Utility of routine urine CMV PCR and total serum IgM testing of small for gestational age infants: a single center review.

BACKGROUND: Due to the extremely low incidence of TORCH (toxoplasmosis, rubella, CMV, herpes simplex virus) infections, diagnostic testing of all small for gestational age (SGA) infants aimed at TORCH etiologies may incur unnecessary tests and cost. OBJECTIVE: To determine the frequency of urine CMV PCR and total IgM testing among infants with birth weight <10% and the rate of test positivity. To evaluate the frequency of alternative etiologies of SGA in tested infants. METHODS: Retrospective chart review of SGA infants admitted to the neonatal intensive care unit (NICU) at NYU Langone Medical Center between 2007 and 2012. Subjects were classified as being SGA with or without intrauterine growth restriction (IUGR). The IUGR subjects were then further categorized as having either symmetric or asymmetric IUGR utilizing the Fenton growth chart at birth. Initial testing for TORCH infections, which included serum total IgM, CMV PCR and head ultrasound, were reviewed and analyzed. RESULTS: Three hundred and eighty-six (13%) infants from a total of 2953 NICU admissions had a birth weight ≤10th percentile. Of these, 44% were IUGR; 34% being symmetric IUGR and 10% asymmetric. A total of 32% of SGA infants had urine CMV PCR and total IgM tested with no positive results. As expected, significantly higher percentage of symmetric IUGR infants were tested compared to asymmetric IUGR and non-IUGR SGA infants, (64% vs. 47% vs. 19%) P≤0.01. However, 63% of infants with a known cause for IUGR had same testing done aimed at TORCH infections. We calculated additional charges of $64,065 that were incurred by such testing. CONCLUSIONS: The majority of infants in our study who received testing for urine CMV PCR and total IgM aimed at TORCH infections had one or more other known non-infectious etiologies for IUGR. Because the overall yield of such testing is extremely low, we suggest tests for possible TORCH infections may be limited to symmetric IUGR infants without other known etiologies. Improved guidelines testing for TORCH infections can result in reducing hospital charges and unnecessary studies.

Utilization of ultrasonography to detect developmental dysplasia of the hip: when reality turns selective screening into universal use.

BACKGROUND: Developmental dysplasia of the hip (DDH) occurs in 3-5 of 1000 live births and is associated with known risk factors. In most countries, formal practice for early detection of DDH entails the combination of risk factor identification and physical examination of the hip, while the golden standard diagnostic instrument is hip ultrasonography (US). This practice is commonly referred to as selective screening. Infants with positive US findings are treated with a Pavlik harness, a dynamic abduction splint. The objective of our study was to evaluate hip US utilization patterns in Maccabi Healthcare Services (MHS), a large health plan. METHODS: Study population: All MHS members, born between June 2011 and October 2014, who underwent at least one US before the age of 15 months. STUDY VARIABLES: Practice specialty and number of enrolled infants. Positive US result was defined as referral to an abduction splint. Cost was based on Ministry of Health price list. Chi square and correlation coefficients were employed in the statistical analysis. RESULTS: Of the 115,918 infants born during the study period, 67,491 underwent at least one hip US. Of these, 60.6% were female, mean age at performance: 2.2 months. Of those who underwent US, 625 (0.93%) were treated with a Pavlik harness: 0.24% of the male infants and 1.60% of the female infants (p < 0.001). Analysis of physician practice characteristics revealed that referral to US was significantly higher among pediatricians as compared with general practitioners (60% and 35%, respectively). Practice volume had no influence on referral rate. Direct medical costs of the 107 hip US examinations performed that led to detection of one positive case (treated by Pavlik): US$10,000. CONCLUSIONS: Current pattern of hip US utilization for early detection of DDH resembles universal screening more closely than selective screening. This can inform policy decisions as to whether a stricter selective screening or a formal move to universal screening is appropriate in Israel.

[Newborn Hearing Screening - Results of a Parental Survey in Saxony-Anhalt]. / Neugeborenen-Hörscreening ­ Ergebnisse einer Elternbefragung in Sachsen-Anhalt.

