British Paediatric Surveillance Unit | Annual report 2016-2017 by Royal College of Paediatrics and Child Health

BPSU British Paediatric Surveillance Unit

Annual Report 2016-2017

Royal College of Paediatrics and Child Health 5-11 Theobalds Road, London, WC1X 8SH The Royal College of Paediatrics and Child Health (RCPCH) is a registered charity in England and Wales (1057744) and in Scotland (SC038299).

Aims of the British Paediatric Surveillance Unit To: â&#x20AC;˘ Facilitate research into uncommon childhood infections and disorders for the advancement of knowledge and to effect practical improvement in prevention, treatment and service planning â&#x20AC;˘ Allow paediatricians to participate in the surveillance of uncommon disorders and to lessen the burden on reporting doctors of such requests arising from numerous different sources â&#x20AC;˘ Increase awareness within the medical profession of the less common disorders studied and respond rapidly to public health emergencies.

http://www.rcpch.ac.uk/bpsu

Contents Foreword

By Dr Richard Reading Chair, BPSU

1. How the Surveillance System Works

- Background

- Selection of studies for inclusion in the scheme

3. Surveillance Studies Undertaken in 2016

- Attention Deficit Hyperactivity Disorder 6 in transition from children’s services to adult services - Behçet’s syndrome

- Congenital rubella 10 - Congenital Zika syndrome

- Female genital mutilation

- The reporting system

- HIV infection & perinatal HIV exposure

- Follow-up and confirmation of case reports

- Nutritional rickets

- Pierre Robin sequence

2. Scientific Coordinator’s Yearly Review of Activities

- Participation in the scheme during the 4 year 2016 - Public and patient engagement

- International activities

- Funding

- Regional response study outcomes

BPSU Annual Report 2016-2017

- Progressive intellectual & 25 neurological deterioration in children (Including Creutzfeldt - Jakob disease) - Visual impairment and blindness

Appendix 29 - Publications 2016-17

- Presentations 2016-17

Foreword

I am delighted to introduce this year’s annual report from the BPSU. We have had a busy year - this included the publication of a 30 year round-up report (http://www.rcpch.ac.uk/bpsu/30yearreport) which I hope you have read, if not it is well worth downloading! The 30 year report details the enormous impact the BPSU has had over this time, and how the monthly reports provide rich detailed and accurate data on childhood rare disease. This year some of our activities have included a second rare disease conference in Birmingham which was filled, almost literally, to the rafters of the lecture theatre. We continue to host the Rare Disease Day tea party and Richard Lynn, our scientific coordinator, is increasingly involved with the rare disease movement. It is heartening to note the frequent mentions of the importance of the BPSU in reports and documents from the government, partlicularly in relation to the implementation of a rare disease plans.

Dr Richard Reading Chair, BPSU

Some specific impacts of this year’s work include contributions to the National Screening Committee’s deliberations on Group B strep screening, and the rapid implementation of surveillance for congenital Zika syndrome. The BPSU was the first surveillance unit in the developed world to set up surveillance and we collaborated with other International Network of Paediatric Surveillance Units (INoPSU) centres in Australia, New Zealand, and Canada to commence congenital Zika syndrome surveillance in those respective countries. We are intending to develop on this work with a wider study on microcephaly which will set the Zika surveys into a context of other causes of microcephaly. Behind the scenes we continue to work towards streamlining the ethics and governance process for studies. This is a hugely complex task as all four devolved nations and Ireland now have separate systems which require different approval processes. Our thanks as ever to Richard who has made an impossible task into a negotiable process. If you are an investigator and your eyes roll upwards at this, please remember that it would be a whole lot worse without the help of the BPSU office, and we are still working on making this ever easier. One way of doing this is to work towards collecting and storing data electronically in a secure “safe haven”. We hope to make significant progress on this in the next year. We look forward, with your help, to another successful year. The BPSU is nothing without the regular monthly reports made by all paediatricians and we reflect on that all the time. Thank you for your continued support.

Richard Reading. Chair BPSU, November 2017

BPSU Annual Report 2016-2017

How the Surveillance System Works

Background Rare diseases and infections are a numerically important cause of morbidity and mortality in childhood. Individually uncommon, together they number thousands, and many result in severe sequelae. Many are characterised by chronicity, high rates of disability or death. These conditions pose a large financial and emotional burden for affected children, their families and health systems.

Figure 1: Orange Card

To address this problem in the UK and Ireland, the BPSU was set up in July 1986, enabling paediatricians to participate in the surveillance and further study of rare disorders affecting children. Several agencies founded and continue collaborating to support the work of the BPSU: the Royal College of Paediatrics and Child Health (RCPCH), Public Health England, University College London - Institute of Child Health, GOSH Children’s Charity and the Faculty of Paediatrics of the Royal College of Physicians of Ireland. The BPSU’s Scientific Committee meets six times a years to consider individual applications and the progress of studies.

Selection of studies for inclusion in the scheme Details on the selection process and application process for the BPSU is now available online at http://www.rcpch.ac.uk/bpsu/apply. Each application requires approval from the BPSU Scientific committee, a Research Ethics Committee (REC), the Confidentiality Advisory Group (CAG) of the Health Research Authority and the Scottish Public Benefits and Privacy Panel (PBPP).

The reporting system Surveillance is ‘active’ in that the BPSU office actively sends out an electronic orange card (eCards) to consultant paediatricians in the UK and Ireland asking for cases to be reported on the BPSU orange ‘eCard’ (Figure 1). Each month, all clinicians participating in the surveillance scheme are sent an electronic orange card (eCard) listing the conditions currently under surveillance; follow-up reminders are sent to those who have not returned their eCard. A set of instructions for completing the card, including the case definition of the conditions under surveillance can be accessed via the eCard. When a new study begins, the mailing also includes a specially produced protocol card and other information about the study.

Follow-up reports

and

confirmation

case

On receiving a case report the BPSU informs the relevant study team who send a short questionnaire to the reporting clinician to gather further information. As the questionnaire cannot be fully anonymised, the amount of patient identifiable data collected is strictly limited to preserve patient confidentiality. The study investigators report back to the BPSU indicating when cases have been confirmed or are duplicate case reports (see Figure 2). Duplication of reporting is most likely to occur when the condition requires referral to another clinician, but this is encouraged, as it is better to receive duplicate reports than to miss a case. To improve case ascertainment for specific studies where a child may see specialist clinicians, consultants working in a number of other specialties have been invited to participate in the scheme. Apart from helping to improve ascertainment such complementary data sources help to validate the surveillance system.

Figure 2: Surveillance mechanism

Participants are expected to return eCards even if they have no cases to report - there is a ‘nothing to report’ box for them to tick. This is an important feature of the surveillance scheme as it allows us to measure compliance, which is continually monitored, to the reporting system.

BPSU Annual Report 2016-2017

2 Scientific Coodinator’s Yearly Review of Activities Four new studies have commenced in 2016-17: congenital Zika syndrome, Professor Richard Pebody, Public Health England, childhood disintegrative disorder, Dr Michael Absoud, St Thomas’s Hospital, death due to epilepsy, Dr Omar Abdel- Richard Lynn, Mannan, UCL GOS Institute Scientific Coordinator of Child Health, bronchopulmonary dysplasia, Dr Sundeep Harigopal, Dr Janet Berrington, Dr Sridhar Ramaiah, Royal Victoria Infirmary, Newcastle. Five studies had their period of surveillance extended: HIV, congenital rubella, progressive intellectual and neurological deterioration, female genital mutilation and Behçet’s syndrome. During 2016-17, there were 16 publications relating to BPSU studies and 22 conference presentations (see Appendices, p.31).

Participation in the scheme during the year 2016 Reporting rates for returning the orange ‘eCards’ remain high - the overall card return compliance rate for the year 2016, calculated as a proportion of orange cards returned, was 94.2% (39,545/41,987) a fall of 0.1% from 2016. Monthly response rates ranged from 95.2% in January to 93.2% in November with a media of 94.4%. Details of regional response rates are provided in Table 1 (p.5). The BPSU has continued to develop its e-reporting system and has been working with several of the research teams on collecting data online. Feedback from reporting clinicians using these systems continues to be positive. Table 2 summarises the outcome of the followup of cases and provides evidence for their level of accuracy of reporting by clinician. By the end of a study 80-95% of the questionnaires will have been returned. The time taken to follow-up varies between conditions and may be longer if microbiological/pathological details are required, or if a specialist committee has to convene to adjudicate on the case data.

Workload of those reporting in the scheme: 798 of 3,577 (22%) receiving a card reported a case in 2016. 14% (514) reported a single case, 6% (218 reported between two and four cases and 2% (66) reported five or more cases. The greatest number of cases reported was by HIV specialists, one of whom reported 68 cases.

Public and patient engagement The BPSU is committed to wider public patient engagement (PPE) in the development and dissemination of our work and that of the studies. To support clinicians when preparing their protocols several resource packs have been introduced. These are available at http://www.rcpch.ac.uk/ bpsu/ppe. In February 2017, the BPSU in collaboration with Rare Disease UK hosted its fourth annual rare disease day tea party (http://www.rcpch.ac.uk/ bpsu/rarediseaseday17). At the event the BPSU with Rare Disease UK and Birmingham Children’s Hospital launched its RareTogether initiative. The aim is to act as a conduit for children and young people affected by rare disease to communicate. Our first activity is to work with Rare Revolution Magazine (http://www.rarerevolutionmagazine. com) producing a children and young people’s edition of the online rare disease magazine.

International activities The BPSU continues to take an important role in the activities of the International Network of Paediatric Surveillance Units (INoPSU). We maintain the website (http://www.inopsu.com) where you will find information on affiliated national paediatric surveillance units, studies currently being undertaken, published papers, study protocols and questionnaires. The BPSU is pleased to announce that it has won the bid to host the INoPSU conference. This will be held in parallel with the RCPCH scientific meeting in Glasgow on 12-13th March 2018. More information at http://www.inopsu.com/conference2018.

Funding BPSU is currently funded through grants from UCL GOS Institute of Child Health, RCPCH, and Public Health England with additional support from Great Ormond Street Children’s Charity and with contributions from researchers.

