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.     

Hypernatraemic dehydration and breast feeding: a population study.

As part of a population based regional review of all neonatal readmissions, the incidence of dehydration with hypernatraemia in exclusively breast fed infants was estimated. All readmissions to hospital in the first month of life during 1998 from a population of 32 015 live births were reviewed. Eight of 907 readmissions met the case definition, giving an incidence of at least 2.5 per 10 000 live births. Serum sodium at readmission varied from 150 to 175 mmol/l. One infant had convulsions. The sole explanation for hypernatraemia was unsuccessful breast feeding in all cases. The eight cases are compared with the 65 cases published in the literature since 1979. Presentation, incidence, risk factors, pathophysiology, treatment, and prevention are discussed.     

Hypernatraemic dehydration and breast feeding: a population study

As part of a population based regional review of all neonatal readmissions, the incidence of dehydration with hypernatraemia in exclusively breast fed infants was estimated. All readmissions to hospital in the first month of life during 1998 from a population of 32 015 live births were reviewed. Eight of 907 readmissions met the case definition, giving an incidence of at least 2.5 per 10 000 live births. Serum sodium at readmission varied from 150 to 175 mmol/l. One infant had convulsions. The sole explanation for hypernatraemia was unsuccessful breast feeding in all cases. The eight cases are compared with the 65 cases published in the literature since 1979. Presentation, incidence, risk factors, pathophysiology, treatment, and prevention are discussed.     

Infection and neonatal meningitis: epidemiology, pathogen spectrum, therapy

Data from 196 infants were analyzed who had been treated for neonatal septicemia and/or meningitis between 1962-1974 (n = 88) and 1975-1985 (n = 108). In addition to an increase in the incidence of septicemia (1962-1974: 0.88 cases/1000 live births/year; 1975-1985: 1.8 cases/1000 live births/year) there was also a change in the pattern of infection. Group B streptococcal infections were first observed in 1975. Infections with Escherichia coli increased (1962-1974: 0.25 cases/1000 live births/year; 1975-1985: 0.65 cases/1000 live births/year). Although the incidence of meningitis was similar in both periods (1962-1985: 0.45 cases/1000 live births/year) the relative number of cases declined (1962-1974: 51 of 88 patients; 1975-1985 25 of 108). Mortality also decreased during the second period (1962-1974: 53%; 1975-1985: 29%). All infants were primarily treated with a combination of ampicillin and gentamicin. The decision to discontinue this therapy was based on the clinical course of the patient and the results of culture and susceptibility studies. Ampicillin and/or gentamicin were effective in vitro against all microorganisms which caused septicemia and/or meningitis within the first four days of life. In contrast this antimicrobial combination was only active in vitro against 77% of the pathogens isolated after this time period.     

Familial hypophosphataemic rickets: experience with 24 children from Kuwait.

Between 1982 and 1988, familial hypophosphataemic rickets (FHR) was diagnosed in 24 children, in nine during screening of the families of index patients. The average annual incidence was 0.2/1000 live births. There were 16 boys and 8 girls in 10 families, of which nine had more than one affected child. Their ages at the onset of the disease ranged between 10 months and 14 years (mean 6.9 yrs). Growth retardation and bowing of the legs were the most prominent features, observed in all index patients and in four of the patients diagnosed by screening. Treatment with 1 alpha-hydroxyvitamin D3 and phosphates was associated with acceleration of growth in all children, healing of rickets in 21, and normalization of the serum phosphate in 22. Two children with late diagnosis are now older than 16 years with a final height below the 3rd centile. Three more pubertal children are also shorter than the 3rd centile. In areas where nutritional rickets is common, FHR is likely to be missed and the treatment delayed with grave consequences; in particular, growth retardation and bone deformity.     

Routine lumbar punctures in the newborn — are they justified?

The records of 62,107 neonates cared for at three neonatal referral units between 1979 and 1985 were analysed with regard to the number of lumbar punctures (LP) performed and the results obtained. The mean perinatal mortality rate was 9.3/1000 live births and the neonatal mortality rate was 5.9/1000. The units were comparible in this respect. Two hundred and sixty three (0.4%) babies weighed less than 1.0 kg at birth and 510 (0.8%) babies weighed 1.0–1.5 kg. A total of 1554 LPs were performed on 1084 babies, 1.7% of the whole population. Seventeen babies were diagnosed as having meningitis following CSF examination; 5 weighed less than 1.5 kg (VLBW) (incidence of meningitis 6.5/100 births) and 12 weighed more than 1.5 kg (incidence 0.2/1000 live births). An LP was performed on 44% of VLBW babies and 1.2% of babies weighing more than 1.5 kg. In both groups approximately 1.5% of CSF samples were positive. Eight of the 17 positive results were obtained during the first 3 postnatal days. Only one VLBW baby had meningitis on the 1st day of life (1.3/1000). In view of the low incidence of meningitis and the risk factors associated with an LP it is questionable whether this procedure should be a routine investigation in the VLBW newborn.     