Background: In recent years quality assurance has become an essential part of today's health-care system in the wake of the modern patient-oriented quality management. With the statutory introduction of newborn hearing screening (NHS) in 2009, a quality assurance of these early detection methods has become necessary. The aim of the study was to determine patient satisfaction in relation to the NHS in Saxony-Anhalt. Patients/Methods: During the period from November 2013 to April 2014, 394 parents were retrospectively interviewed about their experiences and expectations in relation to the NHS, using a standardised questionnaire. In total, 21 child care centres and 6 paediatric primary care centres from all over Saxony-Anhalt were involved. Results: It turns out that the majority of parents are satisfied with the NHS and 97.7% are in favour of the offer of an NHS. Of the surveyed parents, 69.3% felt the information as sufficient. However, only 66.2% of parents took a closer look at the leaflet issued by the G-BA. In addition, 17.7% of respondents are dissatisfied with the professional competence of the examining staff. Conclusion: The study shows that the general attitude among parents towards newborn hearing screening was very positive. They felt reassured by it although there are some aspects still open to criticism.

[Whole-genome sequencing in German clinical practice : Economic impacts of its use in selected areas of application]. / Ganzgenomsequenzierung in der deutschen Versorgung : Ökonomische Auswirkungen eines Einsatzes in ausgewählten Anwendungsgebieten.

BACKGROUND: The diagnostic use of whole-genome sequencing (WGS) is a growing issue in medical care. Due to limited resources in public health service, budget-impact analyses are necessary prior to implementation. OBJECTIVE: A budget-impact analysis for WGS of all newborns and diagnostic investigation of tumor patients in different oncologic indications were evaluated. METHODS: A cost analysis of WGS based on a quality-assured process chart for WGS at the German Cancer Research Center (DKFZ), Heidelberg, constitutes the basis for this evaluation. Data from the National Association of Statutory Health Insurance Funds and the Robert-Koch-Institute, Berlin, were used for calculations of specific clinical applications. RESULTS AND DISCUSSION: WGS in newborn screening leads to costs of € 2.85 bn and to an increase of total expenditure by 1.41%. Sequencing of all tumor patients would cost approximately € 0.84 bn, which corresponds to 0.42% of total expenditures. In all scenarios, the sole consideration of procedure costs results in increasing costs. However, in cost discussions potential savings (reduction of disease-related follow-up-costs, improved cost-effectiveness of medical measures etc.) should be considered. Such considerations are the subject of economic indication-specific evaluations. WGS has the potential to generate a large number of deterministic findings for which treatment options are limited. Hence, it is necessary to limit indications, in which WGS has proven medical evidence.

Rastreramento da sífilis no pré - natal: oportunidades perdidas em uma maternidade pública na cidade do Recife, Brasil / Syphilis Screening during prenatal development: missed opportunities in a public maternity hospital in Recife, Brazil

De acordo com as normas do Programa de Humanização no Pré-Natal e Nascimento, do Ministério da Saúde, a gestante deve realizar dois exames laboratoriais para detecção da sífilis. Objetivo: Avaliar oportunidades perdidas no rastreamento de sífilis gestacional e identificar fatores associados à não realização do teste Venereal Disease Research Laboratory (VDRL) no pré-natal. Métodos: Estudo de corte transversal realizado em maternidade do Sistema Único de Saúde da cidade do Recife, no Nordeste do Brasil. Foram estudadas 460 mulheres admitidas por término da gravidez e/ou abortamento, entre setembro e outubro de 2013, que realizaram ao menos uma consulta de pré-natal. Foram realizadas entrevistas e consulta ao cartão de pré-natal e prontuários. As mulheres que não realizaram pelo menos um VDLR no pré-natal (categoria de referência) foram comparadas com aquelas que realizaram. Nas informações colhidas nos 408 cartões da gestante, foi utilizada a regressão logística para identificar fatores associados com a não realização do rastreio. Resultados: Uma parte correspondente a 17,90% das mulheres não realizou o VDRL. Na análise multivariada, apresentaram maior chance de não realizar o VDRL as mulheres que: enfrentaram dificuldades para realizar o exame; realizaram a última consulta antes do último trimestre da gravidez; passaram por menos de seis consultas; realizaram pré-natal em unidade que não realizava agendamento das consultas subsequentes; tinham 19 anos ou menos de idade; tinham três ou mais gravidezes. Conclusão: Os resultados mostram que, apesar da elevada cobertura da atenção pré-natal, persiste uma baixa efetividade das ações de prevenção da sífilis congênita.