2017 in pictures - higlights from the BPSU

BPSU Annual Report 2016-2017

Figure 3: Regional Response rate 2016

Table 1: Regional Response rate 2015 and 2016 Region

% return

Rank 2016

Rank 2015

East Anglia

96.4%

Mersey

93.6%

NET

92.0%

North Scotland

95.7%

North Western

95.2%

Northern

93.5%

Northern Ireland

92.9%

NWT

92.6%

Oxford

94.0%

Republic of Ireland

92.6%

SET

92.9%

South Scotland

95.9%

South Western

95.0%

SWT

96.0%

Trent

93.5%

Wales

94.2%

Wessex

95.1%

West Midlands

94.9%

West Scotland

95.6%

Yorkshire

95.8%

Table 2: Outcome of follow-up of the cases reported in 2016 for conditions under surveillance at July 2017 Condition under surveillance

Date when reporting began

Valid reports

Duplicates

Errors

(D&E) %

Not yet known

Total

HIV

Jun-86

8,982

880

763

1,377

12,002

CRU

Jun-91

201

PIND

May-97

2,253

532

1,094

258

4,137

RKT

Mar-15

124

274

BEH

May-15

118

ARF

May-15

VIB

Oct-15

173

337

FGM

Nov-15

ADHD

Nov-15

219

356

PRS

Jan-16

112

181

EPI

Nov-16

CDD

Nov-16

100

12,112

1,517

2,232

1,927

17,788

ARF VIB FGM ADHD PRS EPI CDD

Acute rheumatic fever Visual impairment and blindness Female genital mutilation Attention deficit and hyperactivity disorder Pierre Robin Sequence Deaths in children with epilepsy (excl. Scotland) Childhood disintegrative disorder

Total

HIV CRU PIND EBT RKT BEH

HIV infection and perinatal HIV exposure Congenital rubella Progressive intellectual and neurological deterioration Neonatal exchange blood transfusion Nutritional rickets Behçet’s syndrome

BPSU Annual Report 2016-2017

Surveillance Studies Undertaken in 2016

Once again individual reports have concentrated on the summary of the condition and on the analysis. General methodology information is contained in the study protocols and can be found at http://www.rcpch.ac.uk/bpsu/currentstudies. Please take into consideration that the analysis presented here is provisional and has yet to be peer reviewed. The investigators would like to acknowledge all those who are involved in their projects but are not mentioned. The BPSU would like to thank all those who have returned cards, reported cases and completed the questionnaires.

Attention Deficit Hyperactivity Disorder (ADHD) in transition from children’s services to adult services Key points • 13 month surveillance period completed for CAPSS and BPSU – 355 eligible cases reported (BPSU: 220). • 28% of paediatricians had a handover period. • 29% of cases reported by paediatricians had an accepted referral to adult services.

Professor Tamsin Ford

Summary This project focuses on what happens to young people with Attention Deficit Hyperactivity Disorder (ADHD) when they are too old to stay with children’s services. Little is known about how many areas have specialist services for adults with ADHD and how many young people need to move to them when they are too old for children’s services. Until the late twentieth century ADHD was a controversial diagnosis. Once generally accepted, it is seen as a developmental disorder of children, and so mental health services for adults are not set up to manage young adults who have ADHD and continue to want support to cope with their lives. There are National Institute for Health and Care Excellence (NICE) guidelines about the management for ADHD in adulthood, and this often involves taking medication that General Practitioners feel inexperienced to prescribe without support from specialists, as happens with children. Existing work suggests that young people with developmental disorders like ADHD are particularly likely not to transfer to adult mental health services but there has yet to be an in depth study of this issue in the UK. This is the first national study to examine how many young people are in need of services for ADHD as adults. A 13 months surveillance study tried to find out what happens to young people with ADHD on medication who are within six months of the age-boundary for discharge from their children’s service.

Surveillance period November 2015 - November 2016 (inclusive). Follow-up period: Follow-up questionnaire at nine months after initial diagnosis, ending in August 2017.

Methodology Data capture used a dual surveillance methodology using the Child and Adolescent Psychiatry Surveillance System (CAPSS) in addition to the BPSU, to identify cases of ADHD; details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/adhd

Analysis As of June 2017 there have been 350 BPSU notifications, 259 returned questionnaires, 218 of which are eligible. CAPSS have reported 349 notifications of which 161 have been returned, 132 of which are eligible. There have been 90 cases (42 BPSU and 48 CAPSS) that have been reported in error and are not eligible and therefore the questionnaire will not be returned. Currently the response rates are 86% for BPSU and 60% for CAPSS which is very encouraging.

Discussion This is a novel approach to the surveillance study as ran by BPSU and CAPSS; this study explores the incidence of a transition of a young person with ADHD between children’s services and adult services. It is too early to report on the study results and reflect on the method used to answer this research question. This study will provide insight in the methodology of the surveillance system as an instrument to study a rare event. In addition, this surveillance study will provide us with national level data of how many young people want to graduate to adult mental health services, which is essential for service commissioners and service providers in

BPSU Annual Report 2016-2017

service planning and provision. Such information is currently not available given the primitive state of administrative databases and the incomplete nature of the available data, particularly on mental health diagnoses.

Public and patient engagement UK ADHD Network (UKAAN) and Adult Attention Deficit Disorder UK (AADD-UK) Web: https://www.ukaan.org; https://aadduk.org

Funding This study is funded by National Institute for Health Research (NIHR) Health Services and Delivery Research Programme funding (14/21/52). See: h t t p s : / / w w w. j o u r n a l s l i b r a r y. n i h r. a c . u k / programmes/hta/142152#/

BPSU Annual Report 2016-2017

Researcher contacts Professor Tamsin Ford, Professor of Child and Adolescent Psychiatry, University of Exeter Medical School, South Cloisters, St Lukeâ&#x20AC;&#x2122;s Campus, Exeter EX1 2LU Tel: 0139 272 2973 Email: t.j.ford@exeter.ac.uk Co-investigators Imperial College London: Dr Cornelius Ani, Dr Susan Young Kingâ&#x20AC;&#x2122;s College London: Professor Philip Asherson University of Exeter: Dr Astrid Janssens, Dr Tamsin Newlove-Delgado, Dr Catherine Shotton, Professor Stuart Logan, Helen Eke University of Nottingham: Professor Kapil Sayal, Professor Chris Hollis University of Warwick: Dr Moli Paul University of York: Professor Bryony Beresford Cerebra, Charity organisation: Tracy Elliot

Behçet’s syndrome Key points • UK children with confirmed Behçet’s have a wide array of clinical manifestations. • A range of clinical teams see UK children with confirmed Behçet’s. • Most UK children with confirmed Behçet’s are either controlled on medication or are stable off medication.

Summary Behçet’s syndrome is a rare condition which can cause inflammation in many parts of the body. In particular, it can cause repeated attacks of mouth and/or genital ulcers (sores), which can sometimes occur with skin rashes, tiredness, joint pains, tummy pains, headaches or eye problems. Behçet’s syndrome can affect children although we currently do not know how many children are affected in the UK or why it develops. Because of the perceived rareness of the condition the investigators plan to investigate both incidence and prevalence. The study aims to understand how many children in the UK are affected by Behçet’s syndrome; understand how Behçet’s syndrome affects children; understand who is involved in the medical care and treatment of children with this condition; see if there is a delay in children receiving care from doctors with expertise in this condition. We hope that the results of this study will have benefits for future children with the condition by providing us with more information on how many

Dr Clare Pain

children are affected and how Behçet’s syndrome makes them ill. In particular, we currently do not know how many children have eye inflammation or whether we should routinely screen children for eye inflammation even if they have no symptoms. Understanding how many children have eye disease or other organ involvement will help us standardise care and design healthcare services that meet the needs of children with Behçet’s syndrome. Knowing how Behçet’s syndrome affects UK children will also help us explain the condition and what to expect to children and families.

Surveillance period May 2015 May 2017 (inclusive). Follow-up period: Follow-up questionnaire at 12 months after initial diagnosis, ending in June 2018.

Methodology Data capture uses standard BPSU methodology. Details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/bht

Table 3: Clinical teams involved in care, outcomes at baseline and current medication in 49 confirmed cases

Clinical teams involved

Medication

Outcomes

Paediatric Rheumatologist

44 / 89.8%

Ophthalmologist

38 / 77.6%

General Paediatrician

30 / 61.2%

Oral Medicine/Paediatric Dentist

24 / 49.0%

Adult Rheumatologist

22 / 44.9%

Paediatric Dermatologist

15 / 30.6%

Specialist Nurse

15 / 30.6%

Clinical Psychologist

9 / 18.4%

Gynaecologist

3 / 6.1%

Paediatric Immunologist

3 / 6.1%

Support Worker

3 / 6.1%

Systemic treatment

35 / 71.4%

Topical treatments only

7 / 14.3%

No treatment

6 / 12.2%

Not known

1 / 2.0%

Controlled on medication

29 / 59.2%

Active disease despite medication

11 / 22.4%

Stable off medication

5 / 10.2%

Not known

4 / 8.2% BPSU Annual Report 2016-2017

Analysis To the end of April 2017 (24 months), 138 cases were notified and 83 completed questionnaires analysed (49 cases excluded: 35 errors; 14 duplications; 22 questionnaires yet to be completed). 49 of the analysed cases are confirmed Behçet’s syndrome, defined as an International Criteria for Behçet’s Disease (ICBD) score of four or more.3 Cases which scored less than four on the ICBD scale (16 to date) are being reviewed by at least four of the study investigators and categorised as either definite Behçet’s; probable/incomplete Behçet’s; or not Behçet’s. Cases which are reviewed as being probable/incomplete and definite Behçet’s will be included in the final research findings. Twenty-seven (55%) of the cases were female and 22 (45%) male. Mean age at presentation was 9.1 years and diagnosis 10.1 years. With regards ethnicity, 40 (81.6%) cases were white, four (8%) were from Pakistani origin, higher than the population, with one (2%) from Indian, Black, mixed and other.

in a non-first degree relative in five (10.2%). This study highlights the extreme rareness of Behçet’s syndrome in UK children. The commonest sub-type was the mucocutaneous variant. There may be important differences in patterns of disease between UK and non-UK cohorts, for example a low frequency of eye involvement. The high number of specialists involved in the case of the children shows that they have complex care needs.

Public and patient engagement Behcet’s Syndrome Society Web: http://www.behcets.org.uk/

Funding This study is funded by Alder Hey Children’s Charity, Behcet’s Syndrome Society Charity (from funds raised by the Worshipful Company of Horner’s), Professor Farida Fortune, Professor Robert Moots and Vasculitis UK.

References 1. Dejaco, C. et al, Meeting report of 13th international conference on Behçet’s Disease. The Journal of Rheumatology, 2009. 36 (6) 1312-1317; DOI: https://doi.org/10.3899/jrheum081008

Children presented with a wide array of clinical manifestations – 49 (100%) with oral ulceration, 45 (91.8%) with genital ulceration 22 (44.9%) with skin involvement, 11 (22.4%) eye involvement whilst neurological and vascular involvement was less common affecting six (12.2%) and three (6.1%) respectively. The most common other manifestations were arthralgia and arthritis, both five (10%) and abdominal pain four (8%).

2. Zouboulis, CC. et al, Epidemiological Features of Adamantiades-Behçet’s Disease in Germany and in Europe. Yonsei Medical Journal, 1997. 38(6):411-422

Thirty-nine (79.6%) of the 49 children were seen by three or more different specialities depending on disease manifestations. Only six (12.2%) were not on regular treatment, seven (14.3%) were managed on topical treatment only, 35 (71.4%) required systemic immunosuppression and 11 (22.4%) had active disease despite medication (Table 3).

