Phenylketonuria does not cause cataracts

In a study of 46 adults aged 28–71 years with untreated phenylketonuria (PKU) there were 3 (6.5%) with cataracts. This incidence was similar to that in the Australian population and in a control series of intellectually disabled adults. Only two of the PKU patients with cataracts could be examined by slit-lamp biomicroscopy and in both the findings suggested that the prolonged use of phenothiazines may have played a role. Slit-lamp examination of a further ten untreated PKU patients and 13 PKU adults who had been treated in childhood revealed only small lens opacities (in 40%) of a type found in 72.7% of a control group. The study provides no support for claims that PKU can cause cataracts.     

Effect of helicobacter pylori eradication on sideropenic refractory anaemia in adolescent girls with Helicobacter pylori infection

We investigated the effect of Helicobacter pylori eradication on sideropenic refractory anaemia in adolescent girls with H. pylori-associated antral gastritis without evidence of haemorrhage or clinical symptoms other than sideropenic anaemia. We conducted an open therapeutic trial in 21 adolescent girls aged 15-17 y with sideropenic refractory anaemia, which was defined as iron-deficiency anaemia refractory to oral iron therapy for 3 mo. All subjects underwent gastroduodenal endoscopy. Thirteen patients with confirmed H. pylori infection were given a 2-wk course of triple therapy and 6 wk of oral ferrous sulfate. We compared the mean levels of haemoglobin and serum ferritin among the “initial sample” (the time when the sampling was done before treatment with oral iron), “before eradication” (the time prior to triple therapy for eradication after subjects had been given oral iron for 3 mo) and “after eradication” (the time when the follow-up endoscopy was performed) data in 11 subjects in whom H. pylori infection was eradicated. Haemoglobin levels (g/dl) were 8.6 ± 1.9, 8.6 ± 1.4 and 11.3 ± 2.3, respectively. Serum ferritin levels (μg/l) were 4.6 ± 2.4, 4.2 ± 2.3 and 17.5 ± 6.7, respectively. After eradication of H. pylori, mean levels of haemoglobin (p = 0.0002) and serum ferritin (p = 0.0002) showed a prominent increase between “before eradication” and “after eradication”. In conclusion, adolescent girls with sideropenic refractory anaemia should be evaluated for H. pylori infection. If H. pylori infection is coexistent, its eradication along with iron supplementation could correct the anaemia.     

Attitudes and feelings towards menstruation and womanhood in girls at menarche

Aim: To elucidate early adolescent girls' attitudes, thoughts and feelings towards menstruation and their bodies. Methods: 309 12-y-old girls answered questionnaires. One part of the questionnaire dealt with thoughts and feelings towards menstruation. The other part dealt with thoughts and feelings towards menstruation and sex and ability to communicate on aspects of womanhood. Results: Postmenarcheal girls were less positive towards menstruation than premenarcheal girls (p=1×10^-6). Many girls (43%) did not reaffirm the statement “I like my body” and almost one quarter stated being teased for their appearance. Many of the girls claimed that they had been called “cunt” (38%) or “whore” (46%). If called “cunt” or “whore”, 17% stated that they felt alone, 76% felt anger and 50% were offended. Mothers were those with whom girls could most easily “chat” about their period. Sixty-seven per cent received information about menstruation from school nurses.

Conclusion: Wanting to be an adult and liking that their body develops seem to be associated with a more positive feeling towards menstruation. Furthermore, mothers' timing and ability to communicate attitudes towards menstruation and the body are as important as those in a girl's immediate environment.     

Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?

Aim: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Methods: The population consisted of infants born to HIV-infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow-up visits at 1 wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infant's HIV status was assessed according to a predetermined algorithm. Results: HIV-infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91-20.63, p = 0.05]. During the first 2 mo of life, never-breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1.17-3.13, p = 0.006).

Conclusion: The significant extra morbidity experienced in the first few months by all never-breastfed infants and at all times by HIV-infected infants who are not breastfed needs to be considered in all decisions by mothers, health workers and policy makers so as not to offset any gains achieved by decreasing HIV transmission through avoiding breastfeeding.     