According to the norms issued by the Ministry of Health for the Prenatal and Birth Humanization Program, pregnant women should undergo two tests for syphilis detection. Objective: To evaluate missed opportunities for screening gestational syphilis and to identify factors associated with the missing application of the Venereal Disease Research Laboratory (VDRL) test during prenatal development. Methods: This cross-sectional study was undertaken in the maternity ward of a Unified Public Health System (SUS) hospital in the city of Recife in northeastern Brazil. We studied 460 women admitted for termination of pregnancy and/or abortion, between September and October 2013, who had at least one prenatal consultation. We conducted interviews and checked patients' prenatal care records and medical records. Women who did not take at least one VDRL test during prenatal development (reference category) were compared with those who did. Logistic regression was performed on the data collected from the 408 pregnancy records analyzed in order to identify factors associated with a failure to undergo syphilis screening. Results: 17.90% of the women in the sample did not take the VDRL test. In multivariate analysis, women who fit the following factors presented a greater chance of not having taken the VDRL test: facing difficulties in taking the test; attendance of the last prenatal consultation before the last trimester of pregnancy; attending less than six consultations; receiving prenatal care in hospital units which did not schedule subsequent exams; being 19 years of age or younger; having had three or more pregnancies. Conclusion: Results show that despite the high availability of prenatal care, actions aimed at preventing congenital syphilis still present low effectiveness.

Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China.

OBJECTIVES: To estimate the incidence of MMA on newborn screening in Shandong province from May 2011 to May 2014 and summarize the clinical presentation, biochemical features, mutation analysis, and treatment regime of early-treated patients with cblC disease. METHODS: Between May 2011 and May 2014, 35,291 newborns were screened for MMA in Jinan maternal and Child Care Hospital, Shandong province. The levels of C3, C3/C2, methionine and tHcy were measured. Most patients received treatment with intramuscular hydroxocobalamin after diagnosis. Metabolic parameters, clinical presentation and mental development were followed up. RESULTS: Nine patients were identified among 35,291 by newborn screening, giving an estimated incidence of 1:3920 live births for MMA, and all were classified as cblC disease. Among them, five patients received treatment with intramuscular hydroxocobalamin and two patients did not receive any treatment. One patient died of metabolic crises triggered by infection at the age of 38 days. Seven different mutations (c.609G>A, c.455_457delCCC, c.394C>T, c.445_446insA, c.658_660delAAG, c.452A>G and IVS1+1G>A) were detected. The mutations (c.455_457delCCC and IVS1+1G>A) are novel. Five patients who received treatment had favorable metabolic response, with both reduction of urine MMA and tHcy and increase of methionine. We obtained 7 records of DQ assessment. The five patients who received treatment presented with developmental delay and obvious neurological manifestations. In two patients who did not receive any treatment, case 8 presented with severe mental retardation and developmental delay, while case 9 had nearly normal DQ values at the age of 1(1/12)years. CONCLUSION: Our study characterized variable phenotypes of neurodevelopment in early-treated cblC patients diagnosed on newborn screening. The long-term outcomes of cblC disease are unsatisfactory in spite of conventional treatment and improvement of biochemical abnormalities. Although the number of patients is too small, the information provided in this work is of value in highlighting possible genotype-phenotype correlation that influences outcomes in cblC disease by future studies.

Three cost-utility analyses of screening for intracranial hemorrhage in neonates with hemophilia.

BACKGROUND: Intracranial hemorrhage (ICH) in the newborn period is a potential cause of serious morbidity and mortality in individuals with hemophilia. The incidence of ICH is estimated to be 2% to 4%; however, depending on the mode of delivery, it may be considerably higher. Considering the varying sensitivities and costs of various imaging modalities, there remains controversy surrounding universal cranial imaging. Cost-utility analysis is the ideal tool to display the consequences of a decision made. METHODS: We constructed a decision tree to evaluate the direct and indirect costs, possible outcomes, and probabilities of ICH in neonates with hemophilia. We created 3 decision analysis models to evaluate the cost-utility of different screening modalities for ICH: ultrasound, computed tomography, and magnetic resonance imaging. Within each model, 3 different strategies were compared: screen all neonates; screen only neonates born by instrumented delivery; and not screen any neonates. A societal perspective was used for all models. The base case models were later reanalyzed in sensitivity analysis to account for uncertainties. RESULTS: Total costs for screening all neonates, screening only neonates born by instrumented delivery, and not screening any neonates were $9501, $9297, and $9347, respectively, for US, and $9761, $9351, and $9353, respectively, for CT. Screening instrumented deliveries using MRI had an incremental cost-effectiveness ratio of $12,440. CONCLUSIONS: Screening newborns born by an instrumented delivery appears to be the most cost-effective strategy irrespective of the imaging modality. Subsequent studies will require a longer time frame to factor in possible late effects of radiation, anesthesia, and the high cost of factor replacement and hospital admission.