Researcher contacts

Discussion The 49 children confirmed as having Behçet’s have a wide array of clinical manifestations. Recurrent oral ulceration is the most common, then genital ulceration and skin involvement. Eye, neurological and vascular involvement are all less common. On average there is one year between first presentation and date of diagnosis. There is a family history of Behçet’s syndrome in a first degree relative in 13 (26.5%) and

BPSU Annual Report 2016-2017

3. International Team for the Revision of the International Criteria for Behçet’s Disease (ITRICBD), The International Criteria for Behçet’s Disease (ICBD). J Eur Acad Dermatol Venereol. 2014. 28: 338-347 Dr Clare Pain, Consultant Paediatric Rheumatologist, Alder Hey Children’s NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP Tel: 0151 282 4521 E-mail: clare.pain@alderhey.nhs.uk Co-investigators University Hospital Aintree: Professor Robert Moots Great Ormond Street Hospital: Dr Paul Brogan Queen Mary’s School of Medicine and Dentistry: Professor Farida Fortune Queen’s Medical Centre, Nottingham: Dr Ruth Murphy University of Liverpool: Professor Michael W. Beresford

Congenital rubella Key points • Since 2005, 12 congenital rubella births have been reported in the UK; none were reported between April 2015 and March 2017. • Congenital rubella syndrome can occur when a women contracts rubella during the first trimester of pregnancy. It can cause deafness, blindness and heart defects in the fetus, amongst other symptoms. • Antenatal screening for rubella susceptibility was discontinued in England in April 2016.

Summary Surveillance of congenital rubella (CR) has been in place since 1971, when the National Congenital Rubella Surveillance Programme (NCRSP) was set up to monitor the impact of rubella vaccine; there has been active surveillance throughout the UK and Ireland through the BPSU since 1990. The last confirmed CR births reported were in 2014 (n=2) and 2015 (n=1). Following policy reviews in 2003 and 2012,1 antenatal screening for rubella susceptibility was discontinued in England in April 2016 (and subsequently also in Scotland and Wales) but continues in Northern Ireland and in the Republic of Ireland. The PHE’s National Screening Programme supports on-going national surveillance of CR through the BPSU, in order to help maintain professional awareness of this rare but potentially devastating infection, and to provide a mechanism for the timely reporting of the circumstances of any cases which do occur. Congenitally infected infants can shed rubella virus for an extended period of time, and every infected infant must be diagnosed and managed appropriately to avoid the risk of contributing to further community transmission. A review by the World Health Organization (WHO) in 2008 estimated that more than 110,000 infants were born with congenital rubella syndrome (CRS) each year in developing countries, and rates are highest in the WHO African and South-East Asian regions where vaccine coverage is lowest. In April 2015 the WHO Region of the Americas became the first in the world to be declared free of endemic transmission of rubella, and the WHO aims to eliminate measles, rubella and congenital rubella (elimination defined as <1 case of CRS per 100,000 births) from five of the seven WHO regions by 2020. Although in the UK reported cases of CRS have been below this level for many years, rubella outbreaks and associated CR births have been reported in several European countries in the last decade, including Romania, Poland and Italy, and continued vigilance is necessary.

Dr Helen Bedford

Surveillance period January 1990 and is reviewed yearly.

Methodology Data capture uses standard BPSU methodology; details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/cr

Analysis Between April 2016 and March 2017 there were six reports to the BPSU. Two of these were duplicates of previously reported cases, and four were reports made in error, relating to three infants who had other conditions. The surveillance case definition was revised in 2005 to include newly diagnosed children who were born abroad, in order not to miss any cases, and to contribute to European surveillance data; no reports received in this period related to children born abroad. Congenital rubella births in the UK or Ireland 19902017: 67 children and four stillborn infants with confirmed or compatible CR have been born and reported since active surveillance was established in 1990; 54 of these (76%) were first reported through the BPSU (Table 4). Table 4: Confirmed and compatible congenital rubella births in the UK and Ireland 1990 to March 2017 Primary Source of notification Year of birth

BPSU

Other

1990-94 * ^

Total 32

1995-99

2000-04 *

2005-09 *

2010-17

Total

* includes a stillborn infant ^ includes a set of triplets, one of whom was stillborn

Since 2005 there have been 12 confirmed reports, including one stillborn infant. None of the mothers were UK-born, and none had a previous pregnancy in the UK. Three women arrived in the UK in childhood, and at least one reported having had MMR vaccination as a teenager. Half of the women acquired their infection abroad in early pregnancy, but six came into contact with rubella in the UK.

BPSU Annual Report 2016-2017

Discussion

Public and patient engagement

Very few cases of CR have been reported in the last decade and most reports concern infants with neonatal symptoms who also have serious rubella-associated defects identified at birth or soon afterwards. About half of the recent maternal infections were acquired in the UK. Pregnant women may enter the UK having acquired infection in early pregnancy elsewhere, and susceptible women resident in the UK who travel abroad during early pregnancy may also come into contact with rubella. Health professionals, particularly paediatricians and those working in primary care and antenatal care, or with refugees or other recent migrants, must continue to be aware of the potential serious implications of rash illness in early pregnancy, the guidelines for the management of rash illness in pregnancy,2 and also of the early signs of congenital rubella.

Sense. Web: http://www.sense.org.uk

Funding This study is funded UCL GOS Institute of Child Health and the NHS Infectious Diseases in Pregnancy Screening (IDPS) programme (PHE).

BPSU Annual Report 2016-2017

References 1. Tookey PA. Review of antenatal rubella susceptibility screening and the standard criteria for screening. National Screening Committee 2012; available at http://legacy.screening.nhs. uk/rubellasusceptibility 2. HPA Rash Guidance Working Group. Guidance on viral rash in pregnancy. Available at https://www.gov.uk/government/publications/ viral-rash-in-pregnancy

Researcher contacts Dr Helen Bedford, National Congenital Surveillance, Population, Policy & Programme, UCL Great Ormond Street of Child Health, 30 Guilford Street WC1N 1EH Tel: 0207 905 2333 E-mail: h.bedford@ucl.ac.uk

Rubella Practice Institute London

Congenital Zika syndrome Key points • BPSU surveillance of congenital Zika syndrome (CZS) commenced April 2016. • Over 12 months five suspected cases have been reported.

Summary Since May 2015 when Zika virus infections were first confirmed in Brazil, the virus has spread to many countries in South and Central America and the Caribbean. The majority of countries in the Southern hemisphere are now known to be affected. It has been shown that babies of mothers who were infected with Zika virus during pregnancy are at risk of being born with abnormalities, such as a small head (microcephaly) and other abnormalities of the brain and central nervous system.1 Every year a large number of UK residents travel to countries where Zika virus is present. Pregnant travellers are at risk of acquiring the infection which may then affect their unborn baby (see Figure 4 and Figure 5).

Dr Richard Pebody

only limited evidence available, often making it necessary to base guidance and recommendations on single case reports. This lack of knowledge also set challenges for developing an appropriate case definition for surveillance. Since then, the WHO has declared an end to the Public Health Emergency of International Concern and, due to decreasing numbers of new cases, many affected countries have been reported as having a lower risk of Zika transmission than previously. In one year of BPSU surveillance, during the period of apparent higher transmission in affected countries, only very few potential cases have been reported, showing that there is very low risk of travel associated congenital Zika syndrome (CZS) in the UK.

This study aims to identify all babies with microcephaly or other brain abnormalities, born in the UK, to mothers who have travelled to countries affected by Zika virus during their pregnancy or in Methodology the three months before conception. Data capture uses standard BPSU methodology; In the start of the epidemic, very little was known details of the study protocol are available at about the disease and, of particular concern, the http://www.rcpch.ac.uk/bpsu/zika level of risk infection posed to pregnant women travelling to affected areas and their babies. In light Surveillance period of this uncertainty and the rapid spread of the virus, April 2016 – April 2018 (inclusive). surveillance of numbers of babies affected by Zika Follow-up period: Follow-up questionnaire at 24 virus infection needed to be established urgently, months after initial diagnosis, ending in April 2020. to estimate the risk to the UK population and, if required, to help planning for services to care for Analysis these children. Five suspected cases in total have been reported As one of the BPSU’s main purposes is to facilitate during the surveillance period. Of those, one case rapid response to public health emergencies was excluded, one discarded, and three potential and international surveillance of rare diseases, cases remain under follow up. processes were in place to enable timely establishment of surveillance of congenital Zika Discussion syndrome in returning travellers in the UK. The number of suspect cases reported was at the At the time of development of this study, the Zika lower end of the number of cases we predicted for epidemic was a rapidly evolving situation with this time period.

Source: CDC image library; CDC – Nat. Cntr. For Infectious Diseases; Div. of Vector-Borne Infectious Dieases; Dengue Fever

Figure 4: Aedes aeqypti, Yellow Fever mosquito

The total number of visits by UK residents to South and Central America and the Caribbean was 1.66 million in 2015; 28% of these visits were made by women of child bearing age. Travel advice, in particular to pregnant women or those planning pregnancy, has been issued in January 2016; however, there has not been a noticeable decrease in travel activity to affected countries in 2016. The UK Obstetric Surveillance System (UKOSS) has been monitoring numbers of women who travelled to affected countries during pregnancy since 1st March 2016 and recorded 825 individuals

BPSU Annual Report 2016-2017

Figure 5: Zika virus

References

Source: CDC image library; CDC - National Center for Emerging and Zoonotic Infectious Diseases (NCEZID); Division of Vector-Borne Diseases (DVBD); Zika virus

1. Krauer F, et al. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and GuillainBarre Syndrome: Systematic Review. PLoS Med 2017; 14(1): e1002203

by 28th February 2017, with no decline in average numbers travelling each month. This would indicate that, even though small, there is ongoing potential risk of identifying cases of CZS in the UK despite Public Health Englandâ&#x20AC;&#x2122;s recommendation for pregnant women to avoid travel to Zika affected countries. The risk for Zika virus infection has changed since last year. The WHO declared the end of the Public Health Emergency of International Concern on 18th November 2016, overall numbers of new cases in affected countries has been declining and no further countries have reported a case of CZS since beginning of 2017. However, a large proportion of the Southern hemisphere is now known to be affected by Zika virus transmission, including countries in South East Asia and Africa and the US. To date, 31 countries have reported approximately 3,000 cases of CZS. This includes travel associated cases in the US, Canada (2 cases) and Europe (1 case in Slovenia and 2 cases reported from Spain). There is also still uncertainty about the level of risk of having an affected baby if a woman was exposed to Zika during pregnancy. Evidence so far has been conflicting and there is no consensus on the rate of unfavourable outcomes after exposure.2,3 Moreover, it is unclear how long previous infection will provide immunity which makes predictions of patterns of resurgence of the virus unreliable.4 Therefore, in view of these significant gaps in knowledge of the natural history of the condition and the on-going transmission of Zika virus, the study was extended until April 2018.

BPSU Annual Report 2016-2017

2. Brasil, P et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med 2016; 375: 2321-34 3. Honein, MA et al. Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection during Pregnancy. JAMA 2017; 317 (1): 59-68 4. Aubry, M et al. Zika Virus Seroprevalence, French Polynesia, 2014-2015. Emerg Infect Dis 2017 23 (4): 669-672

Funding This study is funded by Public Health England.

