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The commonest autosomal deletion, 22q11.2 deletion syndrome (22q11DS) is a multisystem disorder varying greatly in severity and age of identification between affected individuals. Holistic care is best served by a multidisciplinary team, with an anticipatory approach. Priorities tend to change with age, from feeding difficulties, infections and surgery of congenital abnormalities particularly of the heart and velopharynx in infancy and early childhood to longer-term communication, learning, behavioural and mental health difficulties best served by evaluation at intervals to consider and initiate management. Regular monitoring of growth, endocrine status, haematological and immune function to enable early intervention helps in maintaining health. Conclusion: Guidelines to best practice management of 22q11DS based on a literature review and consensus have been developed by a national group of professionals with consideration of the limitations of available medical and educational resources.

BackgroundPostnatal corticosteroids are used to improve lung function and reduce the incidence of bronchopulmonary dysplasia (BPD) in preterm babies. However, corticosteroids may be associated with adverse neurodevelopment. Despite a lack of evidence, some clinicians in the UK use very low-dose regimens of dexamethasone hoping for positive pulmonary effects and optimal neurodevelopment.ObjectivesTo assess the efficacy and safety of very low-dose dexamethasone at facilitating the extubation of ventilator-dependent preterm babies born at DesignA multicentre, randomised, masked, parallel-group, placebo-controlled Phase 2b trial. The trial was designed as a feasibility study for a subsequent trial of clinical effectiveness.SettingThe study was set in 11 tertiary neonatal units in the UK.ParticipantsVentilator-dependent preterm babies born at InterventionsBabies were randomised to very low-dose dexamethasone (50 µg/kg/day for 13 doses) or a matched placebo. Samples of blood and bronchoalveolar lavage fluid from a subset of babies randomised at three participating sites were sent for cytokine analysis at randomisation and at days 5, 7, 10 and 14 of treatment.Primary outcomeTime to extubation.Secondary outcomesSecondary outcomes included rates of extubation by day 7 of the intervention; survival to 36 weeks’ postmenstrual age (PMA) or discharge home; respiratory morbidity to 36 weeks’ PMA or discharge home; cytokine profile; safety outcomes; and parent/family experience.ResultsThe main metric of feasibility, namely recruitment, proved difficult. There was a tendency for open-label medication and a higher than predicted rate of suspected/confirmed sepsis among babies. Recruitment was halted after 22 babies had been enrolled. It was found that, compared with the placebo group, a higher proportion of babies were extubated at day 7 of life [5/8 (62.5%) in the very low-dose dexamethasone group vs. 2/6 (33.3%) in the placebo group] and duration of invasive ventilation was lower (a median of 23 days for the very low-dose dexamethasone group vs. a median of 31 days for the placebo group) in the very low-dose dexamethasone group. This is supported by a trend for an increased requirement for open-label rescue steroids in control group babies (41.7% in the very low-dose dexamethasone group vs. 80% in the placebo group). Given the limited sample size, only descriptive statistics can be given; firm conclusions cannot be drawn.LimitationsSmall sample size and high rates of open-label treatment use.ConclusionsIt is not feasible to conduct the required pragmatic trial of clinical effectiveness.Future workAssessment of very low-dose dexamethasone in this patient group requires careful consideration.Study registrationClinical Controlled Trials ISRCTN81191607.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The report will be published in full inEfficacy and Mechanism; Vol. 6, No. 8. See the NIHR Journals Library website for further project information. The funding for the cytokine analysis is provided by the Children’s Charity Cerebra and is being carried out beyond the lifespan of the NIHR funding.