Immunologic changes associated with the development of tolerance in children with cow milk allergy.

The purpose of this study was to determine whether cow milk-specific antibody responses correlated with the development of clinical tolerance in cow milk-allergic children. Double-blind, placebo-controlled food challenges were performed annually in 29 patients with cow milk allergy. Clinical reactivity was lost in 11 (38%) of 29 patients. The median age for all patients at the time of diagnosis by these food challenges was 3 years; more than 80% of patients in each group had atopic dermatitis as part of their presenting symptoms. Casein-specific and beta-lactoglobulin-specific IgE, IgG, IgG1, and IgG4 antibody concentrations were analyzed in all patients at regular intervals. In the patients becoming clinically tolerant to cow milk, the IgE-specific antibody concentrations and IgE/IgG-specific ratios for both milk proteins were lower initially and decreased significantly with time, in comparison with those in the group who retained clinical sensitivity. The concentrations of IgG1- and IgG4-specific antibody to casein and the IgE/IgG1 and IgE/IgG4 ratios for both casein and beta-lactoglobulin were significantly less in the patients losing clinical reactivity. No differences in the IgG-specific concentrations were observed in either group at any of the evaluation times noted above. Monitoring similar casein-specific and beta-lactoglobulin-specific IgE concentrations and IgE/IgG ratios may help predict which patients will ultimately lose their clinical reactivity to cow milk.     

Epidemiological characteristics of new borns in a rural community

All births (1211) were recorded in a rural area for 1985 by monthly domiciliary visits and the sociological characteristics were collected from mothers within a month. The analysis of 1201 births is presented: 52.7% were male births, 95.7% were delivered in village itself, 80.4% were delivered by trained dais, 99.5% were live born, 12.9% were born before 37 weeks of gestation, 61.5% were put to breast feed within 6 hours, 35% were of gravida 4 and above, 68.9% did not receive any antenatal care, 67.1% had not received any tetanus toxoid, 70.8% did not receive any folifer tablet, 0.8% had abortion and another 0.8% had still birth in preceeding outcome, 1.58% had lost a live born dead in preceding out come, 89.6% stopped breast feeding at conception, 31.7% had birth interval less than 2 years, but 2.2% had less than ore year, 2/3rd were born in second half of the year, 17.8% had taken extra food during pregnancy, 21.2% reduced the work after becoming pregnant, 9.5% were born to mothers of less than 20 years age, 98.5% of mothers were housewifes and 95.9% mothers were illiterate, 33.5% were born in nuclear family, 22.3% were living in Kacha' house, 34.8% had no electricity connection, 37.0% were born to land less, 42.2% had no radio in the house, 7.1% had no conveyance, 52.0% families had piped water supply. These findings have been discussed here.     

CLINICAL AND IMMUNOLOGICAL ASPECTS OF FOOD ALLERGY IN CHILDHOOD I. Estimation of IgG, IgA and IgE Antibodies to Food Antigens in Children with Food Allergy and Atopic Dermatitis

Abstract Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93

AIMS: To review the results of long term high dose intravenous immunoglobulin treatment. METHODS: 162 treatment years in 18 patients with hypogammaglobulinaemia who received intravenous immunoglobulin treatment between 1973 and 1993 were reviewed. RESULTS: A mean dose of 0.42 g/kg immunoglobulin resulted in a mean trough IgG concentration on the 23.5th centile for age. The subjects enjoyed a good standard of health. Infection rates were similar to the general paediatric population and a similar pattern of infections occurred. There were only 0.06 episodes of pneumonia and 0.11 hospital admissions per year of treatment. The development of chronic pulmonary disease was significantly related to trough IgG concentrations less than the 10th centile (p < 0.009), however, this developed in only two children after the start of treatment. All children had normal growth parameters. Adverse reactions to immunoglobulin infusions reduced from 9.1% to 0.8% after the introduction of low pH modified intravenous immunoglobulin in 1986. Although minor, transient increases in liver transaminase values were common; none of the 11 patients tested by hepatitis C polymerase chain reaction were positive. CONCLUSION: Children with hypogammaglobulinaemia who are receiving replacement treatment grow normally and have an infection rate similar to that of non-immunodeficient children. No evidence of transmission of hepatitis C virus by the Commonwealth Serum Laboratories immunoglobulin was found.     