The case for mandatory newborn screening for severe combined immunodeficiency (SCID).

Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency and is a paediatric emergency. Delay in recognising and detecting SCID can have fatal consequences and also reduces the chances of a successful haematopoietic stem cell transplant (HSCT). Screening for SCID at birth would prevent children from dying before HSCT can be attempted and would increase the success of HSCT. There is strong evidence to show that SCID fulfills the internationally-established criteria for a condition to be screened for at birth. There is also a test (the T-cell receptor excision circle (TREC) assay) that is now being successfully used in an increasing number of US states to screen for SCID in routine newborn Guthrie samples. Concerted lobbying efforts have highlighted the need for newborn screening (NBS) for SCID, and its implementation is being discussed in Europe both at EU and individual country level, but as yet there is no global mandate to screen for this rare and frequently lethal condition. This paper summarizes the current evidence for, and the success of SCID NBS, together with a review of the practical aspects of SCID testing and the arguments in favour of adding SCID to the conditions screened for at birth.

Attitudes of parents of children with serious health conditions regarding residual bloodspot use.

BACKGROUND/OBJECTIVES: Studies have shown that the general public is supportive of newborn screening (NBS) and supportive of the storage and use of residual bloodspots for quality assurance and biomedical research. However, the attitudes of parents of children with serious health conditions have not been assessed. In this study, we assessed attitudes of parents with children who have phenylketonuria (PKU) and leukemia towards NBS and storage and use of residual bloodspots for research. METHODS: A total of 49 individuals were recruited and responded to a validated 41-item survey regarding NBS and the retention and use of residual bloodspots. Of these participants, 22 had a child with PKU and 27 had a child with leukemia. We compared their responses to those of 1,927 individuals from the general public obtained in a previous study using the same survey instrument. RESULTS/CONCLUSIONS: We found that parents of children with a serious health condition had higher levels of support than the general public towards the use of residual NBS samples for research but similar attitudes regarding choice and privacy protections. It is important to assess the attitudes of various stakeholders for policy development.

ICON: the early diagnosis of congenital immunodeficiencies.

Primary immunodeficiencies are intrinsic defects in the immune system that result in a predisposition to infection and are frequently accompanied by a propensity to autoimmunity and/or immunedysregulation. Primary immunodeficiencies can be divided into innate immunodeficiencies, phagocytic deficiencies, complement deficiencies, disorders of T cells and B cells (combined immunodeficiencies), antibody deficiencies and immunodeficiencies associated with syndromes. Diseases of immune dysregulation and autoinflammatory disorder are many times also included although the immunodeficiency in these disorders are often secondary to the autoimmunity or immune dysregulation and/or secondary immunosuppression used to control these disorders. Congenital primary immunodeficiencies typically manifest early in life although delayed onset are increasingly recognized. The early diagnosis of congenital immunodeficiencies is essential for optimal management and improved outcomes. In this International Consensus (ICON) document, we provide the salient features of the most common congenital immunodeficiencies.

[Should the whole population be screened for coeliac disease?]. / Faut-il faire un dépistage systématique de la maladie cœliaque dans la population générale ?

To address the issue of mass screening in coeliac disease strict criteria shall be defined. Principles and practice of screening for disease have been defined 40 years ago by Wilson and Jungner, there are still accurate and applied, specially in France for neonatal screening. Screening the whole population for gluten intolerance is not recommended at this time. Aress with gap in scientific knowledge are identified and further prospective epidemiologic studies are needed. These include the timing of screening, defining the natural history of screening-identified asymptomatic patients, developing tools to predict disease onset and disease remission and the potential risks of screening. At the present time, only identification and testing of high-risks groups is recommended.

Management of term newborns following maternal intrapartum fever.

