Martijn G. Slieker

Chronic infection and inflammation affect exercise capacity in cystic fibrosis

Pulmonary function and nutritional status are important determinants of exercise capacity in patients with cystic fibrosis (CF). Studies investigating the effects of determinants, such as genotype or infection and inflammation, are scarce and have never been analysed in a multivariate longitudinal model. A prospective longitudinal cohort study was performed to evaluate whether genotype, chronic inflammation and infection were associated with changes in exercise capacity. Furthermore, we investigated whether exercise capacity can predict clinical outcome. 504 exercise tests of 149 adolescents with CF were evaluated. Maximal oxygen uptake corrected for body mass % predicted declined 20% during adolescence, and was associated with immunoglobulin (Ig)G levels and chronic Pseudomonas aeruginosa infection. A lower exercise capacity was associated with a higher mortality, steeper decline in pulmonary function and greater increase in IgG levels. Since a decline in exercise capacity during adolescence was negatively associated with IgG levels and chronic P. aeruginosa infection, these data emphasise the importance of prevention and treatment of chronic inflammation and infections in patients with CF. Furthermore, a lower exercise capacity was associated with a higher mortality rate, steeper decline in pulmonary function and higher increase in IgG levels with increasing age in adolescents with CF. This stresses the value of regular exercise testing for assessing prognosis in adolescents with CF.

Diagnostic value of serological tests against Pseudomonas aeruginosa in a large cystic fibrosis population

Background: Serological methods to monitor Pseudomonas aeruginosa colonisation in patients with cystic fibrosis (CF) are advocated but the diagnostic value of a commercially available P aeruginosa antibody test to detect early and chronic P aeruginosa colonisation in a non-research setting has not been assessed. Methods: Colonisation with P aeruginosa was estimated by regular culture of sputum or oropharyngeal swabs during three consecutive years in 220 patients with CF aged 0–65 years. Commercially available ELISA tests with three P aeruginosa antigens (elastase, exotoxin A, alkaline protease) were performed at the end of the study period. In a subgroup of 57 patients (aged 4–14 years) serological tests were performed annually. Results: Using culture as the reference standard, the ELISA tests using the advised cut off values had a sensitivity of 79% and a specificity of 89% for chronic colonisation. Receiver-operator characteristic curves were created to optimise cut off values. Applying these new cut off values resulted in a sensitivity of 96% and a specificity of 79%. All three individual serological tests discriminated well between the absence and presence of chronic P aeruginosa colonisation. The sensitivity of the individual antibody test was 87% for elastase, 79% for exotoxin A, and 76% for alkaline protease. First colonisation was preceded by positive serological results in only five of 13 patients (38%). Conclusion: In patients with CF, serological tests using specific antigens are sensitive for diagnosing chronic P aeruginosa colonisation. However, the failure of serological tests to detect early colonisation in young patients emphasises the need for continued reliance on cultures.

Is cardiovascular evaluation necessary prior to and during beta-blocker therapy for infantile hemangiomas?: A cohort study.

BACKGROUND Although consensus guidelines for pretreatment evaluation and monitoring of propranolol therapy in patients with infantile hemangiomas (IH) have been formulated, little is known about the cardiovascular side effects. OBJECTIVES We sought to analyze cardiovascular evaluations in patients with IH at baseline and during treatment with an oral beta-blocker. METHODS Data from 109 patients with IH were retrospectively analyzed. Patient and family history, pretreatment electrocardiogram (ECG), heart rate, and blood pressure were evaluated before initiation of beta-blocker therapy. Blood pressure and standardized questionnaires addressing side effects were evaluated during treatment. RESULTS Questionnaire analyses (n = 83) identified 3 cases with a family history of cardiovascular disease in first-degree relatives. ECG findings were normal in each case and no serious complication of therapy occurred. ECG abnormalities were found in 6.5% of patients but there were no contraindications to beta-blocker therapy and no major complications. Hypotension in 9 patients did not require therapy adjustment. In all, 88 parents (81%) reported side effects during beta-blocker treatment. LIMITATIONS The relatively small patient cohort is a limitation. CONCLUSION Pretreatment ECG is of limited value for patients with an unremarkable cardiovascular history and a normal heart rate and blood pressure. Hypotension may occur during treatment.

Comparability of Z-score equations of cardiac structures in hypoplastic left heart complex.

