Paediatric apnoeas are not related to a specific respiratory virus, and parental reports predict hospitalisation.

AIM: The aim of this study was to determine the frequency of apnoeas in previously healthy young infants with acute respiratory tract infection (ARI) and correlate their occurrence with isolated micro-organisms, clinical findings, disease severity and outcome. METHODS: We performed reverse transcriptase real-time polymerase chain reaction (RT-PCR) on the nasal wash specimens of a prospective cohort study of 582 children with ARI. Clinical data on a subgroup of 241 infants under three months of age, with and without apnoeas, were compared. RESULTS: Our study found that 19 (7.9%) of the 241 infants under three months old had a history of apnoeas: eight had a respiratory syncytial virus (RSV), five had a different virus than RSV and seven RT-PCR results were negative. Infants with apnoeas were more likely to have cyanosis, had longer hospital stays and required extra oxygen for a longer period. Most patients with parental reported apnoeas also experienced apnoeas during hospitalisation. CONCLUSION: This study observed apnoeas irrespective of the isolated micro-organism, and we hypothesise that they were related to the pathophysiology of the respiratory infection and not to the micro-organism itself. Parental reported apnoeas were a major warning sign and predicted that apnoeas would occur in hospital.

Decline of IgG pertussis toxin measured in umbilical cord blood, and neonatal and early infant serum.

Maternal pertussis-specific antibodies are passively acquired by infants during pregnancy. An IgG pertussis toxin (IgG-PT) concentration of >20 U/ml is considered to protect neonates against pertussis. To evaluate the IgG concentration at birth and during the first two months of life, we examined the IgG-PT concentration in the umbilical cord blood and three times during the neonatal and early infant period. IgG-PT was measured by validated IgG-specific enzyme-linked immunosorbent assays (ELISA) in umbilical cord blood and in Guthrie card blood samples of umbilical cord blood in 2,790 children, born between 1 August 2006 and 1 December 2008. These measurements were comparable. All children with concentrations of IgG-PT >30 U/ml were included. IgG-PT was also measured in Guthrie card blood samples, when the neonates or early infants were 5 days, 1 month and 2 months old. The mean concentrations of IgG-PT were calculated. The mean concentration of IgG-PT in umbilical cord blood was 60.1 U/ml (LN 4.1; 0.6 SD; n = 103). At the age of 5 days, 1 month and 2 months, the mean concentration of IgG-PT was 40.6 U/ml (LN 3.7; 0.5 SD; n = 103), 20.7 U/ml (LN 3.0; 0.7 SD; n = 62) and 16.7 U/ml (LN 2.8; 0.9 SD; n = 61), respectively. Four percent of the neonates had a concentration of IgG-PT >30 U/ml in umbilical cord blood, which declined to levels around the concentration needed for protection against pertussis (>20 U/ml) in the first two months of life. Hence, it is of great importance to further investigate the safety of maternal immunisation during pregnancy to prevent life-threatening pertussis in newborns.

An enterovirus epidemic in infants in the summer and fall of 2006.

The aim of this study was to evaluate the diagnostic procedures in infants presenting with febrile illness in the summer and fall of 2006. Infants younger than 90 days presenting with febrile illness were included. A sepsis evaluation was performed. Stool and/or cerebrospinal fluid were tested for enterovirus (polymerase chain reaction [PCR]). Twenty-four infants were included, with a median age of 36 days (range 5-87). Nineteen infants (79%) were diagnosed with enterovirus infection. In nine infants, both stool and cerebrospinal fluid were tested for enterovirus; both specimens were positive in three infants. In seven infants, only the stool and in three infants, only the cerebrospinal fluid was tested. The five infants without enterovirus infection were only partly tested; in four infants, only the stool and in one infant, only the cerebrospinal fluid was tested. Three infants (13%) were diagnosed with a urinary tract infection, one of which tested positive for enterovirus as well. Twenty-three infants received antibiotic treatment. The median duration of antibiotic treatment of infants without bacterial infection was 3.2 days. Thorough diagnostic evaluation for enterovirus in different specimens is important, as, often, only one specimen is positive for enterovirus. When enterovirus is diagnosed, patient management may be influenced.

Renal Fanconi syndrome with ultrastructural defects in lysinuric protein intolerance.