OBJECTIVE: To evaluate the diagnostic and therapeutic approach to full term neonates born to mothers with intrapartum fever. METHODS: In a retrospective study, neonates born to mothers with intrapartum fever, (≥ 37.8°C), were compared to control group matched by gestational age and birthweight. RESULTS: Overall, 159 singleton full term neonates born to women with intrapartum fever (study group) were compared to 159 control infants. No differences in neonatal outcomes were found between the two groups except for a higher rate of meconium-stained amniotic fluid in the maternal-fever group. There were no cases of neonatal infection, severe neonatal morbidity, or neonatal mortality in either of the groups. Full sepsis workup and intravenous antibiotic treatment were provided to 17.6% of the neonates in the study group. Logistic regression analysis revealed that delivery by Cesarean section was the only factor independently associated with the decision to perform a full sepsis work up and antibiotic treatment in cases of maternal intrapartum fever (OR 32.0, 95% CI 9.4-112.1). CONCLUSIONS: In low-risk women with asymptomatic intrapartum fever, neonatal infection is uncommon, so that aggressive evaluation and management of these infants may not be necessary and should be balanced against the low risk of neonatal sepsis.

[Pedaudiological diagnostics in the first year of life . Clinical follow-up, risk factors, and middle ear function]. / Pädaudiologische Diagnostik im ersten Lebensjahr. Klinische Verläufe, Risikofaktoren und Mittelohrfunktion.

The universal neonatal hearing screening (UNHS) program demands detection of hearing loss within the first 3 months of life. Practicability and different screening methods should be evaluated. Thus, 617 patients (329 m., 288 w.) were analyzed; 246 children were referred in the UNHS, 389 with risk factors. In 459 children (74%), automated auditory brainstem response (ABR) screening in our department excluded hearing loss, thereof 129 (21%) underwent diagnostic auditory brainstem-evoked audiometry responses: 20 (16%) showed normal and 109 (84%) elevated ABR thresholds. A total of 91 children (83%) received hearing aids and 11 children (10%) treatment of middle ear effusion. Hearing loss was diagnosed in 18% of all children, 24% with UNHS referral and 34% with both referral and risk factors. Craniofacial anomalies, premature birth < 32 weeks of pregnancy, and syndromes were the most frequent risk factors. Reevaluation by ABR showed an improvement to normal hearing in 3 (of 14) children. The 226 Hz compared to 1,000 Hz-tympanometry showed different specificity (95.5 vs. 85.5%) and sensitivity (32.5 vs. 57.1%). Diagnosis within 3 months is possible, but very challenging in children with risk factors.

How to motivate newborn hearing screening in the absence of a national programme: a collaboration between parents and professionals.

The establishment of the Italian Pediatric Federation Newborn Hearing Screening Network and the Italian Society of Neonatology Infant Hearing Study Group is the result of an international collaboration between Parents and Medical Professionals in order to promote an effective model in developing Early Hearing Detection Intervention Programs that recognize the role of parents as partners in the process. Among other factors, one important component frequently underestimated in most early intervention programs, both in the USA and other countries, involves the role of parental involvement within the Early Hearing Detection Intervention (EHDI) process. When a parent receives the news of their child's hearing loss, reactions may include, but are not limited to denial, grief, guilt, shame, fear and impotency. A parent may begin to ask certain questions: How do we know if the professionals in our children's lives are capable, educated, trained, up to date in their chosen fields of expertise? Do they respect our children and us as parents? Do they understand the needs of children who are deaf or hard of hearing? A life-long health professional - parental collaboration begins at the moment of the diagnosis of that child. When analyzing the habilitation process of a deaf child, the relationship between health professionals and the crucial role of parents in raising that child is a 50-50 shared responsibility. An objective of EHDI programs must be to empower parents by providing support from the beginning of the process. Distributing informative literature regarding the newborn hearing screening process and providing parents with access to resources such as parental support groups upon diagnosis equips parents with the tools necessary to immediately begin advocating for their children. The Italian Federation Pediatric Audiology Network was created by combining the parental perspective and medical protocols in order to establish the roots for stronger EHDI programs.

Early detection of infant hearing loss in the private health care sector of South Africa.