BACKGROUND Hypoplastic left heart complex (HLHC) is characterized by a mitral valve or an aortic valve annular Z score < -2, antegrade flow in the ascending aorta, ductal dependency, coarctation or aortic arch hypoplasia, and absence of significant (sub)valvar stenosis. The Z scores of the mitral and aortic valve annuli are major determinants of HLHC. Therefore, the algorithm for Z-score calculation is essential for diagnosis. However, no single universal method of calculation is in use. In the scientific literature addressing HLHC, various Z-score calculation methods have been applied. The aim of this study was to evaluate Z scores derived from two-dimensional echocardiographic dimensions in patients with HLHC. METHODS To compare the different published methods using two-dimensional echocardiographic measures for Z-score calculation, a cohort of 18 newborns diagnosed with HLHC was retrospectively evaluated. In addition, the methods to determine body surface area in newborns were evaluated. RESULTS Three Z-score calculation methods were included and compared. Using the method of Daubeney et al. to calculate Z scores in our cohort illustrated a lack of correlation beyond a Z score < 0, compared with the methods of Zilberman et al. and Pettersen et al. Z scores calculated using Zilberman et al.s and Pettersen et al.s methods were fairly consistent. The equations used by Pettersen et al. are based on the largest population of neonates. CONCLUSION Although the different methods for calculating Z scores for mitral and aortic valve dimensions correspond fairly well in the normal range, Z scores < -2 diverge substantially. A useful scientific comparison of published data and outcomes of patients with HLHC remains elusive. The Z-score calculation algorithms used by Pettersen et al. appear to be the most appropriate for use in an evaluation of HLHC. Because these different methods can yield different values, reporting the method as well as the Z score is essential for an accurate diagnosis. Similarly, the method used to determine body surface area should be reported.

A prediction rule for food challenge outcome in children.

To cite this article: Zomer‐Kooijker K, Slieker MG, Kentie PA, van der Ent CK, Meijer Y. A prediction rule for food challenge outcome in children. Pediatric Allergy Immunology 2012: 23: 353–359.

Fetal Heart Disease: Severity, Associated Anomalies and Parental Decision

Objective: This study describes the association between the complexity of congenital cardiac and extracardiac malformations, and the parental decision of pregnancy continuation or termination. Methods: Congenital heart defects (CHD) was diagnosed by ultrasound in 251 fetuses before the 24th week (23 + 6 weeks) of gestation during the four year period from 2007 to 2010. All fetuses from the Utrecht region were referred to our center due to a strict referral pattern. The complexity and severity of the cardiac and possible extracardiac malformations were retrospectively categorized by a pediatric cardiologist and a perinatologist who were blinded to the pregnancy outcome. The groups with and without termination of pregnancy were compared using a univariate analysis and multivariate logistic regression. Results: In 119 (47%) of the 251 fetuses, parents opted for termination of pregnancy. In 103 of these cases (87%) there was a high complex or lethal cardiac, or a major or lethal extracardiac malformation. Of the 132 continued pregnancies, 42 fetuses (32%) had a high complex or lethal cardiac, or a major or lethal extracardiac malformation. There were significantly more terminations of pregnancy in case of a high or lethal complex cardiac or extracardiac anomaly (71 vs. 15%, p <0.001). Conclusion: Parents opted for termination of pregnancy significantly more often in cases with high complex cardiac and extracardiac malformations. It was rare for parents to opt for pregnancy termination in the absence of a severe cardiac or extracardiac malformation.

Long-term effects of birth order and age at diagnosis in cystic fibrosis: a sibling cohort study.

Siblings with cystic fibrosis (CF) share many genetic and environmental factors but may present different phenotypes. Younger sibs are mostly earlier diagnosed with CF than their older sibs, but might be at risk for an earlier colonization with Pseudomonas aeruginosa (PA) than their older counterparts due to cross‐infection within families.