Renal Fanconi syndrome developed rapidly in a 3-year-old Moroccan girl with established lysinuric protein intolerance. She was hospitalized because of lowered consciousness, uncoordinated movements and hepatosplenomegaly after a febrile period. Laboratory investigations revealed plasma ammonia 270 micromol/L (normal <70 micromol/L), ferritin 159 micromol/L (normal 2-59 micromol/L), LDH 1180 U/L (normal 26-534 U/L). LPI was diagnosed based on the findings of reduced plasma ornithine, arginine and lysine, and an increased level of glutamine. Urinary orotic acid (645 micromol/mmol creatinine; normal <3.6) was strongly increased. A defect in the SLC7A7 amino acid transporter was established (homozygous c.726G > A mutation). Detailed renal function tests including an acid challenge test, bicarbonate loading, and tubular maximal reabsorption of glucose showed complex tubular dysfunction. No evidence of respiratory chain defects was found in muscle or kidney tissue. No morphological abnormalities were demonstrated in the mitochondria. Ultrastructural analysis of proximal tubular cells showed vacuolization and sloughing of the apical brush border (Fig. 1). Renal involvement in LPI has only been described in a few reports; however, no detailed studies of the renal acidification mechanism were performed. Our patient had evidence of a full-blown Fanconi syndrome. Surprisingly, a metabolic acidosis was found with a moderately increased serum anion gap combined with repeatedly normal plasma organic acid values. This finding is in contrast with the diagnosis of renal tubular acidosis. Patients with hyperlysinaemia have a similar heavy load on the renal tubules; they never develop a renal Fanconi syndrome. Therefore, we consider the intratubular accumulation of lysine an unlikely candidate for the development of the renal Fanconi syndrome.

Community-acquired pathogens associated with prolonged coughing in children: a prospective cohort study.

A 2-year prospective study was performed of children with prolonged coughing to investigate the frequency of different respiratory pathogens, the rate of mixed infections, and possible differences in severity of disease between single and mixed infections. Sera from 135 children (136 episodes of prolonged coughing lasting 1-6 weeks) were tested for antibodies to different viruses and bacteria. Swabs were taken for culture and PCR to detect different viral and bacterial pathogens. One or more pathogens were found in 91 (67%) patients. One infectious agent was found in 49 (36%) patients, two agents in 35 (26%) patients, and more than two agents in seven (5%) patients. The most frequent pathogens encountered were rhinovirus (n = 43; 32%), Bordetella pertussis (n = 23; 17%) and respiratory syncytial virus (n = 15; 11%). The most frequent mixed infection was B. pertussis and rhinovirus (n = 14; 10%). No significant differences in clinical symptoms were observed between patients with or without pathogens; however, patients with mixed infections were significantly older. There was a strong seasonal influence on the number of infections, but not on the number of mixed infections. In children with prolonged coughing, there was a high frequency of mixed infections regardless of the season. However, mixed infection was not associated with increased disease severity. No clinical symptoms were found that allowed discrimination between specific pathogens.

Duane retraction syndrome, a new feature in 22q11 deletion syndrome?

A female child with Duane retraction syndrome is described. A microdeletion on chromosome 22(q11) was discovered using FISH analysis. It is postulated that Duane retraction syndrome might be a new feature in 22q11 deletion syndrome.

[Activated charcoal as first-choice therapy in poisoning]. / Actieve kool als eerstekeustherapie bij intoxicaties.

In gastrointestinal detoxication, three methods are possible: ipecac induced emesis, gastric lavage and administration of activated charcoal. The method of treatment predominantly used in the Netherlands is gastric lavage in combination with activated charcoal. Published evidence suggests that activated charcoal not preceded by gastric emptying is preferred. Additional advantages of using activated charcoal alone as the method of choice for gastrointestinal decontamination are patient friendliness, low cost and time saving because quick intervention by general practitioners is possible.

[Magnesium poisoning in an infant]. / Magnesiumintoxicatie bij een zuigeling.

We present the case of a girl aged 3 weeks with extreme hypermagnesaemia (7.94 mmol/l) due to an overdose of magnesium oxide, prescribed as a laxative. We treated her successfully with a combination of hyperhydration, forced diuresis and natriuresis, and additional intravenous calcium and insulin. We also performed an exchange transfusion which, however, had a questionable effect on the final outcome.

[An epidemic of hand, foot and mouth disease]. / Een epidemie van hand-, voet- en mondziekte.