Public and patient engagement Microcephaly Support Group. Web: http://www.microcephaly.co.uk

Researcher contacts Dr Richard Pebody, Public Health England, 61 Colindale Avenue, London NW9 5EQ Tel: 020 8327 7423 E-mail: richard.pebody@phe.gov.uk Dr Clarissa Oeser, Public Health England, 61 Colindale Avenue, London NW9 5EQ Tel: 020 8327 6729 E-mail: clarissa.oeser@phe.gov.uk Co-investigators Public Health England: Professor Dilys Morgan. Dr Hilary Kirkbride, Dr Nick Andrews, Dr Andre Charlett Head Leeds General Infirmary: Dr Kathryn Johnson St Georgeâ&#x20AC;&#x2122;s, University of London: Professor Paul Heath, Dr Shamez Ladhani, University of Bristol: Professor Alan Emond

Female genital mutilation Key points • The interim data shows that numbers reported to the BPSU are far smaller than expected from the published figures of estimated risk. • Geographical distribution is unexpected as some large inner cities where there are high numbers from practising communities are not represented. • None of the reported cases were illegally.

done

Summary Female genital mutilation (FGM) is the name given to procedures that involve cutting, removing flesh or other injury to the genitals of women or girls for a nonmedical reason. There are many different types of FGM also known as female circumcision, cutting or ‘Sunna’. FGM can involve a cut or prick, removing flesh in varying amounts (e.g. partial clitoroidectomy, removal of the labia minora), or sealed to leave a small opening. FGM is illegal in the UK and since 2003 it has been illegal to take a child out of the country for the purpose of FGM. In 2015, it became mandatory to report cases to the police. There are few dedicated women’s clinics for FGM. Of the 14 clinics listed on the Department of Health website, nine are in London. There is only one clinic in the UK for children, which is in London. No one really knows how common FGM is in the UK, but at the moment it is thought to be rare for doctors or any other professional working with children to see FGM but it could also be because professionals are not asking about FGM nor do they recognise the signs. Information on why children with FGM are seeing doctors, how FGM is presenting, associated medical problems and what care is needed for

Dr Deborah Hodes

these children is required. This information will be used to plan health services, to educate professionals and to produce guidelines.

Surveillance period November 2015 - November 2017 (inclusive). Follow-up period: Follow-up questionnaire at 12 months after initial diagnosis, ending in November 2018.

Methodology Data capture uses standard BPSU methodology; details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/FGM As a second source of ascertainment, the Sexual Assault Referral Clinic Service (SARCS) were also asked to report through a monthly direct email system. It should be noted that reporting to the BPSU does not replace statutory reporting to the appropriate bodies which became mandatory from 31st October 2015.

Analysis Data based on analysis as of April 2017 Of the 55 cases reported to the BPSU in the first year, 29 (53%) had confirmed FGM of which we are awaiting outstanding information, 20 were reported in error, or were duplicates, six questionnaires are incomplete.

Figure 6: Classification of FGM by type (as of 27 September 2017)

BPSU Annual Report 2016-2017

The results presented are interim findings on the 29. Of the completed questionnaire items, at the time of diagnosis all children were older than four years (n=26), most children were diagnosed at 4–6 years (n=7) or 13–16 years (n=7), followed by 7–9 years (n=6) and 10–12 years (n=6).

References

Almost all children were born outside of the UK, in African countries (n=25). For confidentiality purposes we cannot disclose the place of birth for those children born outside of African countries (n=2), the place of birth was unknown for two cases. Social care referred most children (66%, n=19), and health professionals the remainder (34%, n=10).

Public and patient engagement

A history of FGM was reported in 26 (83%) cases, and suspected FGM in 3 (10%) cases. No children presented with a history of labioplasty or genital piercing. The circumstances of FGM were known in 19 cases of which seven (32%) were performed by a healthcare professional either in a family members house/village (n=5) or clinic (n=2).

Discussion The first year of reporting has shown that cases are being found and investigated. The reporting of clinical presentation and examination findings can be used to educate healthcare professionals and plan health services. The study extension to 2017 will help to identify the true incidence, presentation and management of cases.

1. Hodes D, Pall K, O’Donnell NA, et al. G78(P) Female genital mutilation (FGM) surveillance in under 16 years olds in the UK and Ireland Archives of Disease in Childhood 2017;102:A32 FORWARD (Foundation for Women’s Health Research and Development). Web: http://forwarduk.org.uk

Researcher contacts Dr Deborah Hodes, University College Hospital, 250 Euston Road, London NW1 2BU E-mail: deborah.hodes@nhs.net Dr Najette Ayadi O’Donnell, University College Hospital, 250 Euston Road, London NW1 2BU E-mail: n.ayadio’donnell@nhs.net Co-investigators Birmingham Children’s Hospital: Dr Geoff Debelle UCL GOS Institute of Child Health: Professor Russell Viner University College London Hospitals: Dr Alison Armitage, Professor Sarah Creighton RCPCH: Karina Pall, Marina Leoni BPSU: Richard Lynn

Funding This study was supported by a grant from the Department of Health.

BPSU Annual Report 2016-2017

HIV infection & perinatal HIV exposure Key points • The number of children born each year in the UK and Ireland to women with diagnosed HIV infection has stabilised in recent years and is currently between 1,100 and 1,200; the mother to child transmission rate among diagnosed women is now below 0.3%. • New diagnoses of children born in the UK and Ireland have fallen from 40-50 per year in the early 2000s to under 10 per year since 2012. • The NSHPC continues to audit circumstances of all perinatal infections reported in the UK (from 2006); 130 children were reported by the end of 2016, with around two-thirds born to women undiagnosed at the time of delivery.

Summary National surveillance of paediatric HIV infection and perinatal HIV exposure is based on comprehensive, anonymised, paediatric and obstetric reporting. Data from all sources are combined as the National Study of HIV in Pregnancy and Childhood (NSHPC) at the UCL Great Ormond Street Institute of Child Health.1 The NSHPC monitors changing patterns of HIV infection and diagnosis in pregnant women and children and tracks changes in obstetric and therapeutic management and mother-to-child transmission (MTCT) rates. Amongst over 2,600 children diagnosed with HIV infection in the UK and Ireland, the majority acquired infection through MTCT, and around two-thirds were born abroad, mostly in sub-Saharan Africa. The number of births in the UK and Ireland to diagnosed women increased markedly from about 100 in 1997 to over 1,400 annually between 2007 and 2010. There has been some decline since then, with around 1,100 births reported each year since 2013. Antenatal HIV screening, introduced as a universal offer from 2000, is taken up by over 95% of pregnant women in the UK, so very few HIV-positive women now remain undiagnosed at the time of delivery (https://www. gov.uk/government/organisations/publichealth-england). By 2009 40% of pregnancies were a second or subsequent pregnancy since the woman’s HIV diagnosis.2 MTCT rates among

C. Goldsmith

Figure 7: Scanning EM of HIV, grown in cultured lymphocytes. Virons are seen as small spheres on the surface of the cell

NSHPC team (names L-R): Helen Peters, Rebecca Sconza, Anna Horn, Kate Francis

diagnosed women have continured to decline from 2.1% in 2000-2001 to under 0.5% in 2010-20113 and below 0.3% in 2012-14;4 this compares with an estimated 20-30% from undiagnosed women.3 Fewer than 10 infants now acquire infection each year in the UK and Ireland, and most of these have mothers who were not aware of their HIV status at the time of delivery. The circumstances of recent UK-born cases were explored in the NSHPC audit of perinatal HIV infection.

Methodology The BPSU uses its standard methodology and data capture to facilitate the NSHPC paediatric surveillance. Further details of the BPSU study protocol can be found at http://www.rcpch.ac.uk/ bpsu/hiv and more information on the NSHPC at http://www.ucl.ac.uk/nshpc.

Surveillance period National surveillance of paediatric AIDS began in 1986. Surveillance was extended to include HIV infection and perinatal HIV exposure in 1989. Follow-up period: Infection status of perinatallyexposed infants is usually reported during the child’s first year of life. Long-term follow-up information on children with confirmed HIV infection is collected through the Collaborative HIV Paediatric Study (CHIPS), a collaboration between the NSHPC, the MRC Clinical Trials Unit, and clinicians (https:// www.chipscohort.ac.uk).

Analysis Cumulatively there have been 11,593 BPSU reports by the end of 2016. Of these 8,905 were confirmed cases of HIV infection or exposed infants at risk of vertical transmission; 1,095 reports have not yet had status confirmed. The remaining 1,593 reports were duplicates or errors. A further 13,205 confirmed cases and exposed infants have been reported through other sources (see study protocol). The remainder of this report includes verified data from all reporting sources. By the end of December 2016, 22,166 HIVinfected or exposed children had been reported to the NSHPC, 20,163 (91%) of these since 2000 (see Table 4). In England, the proportion of reports made from the London regions has decreased from over 70% prior to 2000 to around half since then. Children born to HIV-positive women: Most

BPSU Annual Report 2016-2017

Table 5: HIV infection and infants born to HIV-positive women (all reporting sources) Region and time period of report (notified by 31 December 2016)

Region of first report

1986-1999

2000-2016

Total

England total London North Midlands & East South

1,571 1,118 (71%) 181 (11%) 128 (8%) 144 (9%)

17,353 8,446 (59%) 2,796 (16%) 3,878 (22%) 2,233 (13%)

18,924 9,564 2,977 4,006 2,377

276

302

133

138

Scotland

231

627

858

Ireland

170

1,774

1,944

2,003

20,163

22,166

Wales Northern Ireland

Total

paediatric reports (21,714/22,166, 98%) were of children born to HIV-positive women (Table 5). Of these children, 2,194 (10%) were known to be infected, and 17,085 (79%) uninfected by the end of 2016; infection status for the remaining 2,435 (11%) had not yet been reported, but the majority were recent reports and very few are likely to be infected children. Since 2013 the annual number of births to diagnosed women in the UK and Ireland stabilised at 1,100 to 1,200. The NSHPC reported an overall transmission rate of just under 0.3% for births to diagnosed women 2012-2014 (7/2,580, 0.27%, 95% CI: 0.11-0.56 %),3 continuing the decline from 0.46% in 2010-2011 and 2.1% in 2000-2001. The primary reasons are the increased proportion of women on combined antiretroviral therapy (cART) at conception or starting this in early pregnancy and decreased frequency of late initiation or nonreceipt of antenatal cART. A substantial proportion of pregnancies reported are second or subsequent pregnancies since maternal HIV diagnosis.2 In 2012-2014 85% of children were born to mothers who were aware of their HIV status at conception, over 60% of women conceived on cART, and overall almost 90% of women delivered with undetectable viral load.4 At the same time there have been changes in the population of pregnant women with HIV in the UK. These include an increasing number of women aged over 40 years5 and vertically-infected pregnant women. Infected children: Since surveillance started in