Nontuberculous mycobacterial adenitis: effectiveness of chemotherapy following incomplete excision

Background: Management of lymphadenopathy caused by nontuberculous mycobacteria (NTM) is primarily surgical. Where this cannot achieve sufficient clearance of infected nodes, chemotherapy is often given. Aim: This study compared results of surgery alone with surgery followed by chemotherapy in instances where there was incomplete surgical removal of diseased tissue. Methods: Chemotherapy comprised azithromycin 10 mg/kg and rifabutin 6 mg/kg both given once daily for 6 mo. Ninety-eight children with NTM infection were seen in the period 1990-2004. Sixty-eight cases with adenopathy where “time to healing” (discharge stopped and inflammation settled) was known were available to compare response to treatment. Results: The median (range) “time to healing” in weeks for 43 patients who had surgery alone was: incision and drainage (I&D)/curettage 6 (1-72) (n=10); excision 3 (1-28) (n=22); and from the last operation of multiple (repeat) surgery 3 (1-40) (n=11). For 25 patients who required chemotherapy in addition to surgery, the median (range) “time to healing” in weeks was I&D/curettage 10 (1-40) (n=17), excision 14 (8-20) (n=2) and multiple surgery 29 (2-88) (n=6).

Conclusion: In children with adenitis due to NTM, where surgical resection is followed by continued discharge and inflammation, chemotherapy should be considered before further surgery is undertaken.     

Upper endoscopic findings in children with active juvenile chronic arthritis

Aim: To investigate the association between gastroduodenal mucosal damage and symptoms of the digestive tract in children with juvenile chronic arthritis (JCA) Methods: This was a prospective, open, non-randomized study. Gastroscopy was performed on 45 children with active JCA in 1996-2000. Gastrointestinal symptoms before and during the treatment were noted, as was the length of antirheumatic medication, for which the data were retrospectively assessed. Plasma haemoglobin (Hb) and mean corpuscular volume (MCV) levels and erythrocyte sedimentation rate (ESR) were analysed. Mucosal biopsies were obtained for histology and Helicobacter pylori culture. All patients were taking non-steroidal anti-inflammatory drugs (NSAIDs) and 11 (24.4%) were on peroral steroids; 16 (35.6%) were receiving hydorxychloroquine, 9 salazopyrine, 5 myocrisine and 14 methotrexate. Results: Seven children (15.6%) were found to have active inflammation in their gastric and/or duodenal mucosa, two having ulcers and two being infected with H. pylori. Abnormal endoscopic findings were more common in symptomatic children (n = 24) than in children without symptoms (n = 21) (75% vs 38%, p = 0.017). There was no clear association between the Hb or MCV level and the degree of gastroduodenal inflammation (p = 0.98 and 0.7, respectively). Significantly more children (66.6% vs 33.3%) experienced abdominal pain after beginning medical therapy than before therapy (p = 0.02).

Conclusion: Endoscopic evaluation of patients with JCA and receiving NSAIDs should be considered at least in symptomatic cases.     

Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases

Aim: An epidemic of hand, foot and mouth disease (HFMD) occurred in Singapore between September and November 2000. During the epidemic, there were four HFMD-related deaths and after the epidemic, another three HFMD-related deaths. This study sought to determine the risk factors predictive of death from HFMD disease. Methods: The risk factors for fatal HFMD were determined by comparing clinical and laboratory findings between fatal cases (n = 7) and non-fatal controls (n = 131) admitted between September 2000 and April 2001. Enterovirus 71 positive fatal cases (n = 4) and non-fatal controls (n = 63) were also compared. Results: In total, 138 HFMD cases with a mean age of 32 mo were studied. The majority of fatal cases died from interstitial pneumonitis, of whom three also had brainstem encephalitis. Of the 131 non-fatal cases, 3 had concomitant infections (respiratory syncytial virus bronchiolitis, right-sided pneumonia, Haemophilus influenzae type b meningitis), 2 had aseptic meningitis, and 1 each had transient drowsiness, intravenous immunoglobulin-related complications and transverse myelitis. By multivariate logistic regression analysis, atypical physical findings (p = 0.0006), raised total white cell count (p = 0.0128), vomiting (p = 0.0116) and absence of mouth ulcers (p = 0.043) were predictive of a fatal course. Although previous epidemics have described neurogenic pulmonary oedema as the main cause of death, the fatal cases in this study died mainly from interstitial pneumonitis alone or with myocarditis or encephalitis.

Conclusion: Although HFMD is generally a benign disease, risk factors such as vomiting, absence of mouth ulcers, atypical presentation and raised total white cell count should alert the physician of a fatal course of illness.     

