Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities

The incidence of transient hypogammaglobulinaemia of infancy (THI) detected in a major paediatric centre over a 10 year period was examined. A total of 2468 subjects less than 2 years of age had an IgG measurement taken between July 1979 and March 1990. Subjects with known immunodeficiencies were excluded. Fifteen patients were classified as having THI with an initial IgG level less than the fifth centile followed by a second measurement within the normal range. A further 24 patients were identified as having possible THI with a single low IgG concentration. There were 60,174 live births each year in Victoria in the years 1979-88. This gives an incidence of proved THI of 23 per 10(6) births, and including proved and probable THI an incidence of 61 per 10(6) live births. Of those patients with proved THI 12/15 had symptoms of either atopic disease or food allergy/intolerance and three had gastrointestinal symptoms without any evidence of atopic disease. At presentation 12/15 (80%) were IgA deficient and 9/15 had IgM concentrations less than the 20th centile for age. It is suggested that in view of the preponderance of atopic and food intolerant patients that subclinical protein loss from the bowel due to allergic inflammation may be a contributing factor to the development of THI in some patients.     

Echocardiographic abnormalities in infants of diabetic mothers.

In order to evaluate the presence of myocardial hypertrophy and/or abnormalities of postnatal cardiovascular adaptation, echocardiograms were performed on 34 infants of diabetic mothers. Based on cardiopulmonary assessment, the IDM were divided into three groups: Group I with congestive heart failure predominating: Group II with respiratory distress predominating: Group III asymptomatic. Hypertrophy of the interventricular septum and of the walls of left and right ventricles was frequently present in IDM: this change was most notable in association with clinical CHF. Six IDM, four of whom were found to have CHF, had additional echocardiographic signs of subaortic stenosis. All IDM had normal indices of left ventricular performance, despite the presence of CHE. In IDM with respiratory distress, the right ventricular pre-ejection period to ventricular ejection time ratio was elevated, suggesting an abnormality of the transitional pulmonary circulation. Poor maternal diabetes control and maternal systemic hypertension were closely correlated with evidence of myocardial hypertrophy in the infants.     

Metabolic studies of transient tyrosinemia in premature infants.

The recently developed technique of gas chromatography-mass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted to demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5-10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Several infants had fluctuating levels of tyrosine metabolites in urine although dietary protein intake remained constant at 3-4 g/kg/24 hr and ascorbic acid at 50 mg/24 hr. Late metabolic acidosis was seen in four infants, but bore no relation to transient tyrosinemia. The ratio of net acid to urea excretion in urine increased with increasing base deficit, implying a nonprotein origin of the metabolic acid. No unique metabolic patterns were characteristic of late metabolic acidosis.     

Neurologic abnormalities in near miss for sudden infant death syndrome infants.

As part of the Sudden Death Research Project at Stanford University School of Medicine, we have performed systematic neurologic examination of 41 near miss infants, 7 normal siblings of babies who died a sudden infant death, and 21 normal control infants. Many infants were examined longitudinally until 2 years of age. We found that near miss infants under 3 months of age had consistent abnormalities of muscle tone, particularly shoulder hypotonia. These abnormalities disappeared with maturation, but only 60% of older infants who had suffered near miss episodes of neurologically and developmentally normal. In addition, only one of the seven apparently normal siblings had an entirely normal neurologic examination when first seen. Thus, infants who present with near miss episodes may have an underlying central nervous system abnormality or may acquire some abnormality as a result of the episode.     

Radiological abnormalities in infants with urinary tract infections.

An intravenous urogram and micturating cystourethrogram were carried out in 100 infants presenting with documented urinary tract infections. Ninety three cases were identified by suprapubic aspiration and 7 by culture of two voided urine samples containing greater than 100 X 10(6) organisms per litre. The urinary tract abnormalities were analysed in respect of their clinical importance, patient''s age, sex, and prematurity (in the 10 preterm infants). Radiological abnormalities were found in 47% of the infants (40% of boys; 63% of girls). Twenty nine per cent of the infants had a urinary tract abnormality regarded as clinically important--namely grade 3 or 4 vesicoureteric reflux, reflux nephropathy, or obstructive lesions requiring surgery. Six of the 10 preterm infants had radiological abnormalities. Spontaneous resolution or improvement occurred within 6 months of birth in three of the four preterm infants with severe vesicoureteric reflux.     

Extracardiac abnormalities in infants with congenital heart disease.

Extracardiac anomalies (ECA) occur in 25% of infants seen during the first year of life for significant cardiac disease. Often the ECA are multiple and one third of the affected infants have some established syndrome. In infants with endocardial cushion defect, patent ductus arteriosus, atrial septal defect, ventricular septal defect, malpositions, tetralogy of Fallot, and complex coarctation ECA occur in 25% or more of the cases. The most frequent ECA are in the musculoskeletal system or associated with a specific syndrome. The presence of an ECA significantly increases the mortality in infants with CHD.     

Effect of blood transfusion on cardiorespiratory abnormalities in preterm infants.

The effects of red blood cell transfusion on the incidences of apnoea, bradycardia, tachycardia and oxygen desaturation over periods of 72 hours before and after transfusion were assessed in 25 infants with a gestational age of < or = 32 weeks (mean (SEM) 29.2 (0.4) weeks, birthweight 1170 (73) g; postnatal age at transfusion 39 (4) days). During transfusion haemoglobin rose from 78 (2) g/l to 117 (2) g/l. Significant decreases were observed in daily frequencies of apnoeas longer than 15 seconds (median from 2.7 to 0.9 events a day), tachycardias of more than 200 beats per minute (from 34 to 25 events per day), bradycardias below 100 beats per minute (from 65 to 12 events per day) and 80 beats per minute (from 8.4 to 3.3 events per day). Oxygen saturation improved in 20 of the infants. Transfusion improves cardiorespiration in preterm infants for several days.     

Frequency of transient hypothyroxinaemia in low birthweight infants. Potential pitfall for neonatal screening programmes.

Thyroid function was studied in 54 low birthweight infants during a 3-week period. Each infant was placed in one of three groups. Group 1 (n = 21), infants who were well and appropriately grown fro gestational age; group 2 (n = 23), infants who were appropriately grown but who had hyaline membrane disease; group 3 (n = 10), infants who were small-for-gestational-age. In group 1, 5 (24%) infants had at least one serum thyroxine value less than 3.0 micrograms/100 ml (39 nmol/l). There were 8 (35%) infants in group 2 who had similarly low serum thyroxine values as did 5 (50%) of the 10 infants in group 3. Serum thyrotropin levels and serum binding of the thyroid hormones, as measured by a T3-charcoal uptake test, were normal in all infants. In all instances but 2, serum thyroxine values were at least 4.0 micrograms/100 ml (51 nmol/l) by the end of the 3-week period. There is thus a high incidence of transient ''hypothyroxinaemia'' in low birthweight infants, particularly if such infants have hyaline membrane disease or are small-for-gestational-age. These findings must be considered when interpreting results of screening programmes for congenital hypothyroidism and they lend further support to the use of a combination of serum thyroxine and thyrotropin determinations for optimum screening of such infants.     

HLA-haploidentical bone marrow transplantation in three infants with adenosine deaminase deficiency: Stable immunological reconstitution and reversal of skeletal abnormalities

Three infants with severe combined immunodeficiency and adenosine deaminase (ADA) deficiency were treated by T-cell depleted bone marrow transplantation (BMT), using human leukocyte antigen (HLA)-haploidentical parents as donors. In the first patient, two initial transplants failed to engraft and no change of the immunodeficiency was observed. In order to overcome this graft resistance, cytoreductive conditioning was used prior to a third transplant. In the other two patients, similar conditioning was used prior to initial transplants. In all three patients, complete and permanent immunological reconstitution was observed and they survive from 3.5 to 5 years after transplantation. In biopsies obtained from iliac bones prior to BMT, osteochondral abnormalities characteristic of ADA-deficiency were noted in all three patients. After successful transplantation, these abnormalities had completely resolved. Our results demonstrate that cytoreductive conditioning prior to HLA-haploidentical BMT is useful in order to obtain stable engraftment and reversal of abnormalities associated with ADA deficiency.     

Ultrasound screening of healthy infants for urinary tract abnormalities

The purpose of the study was to determine the incidence of silent but significant urinary tract abnormalities that might be detected by screening renal ultrasound studies of apparently healthy infants. Of 437 babies studied, six were found to have uropathology severe enough to warrant surgery for an incidence of 1.37% or one of every 73 babies studied.     

Evolution of immunological abnormalities in HIV infection by vertical transmission

Forty-four children infected through vertical transmission, from a total of 146 born to HIV-positive mothers, were studied. Immunological data were analysed and compared with those of the non-infected children. Two transmission patterns emerge from the clinical and immunological characteristics: (i) infants infected during pregnancy with severe immunodeficiency and clinical manifestations before the age of 1 year, and (ii) children probably infected perinatally, who have better clinical outcome. Immunological data are important for prognosis and early therapeutic protocols to be established.     

Frequency and timing of symptoms in infants screened for sepsis: effectiveness of a sepsis-screening pathway

To determine the frequency and timing of symptoms and to evaluate the effectiveness of a sepsis-screening pathway in term and near-term infants, data were collected prospectively for a period of 1 year from December 1, 2000, to November 30, 2001. Results confirmed that a sepsis-screening pathway using a combination of at least 2 serial complete blood cell count and C-reactive protein measurements in both symptomatic and asymptomatic infants is a safe, simple strategy that prevents unnecessary treatment of infants with risk factors with antibiotics. However, most infants with presumed or suspected early-onset sepsis are symptomatic. Routine treatment of asymptomatic infants with risk factors or prior treatment with intrapartum antibiotics is unnecessary. A combined approach of screening in the presence of risk factors and /or symptoms of sepsis and adequate follow-up for infants discharged at less than 72 hours of age may help reduce unnecessary treatment of infants with antibiotics.     

Tracheobronchial abnormalities in infants with bronchopulmonary dysplasia

Twelve preterm infants with bronchopulmonary dysplasia underwent bronchoscopy to determine if airway abnormalities were contributing to persistent pulmonary problems. Indications for bronchoscopy were persistent atelectasis, lobar hyperinflation, or both on chest radiograph (11 patients), unexplained respiratory distress (three patients), and aspiration of tissuelike material from a tracheostomy (one patient). Bronchoscopy revealed abnormalities of the trachea, bronchi, or both in all infants, including partial or near total airway occlusion by abnormal growth of tissue (10 patients); tracheomalacia, bronchomalacia, or both (three patients); and inspissated secretions (two patients). Seven infants died during initial hospitalization. Tracheobronchial abnormalities should be considered as a cause of persistent pulmonary problems in infants with bronchopulmonary dysplasia.