1986, 2,639 children with HIV infection have been reported; this includes 267 probably infected in the course of treatment for haemophilia, all born before 1985 and reported before 1995, leaving 2,372 mostly perinatally infected children. The population of diagnosed children has changed over time with a rise in the proportion of children born abroad (increasing from around a third of those diagnosed prior to 2000 to about two-thirds in those diagnosed subsequently). Among these children, an increasing proportion are diagnosed abroad with treatment experience on arrival.6 Overall 55% of children reported with HIV infection were born abroad, the majority in sub-Saharan Africa (89%). Among 2,228 mostly perinatally infected children, 266 (12%) are known to have died, 120 (5%) to have gone abroad and 488 (22%) to have transferred to adult services; a further 275 (12%) are lost to follow up. To date there have been over 100 pregnancies in perinatally infected women who were reported to the NSHPC as children. New diagnoses for UK and Irish born children fell from 40-50 per year (2000-2006), to 20-30 (20072011), then further to below 10 (2012 onwards). There has been a decline in the age at diagnosis over time. Among children born in the UK and Ireland between 2000 and 2005, the median age at diagnosis was 9 months (IQR: 2mth-2yr) compared with 3 months (IQR: 0.5yr-1yr) for those born 2010 onwards. Children born abroad were diagnosed at a later age but their median age has declined from 6 years (IQR: 3yr-9yr) for those born

Table 6: Year of birth and infection status of children born in the UK or Ireland to women diagnosed by the time of delivery. (notified by 31 December 2016)

Year of Birth

Infected

Indeterminate

Not infected

Total

1984-1999

111

141

898

1,150

2000-2005

308

4,629

4,999

2006-2008

172

3,888

4,087

2009-2011

273

3,813

4,102

2012-2014

535

2,878

3,421

2015-2016*

926

671

1,601

228

2,355

16,777

19,360

Total

*reports for recent years are subject to reporting delay BPSU Annual Report 2016-2017

2000-2005 to 3 years (IQR: 2yr-3yr) for those born since 2010. NSHPC Perinatal Audit of HIV Infection: Perinatal Audit, funded by the UK National Screening Committee, explored circumstances surrounding perinatal transmissions born and reported since 2006 with the aim of improving antenatal HIV screening protocols. There were 108 children born since 2006 confirmed infected by the April 2014; of these 41 (38%) were born to diagnosed and 67 (62%) to undiagnosed women.7 The number of reports of perinatally infected children born to undiagnosed women during this period is likely to increase as later diagnoses are made. An expert review panel, composed of clinicians from relevant specialties and patient advocacy, has discussed potential recommendations, and the formal Public Health England report will be published in 2017. The Audit process is now embedded within the general NSHPC methodology for any newly reported infected children. Since April 2014 a further 22 perinatally infected UK-born children (born since 2006) have been reported to the NSHPC, and for these cases enhanced data collection is taking place.

Discussion The epidemiology of HIV in pregnancy in the UK has changed considerably since surveillance started. Today, only 15% of reported pregnancies are in women diagnosed during pregnancy, with a high proportion on cART at conception. In the context of the policy of treating all people living with HIV early, this proportion is likely to increase in the future. The number of births to HIV-positive women in the UK and Ireland has declined from a peak of 1,400 per year around 10 years ago, and has been relatively consistent at around 1,100-1,200 a year since 2013; this decline partly reflects a stabilization in the number of sequential pregnancies to women having subsequent pregnancies after their initial HIV diagnosis. The increasing numbers of women aged over 40 years and of vertically-infected pregnant women are of note, given that these groups may be at increased risk of adverse outcomes and/or require more intensive management during pregnancy in order to optimise maternal and child health. The downward trajectory of the MTCT rate in the UK has continued in recent years, with this being under 0.3% since 2012-2014. Even lower risk of vertical transmission is seen among women who have an undetectable viral load at the end of pregnancy, most of whom are now suppressed throughout pregnancy. These trends mean that there are now large and increasing numbers of uninfected infants born each year who have been exposed to antiretroviral drugs for their entire gestation. Such â&#x20AC;&#x153;HIV-exposed uninfectedâ&#x20AC;? or HEU children are currently the focus of considerable interest from the research and policy communities with respect to potential impact of exposure to both maternal HIV and antiretroviral drugs in fetal and early life.

Despite high uptake of antenatal testing and interventions to prevent MTCT, some infants are still acquiring HIV infection perinatally or through breastfeeding. The NSHPC audit of perinatal HIV infections in children born from 2006, confirmed that at least 60% of these (67/108) were born to the minority of women with HIV infection who remain undiagnosed at delivery. The audit has provided supplementary information to understand better the circumstances around transmissions that occur despite such low background MTCT rates. The main reasons identified for transmission amongst undiagnosed women were declining antenatal HIV testing and seroconversion. Amongst diagnosed women, the main reasons identified were difficulties with adherence and late antenatal booking. Furthermore, the majority of these mothers were found to have at least one additional complicating social issue such as immigration status or housing problems. Almost two-thirds of infected children reported since 2000 in the UK or Ireland were born abroad, mostly in sub-Saharan Africa, with the proportion increasing over time. Median age at diagnosis continues to decline as children are picked up earlier through maternal screening and an increasing proportion are being diagnosed and on treatment prior to arrival in the UK which reflects improvements in HIV diagnosis and treatment coverage across sub-Saharan Africa; however median age of newly diagnosed children is likely to remain higher than for those born in the UK. It is essential to continue to monitor the health and well-being of perinatally infected young people into adult life. AALPHI (Adolescents and Adults Living with Perinatal HIV), a prospective cohort study, is built on the NSHPC and CHIPS surveillance studies. AALPHI started recruitment at the end of 2012, and by 2015 had enrolled over 300 young people living with HIV and about 100 controls. It aims to explore the impact of life-long HIV and long-term antiretroviral therapy on neurocognitive, cardiac and metabolic function, growth, and sexual and reproductive health (more details at www.ctu. mrc.uk ). The pregnancies now being reported in women themselves infected vertically highlight how the HIV epidemic in the UK is maturing and that ongoing surveillance, research and collaboration is vital to capture and respond to ever changing needs.

Acknowledgements During 2016-17 the NSHPC team at ICH included Helen Peters (Study Coordinator), Kate Francis, Rebecca Sconza (Research Assistants), Anna Horn and Icina Shakes (Study Administrators). We were also supported by Catherine Peckham and our steering group (http://www.ucl.ac.uk/ nshpc/steering-group). Past and current PhD students (Claire Townsend, Shema Tariq, Clare French and Laura Byrne) and Graziella Favarato (Statistician) have also made substantial contributions to recent analyses and publications.

BPSU Annual Report 2016-2017

Funding This study is funded mainly from Public Health England’s Centre for Infectious Disease Surveillance and Control, and NHS Infectious Diseases in Pregnancy Screening (IDPS) programme (part of PHE); additional support has come from the collaborating institutions.

Public and patient engagement Avert. Web: https://www.avert.org Body and Soul. Web: http://www.bodyandsoulcharity.org Children’s HIV Association (CHIVA). Web: https://www.chiva.org.uk/ Positively UK. Web: http://www.positivelyuk.org

References 1. Townsend CL, Cortina-Borja M, Peckham CS, Tookey PA. Trends in management and outcome of pregnancies in HIV-infected women in the United Kingdom and Ireland, 1990-2006. BJOG 2008; 115:1078-86 2. French CE, Cortina-Borja M, Thorne C, Tookey PA. Incidence, patterns, and predictors of repeat pregnancies among HIV-infected women in the United Kingdom and Ireland, 1990-2009. J AIDS 2012; 59:287-93 3. Townsend CL, Byrne L, Cortina-Borja M, Thorne C, de Ruiter A, Lyall H, et al. Earlier initiation of ART and further decline in mother-to-

BPSU Annual Report 2016-2017

child HIV transmission rates, 2000-2011. AIDS. 2014; 28(7):1049–1057 4. Peters H, Francis K, Sconza R, Horn A, Peckham C, Tookey PA, et al. UK mother-to-child transmission rates continue to decline: 2012-2014. Clin Infect Dis. 2016 5. Townsend CL, de Ruiter A, Peters H, NelsonPiercy C, Tookey P, Thorne C. Pregnancies in older women living with HIV in the UK and Ireland. HIV Med. 2016 Nov 16 6. Peters H, Francis K, Judd A, Collins IJ and Thorne C. Current trends in HIV-positive children living in the UK and Ireland. In Seattle, USA; 2017 7. Peters H, Thorne C, Tookey PA, Byrne L. National audit of perinatal HIV infections in the UK 2006-2013: what lessons can be learnt? Submitted to HIV Medicine 2017

Researcher contacts Dr Claire Thorne, Population, Policy and Practice Programme, UCL GOS Institute of Child Health, 30 Guilford St, London, WC1N 1EH Tel: 0207 905 2604 E-mail: claire.thorne@ucl.ac.uk Helen Peters, Population, Policy and Practice Unit, UCL GOS Institute of Child Health, 30 Guilford Street, London, WC1N 1EH Tel: 0207 905 2693 Email: helen.peters@ucl.ac.uk Co-investigators UCL GOS Institute of Child Health: Dr Pat Tookey; Professor Mario Cortina-Borja

Nutritional Rickets presenting to secondary care Key points â&#x20AC;˘ 319 cases were notified, and questionnaires met the case definition.

130

â&#x20AC;˘ Although a completely treatable condition, rickets continues to affect children in the UK. â&#x20AC;˘

Two deaths have occurred.

Summary Rickets is a disease of growing children. It results in the softening of their bones, so that they bend (bow-legs or knock-knees, widening of the wrists and ankles) and in very severe cases, can break. Rickets also causes pain in the bones so children may be reluctant to walk. In the long term, if not treated, it can cause poor growth so that children are smaller than usual when they grow up. It is a completely preventable disease, and is also easily treated. The commonest cause of rickets is a lack of vitamin D. The main source of vitamin D is the sun and whilst there is some vitamin D in certain foods, we cannot get enough vitamin D just from eating a balanced diet. Recently the number of cases of rickets appears to have been increasing. Possible reasons include; lack of good quality sunlight in the UK or, not exposing ourselves to sunlight. Children with darker skin e.g. African, Caribbean, Asian and Middle Eastern, those who are growing rapidly (premature babies, infants, adolescents) and overweight children are also more at risk. It is not known how great a problem we have with rickets in the UK. To inform policy and guidance on prevention and treatment, we aim to identify the number of children who are diagnosed with rickets in the United Kingdom and Republic of Ireland each year and, collect information about how it presents in children and how it is treated.

Dr Priscilla Julies

Surveillance period March 2015 - March 2017 (inclusive).

Methodology Data capture uses standard BPSU methodology; details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/rkt.