Autonomic nervous system functions in children with breath-holding spells and effects of iron deficiency

Aim: To analyse the activity of the autonomic nervous system during breath-holding spells, we assessed the ECG changes, including ventricular repolarization parameters before and during the spell. We also analysed the effects of iron deficiency on these ECG parameters. Methods: The study group consisted of 37 children with breath-holding spells (30 cyanotic, 7 pallid) (mean age±SD: 12.9±10.8 mo). Twenty-six healthy children (mean age±SD: 14.4±8.6 mo) served as a control group. All patients and controls had standard 12-lead simultaneous surface ECG. All patients had ECG recordings during at least one severe breath-holding spell obtained by “event recorder”. Traces obtained by “event recorder” were analysed in terms of mean heart rate and the frequency and duration of asystole during the spell. Results: Respiratory sinus arrhythmia on standard ECGs and asystole frequency during spells were higher in patients with pallid breath-holding spells. Patients with iron deficiency had a lower frequency of respiratory sinus arrhythmia and prolonged asystole time during the spell. There was no difference in terms of ventricular repolarization parameters (QT/QTc intervals and QT/QTc dispersions) between patients and controls and between patient subgroups (cyanotic versus pallid).

Conclusion: These results confirmed the presence of autonomic dysregulation in children with breath-holding spells. Iron deficiency may have an impact on this autonomic dysregulation. Ventricular repolarization was unaffected in patients with breath-holding spells.     

The effect of maturation and sedation on amplitude-integrated electroencephalogram of the preterm neonate: results of a prospective study

Background and aim: Amplitude-integrated electroencephalogram (aEEG) is becoming more common in NICUs for monitoring infants after perinatal asphyxia. We used aEEGs for preterm infants, and analysed the influence of sedation and maturation on their aEEG, focusing on continuous activity. Methods: Weekly or biweekly aEEGs were performed in preterm infants and evaluated by visual analysis. Results: We analysed 92 aEEGs of 56 preterm infants (gestational age (GA) 24 + 6 to 34 + 0 wk, median 30 + 0 wk). In their first week of life, children with higher GA had a higher percentage of continuous activity: with a GA ≤ 28 + 0 wk it was 8.1%, 33.5% with a GA from 28 + 1 to 30 + 0 wk (p=0.02), 85.9% with a GA from 30 + 1 to 32 + 0 wk (p=0.005), and 89.1% with a GA from 32 + 1 to 34 + 0 wk. Continuous activity increased with growing postnatal age. With a GA ≤ 28 + 0 wk, it rose from 8.1% (first week) to 55.3% (second week) and reached 96.8% (week 6/7) (p=0.017). With GA from 28 + 1 to 30 + 0 wk, continuous activity was 33.5% (first week) and 86.6% (second week) (p=0.03).

Conclusion: The aEEG of preterm infants appears to be a good tool for monitoring cerebral activity. Continuous activity seems to indicate maturation in the neonatal brain. Further investigations of aEEGs in preterm infants should be performed.     

Bacterial aetiology of acute osteoarticular infections in children

Aim: To study the bacterial aetiology of acute osteoarticular infections in children and to analyse the efficiency of culture methods. Methods: Bacteriological data of 407 cases of clinically suspected osteoarticular infections affecting 406 children hospitalized in an orthopaedic surgery department between 1999 and 2002 were retrospectively reviewed. Results: Bacterial cultures from clinical specimens were positive in 74 cases (18%): 38 cases of septic arthritis and 36 cases of bone infections (osteitis, osteomyelitis or osteoarthritis). The use of liquid medium bottles to grow bacteria from articular fluids increased the rate of positive cultures compared to the use of standard solid media (p=0.0001). The most commonly recovered pathogen was Staphylococcus aureus (44%) followed by Kingella kingae (14%), Streptococcus pyogenes (10%) and Streptococcus pneumoniae (10%). K. kingae was most frequently isolated among children under 36 mo of age (p=0.0003), whereas S. aureus was most frequently isolated among children over 36 mo (p=0.0015).

Conclusion: By improving our culture method, we observed a recrudescence of isolation of K. kingae, but S. aureus remains the main pathogen isolated from osteoarticular infections in children. This finding is useful for the adaptation of a probabilistic antibiotic treatment of these infections.     

