5- to 6-year neurologic outcome best for children who were either neurologically suspect or abnormal at age 1 year. The 1-year neurologic score did not correlate with 5- to 6-year IQ and Beery Visual Motor Integration Test scores.

The development of pyloric stenosis during transpyloric feedings.

Three infants, ages 3 to 4 months, had nasojejunal feeding tubes placed for recurrent aspiration and/or feeding intolerance after upper gastrointestinal cineradiographs (ugi) had documented gastroesophageal reflux (GER) with normal pyloric channels and prompt gastric emptying. The tubes had been in place for 3 and 4 weeks, respectively, in the first two infants when classic hypertrophic pyloric stenosis (HPS) was found during fundoplication and gastrostomy tube placement. The last child had a failed attempt at nasogastric tube feedings following 3 months of nasojejunal tube feedings. A repeat ugi suggested HPS, which was confirmed by pyloric ultrasound. This infant underwent pyloromyotomy alone. The late presentation of HPS in these infants suggests that transpyloric tubes might cause the development of HPS and exacerbate the symptoms of preexisting GER. In infants who are expected to eat by mouth, pyloromyotomy alone might allow the reinstitution of orogastric feedings without the perioperative morbidity of fundoplication and gastrostomy tube placement.

Management and follow-up of arterial thrombosis in the neonatal period.

The management and follow-up of 12 patients with major aortic thrombus formation occurring in the neonatal period between 1982 and 1987 are reported. Umbilical arterial catheters were inserted in 8 of the 12 patients before thrombus formation. Two patients had congenital thrombi. Hypertension, oliguria, hematuria, and elevated blood creatinine concentration were found at the time of diagnosis of the thrombus; nine of the patients had a patent ductus arteriosus. Supportive care was instituted in seven patients who were hemodynamically stable. Five of the patients had congestive heart failure, shock, or both, and were treated with surgical thrombectomy. Thrombolytic therapy was not used in either group. The five surgically treated patients and six of seven medically treated patients survived. Ultrasound examination suggested resolution of the thrombus in all survivors in 6 to 30 days. Sequelae from thrombus formation were present in all patients at the time of discharge and included hypertension in 9 of the 11 survivors and decreased renal function in six of them. Follow-up at 1 to 3 years revealed normal blood pressure, good growth, and good renal function in 10 of the survivors.

Hypogammaglobulinemia in infants infected with human immunodeficiency virus.

Two premature infants were infected with HIV via blood transfusions during the neonatal period. Although neither patient had serum antibody to HIV owing to severe hypogammaglobulinemia, HIV infection was confirmed by finding HIV antigen in the sera of both patients. These cases show that HIV infection can produce severe hypogammaglobulinemia, and illustrate the value of HIV antigen detection in the diagnosis of HIV infection in seronegative patients.

Retinopathy of prematurity: a new epidemic?

This study provides the first empiric evidence for the existence of a new epidemic of retinopathy of prematurity-induced blindness. Data from a population-based register of handicapping conditions in the Canadian province of British Columbia, and a birth weight-specific census of live-born infants in British Columbia, were used to determine annual, population-level incidences of retinopathy of prematurity-induced blindness during 1952 to 1983. Changes in incidence since the end of the original epidemic (1954) were determined by subdividing the 29-year period (1955 to 1983) into two intervals (1955 to 1964 and 1965 to 1983). Standardized incidence ratio analyses revealed a marginally significant increase in the overall incidence of retinopathy of prematurity-induced blindness in the later as compared with the earlier period. Infants weighing 750 to 999 g at birth had a significantly increased standardized incidence ratio of 3.07 (95% confidence interval 1.26, 11.06). No increases in risk were observed in heavier or lighter weight infants. Because ascertainment and diagnostic changes do not explain the weight-specific increases in incidence, these results provide the first population-level evidence for a new epidemic.

Protein leaks and surfactant dysfunction in the pathogenesis of respiratory distress syndrome.

This article reviews the phenomenon of surfactant inactivation by soluble proteins. Following surfactant treatment of preterm lambs, the initial clinical response was not maintained. The surface tensions that were low in the lungs following surfactant treatment increased to high values concurrently with the return of severe respiratory failure. The surface properties of the surfactant that remained in the airways and alveoli could be restored if the soluble proteins were removed. These soluble proteins inactivated different surfactants to different degrees and the interaction was very concentration dependent. The proteins entered the lungs of the preterm lamb because of the tendency of these lungs to form pulmonary oedema. Similar surfactant inactivation occurred in the lungs of infants with respiratory distress syndrome. A variety of manipulations influenced the formation of proteinaceous pulmonary oedema, suggesting that new therapeutic strategies could be developed to treat infants with RDS.

[Spontaneous perforation of the bile ducts]. / Perforation spontanée des voies biliaires.

Spontaneous perforation of the extra-hepatic bile ducts in infancy is rare and of unknown etiology. Its finding at laparotomy in a 2 month-old premature with artificial ventilation allows to underline that the diagnosis may be difficult and may necessitate ultrasonography and even hepatobiliary scintigraphy.