Month of birth and subsequent development of type I diabetes (IDDM)

The aim of this study was to find out whether there is a seasonal pattern in the month of birth of children with IDDM in Israel and whether this pattern, if present, differs from that of total live births. One thousand and ninety-five out of 1,188 children and adolescents (0-17 years) who developed IDDM in Israel between 1980-1993 and whose month of birth was known were included in the study. Separate analysis was made for Jews (n = 987) who have a high incidence (10-18/105) and Arabs (n = 108) with a low incidence (2.9/105) of IDDM. The pattern of total live birth distribution in Israel over a 20-year period served as control. A significantly different seasonal pattern was found in the two IDDM populations. Whereas the Jews had the lowest number of births in winter (January-March) and the highest in spring (April-June), the Arabs presented an inverse pattern in the first months of the year. The distribution of births of the children who developed IDDM was different from that observed in total live births in the Jewish population. The findings in the Jewish population in Israel (a high incidence group) support the hypothesis that IDDM is triggered in some children by viral infections transmitted by the mother during pregnancy or in the early postnatal period. In the Arab population (a low incidence group) a protective (immune and/or genetic) mechanism may exist.     

Sudden infant death syndrome in Hamburg. An epidemiological analysis of 150 cases

A retrospective analysis was carried out of 150 SIDS cases seen in the five year period between 1979 and 1983 in Hamburg, Germany. The overall incidence was 2.3 per 1,000 live births. 82% of all infants and 100% of the preterm infants (corrected according to gestational age) dying of SIDS, died within the first 6 months of life. Infants of mothers less than 18 years of age, infants with more than 2 siblings, infants with birthweight less than 1,500 g and SGA-preterm infants were found to be high-risk subgroups. A high percentage (20% of all cases, 43% of infants with mothers less than 18 years) were underweight at death (under the 3rd weight-percentile). The study emphasizes the complexity of internal and external factors in the etiology of SIDS.     

Clinical and immunological aspects of food allergy in childhood. I. Estimation of IgG, IgA and IgE antibodies to food antigens in children with food allergy and atopic dermatitis

Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

Season of birth as predictor of atopic manifestations

The relation between month of birth, sensitisation, and manifestations of atopy was assessed in 209 children who were followed from birth to 12-15 years. Children born during the tree pollen season were less likely to develop allergic rhinoconjunctivitis, IgE antibodies to pollen, or a positive screening test for IgE antibodies (odds ratio 0.28, 0.41, 0.35, respectively) than children born during the rest of the year. The prevalence of IgE antibodies to food and animal dander at 9 months and to atopic disease was higher in children born in the autumn and winter, that is, September to February, compared to the spring and summer (egg 20% v 6%; milk 10% v 2%). Thus sensitisation to pollen and allergic rhinoconjunctivitis is least common in children born in the spring, while birth in September to February is associated with an increased incidence of sensitisation to food and of atopic disease.     

Increasing incidence of childhood celiac disease in Sicily: results of a multicenter study

By screening the patient list of four Sicilian centers of gastroenterology and those with gluten-free product consumption, 1074 patients (607 females and 467 males) with celiac disease, diagnosed between 1975 and 1989, were identified. A maximum cumulative incidence rate by birth cohort was reached in 1986 (1.65/1000). When the incidence rate was adjusted for the years of follow-up, the actual standardized rate was 3 cases per 1000 live births. Growth failure and chronic diarrhea were the most common symptoms, but a diminishing trend for chronic diarrhea was observed when symptoms were distributed by year of diagnosis. Even though 61.1% of all cases were diagnosed within six months from the onset of symptoms, mean age at diagnosis showed an increasing trend, from less than two years to approximately four years of age. The results of our study showed an increasing incidence of celiac disease due to diagnosis of less typical cases at an older age and also to a steady increase in the rate of diagnosis of cases with a classic clinical picture.     

The incidence and presentation of cystic fibrosis in Victoria 1955–1978

The minimum incidence of cystic fibrosis in Victoria, Australia over a 24 year period based on diagnosed cases was 1:2556 live births. There was no significant variation in incidence during the period.
The percentage of patients presenting with chest infection fell from 45% in the first 6 years of the study to 32% in the last 6 years and the percentage presenting with gastrointestinal symptoms rose from 19% in the first 6 years to 32% in the last 6 years. During the 24 year period 18% of patients presented with meconium ileus.     

