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Incidence, aetiology and neurodisability associated with severe microcephaly: a national surveillance study
  1. Rachel L Knowles1,2,
  2. Ameenat Lola Solebo1,3,
  3. Mariana Autran Sampaio1,
  4. Charlotte Rebecca Brown1,
  5. Jenefer Sargent4,
  6. Ngozi Oluonye3,4,
  7. Jugnoo Rahi1,5
  1. 1Population Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, UK
  2. 2Public Health Commissioning and Operations, NHS England, London, UK
  3. 3Moorfields Eye Hospital NHS Foundation Trust, London, UK
  4. 4Neurodisability, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  5. 5Ophthalmology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  1. Correspondence to Dr Rachel L Knowles, UCL Great Ormond Street Institute of Child Health Population Policy and Practice, London, WC1N 1EH, UK; rachel.knowles{at}ucl.ac.uk

Abstract

Objective To determine the incidence, causes and neurodevelopmental impact of severe microcephaly (head circumference <–3SD) up to age 2 years.

Design Binational active paediatric surveillance study undertaken in 2017–2018 to identify and characterise new diagnoses of severe microcephaly.

Setting UK and Ireland.

Participants Infants aged under 12 months at diagnosis.

Interventions Observational study.

Main outcome measures Incidence, aetiology and neurodevelopmental outcomes at age 2 years.

Results Fifty-nine infants met the case definition, of whom 30 (51%) were girls; 24 (41%) were born preterm (<37 weeks’ gestation); and 34 (58%) were of ‘white’ ethnicity. Eight (14%) children died before 12 months of age. Incidence of severe microcephaly was 5.5 per 100 000 infants (95% CI 4.0 to 7.3). Higher relative risk (RR) was associated with preterm birth (RR 7.7, 95% CI 3.8 to 15.1) and British Asian ethnicity (RR 3.6, 95% CI 1.6 to 7.8). Microcephaly was mainly due to genetic causes (59%), brain ischaemia/hypoxia (10%) and congenital infection (8%), and 19% remained undetermined. Each child was referred on average to eight specialists, and 75% had abnormal brain imaging. By 2 years of age, 55 children experienced neurodevelopmental abnormalities, including feeding problems (68%), motor delay (66%), visual impairment (37%), hearing loss (24%) and epilepsy (41%).

Conclusions Although severe microcephaly is uncommon, it is associated with high mortality, complex multimorbidity and neurodisability, thus representing a significant ongoing burden for families and healthcare services. Potentially preventable causes include preterm birth, hypoxic/ischaemic brain injury and congenital infections. Clinical guidelines are essential to standardise aetiological investigation and optimise multidisciplinary management.

  • Paediatrics
  • Epidemiology
  • Neurology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. The data used in this study were collected from medical records and included indirect identifiers. Collection and analysis of this data without consent were supported under section 251 of the Health and Care Act. As the data come from a small population affected by a rare disease and cannot be fully deidentified, we are not able to share an individual-level patient dataset. However, extensive aggregated data tables are provided in this paper and in the online tables.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. The data used in this study were collected from medical records and included indirect identifiers. Collection and analysis of this data without consent were supported under section 251 of the Health and Care Act. As the data come from a small population affected by a rare disease and cannot be fully deidentified, we are not able to share an individual-level patient dataset. However, extensive aggregated data tables are provided in this paper and in the online tables.

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Footnotes

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  • Contributors RLK, JR, ALS, JS and NO conceived the study, developed the study protocol and methodology, and obtained funding. RLK, MAS and CRB collected and prepared the data and undertook preliminary analyses. All authors contributed to the data analysis and interpretation. RLK and ALS drafted the manuscript. RLK had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. RLK is guarantor.

  • Funding The surveillance study was funded by a grant from Great Ormond Street Hospital Charity (V4517). ALS is supported by an NIHR Clinician Scientist award (CS-2018-18-ST2-005). JR is supported in part by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, and an NIHR Senior Investigator award. This work was undertaken at UCL Great Ormond Street Institute of Child Health/Great Ormond Street Hospital for Children, which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, or the funders and sponsor of this study.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.