Analysis Over 25 months (from March 2014 to March 2017) a total of 319 cases have been notified to the BPSU and to date and 208 clinical questionnaires were completed. The analysis includes a total of 130 completed questionnaires. Demographics: Children presenting with rickets were mostly aged between 0 and 4 years 11 months (93%, n=121), fewer children were aged between 5 and 12 years 11 months (3.1%, n=4), with the least children aged between 13 and 16 years (1.5%, n=2). There were more males (70%, 91/130) than females (30%, 39/130) presenting with the condition. The two most common ethnic backgrounds were Black/African/Caribbean/Black British (44.6%, 58/130) and Asian/Asian British (40.8%, 53/130). Nutrition: Feeding practices were notified in 125 cases and showed that most children were on solids (68.5%, 89/130) and only one child was exclusively formula fed compared to 17.7%

Figure 8: Map of confirmed cases

BPSU Annual Report 2016-2017

Figure 9: Seasonal variation of presenting cases

(23/130) who were exclusively breastfed. Cow’s milk allergy/intolerence (7.7%, 10/130), iron deficiency (6.2%; 8/130) and eczema (6.2%, 8/130) were the commonest associated conditions.

x-rays and biochemistry to enable accurate case ascertainment.

Clinical presentation: Of the 130 included cases most children (86.9%, 113/130) presented with bony abnormalities, followed by radiological abnormalities (73.1%, 95/130) and neuromuscular abnormalities (47.7%, 62/130). Of the 130 cases , 24 children presented as a result of an incidental blood test or x-ray. Interestingly 15 children presented with associated fractures (11.5%, 15/130). At the time of diagnosis 77.7% of children (101/130) were not receiving vitamin D supplements.

This study was supported by the Vitamin D Mission Fund (now Nutricia) through an educational grant to the Royal National Orthopaedic Hospital.

Discussion The surveillance study provides us with detailed information on the current burden of nutritional rickets caused by vitamin D deficiency. The commonest risk factors captured by the clinical questionnaire include ethnicity, diet and allergies. It is also important to identify mothers with vitamin D deficiency, as supplementing their children may help in preventing rickets in their offspring. The case definition for this study included 25OH vitamin D <25nmol/L as a cut off and we found that, many hospitals had a range higher than this case definition. This may have impacted on the number of cases notified to the BPSU. The extended year has provided unique information about the clinical management of cases particularly around supplementation practices in the UK. In all, there was also good correlation, in performing

BPSU Annual Report 2016-2017

Funding

References 1. Holick MF. Resurrection of vitamin d deficiency and rickets. J Clin Invest. 2006; 116(8):2062-72 2. Allgrove J. Is Nutritional rickets returning? Arch Dis Child. 2004; 89(8):699-700

Researcher contacts Professor Mitch Blair, Northwick Park Hospital Watford Rd, Harrow HA1 3UJ Dr Priscilla Jules, Royal Free Hospital, Pond St, London NW3 2QG E-mail: p.julies@imperial.ac.uk Co-investigators Birmingham Children’s Hospital: Dr Nick Shaw Children’s University Hospital: Dr Ciara McDonnell Royal Manchester Children’s Hospital: Professor Zulf Mughal Great Ormond Street Hospital: Dr Alastair Calder University Hospital Glasgow: Dr Helen McDivitt RCPCH: Karina Pall, Marina Leoni BPSU: Richard Lynn

Pierre Robin sequence Key points • Surveillance has now ended, and a total of 197 cases were reported to the BPSU. An additional 48 cases were notified by regional cleft lip and palate services. Clinical data have been submitted for 133 confirmed Pierre Robin sequence (PRS) cases to date. • Preliminary data indicate that PRS carries a high treatment burden; 89% required a period of nasogastric tube feeding, and 70% of required the use of an airway adjunct which included tracheostomy insertion in 10% of cases. These interventions are often required for many weeks or months. • 12-month outcome data is currently being collected

Summary Pierre Robin sequence (PRS) is a condition present from birth with three main features: a small lower jaw (micrognathia), backward positioned tongue (glossoptosis), and defect of the roof of the mouth (cleft palate). Together, these abnormalities cause pharyngeal narrowing which can lead to breathing and feeding difficulties in the neonatal period and early childhood. Mild cases can be managed by nursing the infant in a position that best opens the airway, and by using specialised feeding bottles. More severely affected children may need additional support with a feeding tube, an artificial airway adjunct, or surgery. PRS diagnosis has far-reaching consequences for affected children, their families, and responsible healthcare teams. Infants often spend many weeks in hospital and need long-term support from a large multidisciplinary team. Failure to optimally manage breathing and feeding problems can cause respiratory failure and poor growth. Long-standing airway obstruction can result in impaired oxygen delivery, leading to right heart failure and neurodevelopmental problems. Figure 10: Sources of case reporting

Dr Marie Wright

This study aims to provide an updated estimate of PRS birth prevalence in the UK and Republic of Ireland (ROI), and to ascertain whether there are geographical variations in its incidence. We will also describe the current management practices in use in the UK and clinical outcomes at one-year follow-up.

Surveillance period January 2016 - January 2017 (inclusive). Follow-up period: Follow-up questionnaire at 12 months after initial diagnosis, ending in January 2018.

Methodology Data capture uses standard BPSU methodology. In addition an alternative reporting card was distributed to representatives from each regional cleft centre in the UK and ROI that elected to participate in the study. Details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/prs

Analysis Over the 13 month surveillance period a total of 245 case notifications, of which 197 cases were reported via the Orange ‘eCard’ and 48 were notified by regional cleft teams via an alternative reporting card. Eight cases were reported in error or did not meet the case definition, and 62 duplicate reports or questionnaires were received. At the time of writing clinical data has been submitted for 133 confirmed (de-duplicated) cases, and a further 42 questionnaires are awaited. Infants were a

BPSU Annual Report 2016-2017

Figure 11: Initial airway management in infants with PRS

median of 69 days old at the time of questionnaire completion. There was an equal gender distribution (males, n=66). The median gestational age at birth was 39 + 2 weeks, and median birth weight was 3200g (range 1030 â&#x20AC;&#x201C; 4670g). 14 infants (10.5%) were born preterm at < 37 completed weeks. There was only one case of multiple pregnancy. Main ethnic groups consisted of 85.7% white, Indian 3.8% and 3% Pakistan. Diagnosis and antenatal history: 75% of mothers had a detailed antenatal ultrasound scan during pregnancy, but there was an antenatal suspicion of PRS diagnosis in only 19% of cases (n=25). The most common abnormalities seen on ultrasound were micrognathia (n=8) and polyhydramnios (n=7). Cleft palate was suspected antenatally in 2 cases. 11% of infants (n=15) had a first-degree relative with an orofacial cleft, of which over half had a diagnosis of Stickler Syndrome (n=8). Presentation and initial management: 89% of infants (n=119) were diagnosed with PRS within 48 hours of birth, and the diagnosis was made beyond the first week of life in only four cases. Most infants were admitted to a neonatal (79%) or paediatric unit (15%) for observation and management, whilst 6% were discharged home directly from the maternity ward. 42% of infants had other nonPRS associated congenital anomalies, including 10% who were suspected or confirmed to have an underlying genetic syndrome. No congenital anomalies were reported for 77 (57.9%). Minor anomalies were reported in 21(15.8%) and major in 22 (16.5%). Genetic syndromes were confirmed or suspected in 13 (9.8%) and included Stickler syndrome (n=3), Noonan syndrome, SmithMagenis syndrome, Smith-Lemli-Opitz syndrome, Sotos syndrome, Poland syndrome, Congenital disorder of glycosylation (n=1) and chromosomal (n=4).

BPSU Annual Report 2016-2017

Airway management: Signs of upper airway obstruction (UAO) were present in 86% of infants, and 70% of infants required active management of UAO with an airway adjunct (Figure 11). Feeding management: 99% of infants required feeding support, either with specialised bottle feeding equipment (e.g. Haberman feeder, Dr Brown bottle) or nasogastric tube. Most infants were being fed with standard formula or breast milk, but high-energy formula was used in over a quarter of cases. Duration of hospital admission and subspecialty referrals: At the time of questionnaire completion, 65% of infants had been discharged home at median 22 days old. A quarter of infants were either still in their initial hospital or had been transferred to another unit. Five infants had died, which included two with an underlying genetic syndrome and one preterm infant, and post-mortem results are awaited. Prior to hospital discharge, most infants were referred to at least three specialist teams, most commonly the regional cleft team and a clinical geneticist.

Discussion Preliminary analysis based on the data collected to date indicates that PRS carries a substantial treatment burden within the UK and ROI. Over 90% of infants were admitted to a neonatal or paediatric unit for ongoing management, and a diverse multidisciplinary team were involved in their management. At a median of two months old, up to a quarter of infants were still admitted to hospital and over half were still dependent on NGT feeding. Although upper airway obstruction (UAO) was not a mandatory feature in our case definition, it was present in a high proportion of cases and 70% of infants required active airway support. Although the use of a nasopharyngeal airway (NPA) for UAO management appears to

be common practice in the UK, over a quarter of infants required multiple types of airway support during their initial hospital admission and 10% required tracheostomy insertion. Following completion of the study we will be looking for international collaborative studies with other surveillance units or the development of national guidelines relating to the diagnosis and management of infants with PRS.

Funding This study has been funded through the Sir Peter Tizard Bursary.

Public and patient engagement Cleft Lip and Palate Association. Web: https://www.clapa.com

Acknowledgements The study team are grateful to Joan Thomson, Research Support Worker at the Children’s Clinical Research Facility at the Royal Edinburgh Sick Children’s Hospital for her administrative support. We are also grateful to the Cleft and Craniofacial CSG of the NIHR CRN for their input into our study methodology, case definition, and questionnaire design, which included comments by both their clinical and consumer (i.e. lay) representatives. Finally, we thank the members of regional cleft teams who volunteered to complete the alternative reporting card and data collection questionnaires, several of whom completed multiple questionnaires during some months of the surveillance period.

References 1. Vatlach S, Maas C, Poets CF. Birth prevalence and initial treatment of Robin sequence in Germany: a prospective epidemiologic study. Orphanet J Rare Dis. 2014; 9(9) 2. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective populationbased epidemiological study. Cleft Palate Craniofac J. 2004;41(1):47-52 3. Bush PG, Williams AJ. Incidence of the Robin Anomalad (Pierre Robin syndrome). Br J Plast Surg. 1983;36(4):434-7

Researcher contacts Dr Marie Wright Specialty registrar in Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London, SW3 6NP Tel: 0790 631 2371 E-mail: m.wright@rbht.nhs.uk: prs.study@nhs.net Co-investigators Royal Hospital for Sick Children, Edinburgh: Dr Don Urquhart, Dr Felicity Mehendale, Dr Patricia Jackson (retired), Dr Edile Murdoch Our Lady’s Children’s Hospital, Dublin: Dr Sheila Javadpour

BPSU Annual Report 2016-2017

Progressive intellectual and neurological deterioration in children (including Creutzfeldt - Jakob disease) Key points • Continuing surveillance of UK children with progressive intellectual and neurological deterioration (PIND) is important to ensure that new cases of variant Creutzfeldt-Jakob disease (vCJD) are not being missed among the numerous rare neurodegenerative disorders of childhood. • The study provides unique information about the epidemiology of neurodegenerative diseases in UK children. From May 1997 until May 2017 4,194 children have been notified; 1,792 children have a known diagnosis other than vCJD, with over 190 different neurodegenerative disorders in this diagnosed group.