OBJECTIVE: A national survey of early hearing detection services was undertaken to describe the demographics, protocols and performance of early hearing detection, referral, follow-up and data management practices in the private health care sector of South Africa. METHODS: All private hospitals with obstetric units (n=166) in South Africa were surveyed telephonically. This data was incorporated with data collected from self-administered questionnaires subsequently distributed nationally to audiology private practices providing hearing screening at the respective hospitals reporting hearing screening services (n=87). Data was analyzed descriptively to yield national percentages and frequency distributions and possible statistical associations between variables were explored. RESULTS: Newborn hearing screening was available in 53% of private health care obstetric units in South Africa of which only 14% provided universal screening. Most (81%) of the healthy baby screening programs used only otoacoustic emission screening. Auditory brainstem response screening was employed by 24% of neonatal intensive care unit screening programs with only 16% repeating auditory brainstem response screening during the follow-up screen. Consequently 84% of neonatal intensive care unit hearing screening programs will not identify auditory neuropathy. A referral rate of less than 5% for diagnostic assessments was reported by 80% of universal programs. Follow-up return rates were reported to exceed 70% by only 28% of programs. Using multiple methods of reminding parents did not significantly increase reported follow-up return rates. Data management was mainly paper based with only 10% of programs using an electronic database primarily to manage screening data. CONCLUSIONS: A shortage of programs and suboptimal and variable protocols for early hearing detection, follow-up and data management in existing programs mean the majority of babies with hearing loss in the South African private health care sector will not be identified early. Newborn hearing screening must be integrated with hospital-based birthing services, ideally with centralized data management and quality control.

Overview of newborn hearing screening activities in Latin America.

OBJECTIVE: Ascertain the status of early hearing detection and intervention services in Latin America. METHODS: Between June and November 2007, Gallaudet University, in collaboration with the U.S. Centers for Disease Control and Prevention Early Hearing Detection and Intervention Diversity Committee, disseminated a survey to 11 Latin American countries. It included questions about newborn hearing screening (NHS) procedures, the availability of intervention services for infants with hearing loss, and challenges in identifying infants with hearing loss. In addition, a literature review was conducted to help identify the status of NHS efforts in Latin America. RESULTS: Six countries (Chile, Costa Rica, Guatemala, Mexico, Panama, and Uruguay) and one U.S. territory (Puerto Rico) responded to the survey. Responses indicated that efforts to identify infants with hearing loss vary within and across countries in Latin America. In some countries, activities have been implemented at a national level; in others, activities have been implemented at a single hospital or region within a country. Common barriers to implementation of NHS programs include a lack of funding, screening and diagnostic equipment, public awareness, and personnel qualified to work with infants and young children. CONCLUSIONS: In spite of several barriers, NHS programs have been implemented in at least some facilities and regions in Latin America. Additional efforts are needed to expand NHS activities in Latin America.

Newborn screening for Tyr-I: two years' experience of the New York State program.

In 2 years, the New York newborn screening program has analyzed approximately 500,000 samples for succinylacetone (SUAC), the biomarker for Tyrosinemia, type I. There have been five screen-positive results. Two of these results were considered borderline, and a repeat specimen was requested. In three cases, an immediate referral was made to a specialty care center. Two of those three cases were confirmed for Tyr-I.

Delayed cystic fibrosis presentation in children in the absence of newborn screening.

Newborn cystic fibrosis (CF) screening facilitates early diagnosis and nutritional intervention, which prevents malnourishment and improves growth in childhood. To provide baseline information on the natural history of CF in the Republic of Ireland, where newborn screening has not yet been introduced and CF incidence is high (1:1353 live births), we examined the effect of presentation mode, symptom type and gender on age at diagnosis. Median age at diagnosis was calculated by gender and for presentation mode/symptom type for 601 CF registry children diagnosed 1986-2007. Modes of presentation were each significantly associated with delayed presentation. An adjusted odds ratio of 4.5 (95% CI: 1.8, 11.1) was determined for presentation with family history, 43.1 for gastrointestinal symptoms presentation (95% CI: 18.3, 101.4), 96.9 for both respiratory and gastrointestinal symptoms (95% CI: 38.6, 243,4), and 115.4 for respiratory symptoms (95% CI: 45.2, 294.7). Children with respiratory symptoms had the greatest likelihood of delayed diagnosis (median age: 20.4 months), followed by those with respiratory and gastrointestinal symptoms (9.2 months). Gender was not significantly associated with a delayed presentation when presentation mode was taken into account.