Archives of Disease in Childhood最新文献

Objective: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an inherited adrenal steroid synthesis disorder included in Dutch newborn screening (NBS) since 2002. Screening involves measuring 17-hydroxyprogesterone (17-OHP) in dried blood spots (DBS) with gestational age-adjusted cut-offs. Since October 2021, a second-tier 21-deoxycortisol (21-DF) test has replaced the 17-OHP measurement in a second heel prick after inconclusive results. This study evaluates the performance of the second-tier test from 1 October 2021 to 30 September 2023.

Design: 17-OHP was measured by immunoassay in regional NBS laboratories. DBS with inconclusive and positive 17-OHP results was sent to Amsterdam UMC for 21-DF measurement by liquid chromatography tandem mass spectrometry. Genetic analysis of CYP21A2, CYP11B1, POR and HSD3B2 was performed on DBS from newborns with false-positive second-tier results.

Results: Over 2 years, 21-DF was measured in DBS of 147 newborns (=0.04%). Twenty newborns were directly referred to a paediatric endocrinologist based on positive 17-OHP results: 15 had a positive 21-DF and were diagnosed with classical CAH (genetically confirmed), while five were first-tier false-positives. Of 127 newborns with inconclusive 17-OHP results, three had a positive 21-DF and were referred but not diagnosed with CAH: second-tier false-positives. In total, 8/23 referred newborns were false-positives. Genetic analysis of six false-positive second-tier DBS showed pathogenic CYP21A2 variants in five.

Conclusions: The modified protocol improved CAH screening by preventing 127 heel pricks in 2 years and reducing unnecessary referrals (currently 2.4%, previously 7.7%). 5/6 false-positive second-tier tests were most likely due to non-classical CAH. Further optimisation of cut-offs may prevent these false-positives.

Objective: To assess the associations of antenatal steroids with child growth.

Design: Longitudinal observational cohort study started in 1994.

Setting: A single tertiary neonatal centre in Sheffield, UK.

Participants: Of 254 individuals recruited, two were excluded, 48 born at term; 202 (57% boys, 87% white ethnicity) modelled had a median of 19 height measurements each (Q1:12 to Q3:21) up to median age 15.8 years (Q1:9.9 to Q3:16.9).

Interventions: Data on administration of antenatal steroids were collected alongside gestational age and parental height.

Main outcome measures: Height was modelled with SuperImposition by Translation and Rotation (SITAR) to extract each person's peak velocity and age at peak velocity via the SITAR random effects of 'size', 'timing' and 'intensity' and to predict height at 18 years. The association of each random effect and final height with exposure to antenatal steroids was assessed by multiple regression to adjust for covariates.

Results: In girls with covariates available (n=59/87), exposure to antenatal steroids was positively associated with SITAR 'size' and 'intensity' of growth when adjusted for gestational age, maternal and paternal height, equating to a final height 2.8 cm (95% CI 0.3 to 5.3 cm) greater than for those not exposed to antenatal steroids. In boys (n=66/115), exposure to antenatal steroids had no association with final height.

Conclusions: This observational cohort study showed greater height of girls exposed to antenatal steroids not seen in boys. Analysis of existing long-term follow-up data from neonates is indicated to increase understanding of the associations of neonatal interventions on growth.

Objective: To establish a birth rate for catecholaminergic polymorphic ventricular tachycardia (CPVT) diagnosed in childhood and observe trends in presentation and management.

Design: Retrospective cohort study.

Setting: The Inherited Arrhythmia Clinic at The Sydney Children's Hospitals Network, a paediatric tertiary referral network, New South Wales (NSW), Australia (2002-2021), where there are 86 000-97 000 live births/year.

Patients: Children diagnosed with CPVT aged 0-16 years.

Interventions: Clinical data were extracted and evaluated for trends. Using birth year data, the birth rate of CPVT detected in childhood was calculated.

Main outcome measures: Birth rate of CPVT detected in childhood in NSW (with post hoc comparison to New Zealand), trends in diagnosis and management, and outcome at last follow-up.

Results: 32 children in NSW were diagnosed with CPVT between 2002 and 2021 (0-16 years, median 9 years, 14 (54%) female). Of these, 28 (88%) presented with symptoms (cardiac arrest 20/32, 62.5%) and four (12%) were identified through family screening. Relevant genetic variants were identified in 25/31 (78%). During follow-up (median 4.5 years), symptomatic cardiac events (death n=1) occurred in 10 (33%), largely related to suboptimal adherence or monotherapy beta blocker. In NSW, CPVT was diagnosed during childhood following 1 in 65 000 live births (95% CI 1 in 91 000 to 1 in 46 000). In New Zealand, the corresponding figure was 1 in 84 000 live births (95% CI 1 in 138 000 to 1 in 52 000).

Conclusions: The rate of infants born who are later diagnosed with CPVT in childhood is approximately 1 in 65 000 live births. Suboptimal adherence and beta blocker therapy without flecainide appeared related to recurrent cardiac events.

Background and objective: Cardiorespiratory polygraphy (CRP) is the predominant technology used to diagnose obstructive sleep apnoea (OSA) in tertiary centres in the UK. Nocturnal pulse oximetry (NPO) is cheaper and more accessible. This study evaluates NPO indices' ability to predict OSA in children with Down syndrome (DS).

Methods: Indices from simultaneous NPO and CRP recordings were compared in children with DS (aged 2-16 years) referred to evaluate OSA in two tertiary centres across an 8-year period. Receiver operating characteristic curves assessed the diagnostic accuracy of NPO indices, including ODI3 (3% Oxygen Desaturation Index) and ODI4 (4% Oxygen Desaturation Index). Two-by-two tables determined the sensitivities and specificities of cut-off values for predicting OSA.

Results: 387 children with DS were included with stand-alone NPO; 177 female (46.7%), median age 6.1 years (range 2.02-15.97). There were 265 children (68.5%) with Obstructive Apnoea-Hypopnoea Index (OAHI) ≥1/hour, 164 with OAHI ≥1<5/hour (42.4%), 51 with OAHI ≥5<10/hour (13.2%) and 50 with OAHI ≥10/hour (12.9%). ODI3 and ODI4 demonstrated the best predictive value for predicting OSA. An ODI3 ≥19/hour and an ODI4 ≥8/hour were associated with the highest combined sensitivity (59.2%/63.8%) and specificity (74.6%/71.3%), respectively.

Conclusion: Raised ODI3 and ODI4 predict moderate and severe OSA in children with DS with moderate specificity/sensitivity and have a low sensitivity for detecting mild OSA. The poor predictive performance of oximetry reflects the multifactorial nature of sleep disordered breathing in children with DS. We recommend oximetry is not used for diagnosis of OSA in DS and CRP/polysomnography should be used.