Clinical experience with phototherapy.

Clinical experience with phototherapy in 3,999 infants with non-haemolytic hyperbilirubinaemia and 427 infants with hyperbilirubinaemia associated with G6PD deficiency is presented. For non-haemolytic hyperbilirubinaemia, phototherapy was extremely effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1,500 gm) and least effective in full term infants with very low birth weight (gestation greater than 37 weeks, birth weight less than or equal to 1,500 gm) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2,270 gm). The failure rate of phototherapy for non-haemolytic hyperbilirubinemia was only 2.00/1,000 infants. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1,000) with the response to the second exposure comparable to that of the first. No infant required a third exposure. Phototherapy was effective in reducing bilirubin levels in hyperbilirubinaemia associated with G6PD deficiency, the effectiveness being, however, less than in babies with non-haemolytic hyperbilirubinaemia (G6PD normal status). There was no failure in this group of babies. Only a small proportion of infants required a second exposure (4.68/1,000). All the infants tolerated phototherapy well with none developing any illness that could be attributed to the exposure. This clinical experience demonstrates that phototherapy is effective and safe for the treatment of non-haemolytic hyperbilirubinaemia or hyperbilirubinaemia associated with G6PD deficiency.

Relationship between periventricular hemorrhage, leukomalacia and brainstem lesions in prematurely born infants.

The brain pathology in very prematurely born infants with intraventricular hemorrhage (IVH) was studied particularly as to the severity and site of the complicated brain lesions responsible for the prognosis. A high frequency of leukomalacia, pontosubicular necrosis and/or olivocerebellar neuronal loss was found in the cases of IVH, and these non-hemorrhagic brain lesions showed an increasing frequency with the grade of IVH. However, there was marked reduction of IVH, periventricular leukomalacia and, in particular, brainstem lesions in prematurely born cases of sudden infant death. These IVH and associated conditions have different pathogenesis, but factors responsible for their occurrence may be present together in each case.

Non-immune fetal hydrops with hepatic hemangioendothelioma and Kasabach-Merritt syndrome: a case report.

A premature infant presented with non-immune hydrops fetalis, a liver mass, thrombocytopenia, and hypofibrinogenemia. Histologic examination of the liver tumor showed an infantile hemangioendothelioma. The clinical features of this case can be explained by anemia, hypoalbuminemia, and coagulopathy. The association with Kasabach-Merritt syndrome, the pathophysiology of non-immune hydrops fetalis, and primary hepatic neoplasms of the neonate are discussed.

Periventricular intraparenchymal cystic lesions: critical determinant of neurodevelopmental outcome in preterm infants.

During a four-year period, 154 surviving preterm infants of 32 weeks gestation or less were prospectively examined by cerebral ultrasound for periventricular-intraparenchymal cystic lesions (IPCL) subsequent to ischemic and/or haemorrhagic damage. Neurological and developmental outcome was assessed with examinations at 0, 3, 6, 12, 18, 24, 36, 48 months of age corrected for prematurity. Twenty-four (15.5%) patients were found to have IPCL changes at ultrasound. In 8 cases, a porencephalic cyst subsequent to grade IV IVH (Papile's classification) was found; all had cerebral palsy and severe developmental deficit was present in 4. Diffuse bilateral PVL was found in 8 cases: 1 was not evaluable, 7 developed cerebral palsy; the developmental delay was severe in 4, moderate in 2 patients, and only 1 was normal. Four patients had localized bilateral PVL: 3 patients had mild diplegia and 1 was normal; the developmental outcome was normal only in 1 case, 1 had a severe cognitive delay, and 2 were moderate. In the remaining 4 cases, the ultrasound showed a monolateral localized PVL: 1 patient had mild diplegia and moderate cognitive delay, 3 were normal. - This study confirms the important role of the ultrasonographic diagnosis of IPCL in preterm infants to foresee later neurodevelopmental outcome. Extensive parenchymal lesions were strongly associated with major neurodevelopmental handicaps, while localized and small lesions were correlated with more favorable neurological as well as developmental prognosis.

Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia.

There has been considerable debate over whether asymptomatic neonatal hypoglycaemia results in neurological damage. In a detailed multicentre study of 661 preterm infants hypoglycaemia was found to be common. Moderate hypoglycaemia (plasma glucose concentration less than 2.6 mmol/l) occurred in 433 of the infants and in 104 was found on three to 30 separate days. There was considerable variation among the centres, implying differences in decisions to intervene. The number of days on which moderate hypoglycaemia occurred was strongly related to reduced mental and motor development scores at 18 months (corrected age), even after adjustment for a wide range of factors known to influence development. When hypoglycaemia was recorded on five or more separate days adjusted mental and motor developmental scores at 18 months (corrected age) were significantly reduced by 14 and 13 points respectively, and the incidence of neurodevelopmental impairment (cerebral palsy or developmental delay) was increased by a factor of 3.5 (95% confidence interval 1.3 to 9.4). These data suggest that, contrary to general belief, moderate hypoglycaemia may have serious neurodevelopmental consequences, and reappraisal of current management is urgently required.

Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period.

The follow-up records of 605 infants with birth weights of less than 1,500 g, with data available for 2 years after birth, were examined for evidence of abnormal pulmonary signs or symptoms. A total of 119 infants were identified and the neonatal oxygen requirements of these infants were compared with those of 486 infants who had normal pulmonary function. A requirement for oxygen at 28 days of life had a positive predictive value for abnormal pulmonary findings at the time of follow-up of only 38%, whereas 31% of those with normal pulmonary findings at the time of follow-up were still receiving oxygen at this age. The need for oxygen at 28 days was a good predictor of abnormal findings in infants of greater than or equal to 30 weeks' gestational age at birth but became increasingly less useful as gestational age decreased. It was found that, irrespective of gestational age at birth, the requirement for additional oxygen at 36 weeks' corrected postnatal gestational age was a better predictor of abnormal outcome, increasing the positive predictive value to 63%. The prediction of a normal outcome remained 90% for infants not receiving oxygen at this corrected gestational age.

Congenital constriction band syndrome.

A retrospective study of 55 patients with congenital constriction band syndrome was performed. Multiple extremity involvement was found to be the most common clinical feature associated with the disease, and 34% of the patients studied were premature at birth. Malformations included constriction bands, clubfoot, intrauterine amputation, syndactyly, and acrosyndactyly (fenestrated syndactyly). The extremities were most often affected distally, involving the longer central fingers and medial two toes. More proximal involvement with constriction bands was associated with a higher frequency of neurologic deficit. Significant leg-length discrepancy exceeding 2.5 cm was seen in 9 of 38 patients (24%) with lower extremity involvement, a condition that has not been previously reported.

Perinatal antecedents of cerebral palsy.

The dramatic reduction in perinatal morbidity and mortality over the last decade has not been accompanied by any diminution in the incidence of cerebral palsy. We investigated retrospectively the relationship of certain perinatal events to the subsequent development of cerebral palsy in 75 infants. Cerebral palsy occurred in association with acute intrapartum asphyxia in 8% and traumatic delivery in 11%. Thirty-five percent of cases were associated with chronic fetal distress, defined by a unique fetal heart rate (FHR) pattern consisting of a normal baseline rate with persistently absent variability and mild variable decelerations with overshoot. This pattern was found frequently in association with postmaturity, meconium staining, intrauterine growth retardation, and neonatal seizures. Acid-base studies, when available, did not reveal acidosis. Twenty-seven percent of the cases involved a combination of chronic fetal distress, acute intrapartum fetal asphyxia, and/or traumatic delivery. We postulate that antenatal intermittent umbilical cord compression secondary to oligohydramnios results in repetitive transient central nervous system ischemia, insufficient to cause death, but resulting in a characteristic FHR pattern and impaired neurologic development. If these data are confirmed, this FHR pattern may be an important marker for the development of subsequent neurologic handicap or other adverse outcome.

Patent ductus arteriosus and retinopathy of prematurity in infants below 27 weeks gestation.

Retrospective study of infants who survived the neonatal period after delivery at 24-26 weeks gestation revealed patency of the ductus arteriosus (PDA) in 44%. The mean birthweight of infants who developed PDA was lower. Retinopathy of prematurity (ROP) was seen in 79% of survivors with 24% having grade III or IV involvement. All but one of the more severe grades of ROP occurred among infants with PDA. Infants with PDA required more prolonged ventilatory support. Perinatal factors did not have a significant role in the development of these complications.

Early high-dose phenobarbital treatment for prevention of hypoxic-ischemic brain damage in very low birth weight infants.

In a randomized prospective trial, we studied the effect of early high-dose phenobarbital treatment on the early (intraventricular hemorrhage) and late (neurodevelopmental abnormalities) manifestations of hypoxic-ischemic encephalopathy in preterm infants weighing 1500 g or less at birth. The first intravenous dose of 15 mg/kg was given at a mean age of 110 minutes, followed by 15 mg/kg after 4 hours and then by 5 mg/kg at 24-hour intervals for 5 days. The overall incidence of intraventricular hemorrhage was 32% in treated and 46% in control infants, a nonsignificant difference. An ultrasound brain scan at 9 months old revealed no significant difference in the incidence of ventricular dilatation between treated (19%) and control (29%) infants. At 27 months, a similar incidence of mild (10%) and severe (10%) neurodevelopmental handicaps was found in both treated and control groups. Since beneficial effects could not be documented by any of the criteria used, we conclude that routine administration of phenobarbital to low birth weight infants is not justified.

Upper GI examinations in older premature infants with persistent apnea: correlation with simultaneous cardiorespiratory monitoring.

Upper gastrointestinal examinations with simultaneous cardiorespiratory monitoring were performed in 39 older premature infants with persistent apnea. Swallowing incoordination was documented to be causatively related to persistent apnea in such infants, especially with feeding. Direct relationship between apnea and gastroesophageal reflux was not documented in this study.