Five patients with hand-, foot- and mouth disease, caused by infection with Coxsackievirus type A16, are described in an epidemic outbreak of this disease. Hand-, foot- and mouth disease, is characterized by a most distinctive enanthem-exanthemcomplex. In 65% of the cases a vesiculopapular exanthem is noted. Most cases are described in epidemic outbreaks. Although the vast majority of occurrences of the disease have been due to Coxsackie A16 viral infections, occasionally Coxsackie A5, A10 and enterovirus 71, seldom Coxsackievirus B1 or B3, have been etiologically incriminated. In this article attention is paid to the clinical characteristics, the epidemiology and the differential diagnostic aspects of hand-, foot- and mouth disease.

A novel method for evaluating natural and vaccine induced serological responses to Bordetella pertussis antigens.

We studied the time course of serum IgG antibodies against 3 different pertussis vaccine antigens: PT (pertussis toxin), FHA (filamentous hemagglutinin), Prn (pertactin) in sera from individuals vaccinated with four different pertussis vaccines at 4 years of age: (N=44, 44, 23 and 23, respectively,) and compared the responses to/after natural infection with Bordetella pertussis (N=44, age 1-8 years). These longitudinal data were analyzed with a novel method, using a mathematical model to describe the observed responses, and their variation among subjects. This allowed us to estimate biologically meaningful characteristics of the serum antibody response, like peak level and decay rate, and to compare these among natural infections and vaccine responses. Compared to natural infection, responses to PT after vaccination with the tested vaccines are smaller in magnitude and tend to decay slightly faster. When present in vaccines, FHA and Prn tend to produce high peak levels, higher than those in naturally infected patients, but these decay faster. As expected, the Dutch whole cell vaccine produced lower antibody responses than the acellular vaccines. This model allows a better comparison of the kinetics of vaccine induced antibody responses and after natural infection over a long follow up period.

Antibody levels against B. pertussis in neonates measured in dried blood spots.

AIM: We designed this study to investigate if immunoglobuline G-Pertussis toxin (IgG-PT) against Bordetella pertussis in umbilical cord blood can reliably be determined in dried blood spots on filter paper (Guthrie) cards. PATIENTS AND METHODS: We prospectively included 129 mothers and their newborns born in a general hospital in the Netherlands. The relation between IgG-PT against B. pertussis from the umbilical cord measured in dried blood spots (Guthrie card) and in serum samples was studied by means of a Bland-Altman graph, using regression analysis to evaluate the level of agreement of both measurement methods. RESULTS: IgG-PT in Guthrie cards show a high coefficient of correlation with IgG-PT in serum samples from the umbilical cord when calibrated against blood spot calibrators (p<0.05). CONCLUSION: Maternal IgG-PT against B. pertussis measured in cord blood applied to Guthrie cards and calibrated against blood spot calibrators show good agreement with measurement of IgG-PT in cord serum. This offers new perspectives for future studies concerning B. pertussis antibodies.

Bordetella species in children with cystic fibrosis: what do we know? The role in acute exacerbations and chronic course.

Despite vaccination, pertussis is still endemic in the Netherlands. A literature search was performed to verify what is known about the role of Bordetella species in children with cystic fibrosis, with regard to the incidence of Bordetella infections, the involvement in pulmonary exacerbations and the influence on chronic course. Little is known about the frequency of Bordetella infections and the involvement of Bordetella species both in relation to the chronic course of cystic fibrosis and to pulmonary exacerbations. Since it is difficult to detect Bordetella species in cultures and few sputum cultures investigated have been obtained during an exacerbation, it is likely that the frequency of Bordetella species in CF patients is underestimated. Identification of Bordetella species in these patients may have serious consequences for the treatment of exacerbations in CF. Future research investigating the role of Bordetella species in cystic fibrosis should use specific techniques to detect Bordetella in cultures.

Motor Development of Premature Infants Born between 32 and 34 Weeks.

Little is known about motor development in late preterm born infants. Our objective was to determine long-term outcome of motor skills of infants born between 32 and 34 weeks. All infants were assessed at corrected ages of 3 and 9 months, using the Alberta Infant Motor Scale. At corrected ages of 4 years, the Movement Assessment Battery for Children was done. Seventy infants were seen at 4 years of age (median of 3 assessments per infant). Abnormal assessment at 3 or 9 months of age resulted in normal outcome in almost 80% at 4 years. On the other hand, a normal outcome in the first year of life resulted in an abnormal outcome at 4 years in 10% of the infants. Our results suggest that long-term followup of these late preterm born infants is necessary, as the assessments in the first year do not predict the long-term outcome.