Incidence and prevalence of mucopolysaccharidosis type 1 in the Irish republic

Mucopolysaccharidosis type 1 (MPS1) is an autosomal recessive disorder with severe, moderate and mild phenotypes: Hurler, Hurler-Scheie and Scheie syndromes. We estimated incidence (2001-2006) and prevalence (2002 census) of MPS1 in the Irish Republic (ROI) using population data, database and chart review of all live MPS1 patients attending two specialised centres. Patient genotypes, ethnicity, province of origin, age at diagnosis and presenting features were recorded. Thirty-one patients (14 females, 17 males) were alive, 27 of whom were <15 years. Twenty-six patients had Hurler syndrome, four had Hurler-Scheie and one had Scheie syndrome. The birth incidence was 1 in 26 206 births with a carrier frequency of 1 in 81. Of note, 19/26 (73%) Hurler patients were Irish Travellers. Amongst Irish Travellers the incidence was 1 in 371 with a carrier frequency of 1 in 10. This is the highest recorded incidence worldwide. Given the morbidity and mortality associated with delayed treatment we recommend targeted newborn screening for this population.     

Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93.

AIMS: To review the results of long term high dose intravenous immunoglobulin treatment. METHODS: 162 treatment years in 18 patients with hypogammaglobulinaemia who received intravenous immunoglobulin treatment between 1973 and 1993 were reviewed. RESULTS: A mean dose of 0.42 g/kg immunoglobulin resulted in a mean trough IgG concentration on the 23.5th centile for age. The subjects enjoyed a good standard of health. Infection rates were similar to the general paediatric population and a similar pattern of infections occurred. There were only 0.06 episodes of pneumonia and 0.11 hospital admissions per year of treatment. The development of chronic pulmonary disease was significantly related to trough IgG concentrations less than the 10th centile (p < 0.009), however, this developed in only two children after the start of treatment. All children had normal growth parameters. Adverse reactions to immunoglobulin infusions reduced from 9.1% to 0.8% after the introduction of low pH modified intravenous immunoglobulin in 1986. Although minor, transient increases in liver transaminase values were common; none of the 11 patients tested by hepatitis C polymerase chain reaction were positive. CONCLUSION: Children with hypogammaglobulinaemia who are receiving replacement treatment grow normally and have an infection rate similar to that of non-immunodeficient children. No evidence of transmission of hepatitis C virus by the Commonwealth Serum Laboratories immunoglobulin was found.     

Early-onset group B streptococcal sepsis: a current assessment.

Group B streptococcus (GBS) is a common cause of early-onset sepsis in neonates. The most recent reviews describing incidence, diagnosis, treatment, and outcome evaluated data on patients from the early 1980s. To obtain current information about this disease, we retrospectively evaluated data on neonates with GBS early-onset sepsis from nine hospitals in the United States between Jan. 1, 1987, and Dec. 31, 1989. There were 245 infants with GBS bacteremia identified among 61,809 live births, resulting in an incidence of 0.32%. Ninety-six infants (39%) were preterm (less than 38 weeks of gestational age). Maternal risk factors for infected preterm and term infants were similar. Antibiotics were administered during parturition in 10% of infants with bacteremia. Mothers of preterm infants received antibiotics up to 48 hours before delivery; mothers of term infants received antibiotics less than 4 hours before delivery. All preterm infants with bacteremia had symptoms; 22% of term infants with bacteremia had no symptoms. Group B streptococcal meningitis was confirmed in 6.3% of infants. Although 86% survived, GBS sepsis increased the birth weight-specific mortality rate up to eightfold in preterm infants and more than 40-fold in term infants. Although the incidence of GBS early-onset sepsis is not changing, we speculate that the improved birth weight-specific survival rate and the changing clinical presentation are due to improved intrapartum and neonatal management.     

Outcome of low birth weight infants in a West African village

Low birthweight (LBW) infants are at risk of increased mortality, impaired growth, and increased morbidity. We studied the progress of all LBW infants (less than 2.5 kg) born in a West African village where there is a resident pediatrician and midwife. There were 426 live births during the 8 years studied of which 42 (10 per cent) were of LBW. There were 17 infant deaths (IMR = 40/1000). Mean birthweight and gestation of infants dying in the first year were significantly lower than those of all live birth (2.33 kg v. 2.99 kg, P less than 0.001; 36.9 w v. 38.9 w, P less than 0.05). The mean weights of the 32 surviving LBW infants (15 preterm, 17 full term, small for gestational age) were compared with those of 32 full term, appropriate for gestational age matched controls over the first year. Growth velocities of paired groups were identical. The significant differences in weight at 1 year (P less than 0.005) reflected those at birth (P less than 0.001). There were no significant differences in clinic attendance rate or incidence of diarrhoea and respiratory disease between the four groups. We conclude that LBW is a strong risk factor for infant mortality, but not for diarrhoeal and respiratory morbidity in a community with ready access to obstetric and pediatric care.