The PIND Expert Group

The PIND team

Methodology Data capture uses standard BPSU methodology; details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/pind

• Six cases of vCJD have been reported to Surveillance period the study since December 1998; four have been classified as “definite” and two “probable”; all May 1997 – April 2022 (inclusive) have now died. • The National Creutzfeldt-Jakob Disease Research and Surveillance Unit in Edinburgh reports that there have been 178 deaths from definite or probable vCJD in UK patients of all ages. Until 2016 all these cases were methionine homozygous at codon 129 of the prion protein gene (PRNP). It is significant that the first and only confirmed methionine/valine heterozygous vCJD adult case was identified last year (2016).

Summary Active prospective surveillance of UK children with progressive intellectual and neurological deterioration (PIND) commenced in May 1997.1 Funded by the Department of Health (England) [PR-ST-1216-10001] it is being carried out via the BPSU in conjunction with the National CreutzfeldtJakob Disease Research and Surveillance Unit in Edinburgh (NCJDRSU) and Public Health England. The study strategy is to look at the broad group of rare neurodegenerative disorders affecting children, carefully examine the clinical details and determine whether there are cases of vCJD (Figure 12) amongst these PIND cases. This unique dataset provides the opportunity to detect vCJD cases and highlight the variety of PIND conditions in the UK.2

Analysis

By May 2017, 4,194 children had been notified; 190 are still “under investigation” by their paediatricians; 1,916 did not meet the PIND definition, were duplicate or error notifications and 71 cases remain outstanding. The remaining cases were classified as follows: Definite and probable cases of vCJD: Six cases of vCJD (four definite and two probable) have been notified - the youngest was a girl aged 12 years at onset. There were three other girls (two aged 14 years and one aged 13 years at age of onset) and two boys aged 15 years at onset. The last child who developed symptoms did so in 2000. All have now died and neuropathology has confirmed vCJD in four cases; a post-mortem was not carried out on the remaining two cases. Children with PIND who have definite diagnoses other than vCJD: More than 190 distinct disorders were diagnosed in these 1,792 children. In the diagnosed cases the ten commonest groups are outlined in Figure 13 overleaf.

Figure 12: Variant CJD is characterised by amyloid plaques that sit in regions of spongiform change in the brain (haematoxylin and eosin stain).

BPSU Annual Report 2016-2017

Figure 13: Ten most commonly reported PIND diagnostic groups (reviewed December 2015)3

Children with PIND and no underlying diagnosis (idiopathic group): The PIND Expert Group meet regularly to discuss this group of children, currently 219. If a “new” variant of vCJD should arise or if the paediatric presentation differed from the adult presentation, this group could include such a phenotype. However, there is currently no evidence of a “new” unrecognised disorder in this group.

3. Winstone AM, Stellitano L, Verity, CM. Niemann–Pick type C as a cause of progressive intellectual and neurological deterioration in childhood. Developmental Medicine & Child Neurology 2017; 59:965-72

Discussion

5. Mok T, Jaunmuktane Z, Joiner S, Campbell T et al. Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129. N Engl J Med 2017; 376:292-294

During 20 years of surveillance, six children presenting with vCJD under 16 years of age have been notified to the study, including four with definite vCJD and two with probable vCJD. There remains concern that more childhood cases may appear, perhaps related to an underlying genotype, and children within the ‘idiopathic’ PIND group are under regular review. Children are still at risk of vCJD infection by blood,4 plasma products, surgical and dental instruments and theoretically via vertical transmission. Continued surveillance is essential as there are still many unanswered questions about this relatively new disorder – in particular, the number of children who may be incubating vCJD, the length of the incubation period and the exact nature of transmission (particularly as the first confirmed adult case of heterozygous vCJD was described last year5). Meanwhile the study continues to yield unique information about the epidemiology of childhood neurodegenerative disorders in the UK. The PIND team continue to present these data at scientific meetings and to publish papers in the relevant journals.

References 1. Verity CM, Nicoll A, Will RG, Devereux G, Stellitano L. Variant Creutzfeldt-Jakob disease in UK children: a national surveillance study. Lancet 2000;356:1224-7 2. Devereux G, Stellitano L, Verity CM, Nicoll A, Will R., Rogers P. Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND). Arch Dis Child 2004; 89(1):812 26

4. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 264:527-29

Funding Department of Health England [PR-ST-1216-10001]

Public and patient engagement Creutzfeldt-Jakob Disease Support Web: http://www.cjdsupport.net

Network.

Batten Disease Family Association. Web: http://www.bdfa-uk.org.uk Society for Mucopolysaccharide Diseases. Web: http://www.mpsociety.co.uk ALD Life (Adrenoleukodystrophy). Web: http://www.aldlife.org The Cure & Action for Tay-Sachs (CATS) Foundation. Web: http://www.cats-foundation.org

Researcher contacts Dr CM Verity (Principal investigator), Professor A Nicoll, Professor R Will, Ms A Powell, Ms AM Winstone Ms A Powell, Ms A M Winstone - c/o Children’s Services, Box 267, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ Tel: 01223 216299 / 01223 217598 E-mail: alison.powell@addenbrookes.nhs.uk or annemarie.winstone@addenbrookes.nhs.uk

BPSU Annual Report 2016-2017

Visual impairment and blindness Key points • The study is progressing very well with excellent support from paediatricians • 183 case reports of children with severe visual impairment/blindness have been confirmed – this is in keeping with the number we anticipated through the British Paediatric Surveillance Unit and the British Ophthalmological Surveillance Unit.

Summary Most children living in the UK with visual impairment or blindness are likely to be affected from birth or infancy and will experience a significant lifelong impact on their development, education, social and emotional wellbeing. The aim of this second British Childhood Visual Impairment and Blindness Study (BCVIS2) is to determine the incidence, causes, mode/context of detection, associated factors, management and short-term health and social outcomes of all-cause childhood visual disability. All children aged ≤18 years diagnosed during a one year period as being severely visually impaired or blind will be identified through their clinicians using national active surveillance independently but concurrently through the British Paediatric Surveillance Unit and the British Ophthalmological Surveillance Unit (BOSU). There will be simultaneous identification of those children with visual impairment (i.e. less severe impairment) through BOSU as these children are unlikely to seen by a paediatrician. The merged dataset will then encompass the full spectrum of visual disability. It is hoped that the findings from this study will inform planning of prevention and treatment strategies and targeting of screening; ‘map’ clinical and public health services involved in detection and management thereby informing the commissioning and delivery of NHS services; and present an evidence base on the sociodemographic variations in childhood visual disability to inform national public health policies.

Methodology Data capture used a dual surveillance methodology using the British Ophthalmological Surveillance Unit (BOSU) in addition to the BPSU, to identify cases of visual impairment (VI) as well as severe visual impairment and blindness (SVI/ BL); details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/bcvis

Professor Jugnoo Rahi

Surveillance period October 2015 – October 2016 (inclusive). Follow-up period: Follow-up questionnaire at 12 months after initial diagnosis, ending in October 2017.

Analysis Thus far, 349 cases have been reported of which 183 have so far been confirmed. A further 279 were reported through BOSU. Preliminary descriptive analyses on the BPSU cohort is highlighted below. 120 (66%) children were diagnosed with poor vision consistent with SVI/BL before their first birthday (Table 7). Children from ethnic minorities (non-white) and those in the lowest socioeconomic group (bottom quintile) are over-represented in SVI/BL (32% and 29% respectively) compared to the general UK population. Table 7: Age at diagnosis of SVI/BL Age diagnosed with poor vision

<1 year

120

1-4 years

5-14 years

15 years

Unknown

Compared to the general UK child population, SVI/ BL children are more likely to be born premature (<37 weeks, 26%) and born low birth weight (<2.5kg, 23%). The factors operating in the prenatal or perinatal period were responsible for SVI/BL in 60% (n=109) and 14% (n=26) of cases respectively, with 12% (n=22) of cases having an unknown aetiology but thought to be pre- or perinatal e.g. congenital abnormalities. 14% (n=25) of cases were caused by a factor operating in childhood. The majority of children had an additional major non-ophthalmic disorder or impairment (87%, n=181). In terms of the primary disorders leading to SVI/BL, the most frequent was cerebral visual impairment (CVI,

Figure 14: Reporting sources for SVI/BL confirmed reports

BPSU Annual Report 2016-2017

Figure 15: Anatomical sites affected in cases of SVI/BL reported through BPSU*

56%), following by optic nerve hypoplasia (18%) and retinal detachment (5%). Figure 15 illustrates the proportion of each ophthalmic site affected in SVI/BL.

Discussion Preliminary analysis shows that children with SVI/BL are a heterogeneous population, with the majority caused by factors operating in the prenatal and perinatal period. SVI/BL children were significantly more likely to be from an ethnic minority, born prematurely and of low birth weight compared to a child from the general UK population. The most deprived socioeconomic group is over-represented in children with SVI/ BL. Cerebral visual impairment appears to be the largest primary disorder resulting in SVI/BL. The findings will provide the evidence base for advocacy for health, social and educational services for visually impaired children and their families, enabling visual disability to be placed in the broader context of child health, particularly by offering an understanding of the social determinants of childhood visual disability, so as to inform policy. In undertaking the study a unique resource will be created– a representative inception cohort of children spanning the spectrum of visual disability in whom longer term clinical, social and educational outcomes of current and emerging interventions can be determined. This study will enable methodological advances that can be applied in other population-based studies such as outcomes research using ‘e-health’ research approaches and longitudinal studies of causality

to identify modifiable risk factors. Additionally, this study will enable health economic modelling of childhood visual disability – currently challenging because of the lack of robust contemporary data on frequency and outcomes.

References 1. Rahi J. and Cable N. Severe visual impairment and blindness in children in the U.K. Lancet 2003; 362:1356-65

Funding This study is funded by Fight for sight (http://www. fightforsight.org.uk).