Normative Values of Aortic Arch Structures in Premature Infants

Background: Aortic arch abnormalities represent 5% to 8% of all congenital heart disease. Measurements of the aortic arch dimensions on two‐dimensional echocardiographic images remain of critical importance in the diagnosis of aortic arch pathology. To define aortic hypoplasia or coarctation, measured dimensions must be compared with normal values. Normal values have been described for children of all ages in earlier studies. However, normative data for premature infants are not yet available. Therefore, the aim of this study was to develop normative data in a cohort of premature infants, which could be used in the diagnosis of aortic arch abnormalities. Methods: A single‐center study was conducted in a large population of premature infants with gestational ages of ≤32 weeks without hemodynamically important congenital heart disease, chromosomal abnormalities, and/or major cerebral congenital malformations. Two‐dimensional echocardiographic measurements of four aortic arch structures were made on the second, fourth, and sixth days after birth. Results: Three hundred eighty‐five preterm patients were included. No differences in dimensions were found among days 2, 4, and 6. The dimension of the isthmus showed no significant relation to the existence of a patent ductus arteriosus. Reference intervals with mean and SD were calculated across the range of birth weight. Regression analysis was performed with multiple determinants in different models. The best predictive value was found for birth weight in a cubic model. Conclusions: This work provides regression equations for the calculation of Z scores and reference intervals for aortic arch dimensions in a cohort of preterm infants born at gestational ages of ≤32 weeks. The normative data can be used in diagnosis and decision making involving aortic arch pathology in premature infants. HighlightsA comprehensive set of normative data for the dimensions of the aortic arch is lacking for prematurely born infants.This study provides reference intervals for the dimensions of four aortic arch structures in premature infants across the range of birth weight.No significant difference in aortic arch dimensions was found among the second, fourth, and sixth days of life.PDA has no significant effect on the diameter of the aortic isthmus.

Contents Vol. 33, 2013

R. Achiron, Tel Hashomer N.S. Adzick, Philadelphia, Pa. L. Allan, London A.A. Baschat, Baltimore, Md. K.J. Blakemore, Baltimore, Md. T.-H. Bui, Stockholm F.A. Chervenak, New York, N.Y. T. Chiba, Tokyo R. Chmait, Los Angeles, Calif. F. Crispi, Barcelona J.E. De Lia, Milwaukee, Wisc. J.A. Deprest, Leuven G.C. Di Renzo, Perugia J.W. Dudenhausen, Berlin N.M. Fisk, Brisbane, Qld. A.W. Flake, Philadelphia, Pa. U. Gembruch, Bonn M.R. Harrison, San Francisco, Calif. J.C. Hobbins, Denver, Colo. L.K. Hornberger, San Francisco, Calif. E.R.M. Jauniaux, London M.P. Johnson, Philadelphia, Pa. C. Jorgensen, Copenhagen J.-M. Jouannic, Paris P.M. Kyle, London O. Lapaire, Basel S. Lipitz, Tel-Hashomer G. Malinger, Holon G. Mari, Detroit, Mich. M. Martinez-Ferro, Buenos Aires K.J. Moise, Houston, Tex. F. Molina, Granada K.H. Nicolaides, London D. Oepkes, Leiden L. Otaño, Buenos Aires Z. Papp, Budapest R.A. Quintero, Miami, Fla. G. Ryan, Toronto J. Rychik, Philadelphia, Pa. H. Sago, Tokyo W. Sepulveda, Santiago P. Stone, Auckland D.V. Surbek, Bern B.J. Trudinger, Westmead, N.S.W. J.M.G. van Vugt, Amsterdam Y. Ville, Paris Clinical Advances and Basic Research

618 Benefit of Prenatal Diagnosis of Complex Congenital Heart Defects on Neonatal Morbidity

Background and Aims As survival rates in neonatal cardiac surgery improve over time, morbidity becomes more important in complex congenital heart disease (cCHD). We investigated whether prenatal diagnosis of cCHD affects preoperative and early postoperative morbidity in neonates. Methods Retrospective observational study, performed between July 1st 2004 and July 1st 2011, including 247 infants with cCHD requiring surgery within the neonatal period. 113/247 patients were diagnosed with cCHD by prenatal screening (PreDx). Morbidity was based on preoperative use of high dose prostaglandin E and pre- and postoperative cardiac function, ventilation time, length of admission (LOF), inotropic support requirement and presence of severe complications (resuscitation, acute kidney and liver injury, and neurological events). Results Complexity of cCHD was higher in children diagnosed PreDx. After correction of complexity, median pre-operative ventilation time (3 vs 0 days), LOF (7 vs 9 days) and preoperative cardiac function were significantly better in PreDx neonates; and correction of acidosis, preoperative inotropic support and high dose prostaglandin E was significantly less common. Severe complications occurred significantly less when PreDx. There were no significant differences in postoperative morbidity and overall mortality. Conclusions Prenatal diagnosis of cCHD improves pre-operative morbidity significantly. The patient condition is better compared to postDx and the need for preoperative intensive care treatment is less. Seemingly, intensive care treatment can achieve a good pre-operative condition, even in neonates deteriorated due to an at birth unknown cCHD. This could explain why post-operative morbidity was equal in both groups.