Vitamin A for acute respiratory infection in developing countries: a meta-analysis

Aim: To determine the efficacy of intervention with high-dose vitamin A as an adjunct to standard treatment on outcome in acute lower respiratory tract infection in children in developing countries. Methods: A systematic review of double-blinded, randomized, controlled intervention studies of high-dose vitamin A or placebo in children aged between 1 mo and 6 y presenting with acute non-measles lower respiratory tract infection. Results: Five studies fulfilling the criteria were identified and included a total of 2177 children (1067 intervention, 1110 control). The main outcome measures were time to normalization of fever, respiratory rate and oxygen dependence, time to discharge, and mortality. On meta-analysis, there were no significant differences in any of the recovery measures or mortality between the intervention and control groups. Pooled results for recovery times are given showing difference in days to recovery days and 95% confidence intervals. Positive summary measures indicate faster recovery in the vitamin A group and negative in the placebo: fever: 0.03 (-0.10 to 0.17); oxygen requirement: -0.08 (-0.31 to 0.16); raised respiratory rate: -0.09 (-0.38 to 0.19); hospital stay: -0.06 (-0.52 to 0.40). Mortality was below 2% in both groups, with a non-significantly higher risk in the intervention group (odds ratio 1.16, 95% CI: 0.61-2.21).

Conclusion: There is no evidence from this meta-analysis that intervention with high-dose vitamin A improves recovery from pneumonia in children in developing countries aged from 1 mo to 6 y.     

Survival after surgery for congenital heart defects: Does reduced early mortality predict improved long‐term survival?

Aim: The objectives of this study were 1) to compare early mortality (first 30 d after surgery) and long-term survival between two cohorts of patients operated on for congenital cardiac defects, and 2) to evaluate the impact of possible changes in early mortality on long-term survival. Methods: 945 patients with congenital cardiac defects, born in 1990-1999 and operated on in the same period were examined in a retrospective cohort study. The patients were divided into three groups: “univentricular cardiac defects”, “severe cardiac defects” and “less severe cardiac defects”. The study population was divided into two cohorts: group 1 included patients born and operated on in 1990-1994; group 2 included patients born and operated on in 1995-1999. The survival patterns in the two groups were compared. Results: For all patients, except those with univentricular cardiac defects, early mortality (30 d after surgery) was reduced. Among patients with severe cardiac defects, early mortality was reduced from 18.6% in group 1 to 2.9% in group 2. Among patients with less severe cardiac defects, early mortality was reduced from 6.2% to 1.9%. The improved outcome was maintained during the following 5 y. Overall relative risk of death during follow-up was reduced to 0.31 (95% CI: 0.15-0.56) for patients with severe cardiac defects, and to 0.53 (95% CI: 0.31-0.93) for patients with less severe cardiac defects born and operated on in 1995-1999.

Conclusion: Early mortality has been substantially reduced in congenital heart defect patients, and corresponds with significantly improved long-term survival.     

Randomized study of nasal continuous positive airway pressure in the preterm infant with respiratory distress syndrome

Aim: To evaluate whether very preterm babies can be extubated successfully to nasal continuous positive airway pressure (nCPAP) within one hour of birth after receiving one dose of surfactant in the treatment of respiratory distress syndrome (RDS). Methods: Forty-two infants of 25 to 28[Formula: See Text] wk of gestation were intubated at birth and given one dose of surfactant. They were then randomized within one hour of birth to either continue with conventional ventilation or to be extubated to nCPAP. Results: Eight out of 21 (38%) babies randomized to nCPAP did not require subsequent reventilation. (Ventilation rates of 62% vs 100%, p = 0.0034). The smallest baby successfully extubated weighed 745 g. There were also significantly fewer infants intubated in the nCPAP group at 72 h of age (47% vs 81%, p = 0.025). There was no significant difference between the two groups in the number of babies that died, developed chronic lung disease or severe intraventricular haemorrhage.

Conclusion: A significant number of very preterm babies with RDS can be extubated to nCPAP after receiving one dose of surfactant. nCPAP is a potentially useful modality of respiratory support even in very premature infants.     

Characteristics and outcome of long-stay patients in a paediatric intensive care unit: a case-control study

Aim: To identify differences in baseline characteristics and outcome between long-stay and other patients admitted to a paediatric intensive care unit with the same diagnosis. Methods: Over a period of 6 y, data of paediatric intensive care unit patients with a length of stay of 30 or more days (long-stay patients) and aged 1 to 18 y were retrospectively collected. Long-stay patients were matched with the next patient who was admitted to the paediatric intensive care unit with the same diagnosis. Evaluated characteristics on admission included: age, sex, presence of chronic morbidity, functional status, Pediatric Risk of Mortality score, presence of multiple organ system failure and complications during admission. Outcome (survival and functional status) was assessed 2.5 to 8.5 y after admission. Results: Of 19 long-stay patients identified, 15 could be matched with a control patient admitted with the same diagnosis. No significant difference in baseline characteristics was found between long-stay patients and the matched controls. The mean number of complications per long-stay patient was 2.9, compared to 1.2 per control patient (p = 0.02). Infection accounted for half of the complications. Mortality rate in long-stay patients was not higher than in the matched controls (36.8 vs 26.7%, p = 0.54). Paediatric intensive care unit stay did not change functional status in either long-stay patients or controls.

Conclusion: Long-stay patients in the paediatric intensive care unit had more complications, but baseline characteristics, mortality and functional outcome were not different from a control group admitted with the same diagnosis.     

Prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis

Aim: To ascertain the prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis (JT) in non-autoimmune patients. TSH receptor gene mutations are not seen in autoimmune-active patients. Methods: In a nationwide study on JT, 123 patients were re-examined 10 y (range 4 to 21 y) after diagnosis. Two patients with toxic adenoma were excluded. In 25 patients, no TPO, TG or TSH-R antibodies were found. In 17 patients, DNA material was available for TSH receptor gene analysis. The entire TSH receptor gene was sequenced in five patients. TSH receptor “hot spots” for mutations in exon 9 and 10 were sequenced in the remaining 12 patients. Results: A TSH receptor gene germline mutation was identified in only one patient of a total number of 121 patients with JT, of which 17 patients were presumed to have non-autoimmune JT by the lack of thyroid autoantibodies.

Conclusion: In Denmark the prevalence of germline mutations in the TSH receptor gene is one in 121 patients with JT (0.8%; 95% CI: 0.02-4.6%) and one in 17 patients with presumed non-autoimmune JT (6%; 95% CI: 5.88% (0.15-28.69)).     

Lung volume and the response to high volume strategy, high frequency oscillation

Background: Infants with severe respiratory failure are frequently transferred to high volume strategy, high frequency oscillation (HFO). Mean airway pressure (MAP) is then elevated, the aim being to open up atelectatic lungs and hence improve gas exchange. Aim: To test the hypothesis that lung volume prior to transfer would predict the response to high volume strategy HFO and identify which factors related to poor outcome (death). Methods: Lung volume was assessed by measurement of functional residual capacity (FRC) and the response to HFO determined by the change in the alveolar arterial gradient (AaDO ₂ ) on transfer from conventional mechanical ventilation (CMV) to the optimal MAP on high volume strategy HFO. Patients: Forty-two infants with a median gestational age of 28 (range 23 to 40) wk were studied. Results: FRC prior to transfer correlated significantly with the change in MAP necessary to optimize oxygenation (p = 0.012), but not the change in AaDO ₂ in response to HFO. There were no significant differences in the lung volumes of survivors and non-survivors, but those who died were more immature (p = 0.0009) and had a smaller response to HFO (p = 0.035).

Conclusion: Lung volume prior to transfer to high volume strategy HFO might be helpful to guide oscillatory settings, but is a poor predictor of the response to high volume strategy HFO.     

Mother-infant skin-to-skin contact after delivery results in early recognition of own mother's milk odour

Aim: To determine the effects of mother-infant skin-to-skin contact immediately after birth on infant recognition of their own mother's milk odour and breastfeeding duration until 1 y of age. Methods: Sixty healthy, full-term neonates were randomly assigned to group A with skin-to-skin contact and group B without. One and 4 d after birth, infant responses to the following odour stimuli were observed: own mother's milk, another mother's milk, formula, orange juice and distilled water. Infant facial action was videotaped and the frequency of mouthing movements was evaluated for each stimulus. Nutritional assessment, focused particularly on breastfeeding, was performed every 3 mo on participating infants. Statistical analysis comparing the frequency of mouthing movements with the aforementioned five different odour exposures was performed by ANOVA with Fisher's PLSD. Kaplan-Meier analysis with a log-rank test was used to compare breastfeeding rates between groups. Results: Infants in both groups responded differently to mother's milk odour (either their own or another mother's milk) compared to the other stimuli on days 1 and 4. However, infants in group A demonstrated a larger difference in mouthing movements between their own and another mother's milk odour at 4 d of age (2.6 ± 1.6) compared to infants in group B (0.9 ± 2.0, p = 0.01). Infants in group A were breastfed an average of 1.9 mo longer than the others.

Conclusion: Our study provides evidence that mother-infant skin-to-skin contact for more than 50 min immediately after birth results in enhanced infant recognition of their own mother's milk odour and longer breastfeeding duration.     

Cerebral excitatory amino acids and Na+, K+-ATPase activity during resuscitation of severely hypoxic newborn piglets

We tested the hypothesis that early brain recovery in hypoxic newborn piglets is improved by resuscitating with an O₂ supply close to the minimum level required by the newborn piglet brain. Severely hypoxic 2-5-d-old anaesthetized piglets were randomly divided into three resuscitation groups: hypoxaemic (n = 8), 21% O₂ (n = 8), and 100% O₂ groups (n = 8). The hypoxaemic group was mechanically ventilated with 12-18% O₂ adjusted to achieve a cerebral venous O₂ saturation of 17-23% (baseline; 45±1%, mean±SEM). During the 2h resuscitation period, extracellular aspartate and glutamate concentrations in the cerebral striatum were higher during hypoxaemic resuscitation (p = 0.044 and p = 0.055, respectively) than during resuscitation with 21% O₂ or 100% O₂, suggesting an unfavourable accumulation of potent excitotoxins during hypoxaemic resuscitation. The cell membrane Na⁺,K⁺-ATPase activity of cerebral cortical tissue after 2 h resuscitation was similar in the three groups (p = 0.30). In conclusion, hypoxaemic resuscitation did not normalize early cerebral metabolic recovery as efficiently as resuscitation with 21% O2 or 100% O₂. Resuscitation with 21% O₂ was as efficient as resuscitation with 100% O₂ in this newborn piglet hypoxia model.     

Low-dose warfarin for the prevention of central line-associated thromboses in children with malignancies--a randomized, controlled study

Background: Central venous lines (CVLs) are essential in the care of children with malignancies, but are associated with venous thromboembolism (VTE) and infections. Effective and safe prophylactic approaches are deficient. Aim: To perform a study of adjusted low-dose warfarin for the prevention of CVL-related VTE in children with malignancies. Methods: Children with newly diagnosed cancer, a CVL in a jugular vein and an expected treatment period of over 6 mo were eligible for the study. Participants were randomized to low-dose warfarin, with intended international normalized ratio (INR) 1.3-1.9, or to a control group. Primary outcome was VTE in a jugular vein diagnosed by ultrasonography at 1, 3 and 6 mo after inclusion. Secondary outcome was CVL-related infections, mainly measured as days on antibiotics or positive blood cultures. Results: The study enrolled 73 children, and 62 completed it fully. Asymptomatic CVL-related VTE was frequent (42%), but often transient. Regardless of severity, timing and duration, CVL-related VTE was equally frequent among children on warfarin as compared to controls (p=0.44). Low-dose warfarin (p=0.59) or jugular CVL-related VTE (p=0.91) did not have any impact on days on antibiotics, but we observed a tendency towards an association between CVL-related VTE and positive blood cultures (p=0.15).

Conclusion: Our randomized study of low-dose oral anticoagulation for the prevention of CVL-related asymptomatic VTE in children with cancer did not show any benefit of warfarin adjusted to maintain INR between 1.3 and 1.9.     

Difference in plasma bilirubin concentration between monozygotic and dizygotic newborn twins

Aim: To investigate whether inherited factors, other than those already known, influence the bilirubin concentration in neonates of northern European descent, by comparison of monozygotic and dizygotic twins with respect to differences in the plasma bilirubin concentrations between the twins. Methods: 77 healthy pairs of twins of the same gender with a gestational age ≥250 d and of northern European descent were included. Fourth postnatal day blood sampling was done. A multiple linear regression analysis was carried out with the difference in serum bilirubin concentration between the twins as the independent factor, and zygosity, gender, gestational age, postnatal age, maternal smoking, ABO blood-type incompatibility, and the differences between the twins in blood haemoglobin concentration, formula feeding and weight loss as dependent factors. Results: 27 pairs of twins were monozygotic and 50 pairs dizygotic. The analysis showed that the difference in serum bilirubin concentration between the twins was dependent on whether the twins were monozygotic or dizygotic, i.e. the estimated difference in serum bilirubin concentration between the monozygotic twins was 17.8 μmol l^-1 [SE 6.6 μmol l^-1, p = 0.02, 95% confidence interval (95% CI) 3.4, 32.3 μmol l^-1] less than the difference between the dizygotic twins, adjusted for the above-mentioned potential confounders. The difference in serum bilirubin concentration between the twins was positively correlated to the difference in weight loss (%) between the twins (adjusted estimate 5.2 μmol l^-1, SE 2.1 μmol l^-1, p = 0.01, 95% CI 1.2, 9.3 μmol l^-1).

Conclusion: In a population of northern European descent, other genetic factors than gender and ABO blood type were significant for the plasma bilirubin concentration in healthy infants.