Public and patient engagement Royal National Institute of Blind People. Web: https://www.rnib.org.uk/

Researcher contacts Professor Jugnoo Rahi, Population, Policy and Practice Unit, UCL GOS Institute of Child Health, 30 Guilford Street, London, WC1N 1EH Tel: 020 7905 2250 E-mail: j.rahi@ucl.ac.uk Twitter: @bcvistudy Co-investigators UCL GOS Institute of Child Health: Lola Ameenat Solebo, Phillippa Cumberland, Lucie Teoh Great Ormond Street Hospital: Dr Jenefer Sargent

BPSU Annual Report 2016-2017

Appendix - Publications 2016 -2017 Acute infectious hepatitis 1. Braccio S, Irwin A, Riordan A, et al. Acute infectious hepatitis in hospitalised children: a British Paediatric Surveillance Unit study. Arch Dis Child Published Online First: April 2017doi:10.1136/ archdischild-2016-311916 https://www.ncbi.nlm. nih.gov/pubmed/28377449 Acute pancreatitis 2. Majbar AA, Cusick E, Johnson P, Lynn RM, Hunt LP, Shield JP; Incidence and Clinical Associations of Childhood Acute Pancreatitis. Pediatrics. 2016 Sep;138(3). pii: e20161198. https://www.ncbi. nlm.nih.gov/pubmed/27535145 Congenital syphilis 3. Simms I, Tookey PA, Goh BT, Lyall H, Evans B, Townsend CL, Fifer H, Ison C. The incidence of congenital syphilis in the United Kingdom: February 2010 to January 2015. BJOG. 2016 Mar 2. doi: 10.1111/1471-0528.13950. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/ pubmed/26931054 Early onset eating disorders 4. Pinhas L, Nicholls D, Crosby RD, Morris A, Lynn RM, Classification of childhood onset eating disorders: A latent class analysis. Madden Int J Eat Disord. 2017 Jan 20. doi: 10.1002/eat.22666. [Epub ahead of print] https://www.ncbi.nlm.nih. gov/pubmed/28106914 HIV infection & perinatal HIV exposure 5. Raffe S, Curtis H, Tookey PA, Peters H, Freedman A, Gilleece Y and on behalf of the British HIV Association Audit and Standards SubCommittee. UK national clinical audit: management of pregnancies in women with HIV. BMC Infectious Diseases. 2017. https://www.ncbi.nlm.nih.gov/ pubmed/28219333 6. Peters H, Francis K, Harding K, Tookey PA, Thorne C. Operative vaginal delivery and invasive procedures in pregnancy among women living with HIV. Eur J Obstet Gynecol Reprod Biol.. 2017; 210 295-299. https://www.ncbi.nlm.nih.gov/ pubmed/28092853

9. Townsend CL, de Ruiter A, Peters H, NelsonPiercy C, Tookey PA, Thorne C. Pregnancies in older women living with HIV in the UK and Ireland. HIV Med. 2017 Aug;18(7):507-512. doi: 10.1111/ hiv.12469. https://www.ncbi.nlm.nih.gov/ pubmed/27862854 10. Thorne C, Tookey PA. Strategies for Monitoring Outcomes in HIV-Exposed Uninfected Children in the United Kingdom. Front. Immunol. 2016; 7:185. https://www.ncbi.nlm.nih.gov/ pubmed/27242792 11. Tookey PA, Thorne C, van Wyk J, Norton M. Maternal and foetal outcomes among 4118 women with HIV infection treated with lopinavir/ritonavir during pregnancy: analysis of population-based surveillance data from the national study of HIV in pregnancy and childhood in the United Kingdom and Ireland. BBMC Infect Dis. 2016; 16:65. https:// www.ncbi.nlm.nih.gov/pubmed/26847625 12. Peters H, Byrne L, de Ruiter A, Francis K, Harding K, Taylor GP, Tookey PA, Townsend CL. Duration of ruptured membranes and mother-to-child HIV transmission: a prospective population-based surveillance study. BJOG 2016 May;123(6):975-81. https://www.ncbi.nlm.nih. gov/pubmed/26011825 Idiopathic Intracranial Hypertension (IIH) 13. Matthews Y, Dean F, Lim MJ, et al Pseudotumor cerebri syndrome in childhood: incidence, clinical profile and risk factors in a national prospective population-based cohort study Archives of Disease in Childhood Published Online First: 29 March 2017. doi: 10.1136/archdischild-2016-312238 Intussusception 14. Samad L, Cortina-Borja M, Sutcliffe AG, Marven S, Cameron JC, El Bashir H, Lynn R, Taylor B. National hospital data for intussusception: Data linkage and retrospective analysis to assess quality and use in vaccine safety surveillance. Vaccine. 2016 Jan 12;34(3):373-9 https://www. ncbi.nlm.nih.gov/pubmed/26667612 Progressive intellectual and neurological deterioration

7. French CE, Thorne C, Byrne L, Cortina-Borja M, Tookey PA. Presentation for care and antenatal management of HIV in the United Kingdom: temporal trends and demographic variations, 2009-2014. HIV Medicine. 2017 Mar;18(3):161170

15. Winstone AM, Stellitano L, Verity, CM. Niemannâ&#x20AC;&#x201C;Pick type C as a cause of progressive intellectual and neurological deterioration in childhood. Dev Med Child Neurol. 2017 Jun 2. doi: 10.1111/dmcn.13476. https://www.ncbi.nlm.nih. gov/pubmed/28574146

8. Peters H, Francis K, Sconza R, Horn A, Peckham C, Tookey PA and Thorne C. UK Mother to Child HIV Transmission Rates Continue to Decline: 2012-2014. Clin Infect Dis. 2017 Feb 15;64(4):527-528. https:// www.ncbi.nlm.nih.gov/pubmed/28174911

16. Stellitano LA, Winstone AM, van der Knaap MS, Verity C. Leukodystrophies and genetic leukoencephalopathies in childhood - a national epidemiological study. Dev Med Child Neurol. 2016 Jul;58(7):680-9. doi: 10.1111/dmcn.13027. https:// www.ncbi.nlm.nih.gov/pubmed/26866636

BPSU Annual Report 2016-2017

Appendix - Presentations 2016 -2017 Bacterial meningitis in Infants aged <90 days 1. Okike I, Ladhani S, Johnson A, Henderson K, Blackburn R, Muller-Pebody B, Cafferkey M, Anthony M, Ninis N, Heath P. Presentation, management and outcome of bacterial meningitis in young infants in the United Kingdom and Ireland. ESPID conference, Brighton UK May 10-15 2016 2. Ladhani S. Epidemiology of Meningococcal Disease in the UK. ESPID conference, Brighton UK, 10-15 May 2016 Behcet’s syndrome 3. Pain C, Rice H, Beresford M, Brogan P, Fortune F, Moots R, Murphy R. British Paediatric Surveillance Unit (BPSU) study of Behcet’s syndrome in children and young people in the United Kingdom. Clinical and Experimental Rheumatology 2016. 34; 6: S157-S157 4. Pain C. Behçet’s syndrome in the UK – preliminary results from the BPSU study. British Paediatric Rheumatology Adolescent Rheumatology Annual Conference 2016. Manchester Nov 2016 Diabetes in childhood 5. Drummond L, Barrett T. Diabetes in childhood – an ever developing concern. BPSU 30th anniversary symposium, RCPCH conference, Liverpool UK April 2016 Group B Streptococcal (GBS) disease 6. O’Sullivan C. Group B Streptococcal (GBS) disease in UK and Irish infants younger than 90 days, 2014-2015. RCPCH conference Liverpool UK April 2016 7. O’Sullivan C, Lamagni T, Patel D, Efstratiou A, Reynolds A, Cunney R, Meehan M, Campbell R, Doherty L, Boyle M, Davies E, Heath P. Group B Streptococcal (GBS) Disease in UK and Irish Infants Younger Than 90 Days Of Age In 2014-15. ESPID conference, Brighton UK, May 10-15 2016 Kawasaki disease 8. Brown K, Tulloh R, Ramanan A, et al. Can we predict the severity of coronary artery changes in the BPSU survey of Kawasaki disease from the phenotypic presentation? Archives of Disease in Childhood 2016;101:A186 Progressive intellectual and neurological deterioration 9. Verity C. Responding to public health emergencies / addressing emerging infectious disease – PIND-H1N1; new vaccines. BPSU 30th anniversary symposium, RCPCH conference, Liverpool UK April 2016 10. Verity C. Leukodystrophies and genetic leukoencephalopathies in childhood - a national epidemiological study. British Paediatric Neurology Association Meeting, Sheffield UK. 27-29 January 2016 30

11. Winstone AM. Children with NiemannPick Type C disease in the UK – review of the clinical spectrum in 53 children. British Paediatric Neurology Association Meeting, Sheffield UK. 2729th January 2016 Surgical ligation of the patent ductus arteriosus 12. Lakshmanan A, Crosby T, Kelsall W, Lee L. Outcome of surgical ligation of the patent ductus arteriosus in premature babies – a national prospective study Arch Dis Child 2016;101:A76-A77. Abstract presented at RCPCH conference Liverpool UK April 2016 Nutritional Rickets 13. Julies P. Vitamin d deficiency – the evidence to date – BPSU 30th anniversary symposium, RCPCH conference, Liverpool UK April 2016 Exchange blood transfusion 14. Gottstein R. Rennie J et al. Oral presentation of interim data analysis at regional meeting: NorthWest Neonatal Study Day; Manchester, January 2016. 15. Gottstein R. Rennie J et al. Poster presentation at 17th Annual NATA Symposium; Dublin, April 2016 Transfusion Medicine 2016; 26 (Suppl 1):39 16. Gottstein R. Rennie J et al. Poster presentation at Royal College of Paediatrics and Child Health (RCPCH) annual conference; Liverpool, April 2016. Arch Dis Child 101(Suppl 1):A254-A255 · April 2016 17. Gottstein R. Invited oral presentation at British Blood Transfusion Society (BBTS) annual Conference; Harrogate, UK, September 2016 18. Gottstein R. Rennie J et al. Poster presentation at the European Association of Paediatric Societies (EAPS) Conference, Geneva October 2016 Congenital Zika syndrome 19. Oeser C. Congenital Zika Syndrome: Obstetric and paediatric surveillance in the UK and ROI. Poster, International Meeting on Emerging Diseases and Surveillance, Vienna, 11/2016 20. Oeser C. BPSU surveillance of congenital Zika syndrome, Presentation, 9th International Network of Paediatric Surveillance Units (INOPSU) Scientific Meeting Vancouver, 08/2016 21. Oeser C, Rapid surveillance systems in emergency situations: the Zika experience, Presentation, PHE annual conference, Warwick, 09/2016 22. Pebody R et al. Congenital Zika Syndrome: Establishing obstetric and paediatric surveillance in the UK and ROI. Poster, PHE annual conference, Warwick, 09/2016

BPSU Annual Report 2016-2017

Notes

BPSU Annual Report 2016-2017

Notes

BPSU Annual Report 2016-2017

Membership of Scientific Committee 2016 Dr Richard Reading Chair Dr Rachel Knowles* Medical Advisor (non-infectious disease), UCL Great Ormond Street Institute of Child Health Dr Olivier le Polain de Waroux** Medical Advisor (infectious disease), Public Health England Medical Advisor (non-infectious disease), UCL Great Ormond Street Institute of Child Health Scientific Coordinator Royal College of Physicians of Ireland Director of Research and Policy. Royal College of Paediatrics & Child Health Vice President Science & Research, Royal College of Paediatrics & Child Health Consultant in Neonatology Consultant Paediatrician Consultant in Intensive Care Senior Epidemiologist, Health Protection Scotland General Paediatrics Consultant in Nephrology Patient and Carers Representative Specialist Registrar in Paediatric Infectious Diseases & Immunology Patient and Carers Representative Consultant in Public Health Medicine Public Health England

* Stepped down in 2016 ** Stepped down in 2017

British Paediatric Surveillance Unit Published October 2017 by the British Paediatric Surveillance Unit: Royal College of Paediatrics and Child Health 5-11 Theobalds Road London WC1X 8SH Telephone: E-mail: Website: Twitter:

+44 (0) 207 092 6173/74 bpsu@rcpch.ac.uk http://www.rcpch.ac.uk/bpsu @BPSUTweet

BPSU parent bodies:

with support from: